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Ruiz-Genao DP, González-Quesada A, Sahuquillo-Torralba A, Rivera-Díaz R, Descalzo MA, García-Doval I. AEDV BIOBADADERM Registry: 15 Year-Contribution to Psoriasis Therapy Safety. ACTAS DERMO-SIFILIOGRAFICAS 2025:S0001-7310(25)00122-X. [PMID: 40081470 DOI: 10.1016/j.ad.2024.11.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 11/04/2024] [Accepted: 11/10/2024] [Indexed: 03/16/2025] Open
Abstract
The objective of this article is to collect and describe the most relevant BIOBADADERM findings since its beginning in 2008. BIOBADADERM is a prospective cohort registry whose main aim is to analyze the safety profile of the new systemic therapy for the management of psoriasis. Data included in the registry allowed the publication of numerous articles over the past 15 years (2008-2023). Data from the registry join those obtained from clinical trials regarding safety and efficacy profile. Additionally, it has expanded our knowledge of population groups excluded from clinical trials and in less frequent settings. Collaboration with other registries has given us a few fact-checking answers in smaller groups.
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Affiliation(s)
- D P Ruiz-Genao
- Servicio de Dermatología, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, España.
| | - A González-Quesada
- Servicio de Dermatología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, España
| | - A Sahuquillo-Torralba
- Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - R Rivera-Díaz
- Servicio de Dermatología, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, España
| | - M A Descalzo
- Unidad de Investigación, Academia Española de Dermatología y Venereología, Madrid, España
| | - I García-Doval
- Servicio de Dermatología, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, España
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Wang J, He C, Guo Y, Zhong Z, Shu L, Fang Z, Zhang Z. Low-molecular-weight heparin sodium inhibits the MAPK pathway for psoriasis treatment in mice. Int J Biol Macromol 2025; 293:139372. [PMID: 39743060 DOI: 10.1016/j.ijbiomac.2024.139372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 12/01/2024] [Accepted: 12/29/2024] [Indexed: 01/04/2025]
Abstract
Psoriasis is difficult to treat clinically and lacks an effective treatment. Low-molecular-weight heparin sodium (LMH) is an animal glycosaminoglycan with anti-inflammatory properties. Transdermal and intradermal retention studies have suggested that LMH sodium can reach the dermis. This study investigated the anti-psoriasis effects of LMH in an imiquimod-induced mouse model, examining pathological changes, inflammation levels, and protein expression. Transdermal application of LMH in imiquimod-induced psoriasis mice revealed that epidermal thickening and scaling were alleviated, as shown by PASI scores. Serum ELISA and real-time quantitative PCR showed that inflammatory factor levels and mRNA expression were reduced. This indicates that LMH inhibits P38 protein phosphorylation and ERK expression, blocking the MAPK pathway. Combining LMH with paeoniflorin further improved psoriasis symptoms in mice. These findings suggest that LMH has significant potential for clinical application in psoriasis treatment.
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Affiliation(s)
- Jing Wang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,100 Shizi Road, Nanjing, Jiangsu 210028, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu 210028, China
| | - Chen He
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,100 Shizi Road, Nanjing, Jiangsu 210028, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu 210028, China
| | - Yanyan Guo
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,100 Shizi Road, Nanjing, Jiangsu 210028, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu 210028, China
| | - Ziyi Zhong
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,100 Shizi Road, Nanjing, Jiangsu 210028, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu 210028, China
| | - Luan Shu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,100 Shizi Road, Nanjing, Jiangsu 210028, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu 210028, China
| | - Zhijun Fang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,100 Shizi Road, Nanjing, Jiangsu 210028, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu 210028, China.
| | - Zhenhai Zhang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,100 Shizi Road, Nanjing, Jiangsu 210028, China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Province Academy of Chinese Medicine, Nanjing, Jiangsu 210028, China.
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Fang R, Zhou Y, Han L, Chen W, Sun Y, Li J. Infection and infestation-related adverse events of biologics in psoriasis: insights from the Food and Drug Administration Adverse Event Reporting System (FAERS). Expert Opin Drug Saf 2024:1-12. [PMID: 39365557 DOI: 10.1080/14740338.2024.2412221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 08/21/2024] [Accepted: 08/27/2024] [Indexed: 10/05/2024]
Abstract
OBJECTIVE The study aims to thoroughly assess the adverse events related to infections and infestations associated with biological agents used for psoriasis using the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database. METHODS We analyzed FAERS data from the first quarter of 2004 to the fourth quarter of 2023. The study included TNF-α inhibitors (etanercept, infliximab, adalimumab), IL-12/23 inhibitors (ustekinumab), IL-23p19 inhibitors (guselkumab), and IL-17 inhibitors (secukinumab, ixekizumab). We used disproportionality analysis and Bayesian methods to quantify the related adverse event (AE) signals. RESULTS Most AEs related to infections and infestations are already listed on the drug packaging labels. Notably, TNF-α inhibitors are associated with a significantly higher incidence of tuberculosis-related diseases compared to other biological agents. In contrast, IL-17 inhibitors show a greater variety and number of fungal infection-related AEs than their counterparts. Furthermore, our study has identified new potential AEs that require the attention of clinicians. CONCLUSION In clinical practice, it is advisable to monitor the risks of infections and infestations in patients receiving biological agents for psoriasis to enable early detection and intervention. Our findings highlight the need for further epidemiological investigations to establish causality and guide clinical practice in managing these risks effectively.
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Affiliation(s)
- Runan Fang
- Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yang Zhou
- Department of Endocrinology, Beijing University of Chinese Medicine, Guang'anmen Hospital of China Academy of Chinese Medicine Sciences, Beijing, China
| | - Lu Han
- Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Wenjing Chen
- Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yuan Sun
- Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jianhong Li
- Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Tatovic D, Marwaha A, Taylor P, Hanna SJ, Carter K, Cheung WY, Luzio S, Dunseath G, Hutchings HA, Holland G, Hiles S, Fegan G, Williams E, Yang JHM, Domingo-Vila C, Pollock E, Wadud M, Ward-Hartstonge K, Marques-Jones S, Bowen-Morris J, Stenson R, Levings MK, Gregory JW, Tree TIM, Dayan C. Ustekinumab for type 1 diabetes in adolescents: a multicenter, double-blind, randomized phase 2 trial. Nat Med 2024; 30:2657-2666. [PMID: 39079992 PMCID: PMC11405276 DOI: 10.1038/s41591-024-03115-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 06/05/2024] [Indexed: 09/18/2024]
Abstract
Immunotherapy targeting the autoimmune process in type 1 diabetes (T1D) can delay the loss of β-cells but needs to have minimal adverse effects to be an adjunct to insulin in the management of T1D. Ustekinumab binds to the shared p40 subunit of interleukin (IL)-12 and IL-23, targeting development of T helper 1 cells and T helper 17 cells (TH1 and TH17 cells) implicated in the pathogenesis of T1D. We conducted a double-blind, randomized controlled trial of ustekinumab in 72 adolescents aged 12-18 years with recent-onset T1D. Treatment was well tolerated with no increase in adverse events. At 12 months, β-cell function, measured by stimulated C-peptide, was 49% higher in the intervention group (P = 0.02), meeting the prespecified primary outcome. Preservation of C-peptide correlated with the reduction of T helper cells co-secreting IL-17A and interferon-γ (TH17.1 cells, P = 0.04) and, in particular, with the reduction in a subset of TH17.1 cells co-expressing IL-2 and granulocyte-macrophage colony-stimulating factor (IL-2+ GM-CSF+ TH17.1 cells, P = 0.04). A significant fall in β-cell-targeted (proinsulin-specific) IL-17A-secreting T cells was also seen (P = 0.0003). Although exploratory, our data suggest a role for an activated subset of TH17.1 cells in T1D that can be targeted with minimal adverse effects to reduce C-peptide loss, which requires confirmation in a larger study. (International Standard Randomised Controlled Trial Number Registry: ISRCTN 14274380).
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Affiliation(s)
- Danijela Tatovic
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
| | | | - Peter Taylor
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
| | - Stephanie J Hanna
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
| | - Kym Carter
- Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK
| | - W Y Cheung
- Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK
| | - Steve Luzio
- Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK
| | - Gareth Dunseath
- Diabetes Research Unit Cymru, Institute for Life Sciences, Swansea University, Swansea, UK
| | | | - Gail Holland
- Swansea Trials Unit, Swansea University Medical School, Swansea, UK
| | - Steve Hiles
- Swansea Trials Unit, Swansea University Medical School, Swansea, UK
| | - Greg Fegan
- Swansea Trials Unit, Swansea University Medical School, Swansea, UK
| | - Evangelia Williams
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Jennie H M Yang
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Clara Domingo-Vila
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Emily Pollock
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Muntaha Wadud
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Kirsten Ward-Hartstonge
- BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Jane Bowen-Morris
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
| | - Rachel Stenson
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
| | - Megan K Levings
- BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
- Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada
| | - John W Gregory
- Division of Population Medicine, Cardiff University School of Medicine, Cardiff, UK
| | - Timothy I M Tree
- Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, UK
| | - Colin Dayan
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
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Higashi Y, Imafuku S, Tsuruta N, Murotani K. Systemic therapy for psoriasis and the risk of cutaneous infections. J Dermatol 2024; 51:939-949. [PMID: 38660962 PMCID: PMC11483952 DOI: 10.1111/1346-8138.17245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 03/21/2024] [Accepted: 04/08/2024] [Indexed: 04/26/2024]
Abstract
Systemic treatments are important for patients with moderate-to-severe psoriasis; however, they may occasionally cause adverse infectious events. Although the risk of severe infections with psoriatic treatments is well established, little is known about cutaneous infections. Therefore, we studied the frequency of cutaneous infections in patients with psoriasis who underwent biologic treatment. A total of 878 patients (237 females and 641 males) were analyzed in this follow-up survey conducted in 2020 and based on the Western Japan Psoriasis Registry. The observed skin phenotypes were psoriasis vulgaris (83.3%), pustular psoriasis (7.5%), and psoriatic arthritis (28.9%). The most frequently prescribed systemic drug was apremilast (11.3%), followed by ixekizumab (11.0%), risankizumab (10.9%), and secukinumab (10.4%). The incidence of cutaneous bacterial infections was 12 (1.37% of the total patients), with cellulitis being the most common (8/12, 67%). The incidence of viral infections was 11 (1.25%) including the most common, herpes zoster (9/11, 82%); and that of fungal infections was 45 (5.13%) including 33 (73%) and seven (16%) patients with trichophytosis and oral candidiasis, respectively. Multivariate analysis revealed that cutaneous bacterial infections were frequently observed in patients receiving tumor necrosis factor-α (odds raio [OR] 9.917, 95% confidence interval [CI] 2.069-47.572, p = 0.004) and interleukin (IL)-17 (OR 10.798, 95% CI 2.35-49.616, p = 0.002) inhibitor treatments. A history of otitis media and treatment with oral medications (OR 4.50, 95% CI 1.281-15.804, p = 0.019 and OR 3.80, 95% CI 1.141-12.679, p = 0.03 respectively) were associated with a higher ORs for cutaneous viral infections. Furthermore, age and use of IL-17 inhibitors were associated with elevated ORs for fungal infections. In conclusion, our study reveals that systemic therapies may increase the risk of cutaneous viral infections. Therefore, dermatologists should exercise caution in this regard.
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Affiliation(s)
- Yuko Higashi
- Department of DermatologyKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Shinichi Imafuku
- Department of DermatologyFukuoka University Faculty of MedicineFukuokaJapan
| | - Noriko Tsuruta
- Division of DermatologyKitakyushu City Yahata HospitalKitakyusyuJapan
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Stephan B, Rustenbach SJ, Ben-Anaya N, Augustin M, Boehncke WH, Hertl M, Mrowietz U, Staubach-Renz P, Thaçi D, von Kiedrowski R, Sorbe C. Basic Susceptibility of Patients with Psoriasis under Systemic Therapy for Respiratory Infections: Data from the German Psoriasis Registry PsoBest. J Clin Med 2024; 13:3713. [PMID: 38999279 PMCID: PMC11242749 DOI: 10.3390/jcm13133713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/06/2024] [Accepted: 06/19/2024] [Indexed: 07/14/2024] Open
Abstract
Background: Patients with psoriasis under systemic treatments are in focus regarding their susceptibility to respiratory infections. To analyse real-world data for respiratory infections in patients with psoriasis under systemic treatments. Methods: We analysed data of the prospective, non-interventional German Psoriasis Registry PsoBest and compared rates for respiratory infections of 13,823 patients on systemic treatments for psoriasis and/or psoriatic arthritis in different therapy cohorts before the COVID-19 pandemic. Results: In total, 1415 respiratory infections were observed in 970 patients. Significant differences were observed between biologics and non-biologics, but not within these groups. The highest event rates (events/100 patient years) were identified for TNF-α inhibitors, 8.1, (CI 7.4-8.9), followed by 7.0 for IL-17 inhibitors (6.2-7.9), 5.7 for IL-12/23 and IL-23 inhibitors (5.1-6.5), 4.8 for methotrexate (4.3-5.4), 3.7 for small molecules (3.3-4.2), and 2.7 for retinoids (1.2-5.1). Conclusions: Overall, the susceptibility for respiratory infections in patients under systemic therapy for psoriasis is low compared to published study data and is sufficient as comparative data for COVID-19 studies.
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Affiliation(s)
- Brigitte Stephan
- Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany; (S.J.R.); (N.B.-A.); (M.A.); (C.S.)
| | - Stephan Jeff Rustenbach
- Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany; (S.J.R.); (N.B.-A.); (M.A.); (C.S.)
| | - Nesrine Ben-Anaya
- Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany; (S.J.R.); (N.B.-A.); (M.A.); (C.S.)
| | - Matthias Augustin
- Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany; (S.J.R.); (N.B.-A.); (M.A.); (C.S.)
| | - Wolf-Henning Boehncke
- Department of Dermatology and Venereology, Geneva University Hospitals, 1205 Geneva, Switzerland;
| | - Michael Hertl
- Department of Dermatology, University Hospital Marburg, 35043 Marburg, Germany;
| | - Ulrich Mrowietz
- Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany;
| | - Petra Staubach-Renz
- Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany;
| | - Diamant Thaçi
- Comprehensive Center for Inflammation Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, 23562 Lübeck, Germany;
| | | | - Christina Sorbe
- Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany; (S.J.R.); (N.B.-A.); (M.A.); (C.S.)
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Lluch-Galcerá JJ, Carrascosa JM, González-Quesada A, Rivera-Díaz R, Sahuquillo-Torralba A, Llamas-Velasco M, Gómez-García FJ, Herrera-Acosta E, de la Cueva P, Baniandrés-Rodríguez O, Lopez-Estebaranz JL, Belinchón I, Ferrán M, Mateu A, Rodríguez L, Riera-Monroig J, Abalde-Pintos MT, Carretero G, García-Donoso C, Pujol-Marco C, Del Alcázar E, Santamaría-Domínguez C, Suárez-Pérez JA, Nieto-Benito LM, Ruiz-Genao DP, Salgado-Boquete L, Descalzo MÁ, García-Doval I. Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry. Br J Dermatol 2024; 190:355-363. [PMID: 37846976 DOI: 10.1093/bjd/ljad382] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 09/27/2023] [Accepted: 09/28/2023] [Indexed: 10/18/2023]
Abstract
BACKGROUND Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.
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Affiliation(s)
- Juan José Lluch-Galcerá
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, IGTP. Badalona, Barcelona, Spain
- Departament de Medicina, Universitat Autonoma de Barcelona (UAB), Barcelona, Spain
| | - Jose Manuel Carrascosa
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, IGTP. Badalona, Barcelona, Spain
- Departament de Medicina, Universitat Autonoma de Barcelona (UAB), Barcelona, Spain
| | - Alicia González-Quesada
- Department of Dermatology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Islas Canarias, Spain
| | - Raquel Rivera-Díaz
- Department of Dermatology, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain
| | | | - Mar Llamas-Velasco
- Department of Dermatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-LP), Madrid,Spain
| | | | | | - Pablo de la Cueva
- Department of Dermatology, Hospital Universitario Infanta Leonor, Madrid, Spain
| | | | | | - Isabel Belinchón
- Department of Dermatology, Hospital General Universitario de Alicante-ISABIAL-UMH, Alicante, Spain
| | - Marta Ferrán
- Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Almudena Mateu
- Department of Dermatology, Hospital Universitario Doctor Peset, Valencia, Spain
| | - Lourdes Rodríguez
- Department of Dermatology, Hospital Virgen del Rocío, Seville, Spain
| | - Josep Riera-Monroig
- Department of Dermatology, Hospital Clinic de Barcelona, UB, Barcelona, Spain
| | - M Teresa Abalde-Pintos
- Department of Dermatology, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - Gregorio Carretero
- Department of Dermatology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Islas Canarias, Spain
| | - Carmen García-Donoso
- Department of Dermatology, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain
| | - Conrad Pujol-Marco
- Department of Dermatology, Hospital Universitario y Politécnico La Fe, Valencia,Spain
| | - Elena Del Alcázar
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, IGTP. Badalona, Barcelona, Spain
- Departament de Medicina, Universitat Autonoma de Barcelona (UAB), Barcelona, Spain
| | - Cristina Santamaría-Domínguez
- Department of Dermatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-LP), Madrid,Spain
| | | | - Lula María Nieto-Benito
- Department of Dermatology, CEIMI, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | - Laura Salgado-Boquete
- Department of Dermatology, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | | | - Ignacio García-Doval
- Research Unit, Spanish Academy of Dermatology and Venereology, Madrid, Spain
- Department of Dermatology, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain
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Wu S, Xu Y, Yang L, Guo L, Jiang X. Short-term risk and long-term incidence rate of infection and malignancy with IL-17 and IL-23 inhibitors in adult patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Front Immunol 2023; 14:1294416. [PMID: 38106423 PMCID: PMC10721978 DOI: 10.3389/fimmu.2023.1294416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 11/10/2023] [Indexed: 12/19/2023] Open
Abstract
The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term treatments. We aimed to estimate the short-term risks and long-term incidence rates of infection and malignancy with IL-17 or IL-23 antagonists in adult patients with psoriasis and psoriatic arthritis through this comprehensive meta-analysis (PROSPERO registration number: CRD42022363127). We searched PubMed, MEDLINE, Web of Science and ClinicalTrials.gov until May 17, 2023 for randomized placebo-controlled trials and long-term (≥ 52 weeks) open-label extension studies. The estimates of short-term risk ratios (RRs) and long-term exposure-adjusted incidence rates (EAIRs) were pooled using R software 4.1.1 and STATA 16.0. This review included 45 randomized placebo-controlled studies and 27 open-label extension studies. Short-term RRs of serious infection, overall infection and malignancy were 1.45 (95% confidence intervals, 95% CI: 0.81-2.59), 1.20 (95% CI: 1.06-1.35), 0.83 (95% CI: 0.41-1.71) with IL-17 inhibitors; and 0.68 (95% CI: 0.38-1.22), 1.13 (95% CI: 1.00-1.28), 0.87 (95% CI: 0.37-2.04) with IL-23 inhibitors. Increased short-term risks of nasopharyngitis and Candida infection with IL-17 inhibitors were found. Long-term EAIRs of serious infection, overall infection, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, nasopharyngitis and upper respiratory tract infection were 1.11/100 patient-years (PYs), 57.78/100PYs, 0.47/100PYs, 0.24/100PYs, 15.07/100PYs, 8.52/100PYs, 3.41/100PYs with IL-17 inhibitors; and 1.09/100PYs, 48.50/100PYs, 0.40/100PYs, 0.43/100PYs, 10.75/100PYs, 5.84/100PYs with IL-23 inhibitors. Long-term EAIR of Candida infection was 3.41/100PYs with IL-17 inhibitors. No active or reactivated tuberculosis was ever reported in all the trials, and only a few cases of latent tuberculosis, hepatitis, and herpes zoster were reported during the long-term extension periods. No evidence of increased EAIRs of infection and malignancy with longer durations was found. Our study suggested that short-term risk and long-term incidence of infections and malignancies in psoriasis patients receiving IL-17 inhibitors and IL-23 inhibitors are generally low. However, close monitoring is required for nasopharyngitis and Candida infection with IL-17 inhibitors. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363127.
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Affiliation(s)
- Shuwei Wu
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yuanyuan Xu
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Lihua Yang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Linghong Guo
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- Tianfu Jincheng Laboratory & Institute of Future Medical Innovation, City of Future Medicine, Chengdu, China
| | - Xian Jiang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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9
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Chiu HY, Hung YT, Huang YH. Comparative short-term risks of infection and serious infection in patients receiving biologic and small-molecule therapies for psoriasis and psoriatic arthritis: a systemic review and network meta-analysis of randomized controlled trials. Ther Adv Chronic Dis 2023; 14:20406223231206225. [PMID: 37901688 PMCID: PMC10612457 DOI: 10.1177/20406223231206225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 09/20/2023] [Indexed: 10/31/2023] Open
Abstract
Background Infection events are a major concern for patients and physicians when making psoriasis treatment decisions. Objective To estimate the relative short-term risks of infection and serious infection for biologic and small molecule therapies in the treatment of moderate-to-severe plaque psoriasis (PsO) and psoriatic arthritis (PsA). Data Sources and Methods A systematic literature search of the PubMed, EMBASE, and Web of Science databases was conducted on 17 June 2022. We included phase II, III, or IV randomized controlled trials (RCTs) of biologic and small-molecule therapies that are licensed or likely to gain approval soon for PsO and PsA, as well as infection data reports. Two investigators independently extracted the data based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis (NMA) was performed to estimate the pooled relative risks (RRs) and corresponding 95% confidence intervals of total infections and serious infections for treatments during placebo-controlled phases of RCTs. The surface under the cumulative ranking area (SUCRA) was calculated to rank the infection risk for each treatment. Results A total of 94 RCTs with a total of 19 treatment arms involving 54,369 participants were analyzed. For patients with PsO, bimekizumab, secukizumab, risankizumab, ustekinumab, apremilast, guselkumab, and adalimumab were associated with significantly higher risks of infection than placebo; SUCRA ranked infliximab, deucravacitinib, and bimekizumab with the highest risks of infection. For patients with PsA, bimekizumab, apremilast, and upadacitinib (30 mg daily) were associated with higher risks of infection; SUCRA ranked bimekizumab with the highest risk of infection. No treatments, except for upadacitinib (30 mg daily), were associated with a higher risk of serious infection than placebo in PsA. Conclusion This NMA provides a comprehensive assessment of the comparative short-term risks of infection, which could help physicians and patients to select individualized treatments for psoriasis. Registration CRD42022359873.
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Affiliation(s)
- Hsien-Yi Chiu
- Department of Dermatology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu
- Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu
- Department of Dermatology, National Taiwan University Hospital, Taipei
- Department of Dermatology, College of Medicine, National Taiwan University, Taipei
| | - Yi-Teng Hung
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan
| | - Yu-Huei Huang
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Guishan Dist., Taoyuan City 333 School of Medicine, Chang Gung University, Taoyuan
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10
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Xiao Y, Mi W, Wang J, Wen D, Wang Y, Gu Y, Hao D, Yan W, Chen X, Li W. A Propensity Score-Matched Study on the Changes of TB Status and TB-IGRA Values in Patients with Psoriasis with Latent TB Receiving Secukinumab. Dermatol Ther (Heidelb) 2023; 13:2387-2401. [PMID: 37615837 PMCID: PMC10539261 DOI: 10.1007/s13555-023-00998-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 08/01/2023] [Indexed: 08/25/2023] Open
Abstract
INTRODUCTION The utilization of biologics in patients with psoriasis with latent tuberculosis infection (LTBI) has garnered significant attention. Although the tuberculosis (TB) safety profile of second-generation biologics, including secukinumab, has been partially confirmed in both clinical trials and real-world studies, the necessity for prophylactic therapy in patients with LTBI prior to administering this class of biologics remains a topic of controversy. METHODS This study enrolled 62 patients with psoriasis with LTBI who underwent secukinumab with routine TB reexamination. Patients were divided into two groups based on whether they received antituberculosis therapy (ATB; n = 48) or not (NTB; n = 16). We performed a propensity score-matched (PSM) analysis between ATB and NTB subgroups and retrospectively reviewed their interferon-gamma release assays (IGRA) and radiographic results. RESULTS No active TB case was reported on the basis of medical records and chest radiographs in either two group. Before PSM, the mean reexamining IGRA value was significantly elevated in patients who received prophylactic therapy (P = 0.00), but no significant increase was observed in patients who were not. After PSM, there was no significant IGRA value enhancement whether or not patients received prophylactic treatment. CONCLUSION Our data provide additional information on the safety profile of secukinumab in patients with psoriasis with LTBI. Furthermore, our presentation of the reexamined IGRA results revealed no significant elevation in the ATB or NTB group. As such, we believe further exploration is necessary to determine whether anti-TB medication is required prior to administering secukinumab.
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Affiliation(s)
- Yue Xiao
- Department of Dermatology & Venereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Wenyao Mi
- Department of Dermatology & Venereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Jinqiu Wang
- Department of Dermatology & Venereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Dingke Wen
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Yiyi Wang
- Department of Dermatology & Venereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Yuanxia Gu
- Department of Dermatology & Venereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Dan Hao
- Department of Dermatology & Venereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Wei Yan
- Department of Dermatology & Venereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Xuerong Chen
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
| | - Wei Li
- Department of Dermatology & Venereology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
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11
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Prestes-Carneiro LE, de Abreu MAMM, Roncada EVM, Muchon DG, Caliani FM, Vasconcelos DM. Impact of Treatment with Ustekinumab on Severe Infections in a Patient with Uncontrolled Psoriasis and Late-Onset Combined Primary Immunodeficiency: Case Report. Pathogens 2023; 12:1156. [PMID: 37764964 PMCID: PMC10537455 DOI: 10.3390/pathogens12091156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/05/2023] [Accepted: 09/09/2023] [Indexed: 09/29/2023] Open
Abstract
A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and Crohn's disease was attended in the Regional Hospital of Presidente Prudente and HC-FMUSP, São Paulo, Brazil. Anti-IL-12/IL-23 (ustekinumab) monoclonal antibody was prescribed due to the failure of other treatments (phototherapy, oral acitretin) for psoriasis and a Psoriasis Area Severity Index >10. We evaluated the impact of treatment with ustekinumab on severe infectious diseases in a patient with uncontrolled psoriasis and LOCID followed for 8 years. Four quarterly doses of ustekinumab 90 mg and human immunoglobulin replacement (10,000 mg at 28-day intervals) were administered. Immunophenotyping, cultures of lymphocytes, genetic sequencing, and whole exome sequencing were performed to investigate the primary immunodeficiency. Normal lymphocyte proliferation; pathogenic variants in genetic sequencing, and clinically significant variants in the whole exome for primary immunodeficiencies were not detected. The main infections before and after treatment with ustekinumab were chronic sinusitis and gastroenteritis. The patient was infected with COVID-19, dengue (twice) and influenza and was hospitalized three times for intravenous antibiotic therapy. Ustekinumab did not influence the susceptibility of the patient with LOCID to severe infections and significantly improved psoriasis, psoriatic arthritis, and Crohn's disease.
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Affiliation(s)
- Luiz Euribel Prestes-Carneiro
- Immunodeficiencies and Infectious Diseases Outpatient Clinic, Faculty of Medicine, Oeste Paulista University, Presidente Prudente 19.050-920, Brazil; (D.G.M.); (F.M.C.)
| | | | - Eduardo Vinicius Mendes Roncada
- Department of Dermatology, Faculty of Medicine, Oeste Paulista University, Presidente Prudente 19.050-920, Brazil; (M.A.M.M.d.A.); (E.V.M.R.)
| | - Diego Garcia Muchon
- Immunodeficiencies and Infectious Diseases Outpatient Clinic, Faculty of Medicine, Oeste Paulista University, Presidente Prudente 19.050-920, Brazil; (D.G.M.); (F.M.C.)
| | - Fernanda Miranda Caliani
- Immunodeficiencies and Infectious Diseases Outpatient Clinic, Faculty of Medicine, Oeste Paulista University, Presidente Prudente 19.050-920, Brazil; (D.G.M.); (F.M.C.)
| | - Dewton Moraes Vasconcelos
- Laboratory of Medical Investigation Unit 56, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo 05403 000, Brazil;
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12
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Lee HJ, Kim M. Challenges and Future Trends in the Treatment of Psoriasis. Int J Mol Sci 2023; 24:13313. [PMID: 37686119 PMCID: PMC10487560 DOI: 10.3390/ijms241713313] [Citation(s) in RCA: 69] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 08/24/2023] [Accepted: 08/24/2023] [Indexed: 09/10/2023] Open
Abstract
Psoriasis is a chronic inflammatory skin disorder, and current treatments include topical therapies, phototherapy, systemic immune modulators, and biologics, aiming to alleviate symptoms and improve quality of life. However, challenges persist, such as adverse effects, treatment resistance, high costs, and variability in response among individuals. The future of psoriasis treatment shows promising emerging trends. New biologic agents targeting novel pathways, such as interleukin 23 inhibitors like mirikizumab, offer enhanced efficacy. Small molecule inhibitors like RORγt inhibitors and ROCK2 inhibitors provide additional treatment options. Combination therapies, including biologics with methotrexate, may improve treatment response. Advancements in topical treatments utilizing microneedles and nanoparticle-based carriers can enhance drug delivery and improve therapeutic outcomes. Biomarkers and multi-omics technologies hold potential for personalized treatment approaches, thus aiding in diagnosis, predicting treatment response, and guiding therapeutic decisions. Collaboration among researchers, clinicians, and industry stakeholders is crucial to translating these scientific breakthroughs into clinical practice. By addressing current challenges and exploring these promising trends, we can optimize psoriasis management and improve the lives of those affected by this chronic condition.
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Affiliation(s)
| | - Miri Kim
- Department of Dermatology, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Yeongdeungpo-gu, Seoul 07345, Republic of Korea;
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13
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Munera-Campos M, Chicharro P, Gonzalez Quesada A, Flórez Menéndez Á, de la Cueva Dobao P, Gimenez Arnau AM, Gilaberte Calzada Y, Rodríguez Serna M, Montero-Vilchez T, Silvestre JF, Elosua-González M, Del Alcázar E, Santamaría C, Sánchez-Pérez J, Carretero Hernández G, Batalla A, Jin Suh Oh H, Mauleón Fernández C, Curto Barredo L, Bertolín-Colilla M, Navarro Bielsa A, Ballano Ruiz A, Botella Estrada R, Arias Santiago S, Betlloch I, Roustan Gullón G, Rosell Díaz A, Descalzo MA, García-Doval I, Carrascosa JM. [Translated article] BIOBADATOP Spanish Atopic Dermatitis Registry: Description and Early Findings. ACTAS DERMO-SIFILIOGRAFICAS 2023; 114:T479-T487. [PMID: 37172898 DOI: 10.1016/j.ad.2023.05.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 03/07/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND In recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. MATERIALS AND METHOD The Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). RESULTS We studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39 AEs) and cyclosporine (38 AEs). The most common AEs were conjunctivitis (11 patients), headache (6), hypertrichosis (5), and nausea (4). There was 1 severe AE (acute mastoiditis) associated with cyclosporine. CONCLUSIONS Initial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD.
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Affiliation(s)
- M Munera-Campos
- Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain.
| | - P Chicharro
- Servicio de Dermatología, Hospital Universitario de La Princesa, Madrid, Spain
| | - A Gonzalez Quesada
- Servicio de Dermatología, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
| | - Á Flórez Menéndez
- Servicio de Dermatología, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - P de la Cueva Dobao
- Servicio de Dermatología, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - A M Gimenez Arnau
- Servicio de Dermatología, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain
| | - Y Gilaberte Calzada
- Servicio de Dermatología, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - M Rodríguez Serna
- Servicio de Dermatología, Hospital Universitario y Politécnico la Fe, Valencia, Spain
| | - T Montero-Vilchez
- Servicio de Dermatología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
| | - J F Silvestre
- Servicio de Dermatología, Hospital General Universitario Dr Balmis, ISABIAL, Alicante, Spain
| | - M Elosua-González
- Servicio de Dermatología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | - E Del Alcázar
- Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain
| | - C Santamaría
- Servicio de Dermatología, Hospital Universitario de La Princesa, Madrid, Spain
| | - J Sánchez-Pérez
- Servicio de Dermatología, Hospital Universitario de La Princesa, Madrid, Spain
| | - G Carretero Hernández
- Servicio de Dermatología, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
| | - A Batalla
- Servicio de Dermatología, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - H Jin Suh Oh
- Servicio de Dermatología, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | - C Mauleón Fernández
- Servicio de Dermatología, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - L Curto Barredo
- Servicio de Dermatología, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain
| | - M Bertolín-Colilla
- Servicio de Dermatología, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain
| | - A Navarro Bielsa
- Servicio de Dermatología, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - A Ballano Ruiz
- Servicio de Dermatología, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - R Botella Estrada
- Servicio de Dermatología, Hospital Universitario y Politécnico la Fe, Valencia, Spain
| | - S Arias Santiago
- Servicio de Dermatología, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
| | - I Betlloch
- Servicio de Dermatología, Hospital General Universitario Dr Balmis, ISABIAL, Alicante, Spain
| | - G Roustan Gullón
- Servicio de Dermatología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | - A Rosell Díaz
- Servicio de Dermatología, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | - M A Descalzo
- Unidad de Investigación, Fundación Piel Sana AEDV, Madrid, Spain
| | - I García-Doval
- Unidad de Investigación, Fundación Piel Sana AEDV, Madrid, Spain; Servicio de Dermatología, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain
| | - J M Carrascosa
- Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain
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14
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Damiani G, Amerio P, Bardazzi F, Carrera CG, Conti A, Cusano F, Dapavo P, DeSimone C, El Hachem M, Fabbrocini G, Gisondi P, Loconsole F, Micali G, Neri I, Parodi A, Piaserico S, Romanelli M, Stingeni L, Pigatto PDM. Real-World Experience of Methotrexate in the Treatment of Skin Diseases: an Italian Delphi Consensus. Dermatol Ther (Heidelb) 2023:10.1007/s13555-023-00930-2. [PMID: 37210684 DOI: 10.1007/s13555-023-00930-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 04/17/2023] [Indexed: 05/22/2023] Open
Abstract
BACKGROUND After decades of use, methotrexate displays an established safety and efficacy profile in both in-hospital and outpatient settings. Despite its widespread use, there is surprisingly little clinical evidence to guide daily practice with methotrexate in dermatology. OBJECTIVES To provide guidance for clinicians in daily practice for areas in which there is limited guidance. METHODS A Delphi consensus exercise on 23 statements was carried out on the use of methotrexate in dermatological routine settings. RESULTS Consensus was reached on statements that cover six main areas: (1) pre-screening exams and monitoring of therapy; (2) dosing and administration in patients naïve to methotrexate; (3) optimal strategy for patients in remission; (4) use of folic acid; (5) safety; and (6) predictors of toxicity and efficacy. Specific recommendations are provided for all 23 statements. CONCLUSIONS In order to optimize methotrexate efficacy, it is essential to optimize treatment using appropriate dosages, carrying out a rapid drug-based step-up on a treat-to-target strategy and preferably using the subcutaneous formulation. To manage safety aspects appropriately, it is essential to evaluate patients' risk factors and carry out proper monitoring during the course of treatment.
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Affiliation(s)
- Giovanni Damiani
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
- Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
- Italian Center of Precisione Medicine and Chronic Inflammation, University of Milan, Milan, Italy.
- UOC Dermatology, Istituto Ortopedico Galeazzi, Via Riccardo Galeazzi, 4, 20161, Milan, Italy.
| | - Paolo Amerio
- Dermatologic Clinic, Department of Medicine and Aging Science, University "G. d'Annunzio", Chieti-Pescara, Italy
| | - Federico Bardazzi
- Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Carlo G Carrera
- Fondazione Cà Granda IRCCS Maggiore Policlinico Hospital, Milan, Italy
| | - Andrea Conti
- Dermatology Unit, Ospedale Infermi di Rimini, AUSL Romagna, Rimini, Italy
| | | | - Paolo Dapavo
- Dermatology Clinic, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Clara DeSimone
- DermatologiaDipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
- UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy
| | - May El Hachem
- Dermatology Unit and Genodermatosis Research Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy
| | - Gabriella Fabbrocini
- Section of Dermatology- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Paolo Gisondi
- Department of Medicine, Section of Dermatology and Venereology, University of Verona, Verona, Italy
| | - Francesco Loconsole
- Department of Biomedical Sciences and Human Oncology, Section of Dermatology, University of Bari, Bari, Italy
| | | | - Iria Neri
- Dermatology, Sant'Orsola-Malpighi Polyclinic University Hospital-IRCCS, University of Bologna, Bologna, Italy
| | - Aurora Parodi
- Dermatology Clinic, DISSAL, Polyclinic Hospital San Martino-IRCCS, University of Genoa, Genoa, Italy
| | - Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | | | - Luca Stingeni
- Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Paolo D M Pigatto
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
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15
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Papp KA, Melosky B, Sehdev S, Hotte SJ, Beecker JR, Kirchhof MG, Turchin I, Dutz JP, Gooderham MJ, Gniadecki R, Hong CH, Lambert J, Lynde CW, Prajapati VH, Vender RB. Use of Systemic Therapies for Treatment of Psoriasis in Patients with a History of Treated Solid Tumours: Inference-Based Guidance from a Multidisciplinary Expert Panel. Dermatol Ther (Heidelb) 2023; 13:867-889. [PMID: 36929121 PMCID: PMC10060504 DOI: 10.1007/s13555-023-00905-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 02/15/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Patients with treated solid tumours (TSTs) are a highly heterogeneous population at an increased risk for malignancy compared with the general population. When treating psoriasis in patients with a history of TSTs, clinicians are concerned about the immunosuppressive nature of psoriasis therapies, the possibility of augmenting cancer recurrence/progression, and infectious complications. No direct, high-level evidence exists to address these concerns. OBJECTIVES We aim to provide a structured framework supporting healthcare professional and patient discussions on the risks and benefits of systemic psoriasis therapy in patients with previously TSTs. Our goal was to address the clinically important question, "In patients with TSTs, does therapy with systemic agents used for psoriasis increase the risk of malignancy or malignancy recurrence?" METHODS We implemented an inference-based approach relying on indirect evidence when direct clinical trial and real-world data were absent. We reviewed indirect evidence supporting inferences on the status of immune function in patients with TSTs. Recommendations on systemic psoriasis therapies in patients with TSTs were derived using an inferential heuristic. RESULTS We identified five indirect indicators of iatrogenic immunosuppression informed by largely independent bodies of evidence: (1) overall survival, (2) rate of malignancies with psoriasis and systemic psoriasis therapies, (3) rate of infections with psoriasis and systemic psoriasis therapies, (4) common disease biochemical pathways for solid tumours and systemic psoriasis therapies, and (5) solid organ transplant outcomes. On the basis of review of the totality of this data, we provided inference-based conclusions and ascribed level of support for each statement. CONCLUSIONS Prior to considering new therapies for psoriasis, an understanding of cancer prognosis should be addressed. Patients with TSTs and a good cancer prognosis will have similar outcomes to non-TST patients when treated with systemic psoriasis therapies. For patients with TSTs and a poor cancer prognosis, the quality-of-life benefits of treating psoriasis may outweigh the theoretical risks.
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Affiliation(s)
- Kim A Papp
- Probity Medical Research Inc., Waterloo, ON, Canada.
- Alliance Clinical Research, Waterloo, ON, Canada.
| | - Barbara Melosky
- Medical Oncology, BC Cancer Vancouver Centre, Vancouver, BC, Canada
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Sandeep Sehdev
- Division of Medical Oncology, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
| | - Sebastien J Hotte
- Juravinski Cancer Centre, Hamilton, ON, Canada
- Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Jennifer R Beecker
- Probity Medical Research Inc., Waterloo, ON, Canada
- University of Ottawa, Ottawa, ON, Canada
- Division of Dermatology, The Ottawa Hospital, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Mark G Kirchhof
- University of Ottawa, Ottawa, ON, Canada
- Division of Dermatology, The Ottawa Hospital, Ottawa, ON, Canada
| | - Irina Turchin
- Probity Medical Research Inc., Waterloo, ON, Canada
- Brunswick Dermatology Centre, Fredericton, NB, Canada
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Jan P Dutz
- Skin Care Centre, Vancouver, BC, Canada
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada
- BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Melinda J Gooderham
- Probity Medical Research Inc., Waterloo, ON, Canada
- SKiN Centre for Dermatology, Peterborough, ON, Canada
| | - Robert Gniadecki
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Chih-Ho Hong
- Probity Medical Research Inc., Waterloo, ON, Canada
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada
- Dr. Chih-ho Hong Medical Inc., Surrey, BC, Canada
| | - Jo Lambert
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
- Dermatology Research Unit, Ghent University, Ghent, Belgium
| | - Charles W Lynde
- Probity Medical Research Inc., Waterloo, ON, Canada
- Lynde Institute for Dermatology, Markham, ON, Canada
- Division of Dermatology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Vimal H Prajapati
- Probity Medical Research Inc., Waterloo, ON, Canada
- Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
- Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Dermatology Research Institute, Calgary, AB, Canada
- Skin Health & Wellness Centre, Calgary, AB, Canada
| | - Ronald B Vender
- Department of Medicine, McMaster University, Hamilton, ON, Canada
- Dermatrials Research Inc., Hamilton, ON, Canada
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16
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Graceffa D, Sperati F, Bonifati C, Spoletini G, Elia F, Caterino M, Cristaudo A, Morrone A. Can Biologics Be Discontinued in Patients with Psoriatic Arthritis in Stable Remission? A Prospective Single‐CenterClinical and Ultrasound Study. Dermatol Ther 2023; 2023. [DOI: 10.1155/2023/5655687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 10/30/2023] [Indexed: 01/12/2025]
Abstract
Biologic disease‐modifying antirheumatic drugs (bDMARDs) and particularly tumor necrosis factor inhibitors (TNFi) have dramatically changed the natural history of psoriatic arthritis (PsA), making complete clinical remission possible in most patients. However, TNFi drugs are not without potential adverse effects such as increased infectious risk. In addition, their extensive use is associated with a significant economic burden. This prospective longitudinal cohort study involving 45 PsA patients treated with TNFi in stable remission aimed to evaluate by both clinical examination and ultrasound timing and predictive factors of disease relapse after discontinuation of TNFi treatment. Thirty‐nine (86.6%) of 45 enrolled patients experienced disease relapse during the follow‐up period, while six patients (13.4%) maintained remission beyond the scheduled 104 weeks. The median survival time of drug‐free remission after TNFi discontinuation was 24 weeks (95% confidence interval (CI): 22.6–25.4). Disease relapse was characterized by marked clinical and ultrasound worsening of dermatologic and rheumatologic conditions. However, resuming previously discontinued treatment allowed all patients to quickly regain clinical remission. Interestingly, axial involvement was a key feature of the symptomatological pattern of disease relapse, being the main reason for treatment restart in 26% of our cohort. Based on a multivariate Cox model, three variables (VAS pain, tender joint count, and swollen joint count) of the clinical assessment performed at the time point of TNFi treatment onset negatively influenced the time to disease relapse. In conclusion, temporary discontinuation of TNFi drugs is feasible and relatively safe. However, as few predictors of the risk and timing of disease relapse have been identified, patients should be closely monitored when therapy is discontinued.
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17
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Balato A, Scala E, Eyerich K, Brembilla NC, Chiricozzi A, Sabat R, Ghoreschi K. Management of Infections in Psoriatic Patients Treated with Systemic Therapies: A Lesson from the Immunopathogenesis of Psoriasis. Dermatol Pract Concept 2023; 13:dpc.1301a16. [PMID: 36892377 PMCID: PMC9946081 DOI: 10.5826/dpc.1301a16] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2022] [Indexed: 02/04/2023] Open
Abstract
Modern treatments continue to be developed based on identifying targets within the innate and adaptive immune pathways associated with psoriasis. Whilst there is a sound biologic rationale for increased risk of infection following treatment with immunomodulators, the clinical evidence is confounded by these agents being used in patients affected with several comorbidities. In an era characterized by an ever greater and growing risk of infections, it is necessary to always be updated on this risk. In this mini-review, we will discuss recent updates in psoriasis immunopathogenesis as a rationale for systemic therapy, outline the risk of infections linked to the disease itself and systemic therapy as well, and provide an overview of the prevention and management of infections.
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Affiliation(s)
- Anna Balato
- Dermatology Unit, University of Campania, Naples, Italy
| | - Emanuele Scala
- Division of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Dermatology and Venereology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Kilian Eyerich
- Division of Dermatology and Venereology, Department of Medicine Solna, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Dermatology and Venereology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Department of Dermatology and Venereology, Unit of Dermatology, Karolinska University Hospital, Stockholm, Sweden
| | | | | | - Robert Sabat
- Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Charité-Universitätsmedizin, Berlin, Germany.,Psoriasis Research and Treatment Center, Department of Dermatology and Allergy and Institute of Medical Immunology, Charité-Universitätsmedizin, Berlin, Germany
| | - Kamran Ghoreschi
- Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin, Berlin, Germany
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18
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Egeberg A, Freilich J, Stelmaszuk MN, Kongerslev R, Apol E, Hansen JB, Levin L. Real-world dose adjustments of biologic treatments in psoriasis and their economic impact: a Swedish national population study. Clin Exp Dermatol 2022; 47:1968-1975. [PMID: 35670046 PMCID: PMC9826076 DOI: 10.1111/ced.15288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND To date, evidence on the dose adjustments of biologics in the real-world treatment of psoriasis is limited. However, dose adjustments may have important clinical and economic implications. AIMS To study the dose adjustments of individual biologics over time in real-world practice in Sweden. METHODS A retrospective observational study of adults with moderate to severe psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Treatment episodes were identified for individual patients from the date of drug dispensation to the end of the supply of the drug. Dosing data were expressed as the proportion of treatment episodes with accumulated syringes/vials equal to, above or below the recommended guidelines. Real-world costs were calculated and compared with costs predicted from dosing guidelines. RESULTS The mean dose was above recommended levels for all biologics investigated. Weighted mean dose adjustments for adalimumab, etanercept, secukinumab and ustekinumab were 13%, 23%, 8% and 3%, respectively, over the entire treatment period. Higher doses translate to higher costs, including notable increases over time vs. expected costs for secukinumab. CONCLUSIONS Dose adjustments of biologics are frequent in clinical practice but differ for the various biologics. The mean observed increases in dose above guideline recommendations might indicate perceptions of suboptimal efficacy for biologics, with implications for the cost and cost-effectiveness of these treatments. Further research is warranted to understand the reasons for dose adjustments in clinical practice.
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Affiliation(s)
- Alexander Egeberg
- Department of DermatologyBispebjerg Hospital, University of CopenhagenCopenhagenDenmark
| | - Jonatan Freilich
- Department of Public Health and Clinical MedicineUmeå UniversityUmeåSweden,Parexel InternationalStockholmSweden
| | | | | | | | | | - Lars‐Åke Levin
- Department of Health, Medicine and Caring Sciences (HMV)Linköping UniversityLinköpingSweden
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19
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Liu M, Wang H, Liu L, Cui S, Huo X, Xiao Z, Zhao Y, Wang B, Zhang G, Wang N. Risk of COVID-19 infection, hospitalization and mortality in psoriasis patients treated with interleukin-17 inhibitors: A systematic review and meta-analysis. Front Immunol 2022; 13:1046352. [PMID: 36389759 PMCID: PMC9648142 DOI: 10.3389/fimmu.2022.1046352] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 10/10/2022] [Indexed: 10/17/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) have brought great disaster to mankind, and there is currently no globally recognized specific drug or treatment. Severe COVID-19 may trigger a cytokine storm, manifested by increased levels of cytokines including interleukin-17 (IL-17), so a new strategy to treat COVID-19 may be to use existing IL-17 inhibitors, which have demonstrated efficacy, safety and tolerability in the treatment of psoriasis. However, the use of IL-17 inhibitors in patients with psoriasis during the COVID-19 pandemic remains controversial due to reports that IL-17 inhibitors may increase the risk of respiratory tract infections. OBJECTIVES The systematic review and meta-analysis aimed to evaluate the effect of IL-17 inhibitors on the risk of COVID-19 infection, hospitalization, and mortality in patients with psoriasis. METHODS Databases (including Embase, PubMed, SCI-Web of Science, Scopus, CNKI, and the Cochrane Library) were searched up to August 23, 2022, for studies exploring differences in COVID-19 outcomes between psoriasis patients using IL-17 inhibitors and those using non-biologics. Two authors independently extracted data and assessed the risk of bias in a double-blind manner. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated and heterogeneities were determined by the Q test and I 2 statistic. And the numbers needed to treat (NNTs) were calculated to assess the clinical value of IL-17 inhibitors in preventing SARS-CoV-2 infection and treating COVID-19. RESULTS Nine observational studies involving 7,106 participants were included. The pooled effect showed no significant differences in the rates of SARS-CoV-2 infection (P = 0.94; I 2 = 19.5%), COVID-19 hospitalization (P = 0.64; I 2 = 0.0%), and COVID-19 mortality (P = 0.32; I 2 = 0.0%) in psoriasis patients using IL-17 inhibitors compared with using non-biologics. Subgroup analyses grouped by age and COVID-19 cases, respectively, revealed consistent results as above. Meanwhile, the pooled NNTs showed no significant differences between the two groups in the clinical value of preventing SARS-CoV-2 infection and treating COVID-19. CONCLUSION The use of IL-17 inhibitors in patients with psoriasis does not increase the risk of SARS-CoV-2 infection or worsen the course of COVID-19. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier CRD42022335195.
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Affiliation(s)
- Meitong Liu
- Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Huijuan Wang
- Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lu Liu
- Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Saijin Cui
- Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiangran Huo
- Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhuoyun Xiao
- Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yaning Zhao
- Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Bin Wang
- Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Guoqiang Zhang
- Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, China
- Candidate Branch of National Clinical Research Center for Skin Diseases, Shijiazhuang, China
| | - Na Wang
- Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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20
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Graceffa D, Sperati F, Bonifati C, Spoletini G, Lora V, Pimpinelli F, Pontone M, Pellini R, Di Bella O, Morrone A, Cristaudo A. Immunogenicity of three doses of anti-SARS-CoV-2 BNT162b2 vaccine in psoriasis patients treated with biologics. Front Med (Lausanne) 2022; 9:961904. [PMID: 36148445 PMCID: PMC9485492 DOI: 10.3389/fmed.2022.961904] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 08/15/2022] [Indexed: 11/16/2022] Open
Abstract
Introduction Psoriasis has not been directly linked to a poor prognosis for COVID-19, yet immunomodulatory agents used for its management may lead to increased vulnerability to the dangerous complications of SARS-CoV-2 infection, as well as impair the effectiveness of the recently introduced vaccines. The three-dose antibody response trend and the safety of BNT162b2 mRNA vaccine in psoriasis patients treated with biologic drugs have remained under-researched. Materials and methods Forty-five psoriatic patients on biologic treatment were enrolled to evaluate their humoral response to three doses of BNT162b2. IgG titers anti-SARS-CoV-2 spike protein were evaluated at baseline (day 0, first dose), after 3 weeks (second dose), four weeks post-second dose, at the time of the third dose administration and 4 weeks post-third dose. Seropositivity was defined as IgG ≥15 antibody-binding units (BAU)/mL. Data on vaccine safety were also collected by interview at each visit. Results A statistically significant increase in antibody titers was observed after each dose of vaccine compared with baseline, with no significant differences between patients and controls. Methotrexate used in combination with biologics has been shown to negatively influence the antibody response to the vaccine. On the contrary, increasing body mass index (BMI) positively influenced the antibody response. No adverse effects were reported, and no relapses of psoriasis were observed in the weeks following vaccine administration in our study population. Conclusions Our data are largely consistent with the recent literature on this topic confirming the substantial efficacy and safety of BNT162b2 mRNA vaccine on psoriatic patients treated with biologics of different types and support the recommendation to perform additional doses in this specific subgroup of patients.
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Affiliation(s)
- Dario Graceffa
- Department of Clinical Dermatology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Francesca Sperati
- Biostatistics Unit, San Gallicano Dermatological Institute IRCCS, Rome, Italy
| | - Claudio Bonifati
- Department of Clinical Dermatology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Gabriele Spoletini
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Viviana Lora
- Department of Clinical Dermatology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Fulvia Pimpinelli
- Microbiology and Virology Unit, Dermatological Clinical and Research Department, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Martina Pontone
- Microbiology and Virology Unit, Dermatological Clinical and Research Department, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Raul Pellini
- Department Otolaryngology Head and Neck Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Ornella Di Bella
- Medical Direction, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Aldo Morrone
- Scientific Direction, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Antonio Cristaudo
- Department of Clinical Dermatology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
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21
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Treatment of Moderate to Severe Psoriasis during the COVID-19 Pandemic: Lessons Learned and Opportunities. J Clin Med 2022; 11:jcm11092422. [PMID: 35566548 PMCID: PMC9101352 DOI: 10.3390/jcm11092422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/20/2022] [Accepted: 04/22/2022] [Indexed: 01/27/2023] Open
Abstract
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, clinicians have been overwhelmed by questions beyond the SARS-CoV-2 infection itself. In dermatology practice, clinicians have been facing difficulties concerning therapeutic management of chronic immune-mediated skin disease, above all psoriasis. Major challenges arisen were to understand the role of immunosuppression or immunomodulation on COVID-19 evolution, the benefit/risk ratio related to discontinuation or modification of ongoing treatment, and the appropriateness of initiating new treatments, the optimization of timing in vaccination administration to patients under immunomodulatory treatments, and finally how to find new strategy of patients’ management through remote assistance. In this comprehensive review, we present the current evidence about the course and management of psoriasis during the COVID-19 pandemic. The general message from dermatologists was that data did not suggest that having PSO or its treatment significantly increased risk of SARS-CoV-2 infection or more severe COVID-19 course, the vaccination is highly recommended in all psoriatic patients, beyond ongoing treatment, and that the telehealth experience was a success overall.
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22
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Carrascosa J, Puig L, Belinchón Romero I, Salgado-Boquete L, del Alcázar E, Andrés Lencina J, Moreno D, de la Cueva P. [Translated article] Practical Update of the Recommendations Published by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology (GPs) on the Treatment of Psoriasis with Biologic Therapy. Part 1. Concepts and General Management of Psoriasis With Biologic Therapy. ACTAS DERMO-SIFILIOGRAFICAS 2022. [DOI: 10.1016/j.ad.2021.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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23
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Carrascosa JM, Puig L, Belinchón Romero I, Salgado-Boquete L, Del Alcázar E, Andrés Lencina JJ, Moreno D, de la Cueva P. Practical update of the Recommendations Published by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology (GPS) on the Treatment of Psoriasis with Biologic Therapy. Part 1. Concepts and General Management of Psoriasis with Biologic Therapy. ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:261-277. [PMID: 35526919 DOI: 10.1016/j.ad.2021.10.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 10/04/2021] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND AND OBJECTIVES A new, updated AEDV Psoriasis Group consensus document on the treatment of moderate to severe psoriasis was needed owing to the approval, in recent years, of a large number of new drugs and changes in the treatment paradigm. METHODOLOGY The consensus document was developed using the nominal group technique and a scoping review. First, a designated coordinator selected a group of Psoriasis Group members for the panel. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. Based on these reviews, the coordinator drew up a set of proposed recommendations, which were then discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted. RESULTS The present guidelines include general principles for the treatment of patients with moderate to severe psoriasis and also define treatment goals and criteria for the indication of biologic therapy and the selection of initial and subsequent therapies. Practical issues, such as treatment failure and maintenance of response, are also addressed.
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Affiliation(s)
- J M Carrascosa
- Departamento de Dermatología, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, IGTP, Barcelona, España.
| | - L Puig
- Departamento de Dermatología, Hospital de la Santa Creu i Sant Pau, Barcelona, España
| | - I Belinchón Romero
- Departamento de Dermatología, Hospital General Universitario de Alicante-ISABIAL, Universidad Miguel Hernández de Elche, Alicante, España
| | - L Salgado-Boquete
- Departamento de Dermatología, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, España
| | - E Del Alcázar
- Departamento de Dermatología, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, IGTP, Barcelona, España
| | - J J Andrés Lencina
- Servicio de Dermatología, Hospital Universitario Vega Baja, Alicante, España
| | - D Moreno
- Departamento de Dermatología, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Sevilla, España
| | - P de la Cueva
- Servicio de Dermatología, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, España
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24
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Al-Janabi A, Yiu ZZN. Biologics in Psoriasis: Updated Perspectives on Long-Term Safety and Risk Management. Psoriasis (Auckl) 2022; 12:1-14. [PMID: 35024352 PMCID: PMC8747772 DOI: 10.2147/ptt.s328575] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Accepted: 12/23/2021] [Indexed: 12/12/2022] Open
Abstract
Biologics targeting Th1/Th17 cytokines have revolutionised psoriasis treatment. In addition to treatment effectiveness, it is important to define and understand the long-term risks of biologic therapy in order to guide therapy selection and minimise these risks for patients where possible. This review article summarises available evidence from trial data, observational studies and pharmacovigilance registries to explore key long-term risks of biologic treatment, and how these risks might be managed in clinical practice.
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Affiliation(s)
- A Al-Janabi
- Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
- The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, M6 8HD, UK
| | - Z Z N Yiu
- Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
- The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, M6 8HD, UK
- Correspondence: ZZN Yiu Dermatology Centre, Salford Royal Hospital, Stott Lane, Manchester, M6 8HD, UK Email
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25
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Arora H, Boothby-Shoemaker W, Braunberger T, Lim HW, Veenstra J. Safety of conventional immunosuppressive therapies for patients with dermatological conditions and coronavirus disease 2019: A review of current evidence. J Dermatol 2021; 49:317-329. [PMID: 34962304 DOI: 10.1111/1346-8138.16182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/16/2021] [Accepted: 09/21/2021] [Indexed: 12/15/2022]
Abstract
The effect of coronavirus disease 2019 (COVID-19) on patients receiving conventional immunosuppressive (IS) therapy has yet to be fully determined; however, research on using IS therapy for treating COVID-19 in acutely ill patients is increasing. While some believe that IS therapy may be protective, others argue that these agents may make patients more susceptible to COVID-19 infection and morbidity and advocate for a more cautious, individualized approach to determining continuation, reduction, or discontinuation of therapy. In this review, we aim to provide an overview of COVID-19 risk in dermatological patients who are receiving conventional IS therapies, including mycophenolate mofetil, methotrexate, cyclosporine, azathioprine, apremilast, JAK inhibitors, and systemic steroids. Additionally, we provide recommendations for management of these medications for dermatological patients during the COVID-19 pandemic. Treatment of dermatological disease during the COVID-19 pandemic should involve shared decision-making between the patient and provider, with consideration of each patient's comorbidities and the severity of the patient's dermatological disease.
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Affiliation(s)
- Harleen Arora
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Wyatt Boothby-Shoemaker
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA.,College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
| | | | - Henry W Lim
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Jesse Veenstra
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA
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Zeng H, Wang S, Chen L, Shen Z. Biologics for Psoriasis During the COVID-19 Pandemic. Front Med (Lausanne) 2021; 8:759568. [PMID: 34938746 PMCID: PMC8685238 DOI: 10.3389/fmed.2021.759568] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/14/2021] [Indexed: 12/12/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), a new form of acute infectious respiratory syndrome first reported in 2019, has rapidly spread worldwide and has been recognized as a pandemic by the WHO. It raised widespread concern about the treatment of psoriasis in this COVID-19 pandemic era, especially on the biologics use for patients with psoriasis. This review will summarize key information that is currently known about the relationship between psoriasis, biological treatments, and COVID-19, and vaccination-related issues. We also provide references for dermatologists and patients when they need to make clinical decisions. Currently, there is no consensus on whether biological agents increase the risk of coronavirus infection; however, current research shows that biological agents have no adverse effects on the prognosis of patients with COVID-19 with psoriasis. In short, it is not recommended to stop biological treatment in patients with psoriasis to prevent the infection risk, and for those patients who tested positive for SARS-CoV-2, the decision to pause biologic therapy should be considered on a case-by-case basis, and individual risk and benefit should be taken into account. Vaccine immunization against SARS-CoV-2 is strictly recommendable in patients with psoriasis without discontinuation of their biologics but evaluating the risk-benefit ratio of maintaining biologics before vaccination is mandatory at the moment.
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Affiliation(s)
- Huanhuan Zeng
- School of Medicine, Zunyi Medical University, Zunyi, China
| | - Siyu Wang
- Department of Dermatology, Institute of Dermatology and Venereology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China
| | - Ling Chen
- Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, China
| | - Zhu Shen
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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27
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Penso L, Dray-Spira R, Weill A, Pina Vegas L, Zureik M, Sbidian E. Association Between Biologics Use and Risk of Serious Infection in Patients With Psoriasis. JAMA Dermatol 2021; 157:1056-1065. [PMID: 34287624 DOI: 10.1001/jamadermatol.2021.2599] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Importance Biologics and targeted therapies, such as apremilast, are efficient treatments to manage moderate to severe psoriasis. More information about the risk of serious infection is needed for the newest treatment options in a real-world setting. Objective To assess the risk of serious infection among biologics and apremilast used to treat psoriasis, with etanercept as the comparator. Design, Setting, and Participants This nationwide cohort study from France involved data from the National Health Data System covering approximately 99% of the French population. All adults with psoriasis, defined as receiving at least 2 prescriptions of a topical vitamin D derivative within a 2-year period, registered in the database between January 1, 2008, and May 31, 2019, were eligible. The study population included those who were new users of biologic agents or apremilast (ie, without any prescriptions of a biologic or apremilast during the previous year). Patients with HIV infection or a history of cancer, transplant, or serious infection were excluded. End of follow-up was January 31, 2020. Main Outcome Measures The primary end point was a serious infection in a time-to-event analysis using propensity score-weighted Cox proportional hazards regression models, estimating weighted hazard ratios (wHRs) and 95% CIs. Results A total of 44 239 new users of biologic treatment were identified (mean [SD] age, 48.4 [13.8] years; 22 866 [51.7%] men; median follow-up, 12 months [interquartile range, 7-24 months]). A total of 29 618 (66.9%) were prescribed a tumor necrosis factor inhibitor first, 6658 (15.0%) an interleukin (IL) 12/23 inhibitor, 4093 (9.3%) an IL-17 inhibitor, 526 (1.2%) an IL-23 inhibitor, and 3344 (7.6%) apremilast. The total number of serious infections was 1656, and the overall crude incidence rate was 25.0 (95% CI, 23.8-26.2) per 1000 person-years. The most frequent serious infections were gastrointestinal infections (645 patients [38.9%]). After adjusting for time-dependent covariables, risk of serious infections was higher for new users of adalimumab (wHR, 1.22; 95% CI, 1.07-1.38) or infliximab (wHR, 1.79; 95% CI 1.49-2.16) vs etanercept, whereas ustekinumab was associated with a lower risk of having a serious infection (wHR, 0.79; 95% CI, 0.67-0.94). Risk of serious infections was not increased for new users of IL-17 and the IL-23 inhibitor guselkumab or apremilast vs etanercept. Risk of serious infections was increased with concomitant nonsteroidal anti-inflammatory drugs or systemic corticosteroids. Conclusions and Relevance In this cohort study of individuals with moderate to severe psoriasis, risk of serious infections was increased in new users of infliximab and adalimumab vs etanercept, whereas ustekinumab users had lower risk of having a serious infection but not new users of IL-17 and IL-23 inhibitors or apremilast. Other observational studies are needed to confirm results for the most recent drugs.
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Affiliation(s)
- Laetitia Penso
- Groupement d'intérêt scientifique Epidémiologie des produits de santé, L'Agence Nationale de Sécurité du Médicament et des Produits de Santé -Caisse Nationale de l'Assurance Maladie, Paris, France.,Epidémiologie en Dermatologie et Evaluation des Thérapeutiques, Université Paris-Est Creteil, Créteil, France
| | - Rosemary Dray-Spira
- Groupement d'intérêt scientifique Epidémiologie des produits de santé, L'Agence Nationale de Sécurité du Médicament et des Produits de Santé -Caisse Nationale de l'Assurance Maladie, Paris, France
| | - Alain Weill
- Groupement d'intérêt scientifique Epidémiologie des produits de santé, L'Agence Nationale de Sécurité du Médicament et des Produits de Santé -Caisse Nationale de l'Assurance Maladie, Paris, France.,Caisse Nationale d'Assurance Maladie des Travailleurs Salariés, Paris, France
| | - Laura Pina Vegas
- Epidémiologie en Dermatologie et Evaluation des Thérapeutiques, Université Paris-Est Creteil, Créteil, France.,Département de Rhumatologie, Assistance Publique-Hôpitaux de Paris, Hôpitaux universitaires Henri Mondor, Créteil, France
| | - Mahmoud Zureik
- Groupement d'intérêt scientifique Epidémiologie des produits de santé, L'Agence Nationale de Sécurité du Médicament et des Produits de Santé -Caisse Nationale de l'Assurance Maladie, Paris, France.,INSERM, Echappement aux anti-infectieux et Pharmacoépidémiologie, Centre de recherche en épidémiologie et santé des populations, Université de Versailles Saint-Quentin-en-Yvelines, Montigny le Bretonneux, France
| | - Emilie Sbidian
- Groupement d'intérêt scientifique Epidémiologie des produits de santé, L'Agence Nationale de Sécurité du Médicament et des Produits de Santé -Caisse Nationale de l'Assurance Maladie, Paris, France.,Epidémiologie en Dermatologie et Evaluation des Thérapeutiques, Université Paris-Est Creteil, Créteil, France.,Département de Dermatologie, Assistance Publique-Hôpitaux de Paris, Hôpitaux universitaires Henri Mondor, Université Paris-Est Creteil, Créteil, France.,INSERM, Centre d'Investigation Clinique 1430, Créteil, France
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28
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Munera-Campos M, Vilar-Alejo J, Rivera R, Carrascosa JM, Daudén E, Herrera-Acosta E, Sahuquillo-Torralba A, Gómez-García FJ, Baniandrés-Rodríguez O, de la Cueva P, López-Estebaranz JL, Belinchón I, Ferran M, Riera-Monroig J, Rodriguez L, Carretero G, García-Donoso C, Ballescá F, Llamas-Velasco M, Herrera-Ceballos E, Pujol-Marco C, Nieto-Benito LM, Ruiz-Genao DP, Alsina M, Descalzo MA, García-Doval I. The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry. J DERMATOL TREAT 2021; 33:2110-2117. [PMID: 33913796 DOI: 10.1080/09546634.2021.1922572] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% CI 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = 0.0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.
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Affiliation(s)
- M Munera-Campos
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Badalona, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - J Vilar-Alejo
- Department of Dermatology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - R Rivera
- Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - J M Carrascosa
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Badalona, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - E Daudén
- Department of Dermatology. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-IP), Madrid, Spain
| | - E Herrera-Acosta
- Department of Dermatology, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - A Sahuquillo-Torralba
- Department of Dermatology, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - F J Gómez-García
- Department of Dermatology, Hospital Universitario Reina Sofía, Cordoba, Spain
| | - O Baniandrés-Rodríguez
- Department of Dermatology, CEIMI Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - P de la Cueva
- Department of Dermatology, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - J L López-Estebaranz
- Department of Dermatology, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - I Belinchón
- Department of Dermatology, Hospital General Universitario de Alicante-ISABIAL, Alicante, Spain
| | - M Ferran
- Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - J Riera-Monroig
- Department of Dermatology, Hospital Clínic de Barcelona, UB, Barcelona, Spain
| | - L Rodriguez
- Department of Dermatology, Hospital Virgen del Rocío, Sevilla, Spain
| | - G Carretero
- Department of Dermatology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - C García-Donoso
- Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - F Ballescá
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Badalona, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - M Llamas-Velasco
- Department of Dermatology. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-IP), Madrid, Spain
| | - E Herrera-Ceballos
- Department of Dermatology, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - C Pujol-Marco
- Department of Dermatology, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - L M Nieto-Benito
- Department of Dermatology, CEIMI Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - D P Ruiz-Genao
- Department of Dermatology, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - M Alsina
- Department of Dermatology, Hospital Clínic de Barcelona, UB, Barcelona, Spain
| | - M A Descalzo
- Research Unit. Fundación Piel Sana AEDV, Madrid, Spain
| | - I García-Doval
- Research Unit. Fundación Piel Sana AEDV, Madrid, Spain.,Department of Dermatology, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
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Penso L, Dray-Spira R, Weill A, Zureik M, Sbidian E. Drop in biological initiation for patients with psoriasis during the COVID-19 pandemic. Br J Dermatol 2021; 185:671-673. [PMID: 33894022 PMCID: PMC8250964 DOI: 10.1111/bjd.20406] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/16/2021] [Accepted: 04/22/2021] [Indexed: 12/01/2022]
Affiliation(s)
- L Penso
- GIS-EPIPHARE, Groupement d'intérêt scientifique Epidémiologie des produits de santé ANSM-CNAM, Paris, F-75020, France.,Université Paris-Est Creteil, EpiDermE, Créteil, F-94010, France
| | - R Dray-Spira
- GIS-EPIPHARE, Groupement d'intérêt scientifique Epidémiologie des produits de santé ANSM-CNAM, Paris, F-75020, France
| | - A Weill
- GIS-EPIPHARE, Groupement d'intérêt scientifique Epidémiologie des produits de santé ANSM-CNAM, Paris, F-75020, France.,Caisse Nationale d'assurance Maladie des Travailleurs Salariés (CNAM), Paris, F-75020, France
| | - M Zureik
- GIS-EPIPHARE, Groupement d'intérêt scientifique Epidémiologie des produits de santé ANSM-CNAM, Paris, F-75020, France.,INSERM, Echappement aux anti-infectieux et Pharmacoépidémiologie, CESP, UVSQ, Montigny le Bretonneux, F-78180, France
| | - E Sbidian
- GIS-EPIPHARE, Groupement d'intérêt scientifique Epidémiologie des produits de santé ANSM-CNAM, Paris, F-75020, France.,Université Paris-Est Creteil, EpiDermE, Créteil, F-94010, France.,AP-HP, Hôpitaux universitaires Henri Mondor, Département de Dermatologie, UPEC, Créteil, F-94010, France.,INSERM, Centre d'Investigation Clinique 1430, Créteil, F-94010, France
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30
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Marko M, Pawliczak R. Can we safely use systemic treatment in atopic dermatitis during the COVID-19 pandemic? Overview of selected conventional and biologic systemic therapies. Expert Rev Clin Immunol 2021; 17:619-627. [PMID: 33866905 DOI: 10.1080/1744666x.2021.1919511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Introduction: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the medical community has faced major challenges that affect disease management in all areas. Dermatologists and immunologists have to choose appropriate treatment strategy taking into consideration the risk of infection and possible exacerbation of the course of the disease in patients with confirmed infection. Management of atopic dermatitis (AD) in moderate to severe cases is based on systemic therapy such as cyclosporine, azathioprine, methotrexate and dupilumab.Areas covered: A literature search in PubMed database was performed until 6 March 2021. In this review, the authors discuss non-biologic and biologic systemic medications for AD and provide an overview of therapeutic recommendations during COVID-19 pandemic.Expert opinion: In case of an active COVID-19 infection, conventional systemic treatment and biological treatment needs to be stopped until clinical recovery. Noninfected patients with systemic treatment of AD should continue their therapy via self-application. The authors can conclude that understanding of dupilumab therapy is better recognized in context AD treatment during COVID-19 pandemic in comparison to cyclosporine, azathioprine and methotrexate. However, this systemic immunosuppressants still require further investigation and literature complementation.
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Affiliation(s)
- Monika Marko
- Department of Immunopathology, Faculty of Medicine, Division of Biomedical Science, Medical University of Lodz, Lodz, Poland
| | - Rafał Pawliczak
- Department of Immunopathology, Faculty of Medicine, Division of Biomedical Science, Medical University of Lodz, Lodz, Poland
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31
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Nast A, Smith C, Spuls P, Avila Valle G, Bata‐Csörgö Z, Boonen H, De Jong E, Garcia‐Doval I, Gisondi P, Kaur‐Knudsen D, Mahil S, Mälkönen T, Maul J, Mburu S, Mrowietz U, Reich K, Remenyik E, Rønholt K, Sator P, Schmitt‐Egenolf M, Sikora M, Strömer K, Sundnes O, Trigos D, Van Der Kraaij G, Yawalkar N, Dressler C. EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris – Part 1: treatment and monitoring recommendations. J Eur Acad Dermatol Venereol 2020; 34:2461-2498. [DOI: 10.1111/jdv.16915] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/13/2020] [Indexed: 12/14/2022]
Affiliation(s)
- A. Nast
- Department of Dermatology, Venereology and Allergology Charité – Universitätsmedizin BerlinCorporate Member of Freie Universität BerlinHumboldt‐Universität zu BerlinBerlin Institute of Health Berlin Germany
| | - C. Smith
- St John’s Institute of Dermatology London UK
| | - P.I. Spuls
- Academic Medical Centre Amsterdam Amsterdam Netherlands
| | - G. Avila Valle
- Department of Dermatology, Venereology and Allergology Charité – Universitätsmedizin BerlinCorporate Member of Freie Universität BerlinHumboldt‐Universität zu BerlinBerlin Institute of Health Berlin Germany
| | | | - H. Boonen
- Office‐Based Dermatology Practice Geel Belgium
| | - E. De Jong
- Radboud University medical centre Nijmegen Netherlands
| | - I. Garcia‐Doval
- Unidad de InvestigaciónFundación Piel Sana AEDV Madrid España
| | | | | | - S. Mahil
- Guy's and St Thomas' NHS Foundation Trust London UK
| | - T. Mälkönen
- Helsinki University Central Hospital Helsinki Finland
| | - J.T. Maul
- Department of Dermatology University Hospital of Zürich Zürich Switzerland
| | - S. Mburu
- International Federation of Psoriasis Associations (IFPA)
| | - U. Mrowietz
- Universitätsklinikum Schleswig‐Holstein Kiel Germany
| | - K. Reich
- Translational Research in Inflammatory Skin Diseases Institute for Health Services Research in Dermatology and Nursing University Medical Center Hamburg‐Eppendorf Hamburg Germany
| | | | | | - P.G. Sator
- Municipal Hospital Hietzing Vienna Austria
| | - M. Schmitt‐Egenolf
- Dermatology Department of Public Health & Clinical Medicine Umeå University Umeå Sweden
| | - M. Sikora
- Department of Dermatology Medical University of Warsaw Warszawa Poland
| | - K. Strömer
- Office‐Based Dermatology Practice Mönchengladbach Germany
| | | | - D. Trigos
- International Federation of Psoriasis Associations (IFPA)
| | | | - N. Yawalkar
- Department of Dermatology, Inselspital Bern University HospitalUniversity of Bern Bern Switzerland
| | - C. Dressler
- Department of Dermatology, Venereology and Allergology Charité – Universitätsmedizin BerlinCorporate Member of Freie Universität BerlinHumboldt‐Universität zu BerlinBerlin Institute of Health Berlin Germany
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32
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Chiricozzi A, Gisondi P, Bellinato F, Girolomoni G. Immune Response to Vaccination in Patients with Psoriasis Treated with Systemic Therapies. Vaccines (Basel) 2020; 8:vaccines8040769. [PMID: 33339348 PMCID: PMC7767096 DOI: 10.3390/vaccines8040769] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/11/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023] Open
Abstract
Psoriasis is a chronic inflammatory skin disease usually treated with immunomodulatory/immunosuppressive agents. The use of these agents has been associated with an increased susceptibility to infections. Vaccination might represent a critical aspect in the management of patients with psoriasis treated with immunomodulatory/immunosuppressive therapies. This narrative review aimed to provide an overview on the immune response to vaccines in subjects treated with systemic agents used to treat patients with moderate to severe psoriasis. Publications appearing in PubMed, Scopus, and ISI–Web of Knowledge database were selected using Medical Subject Headings key terms. Overall, published data confirmed that vaccination with attenuated live vaccines during therapy with immunomodulatory/immunosuppressive therapies should be avoided. For nonlive vaccines, a more favorable safety profile of biologic agents compared to conventional systemic agents is described as the humoral response to vaccines is in general well-preserved. Treatment with cyclosporine and methotrexate is associated with lower antibody titers to vaccines, and thus these agents are better discontinued during vaccination. In contrast, treatment with biological agents is not associated with lower antibody response and can thus be continued safely.
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Affiliation(s)
- Andrea Chiricozzi
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Dermatologia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Correspondence: ; Tel.: +39-3395668320; Fax: +39-0761-571321
| | - Paolo Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, 37129 Verona, Italy; (P.G.); (F.B.); (G.G.)
| | - Francesco Bellinato
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, 37129 Verona, Italy; (P.G.); (F.B.); (G.G.)
| | - Giampiero Girolomoni
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, 37129 Verona, Italy; (P.G.); (F.B.); (G.G.)
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33
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The Risk of COVID-19 Pandemic in Patients with Moderate to Severe Plaque Psoriasis Receiving Systemic Treatments. Vaccines (Basel) 2020; 8:vaccines8040728. [PMID: 33276686 PMCID: PMC7761600 DOI: 10.3390/vaccines8040728] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 11/30/2020] [Accepted: 12/01/2020] [Indexed: 12/12/2022] Open
Abstract
Chronic plaque psoriasis is an inflammatory skin disease affecting 2–3% of the general population. Approximately one-third of patients are candidates for systemic immunosuppressive treatments, such as synthetic or biological disease-modifying antirheumatic drugs, because of disease extensions, localization in sensitive or visible areas and/or resistance to topical treatments. These therapies have been associated with increased risk of infection, including upper respiratory tract viral infection. Psoriasis is frequently associated with cardio-metabolic comorbidities, such as obesity and diabetes, that are risk factors for poor prognosis in the case of coronavirus disease (COVID-19) pneumonia. A narrative review of the literature based on an electronic search of the PubMed® database was undertaken with the objective of investigating whether there is an increased risk of COVID-19 infection in psoriasis patients on systemic treatment. Original articles, such as case reports, published up to 1 November 2020 were included. There is no evidence that patients with moderate-to-severe psoriasis receiving systemic treatments, including biologics, have higher risk of SARS-CoV-2 infection and/or increased hospitalization and death related to COVID-19 compared to the general population. Several case reports described full recovery from COVID-19 with favorable outcomes in psoriasis patients who were being treated with synthetics or biologicals. Nonetheless, caution should be maintained in this setting, and more data are needed to draw definitive conclusions.
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34
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Sadeghinia A, Daneshpazhooh M. Immunosuppressive drugs for patients with psoriasis during the COVID-19 pandemic era. A review. Dermatol Ther 2020; 34:e14498. [PMID: 33141519 DOI: 10.1111/dth.14498] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/23/2020] [Accepted: 10/27/2020] [Indexed: 12/15/2022]
Abstract
The COVID-19 has been spreading around the world. Concerns about the safety of administration of immunosuppressive drugs have been raised for treatment of psoriasis (PSO), and there is insufficient evidence for the risk of COVID-19 infection for psoriatic patients using these drugs, so we did a review, focusing on the risk of overall infection associated with the most commonly used immunosuppressive drugs, such as methotrexate, biologics, cyclosporin, Janus kinase inhibitors for the treatment of PSO. The data on the effect of immunosuppressive drugs on this virus may be ever-changing and remains to be clear. We recommend the initiation and continuation of low-risk immunomodulating drugs, such as Interleukin (IL)-17, IL-12/23, and IL-23 inhibitors, for treatment of PSO during COVID-19 era. For psoriatic patients with comorbidities switching to safer modalities such as systemic retinoids, apremilast, and home phototherapy is recommended. Immunosuppressive drugs should be withheld in psoriatic patients with the COVID-19 infection.
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Affiliation(s)
- Ali Sadeghinia
- Department of Dermatology, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Daneshpazhooh
- Department of Dermatology, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran
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35
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van Winden MEC, van der Schoot LS, van de L’Isle Arias M, van Vugt LJ, van den Reek JMPA, van de Kerkhof PCM, de Jong EMGJ, Lubeek SFK. Effectiveness and Safety of Systemic Therapy for Psoriasis in Older Adults. JAMA Dermatol 2020; 156:1229-1239. [DOI: 10.1001/jamadermatol.2020.2311] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
| | | | | | - Lieke J. van Vugt
- Department of Dermatology, Maastricht University Medical Center, Maastricht, the Netherlands
| | | | | | - Elke M. G. J. de Jong
- Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Satish F. K. Lubeek
- Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands
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36
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Incidence of severe COVID-19 outcomes in psoriatic patients treated with systemic therapies during the pandemic: A Biobadaderm cohort analysis. J Am Acad Dermatol 2020; 84:513-517. [PMID: 33122022 PMCID: PMC7587130 DOI: 10.1016/j.jaad.2020.10.046] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 09/14/2020] [Accepted: 10/17/2020] [Indexed: 11/21/2022]
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Zahedi Niaki O, Anadkat MJ, Chen ST, Fox LP, Harp J, Micheletti RG, Nambudiri VE, Pasieka HB, Shinohara MM, Rosenbach M, Merola JF. Navigating immunosuppression in a pandemic: A guide for the dermatologist from the COVID Task Force of the Medical Dermatology Society and Society of Dermatology Hospitalists. J Am Acad Dermatol 2020; 83:1150-1159. [PMID: 32569797 PMCID: PMC7303642 DOI: 10.1016/j.jaad.2020.06.051] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 06/05/2020] [Accepted: 06/10/2020] [Indexed: 02/07/2023]
Abstract
Dermatologists treating immune-mediated skin disease must now contend with the uncertainties associated with immunosuppressive use in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Although the risk of infection with many commonly used immunosuppressive agents remains low, direct data evaluating the safety of such agents in coronavirus disease 2019 (COVID-19) are scarce. This article reviews and offers guidance based on currently available safety data and the most recent COVID-19 outcome data in patients with immune-mediated dermatologic disease. The interdisciplinary panel of experts emphasizes a stepwise, shared decision-making approach in the management of immunosuppressive therapy. The goal of this article is to help providers minimize the risk of disease flares while simultaneously minimizing the risk of iatrogenic harm during an evolving pandemic.
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Affiliation(s)
- Omid Zahedi Niaki
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Milan J Anadkat
- Division of Dermatology, Washington University in St. Louis School of Medicine, St Louis, Missouri
| | - Steven T Chen
- Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Lindy P Fox
- Department of Dermatology, University of California, San Francisco, California
| | - Joanna Harp
- Department of Dermatology, Weill Cornell Medicine, New York, New York
| | - Robert G Micheletti
- Departments of Dermatology and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Vinod E Nambudiri
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Helena B Pasieka
- Department of Dermatology, Georgetown University School of Medicine, Medstar Washington Hospital Center, Washington, DC
| | - Michi M Shinohara
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington
| | - Misha Rosenbach
- Departments of Dermatology and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Joseph F Merola
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Kapniari E, Papadimitriou P, Dalamaga M, Makavos G, Piaserico S, Egeberg A, Ikonomidis I, Papadavid E. Investigating the Link between Psoriasis and Cardiovascular Disease: Current Evidence, Therapeutic Implications and Perspectives. Curr Vasc Pharmacol 2020; 18:592-609. [DOI: 10.2174/1570161118666200523154318] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 04/24/2020] [Accepted: 04/27/2020] [Indexed: 02/07/2023]
Abstract
Psoriasis; a chronic inflammatory disease is characterized by symmetric hyperkeratotic
plaques affecting any part of the body. Psoriasis is nowadays considered as a systemic inflammation
linked with several comorbidities as metabolic syndrome, depression, anxiety and increased prevalence
of cardiovascular (CV) disease. The hypothesis that psoriasis is an independent CV risk factor leading to
atherosclerosis via inflammation is now widely accepted. Deciphering the underlying mechanisms interconnecting
psoriasis and CV disease may have significant implications in treatment decisions. Accumulating
evidence suggests that systematic therapies and recently introduced biologic agents, that control
psoriasis by suppressing the chronic and systemic inflammation, may alter the progression of CV disease.
We herein attempt a review of current evidence analysing the relationship between psoriasis and
CV comorbidities, comment on the mechanisms underlying this association and investigate the consequences
for the management of psoriasis.
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Affiliation(s)
- Eirini Kapniari
- 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens Medical School, Attikon Hospital, Athens, Greece
| | | | - Marianna Dalamaga
- Department of Biological Chemistry, Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - George Makavos
- 2nd Department of Cardiology, National and Kapodistrian University of Athens Medical School, Attikon Hospital, Athens, Greece
| | | | - Alexander Egeberg
- Departments of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Ignatios Ikonomidis
- 2nd Department of Cardiology, National and Kapodistrian University of Athens Medical School, Attikon Hospital, Athens, Greece
| | - Evangelia Papadavid
- 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens Medical School, Attikon Hospital, Athens, Greece
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Ricardo JW, Lipner SR. Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during the COVID-19 pandemic. Dermatol Ther 2020; 33:e13687. [PMID: 32458536 PMCID: PMC7283778 DOI: 10.1111/dth.13687] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 05/22/2020] [Indexed: 01/10/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is responsible for at least 2 546 527 cases and 175 812 deaths as of April 21, 2020. Psoriasis and atopic dermatitis (AD) are common, chronic, inflammatory skin conditions, with immune dysregulation as a shared mechanism; therefore, mainstays of treatment include systemic immunomodulating therapies. It is unknown whether these therapies are associated with increased COVID-19 susceptibility or worse outcomes in infected patients. In this review, we discuss overall infection risks of nonbiologic and biologic systemic medications for psoriasis and AD and provide therapeutic recommendations. In summary, in patients with active infection, systemic conventional medications, the Janus kinase inhibitor tofacitinib, and biologics for psoriasis should be temporarily held until there is more data; in uninfected patients switching to safer alternatives should be considered. Interleukin (IL)-17, IL-12/23, and IL-23 inhibitors are associated with low infection risk, with IL-17 and IL-23 favored over IL-12/23 inhibitors. Pivotal trials and postmarketing data also suggest that IL-17 and IL-23 blockers are safer than tumor necrosis factor alpha blockers. Apremilast, acitretin, and dupilumab have favorable safety data and may be safely initiated and continued in uninfected patients. Without definitive COVID-19 data, these recommendations may be useful in guiding treatment of psoriasis and AD patients during the COVID-19 pandemic.
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Affiliation(s)
- Jose W. Ricardo
- Department of DermatologyWeill Cornell MedicineNew YorkNew YorkUSA
| | - Shari R. Lipner
- Department of DermatologyWeill Cornell MedicineNew YorkNew YorkUSA
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Topaloğlu Demir F, Özkök Akbulut T, Kıvanç Altunay İ, Aytekin S, Oğuz Topal İ, Kara Polat A, Özkur E, Karadağ AS. Evaluation of the adverse effects of biological agents used in the treatment of psoriasis: A multicenter retrospective cohort study. Dermatol Ther 2020; 33:e14216. [PMID: 32827159 DOI: 10.1111/dth.14216] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 08/09/2020] [Accepted: 08/13/2020] [Indexed: 01/25/2023]
Abstract
The objective was to reveal and compare the adverse effects of infliximab, etanercept, adalimumab, ustekinumab and secukinumab, and determine possible risk factors. The follow-up files and computer-based records of patients with psoriasis were retrospectively screened between January 2007 and September 2019. The five biological agents were compared in terms of their adverse effects, and factors that might be related to these effects were explored. While there was no statistically significant difference between the agents in terms of the rate of serious adverse effects, when all the adverse effects were evaluated together, the highest rate was seen in the use of infliximab and the lowest in secukinumab (P = .001). The rates of adverse effects and related drug discontinuation were higher in the use of anti-TNF agents compared to interleukin inhibitors (P = .004 and P = .012, respectively). The agent with the highest drug discontinuation rate due to adverse effects was infliximab while the least discontinued agent was ustekinumab (P = .036). There were more side effects with anti-TNF than interleukin inhibitors, but the serious adverse effect rate was similar in both groups. The incidence of certain adverse effects increases depending on age, number of comorbidities, biological agent and its group, concomitant systemic therapy, and use of multiple agents.
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Affiliation(s)
- Filiz Topaloğlu Demir
- Department of Dermatology and Venereology, Istanbul Medipol University, Faculty of Medicine, Istanbul, Turkey
| | - Tuğba Özkök Akbulut
- Department of Dermatology and Venereology, University of Health Sciences, Haseki Training and Research Hospital, Istanbul, Turkey
| | - İlknur Kıvanç Altunay
- Department of Dermatology and Venereology, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Sema Aytekin
- Department of Dermatology and Venereology, University of Health Sciences, Haydarpaşa Numune Training and Research Hospital, Istanbul, Turkey
| | - İlteriş Oğuz Topal
- Department of Dermatology and Venereology, University of Health Sciences, Okmeydanı Training and Research Hospital, Istanbul, Turkey
| | - Asude Kara Polat
- Department of Dermatology and Venereology, University of Health Sciences, Istanbul Training and Research Hospital, Istanbul, Turkey
| | - Ezgi Özkur
- Department of Dermatology and Venereology, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Ayşe Serap Karadağ
- Department of Dermatology and Venereology, Istanbul Medeniyet University, School of Medicine, Göztepe Training and Research Hospital, Istanbul, Turkey
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Ladda M, Lynde C, Fleming P. Severe Acute Respiratory Syndrome Coronavirus 2 and the Use of Biologics in Patients With Psoriasis. J Cutan Med Surg 2020; 24:625-632. [PMID: 32757760 DOI: 10.1177/1203475420945234] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Coronavirus disease (COVID-19), a respiratory disease caused by a novel coronavirus designated severe acute respiratory syndrome coronavirus 2, has rapidly spread worldwide and has been recognized as a pandemic by the World Health Organization. Patients with altered immunologic function are at higher risk of acquiring COVID-19. In patients with psoriasis, inhibition of select pro-inflammatory cytokines through the use of biologic agents has been shown to be an effective treatment option. Pro-inflammatory cytokines have key immunomodulatory effects and are known to be involved in the hosts' immune response to a variety of viral infections. Though little is currently known about the role of inflammatory cytokines in COVID-19, early reports have shown patients with severe disease to have elevated serum levels of select inflammatory cytokines such as tumor necrosis factor alpha. This review will summarize key information that is currently known about COVID-19, the role of select cytokines in viral defense, and important considerations for patients with psoriasis using biologic agents during this pandemic. Currently, there is insufficient evidence to discontinue biologic therapy in patients with psoriasis who have not tested positive for COVID-19. The decision to pause biologic therapy should be considered on a case-by-case basis in patients in higher risk populations, and should take into account individual risk and benefit. Until more is known about the impact of biologic therapy on COVID-19 outcomes, we recommend patients with psoriasis who test positive for COVID-19 be instructed to discontinue or postpone biologic treatment until they have recovered from infection.
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Affiliation(s)
- Matthew Ladda
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Charles Lynde
- Lynde Institute for Dermatology, Markham, ON, Canada
- 210484 Division of Dermatology, Department of Medicine, University of Toronto, Toronto ON, Canada
| | - Patrick Fleming
- Lynde Institute for Dermatology, Markham, ON, Canada
- 210484 Division of Dermatology, Department of Medicine, University of Toronto, Toronto ON, Canada
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42
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Balak DMW, Gerdes S, Parodi A, Salgado-Boquete L. Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature. Dermatol Ther (Heidelb) 2020; 10:589-613. [PMID: 32529393 PMCID: PMC7367959 DOI: 10.1007/s13555-020-00409-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Indexed: 01/10/2023] Open
Abstract
Oral systemic therapies are important treatment options for patients with moderate-to-severe psoriasis, either as monotherapy or in therapy-recalcitrant cases as combination therapy with phototherapy, other oral systemics or biologics. Long-term treatment is needed to maintain sufficient disease control in psoriasis, but continuous use of systemic treatments is limited by adverse events (AEs) and cumulative toxicity risks. The primary aim of this comprehensive literature review was to examine the long-term safety profiles of oral agents commonly used in the treatment of adults with psoriasis. Searches were conducted in EMBASE and PubMed up to November 2018, and 157 relevant publications were included. Long-term treatment with acitretin could be associated with skeletal toxicity and hepatotoxicity, although evidence for skeletal toxicity is mixed and hepatotoxicity is rare, particularly at low doses. Other safety issues include hyperlipidaemia and potential for teratogenicity up to 2-3 years after discontinuation of treatment. There is a paucity of data on long-term treatment with apremilast. Continued exposure to apremilast does not seem to increase the incidence of common AEs, such as gastrointestinal (GI) AEs, upper respiratory tract infections and headache, while the long-term risks for depression, suicidal thoughts and weight loss are unknown. Long-term ciclosporin treatment is associated with renal toxicity, hypertension, non-melanoma skin cancer, neurological AEs and GI AEs. Long-term methotrexate treatment is associated with hepatotoxicity, GI AEs, haematological toxicity, renal toxicity and alopecia. Finally, long-term treatment with fumaric acid esters (FAE) is associated with GI AEs, flushing, lymphocytopenia, proteinuria and elevated liver enzymes. Median drug survival estimates varied considerably: ~ 2.9-9.7 months for apremilast; ~ 5.4 months for ciclosporin; ~ 8.6 months for acitretin; ~ 12.1-21.6 months for methotrexate; and ~ 54.8 months for FAE. These long-term safety profiles may help to guide clinicians to select the optimal oral systemic treatment for the long-term treatment of psoriasis in adults.
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Affiliation(s)
- Deepak M W Balak
- Department of Dermatology, LangeLand Ziekenhuis, Zoetermeer, the Netherlands.
| | - Sascha Gerdes
- Department of Dermatology, Psoriasis-Center, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Aurora Parodi
- DiSSal Section of Dermatology, University of Genoa-Ospedale-Policlinico San Martino IRCCS, Genoa, Italy
| | - Laura Salgado-Boquete
- Department of Dermatology, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
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43
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Ghazawi FM, Lim M, Dutz JP, Kirchhof MG. Infection risk of dermatologic therapeutics during the COVID-19 pandemic: an evidence-based recalibration. Int J Dermatol 2020; 59:1043-1056. [PMID: 32621284 PMCID: PMC7361427 DOI: 10.1111/ijd.15028] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 05/25/2020] [Accepted: 06/04/2020] [Indexed: 12/20/2022]
Abstract
Recommendations were made recently to limit or stop the use of oral and systemic immunotherapies for skin diseases due to potential risks to the patients during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic. Herein, we attempt to identify potentially safe immunotherapies that may be used in the treatment of cutaneous diseases during the current COVID-19 pandemic. We performed a literature review to approximate the risk of SARS-CoV-2 infection, including available data on the roles of relevant cytokines, cell subsets, and their mediators in eliciting an optimal immune response against respiratory viruses in murine gene deletion models and humans with congenital deficiencies were reviewed for viral infections risk and if possible coronaviruses specifically. Furthermore, reported risk of infections of biologic and non-biologic therapeutics for skin diseases from clinical trials and drug data registries were evaluated. Many of the immunotherapies used in dermatology have data to support their safe use during the COVID-19 pandemic including the biologics that target IgE, IL-4/13, TNF-α, IL-17, IL-12, and IL-23. Furthermore, we provide evidence to show that oral immunosuppressive medications such as methotrexate and cyclosporine do not significantly increase the risk to patients. Most biologic and conventional immunotherapies, based on doses and indications in dermatology, do not appear to increase risk of viral susceptibility and are most likely safe for use during the COVID-19 pandemic. The limitation of this study is availability of data on COVID-19.
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Affiliation(s)
- Feras M Ghazawi
- Division of Dermatology, University of Ottawa, Ottawa, ON, Canada
| | - Megan Lim
- Division of Dermatology, University of Ottawa, Ottawa, ON, Canada
| | - Jan P Dutz
- Department of Dermatology and Skin Sciences, University of British Columbia, Vancouver, BC, Canada.,BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Mark G Kirchhof
- Division of Dermatology, University of Ottawa, Ottawa, ON, Canada
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Daudén E, Carretero G, Rivera R, Ferrándiz C, Llamas-Velasco M, de la Cueva P, Belinchón I, Gómez-García FJ, Herrera-Acosta E, Ruiz-Genao DP, Ferrán-Farrés M, Alsina M, Baniandrés-Rodríguez O, Sánchez-Carazo JL, Sahuquillo-Torralba A, Fernández-Freire LR, Vilar-Alejo J, García-Donoso C, Carrascosa JM, Herrera-Ceballos E, López-Estebaranz JL, Botella-Estrada R, Segovia-Muñoz E, Descalzo MA, García-Doval I, Daudén E, Llamas-Velasco M, Carretero G, Vilar-Alejo J, Rivera R, García-Donoso C, Ferrándiz C, Carrascosa JM, Ballescá F, Cueva PDL, Belinchón I, Gómez-García FJ, Jiménez R, Herrera-Ceballos E, Herrera-Acosta E, López-Estebaranz JL, Ruiz-Genao DP, Farrés MF, Alsina M, Baniandrés O, Nieto L, Sánchez-Carazo JL, Sahuquillo-Torralba A, Botella-Estrada R, Marco CP, Fernández-Freire LR, Puchades AM, Menéndez ÁF, Salgado L, Sixto BG, Eiris N, García-Doval I, Descalzo Gallego MÁ, de Vega Martínez M. Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. J Am Acad Dermatol 2020; 83:139-150. [DOI: 10.1016/j.jaad.2020.03.033] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 03/05/2020] [Accepted: 03/08/2020] [Indexed: 12/18/2022]
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Galimberti F, McBride J, Cronin M, Li Y, Fox J, Abrouk M, Herbst A, Kirsner RS. Evidence-based best practice advice for patients treated with systemic immunosuppressants in relation to COVID-19. Clin Dermatol 2020; 38:775-780. [PMID: 32419721 PMCID: PMC7224642 DOI: 10.1016/j.clindermatol.2020.05.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The emergence of the COVID-19 pandemic has led to significant uncertainty among physicians and patients about the safety of immunosuppressive medications used for the management of dermatologic conditions. We review available data on commonly used immunosuppressants and their effect on viral infections beyond COVID-19. Notably, the effect of some immunosuppressants on viruses related to SARS-CoV2, including SARS and MERS, has been previously investigated. In the absence of data on the effect of immunosuppressants on COVID-19, these data could be used to make clinical decisions on initiation and continuation of immunosuppressive medications during this pandemic. In summary, we recommend considering the discontinuation of oral Janus kinase (JAK) inhibitors and prednisone; considering the delay of rituximab infusion; and suggesting the careful continuation of cyclosporine, mycophenolate, azathioprine, methotrexate, and biologics in patients currently benefitting from such treatments.
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Affiliation(s)
- Fabrizio Galimberti
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Jeffrey McBride
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Megan Cronin
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Yumeng Li
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Joshua Fox
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Michael Abrouk
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Alexander Herbst
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Robert S Kirsner
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
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Grän F, Kerstan A, Serfling E, Goebeler M, Muhammad K. Current Developments in the Immunology of Psoriasis. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 2020; 93:97-110. [PMID: 32226340 PMCID: PMC7087066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Psoriasis is a frequent inflammatory skin disease. Fundamental research on the pathogenesis of psoriasis has substantially increased our understanding of skin immunology, which has helped to introduce innovative and highly effective therapies. Psoriasis is a largely T lymphocyte-mediated disease in which activation of innate immune cells and pathogenic T cells result in skin inflammation and hyperproliferation of keratinocytes. B cells have thus far largely been neglected regarding their role for the pathogenesis of psoriasis. However, recent data shed light on their role in inflammatory skin diseases. Interestingly, interleukin (IL)-10-producing regulatory B cells have been assumed to ameliorate psoriasis. In this review, we will discuss the development of disease, pathogenicity, and current developments in therapeutic options. We describe different roles of T cells, B cells, and cytokines for the immunopathology and disease course of psoriasis.
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Affiliation(s)
- Franziska Grän
- Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
| | - Andreas Kerstan
- Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
| | - Edgar Serfling
- Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Würzburg, Germany
| | - Matthias Goebeler
- Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
| | - Khalid Muhammad
- Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Würzburg, Germany,Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates,To whom all correspondence should be addressed: K. Muhammad, Tel: +971 3 713 6517, Fax: +971 3 713 4927;
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Sahuquillo-Torralba A, Carretero G, Rivera R, Ferrándiz C, Daudén-Tello E, de la Cueva P, Gómez-García FJ, Belinchón I, Herrera-Acosta E, Ruiz-Genao D, Ferrán M, Alsina M, Sánchez-Carazo JL, Baniandrés O, Fernández-Freire LR, Vilar J, García-Donoso C, Carrascosa JM, Llamas-Velasco M, Herrera-Ceballos E, López-Estebaranz JL, Pujol-Marco C, Descalzo MÁ, García-Doval I. The risk of urinary tract infections in patients with psoriasis on systemic medications in Biobadaderm Registry: A prospective cohort study. J Am Acad Dermatol 2020; 82:738-741. [DOI: 10.1016/j.jaad.2019.07.028] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/03/2019] [Accepted: 07/06/2019] [Indexed: 01/08/2023]
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Burmester GR, Gordon KB, Rosenbaum JT, Arikan D, Lau WL, Li P, Faccin F, Panaccione R. Long-Term Safety of Adalimumab in 29,967 Adult Patients From Global Clinical Trials Across Multiple Indications: An Updated Analysis. Adv Ther 2020; 37:364-380. [PMID: 31748904 PMCID: PMC6979455 DOI: 10.1007/s12325-019-01145-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Indexed: 12/17/2022]
Abstract
INTRODUCTION The safety profile of adalimumab was previously reported in 23,458 patients across multiple indications. Here we report the long-term safety of adalimumab in adults with plaque psoriasis (Ps), hidradenitis suppurativa (HS), rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, non-radiographic axial spondyloarthritis, peripheral spondyloarthritis, Crohn's disease (CD), ulcerative colitis (UC), and non-infectious uveitis (UV). METHODS Safety data from 77 clinical trials were pooled. Safety assessments included adverse events (AEs) and serious AEs (SAEs) that occurred after the first study dose and within 70 days (5 half-lives) after the last study dose. RESULTS A total of 29,967 patients were included, representing 56,916 patient-years (PY) of exposure. The most frequently reported SAE of interest was infection (3.7/100 PY) with highest incidences in CD, RA, UV, and UC (3.5/100 PY-6.9/100 PY); serious infections in Ps (1.8/100 PY) and HS (2.8/100 PY) were lower. The observed number of deaths was below what would be expected in an age- and sex-adjusted population for most adalimumab-treated patients (including Ps). Lack of real-life data and limited long-term data (> 5 years) for most patients are limitations of this analysis. CONCLUSION The safety profile of adalimumab was consistent with previous findings and no new safety signals were observed.
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Affiliation(s)
| | | | - James T Rosenbaum
- Oregon Health and Science University and Legacy Devers Eye Institute, Portland, OR, USA
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Liu LF, Chen JS, Gu J, Xu JH, Jin HZ, Pang XW, Wang G, Yu C, Song ZQ, Guo ZP, Li W, Lai W, Cui PG, Chen M, Fang H, Lyu CZ, Li YZ, Sun Q, Xie HF, Liu XM, Gao XH, Shi YL, Zhao NQ, Zhang W, Zheng M. Etanercept biosimilar (recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein) and methotrexate combination therapy in Chinese patients with moderate-to-severe plaque psoriasis: a multicentre, randomized, double-blind, placebo-controlled trial. Arch Dermatol Res 2019; 312:437-445. [DOI: 10.1007/s00403-019-02024-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 11/12/2019] [Accepted: 12/07/2019] [Indexed: 02/08/2023]
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Zabotti A, Goletti D, Lubrano E, Cantini F. The impact of the interleukin 12/23 inhibitor ustekinumab on the risk of infections in patients with psoriatic arthritis. Expert Opin Drug Saf 2019; 19:69-82. [PMID: 31847608 DOI: 10.1080/14740338.2020.1703946] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Psoriatic arthritis (PsA) is characterized by chronic inflammation mediated by pro-inflammatory cytokines, with clinical features resulting from dysfunctional integrated signaling pathways affecting different constituents of the immune system. Increased understanding of the processes responsible for enthesitis, synovial inflammation, joint erosion, and new bone formation during PsA has led to development of biologic therapies targeting these cytokines. There is an increased risk of opportunistic infections in patients with PsA, and this risk is increased further with targeted biologic therapy.Areas covered: This paper reviews the role of the interleukin (IL)-12, IL-23 and IL-17 axis in the pathogenesis of PsA. The data suggest that ustekinumab is associated with a low risk of infections in patients with PsA, including tuberculosis or hepatitis reactivation. No live vaccines can be safely administered; ustekinumab is contraindicated/cannot be given with live vaccines. However, long-term treatment with ustekinumab does not impair the immune response to these vaccines when administered after an appropriate interval.Expert opinion: Ustekinumab is associated with a low risk of serious and opportunistic infections. More research is needed to confirm these findings specifically in patients with PsA, and comparative studies are needed to investigate the relative risk of infection with different biologics.
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Affiliation(s)
- Alen Zabotti
- Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy
| | - Delia Goletti
- Translational Research Unit, Epidemiology and Preclinical Research Department, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy
| | - Ennio Lubrano
- Dipartimento di Medicina e Scienze della Salute "Vincenzo Tiberio", Università degli Studi del Molise, Campobasso, Italy
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