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Li J, Xiang X, Wang Z, Miao C, Chen Y, Xu Z. Safety of Interleukin Inhibitors in Psoriatic Patients with Latent Tuberculosis Infection Without Chemoprophylaxis: A Systematic Review. Acta Derm Venereol 2025; 105:adv42081. [PMID: 40026108 PMCID: PMC11894292 DOI: 10.2340/actadv.v105.42081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 02/03/2025] [Indexed: 03/04/2025] Open
Abstract
Current guidelines recommend psoriatic patients with latent tuberculosis infection undergo chemoprophylaxis prior to initiating any biologic. However, clinical studies indicate that interleukin (IL) inhibitors may not increase the risk of tuberculosis reactivation. This review evaluates the safety in psoriatic patients with latent tuberculosis infection using IL inhibitors without chemoprophylaxis. PubMed and EMBASE were searched up to 1 November 2024 in accordance with PRISMA. Fifteen studies, including one safety analysis of a clinical trial, 2 case series, and 12 retrospective studies were analysed. The included studies reported a total of 837 cases: 179 patients were treated with secukinumab, 69 with ixekizumab, 8 with brodalumab, 539 with risankizumab, 22 with guselkumab, and 20 with tildrakizumab. Psoriatic patients with latent tuberculosis infection using an IL-12/23 inhibitor without chemoprophylaxis were not found in this review. Three of the 837 cases exhibited reactivation of tuberculosis. The reactivation rate is 0.78% among psoriatic patients with latent tuberculosis infection using IL-17 inhibitors, and 0.17% among those using IL-23 inhibitors. Our analysis shows that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis activation in psoriatic patients with latent tuberculosis infection. The impact of IL-12/23 inhibitors on tuberculosis reactivation among psoriatic patients with latent tuberculosis infection remains uncertain and requires further investigation.
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Affiliation(s)
- Jiaying Li
- Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China
| | - Xin Xiang
- Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China
| | - Zhaoyang Wang
- Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China
| | - Chaoyang Miao
- Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China
| | - Yunliu Chen
- Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China
| | - Zigang Xu
- Department of Dermatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China.
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Jha DK, Kakadiya R, Sharma A, Naidu S, De D, Sharma V. Assessment and management for latent tuberculosis before advanced therapies for immune-mediated inflammatory diseases: A comprehensive review. Autoimmun Rev 2025; 24:103758. [PMID: 39870187 DOI: 10.1016/j.autrev.2025.103758] [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: 05/24/2024] [Revised: 01/16/2025] [Accepted: 01/24/2025] [Indexed: 01/29/2025]
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis , is the most significant infectious cause of mortality across the globe. While TB disease can prey on immunocompetent individuals, it is more likely to occur in immunocompromised individuals. Immune-mediated inflammatory diseases (IMIDs) are a group of diseases (rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriasis, hidradenitis suppurativa, autoimmune blistering diseases, and others) where there may be a need for systemic immunosuppression to control the disease manifestations, treat symptoms and improve long term outcomes. Immunosuppression may predispose them to active TB either from recent infection or reactivation of Latent TB (LTB). The major determinants of reactivation include the type of therapy (highest risk with TNF inhibitors and JAK inhibitors) and the underlying TB endemicity. The strategy to avoid TB reactivation includes the detection of LTB using tests that detect immunoreactivity to TB antigens (interferon-gamma release assays or tuberculin skin test) and treating LTB before or with initiation of IMID therapies. Available diagnostic tests have deficiencies in diagnostic sensitivity to detect LTB and even worse capability in predicting reactivation of TB. In addition to immunological tests, more stringent testing strategy utilizing one or many LTB equivalents may point towards subclinical TB. LTB equivalents include clinical (past history of TB, recent exposure to TB) and radiological criteria (use of chest roentgenogram, computed tomography, or, sometimes positron emission tomography - computed tomography). The present review summarizes the risk factors for TB reactivation in patients initiated on advanced therapies, geographically appropriate strategies for LTB testing, and treatment of LTB.
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Affiliation(s)
| | - Rinkalben Kakadiya
- Department of Gatroenterology, Surat Institute of Digestive Sciences, Surat, Gujarat, India
| | - Ananya Sharma
- Government Medical College and Hospital, Sector 32, Chandigarh, India
| | - Shankar Naidu
- Clinical Immunology and Rheumatology Services, Department of Internal Medicine Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Dipankar De
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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Picchianti-Diamanti A, Aiello A, De Lorenzo C, Migliori GB, Goletti D. Management of tuberculosis risk, screening and preventive therapy in patients with chronic autoimmune arthritis undergoing biotechnological and targeted immunosuppressive agents. Front Immunol 2025; 16:1494283. [PMID: 39963138 PMCID: PMC11830708 DOI: 10.3389/fimmu.2025.1494283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 01/06/2025] [Indexed: 02/20/2025] Open
Abstract
Tuberculosis (TB) is the leading cause of death in the world from an infectious disease. Its etiologic agent, the Mycobacterium tuberculosis (Mtb), is a slow-growing bacterium that has coexisted in humans for thousands of years. According to the World Health Organization, 10.6 million new cases of TB and over 1 million deaths were reported in 2022. It is widely recognized that patients affected by chronic autoimmune arthritis such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) have an increased incidence rate of TB disease compared to the general population. As conceivable, the risk is associated with age ≥65 years and is higher in endemic regions, but immunosuppressive therapy plays a pivotal role. Several systematic reviews have analysed the impact of anti-TNF-α agents on the risk of TB in patients with chronic autoimmune arthritis, as well as for other biologic disease-modifying immunosuppressive anti-rheumatic drugs (bDMARDs) such as rituximab, abatacept, tocilizumab, ustekinumab, and secukinumab. However, the data are less robust compared to those available with TNF-α inhibitors. Conversely, data on anti-IL23 agents and JAK inhibitors (JAK-i), which have been more recently introduced for the treatment of RA and PsA/AS, are limited. TB screening and preventive therapy are recommended in Mtb-infected patients undergoing bDMARDs and targeted synthetic (ts)DMARDs. In this review, we evaluate the current evidence from randomized clinical trials, long-term extension studies, and real-life studies regarding the risk of TB in patients with RA, PsA, and AS treated with bDMARDs and tsDMARDs. According to the current evidence, TNF-α inhibitors carry the greatest risk of TB progression among bDMARDs and tsDMARDs, such as JAK inhibitors and anti-IL-6R agents. The management of TB screening and the updated preventive therapy are reported.
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Affiliation(s)
- Andrea Picchianti-Diamanti
- Department of Clinical and Molecular Medicine, “Sapienza” University, S. Andrea University Hospital, Rome, Italy
| | - Alessandra Aiello
- Translational Research Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani”- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Chiara De Lorenzo
- Department of Clinical and Molecular Medicine, “Sapienza” University, S. Andrea University Hospital, Rome, Italy
| | - Giovanni Battista Migliori
- Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Tradate, Italy
| | - Delia Goletti
- Translational Research Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani”- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
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Torres T, Brembilla NC, Langley RG, Warren RB, Thaçi D, Kolios AGA, Prinz JC, Londono-Garcia A, Nast A, Santin M, Goletti D, Abreu M, Spuls P, Boehncke WH, Puig L. Treatment of psoriasis with biologic and non-biologic targeted therapies in patients with latent tuberculosis infection or at risk for tuberculosis disease progression: Recommendations from a SPIN-FRT expert consensus. J Eur Acad Dermatol Venereol 2025; 39:52-69. [PMID: 39149807 DOI: 10.1111/jdv.20287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 07/12/2024] [Indexed: 08/17/2024]
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.
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Affiliation(s)
- T Torres
- Department of Dermatology, Centro Hospitalar Universitário de Santo António, Porto, Portugal
- Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
| | - N C Brembilla
- Division of Dermatology and Venereology, University Hospitals of Geneva, Geneva, Switzerland
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - R G Langley
- Division of Clinical Dermatology & Cutaneous Science, Dalhousie University, Halifax, Nova Scotia, Canada
| | - R B Warren
- Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, UK
- NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - D Thaçi
- Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lü beck, Germany
| | - A G A Kolios
- Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - J C Prinz
- University Hospital, Department of Dermatology and Allergy, Ludwig-Maximilian-University Munich, Munich, Germany
| | | | - A Nast
- Division of Evidence-Based Medicine, Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - M Santin
- Tuberculosis Unit, Department of Infectious Diseases, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Department of Clinical Sciences, L'Hospitalet de Llobregat, University of Barcelona, Barcelona, Spain
- Centre for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - D Goletti
- Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy
| | - M Abreu
- UMIB-Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universit of Porto, Porto, Portugal
- Department of Infectious Diseases, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - P Spuls
- Department of Dermatology, Amsterdam University Medical Centre, Amsterdam Public Health, Infection and Immunity, University of Amsterdam, Amsterdam, The Netherlands
| | - W H Boehncke
- Division of Dermatology and Venereology, University Hospitals of Geneva, Geneva, Switzerland
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - L Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
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de Oliveira Magalhães V, Bonfiglioli KR, Gomes CMF, Bonfá E, de Medeiros-Ribeiro AC, Saad CGS, de Medeiros Pinheiro M. Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area. Adv Rheumatol 2024; 64:70. [PMID: 39272122 DOI: 10.1186/s42358-024-00406-7] [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: 01/29/2024] [Accepted: 08/25/2024] [Indexed: 09/15/2024] Open
Abstract
OBJECTIVES To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.
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Affiliation(s)
- Vanessa de Oliveira Magalhães
- Spondyloarthritis Section, Rheumatology Division, Federal University of São Paulo, (Unifesp/ EPM), Borges Lagoa Street, 913/ 51-53, Vila Clementino, São Paulo, SP, 04038-034, Brazil
| | - Karina Rossi Bonfiglioli
- Rheumatology DivisionHospital das Clínicas, Faculdade de Medicina (HCFMUSP), Universidade de São Paulo, São Paulo, Brazil
| | | | - Eloisa Bonfá
- Rheumatology DivisionHospital das Clínicas, Faculdade de Medicina (HCFMUSP), Universidade de São Paulo, São Paulo, Brazil
| | | | - Carla Gonçalves S Saad
- Rheumatology DivisionHospital das Clínicas, Faculdade de Medicina (HCFMUSP), Universidade de São Paulo, São Paulo, Brazil
| | - Marcelo de Medeiros Pinheiro
- Spondyloarthritis Section, Rheumatology Division, Federal University of São Paulo, (Unifesp/ EPM), Borges Lagoa Street, 913/ 51-53, Vila Clementino, São Paulo, SP, 04038-034, Brazil.
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Jain A, Hakim S, Woolf CJ. Immune drivers of physiological and pathological pain. J Exp Med 2024; 221:e20221687. [PMID: 38607420 PMCID: PMC11010323 DOI: 10.1084/jem.20221687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 09/25/2023] [Accepted: 04/02/2024] [Indexed: 04/13/2024] Open
Abstract
Physiological pain serves as a warning of exposure to danger and prompts us to withdraw from noxious stimuli to prevent tissue damage. Pain can also alert us of an infection or organ dysfunction and aids in locating such malfunction. However, there are instances where pain is purely pathological, such as unresolved pain following an inflammation or injury to the nervous system, and this can be debilitating and persistent. We now appreciate that immune cells are integral to both physiological and pathological pain, and that pain, in consequence, is not strictly a neuronal phenomenon. Here, we discuss recent findings on how immune cells in the skin, nerve, dorsal root ganglia, and spinal cord interact with somatosensory neurons to mediate pain. We also discuss how both innate and adaptive immune cells, by releasing various ligands and mediators, contribute to the initiation, modulation, persistence, or resolution of various modalities of pain. Finally, we propose that the neuroimmune axis is an attractive target for pain treatment, but the challenges in objectively quantifying pain preclinically, variable sex differences in pain presentation, as well as adverse outcomes associated with immune system modulation, all need to be considered in the development of immunotherapies against pain.
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Affiliation(s)
- Aakanksha Jain
- F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Boston, MA, USA
| | - Sara Hakim
- F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Boston, MA, USA
- Department of Neurobiology, Harvard Medical School, Boston, MA, USA
| | - Clifford J. Woolf
- F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Boston, MA, USA
- Department of Neurobiology, Harvard Medical School, Boston, MA, USA
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Torres T, Chiricozzi A, Puig L, Lé AM, Marzano AV, Dapavo P, Dauden E, Carrascosa JM, Lazaridou E, Duarte G, Carvalho AVE, Romiti R, Rompoti N, Teixeira L, Abreu M, Ippoliti E, Maronese CA, Llamas-Velasco M, Vilarrasa E, Del Alcázar E, Daponte AI, Papoutsaki M, Carugno A, Bellinato F, Gisondi P. Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study. Am J Clin Dermatol 2024; 25:333-342. [PMID: 38265746 PMCID: PMC10867072 DOI: 10.1007/s40257-024-00845-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2024] [Indexed: 01/25/2024]
Abstract
BACKGROUND Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation. OBJECTIVE To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis. METHODS This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded. RESULTS A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant). CONCLUSIONS The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.
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Affiliation(s)
- Tiago Torres
- Department of Dermatology, CAC ICBAS-CHP - Centro Académico Clínico ICBAS - CHP, Rua D. Manuel II, s/n, 4100, Porto, Portugal.
- UMIB - Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
| | - Andrea Chiricozzi
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Luis Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Ana Maria Lé
- Department of Dermatology, CAC ICBAS-CHP - Centro Académico Clínico ICBAS - CHP, Rua D. Manuel II, s/n, 4100, Porto, Portugal
| | - Angelo Valerio Marzano
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Physiopathology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Paolo Dapavo
- Department of Medical Sciences, Dermatology Clinic, University of Turin, Turin, Italy
| | - Esteban Dauden
- Department of Dermatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-IP), Madrid, Spain
| | - Jόse-Manuel Carrascosa
- Department of Dermatology, Germans Trias i Pujol University Hospital (HUGTP), Autonomous University of Barcelona (UAB), Badalona, Spain
| | - Elizabeth Lazaridou
- Second Department of Dermatology-Venereology, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Gleison Duarte
- Instituto Bahiano de Imunoterapias-IBIS, Salvador, Brazil
| | - André V E Carvalho
- Ambulatório de psoríase, Hospital Moinhos de Vento, Porto Alegre, Brazil
| | - Ricardo Romiti
- Faculty of Medicine, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil
| | - Natalia Rompoti
- Department of Dermatology-Venereology, Faculty of Medicine, National and Kapodistrian University of Athens, 'A. Sygros' Hospital for Skin and Venereal Diseases, Athens, Greece
| | - Laetitia Teixeira
- UMIB - Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
- Center for Health Technology and Services Research (CINTESIS), Porto, Portugal
| | - Miguel Abreu
- UMIB - Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
- Department of Infectious Diseases, Centro Hospitalar Universitário de Santo António, Porto, Portugal
| | - Elena Ippoliti
- Dermatologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dermatologia, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Carlo Alberto Maronese
- Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Physiopathology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Mar Llamas-Velasco
- Department of Dermatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-IP), Madrid, Spain
| | - Eva Vilarrasa
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Elena Del Alcázar
- Department of Dermatology, Germans Trias i Pujol University Hospital (HUGTP), Autonomous University of Barcelona (UAB), Badalona, Spain
| | - Athina-Ioanna Daponte
- Second Department of Dermatology-Venereology, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Marina Papoutsaki
- Department of Dermatology-Venereology, Faculty of Medicine, National and Kapodistrian University of Athens, 'A. Sygros' Hospital for Skin and Venereal Diseases, Athens, Greece
| | - Andrea Carugno
- Dermatology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Francesco Bellinato
- Section of Dermatology and Venereology, Department of Medicine, University Hospital of Verona, Verona, Italy
| | - Paolo Gisondi
- Section of Dermatology and Venereology, Department of Medicine, University Hospital of Verona, Verona, Italy
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8
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Brown P, Pratt AG, Hyrich KL. Therapeutic advances in rheumatoid arthritis. BMJ 2024; 384:e070856. [PMID: 38233032 DOI: 10.1136/bmj-2022-070856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2024]
Abstract
Rheumatoid arthritis (RA) is one of the most common immune mediated inflammatory diseases. People with rheumatoid arthritis present with pain, swelling, and stiffness that typically affects symmetrically distributed small and large joints. Without effective treatment, significant joint damage, disability, and work loss develop, owing to chronic inflammation of the joint lining (synovium). Over the past 25 years, the management of this condition has been revolutionized, resulting in substantially higher levels of disease remission and better long term outcomes. This improvement reflects a paradigm shift towards early and aggressive pharmacological intervention coupled with a proliferation in treatment choice, in turn related to enhanced pathobiological understanding and the advent of new drugs for rheumatoid arthritis. Following an overview of these developments from a historical perspective, and with a general audience in mind, this review focuses on newer, targeted treatments in an ever evolving landscape. The review highlights ongoing areas of debate and unmet need, including the proportion of patients with persistent, difficult-to-treat disease, despite recent advances. Also discussed are personalized, strategic approaches to individual patients, the role for imaging in clinical decision making, and the goal of sustained, drug free remission and disease prevention in the future.
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Affiliation(s)
- Philip Brown
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
- National Institute for Health and Care Research Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne Hospitals and Cumbria, Northumberland; and Tyne and Wear NHS Foundation Trusts, Newcastle upon Tyne, UK
| | - Arthur G Pratt
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
- National Institute for Health and Care Research Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne Hospitals and Cumbria, Northumberland; and Tyne and Wear NHS Foundation Trusts, Newcastle upon Tyne, UK
| | - Kimme L Hyrich
- Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK
- National Institute for Health and Care Research Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
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9
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Chandrashekara S, Panchagnula R, Chennupati Y. Prevalence of LTBI in patients with autoimmune diseases and accuracy of IGRA in predicting TB relapse. Rheumatology (Oxford) 2023; 62:3952-3956. [PMID: 37348542 DOI: 10.1093/rheumatology/kead315] [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: 01/27/2023] [Revised: 05/05/2023] [Accepted: 06/12/2023] [Indexed: 06/24/2023] Open
Abstract
OBJECTIVES The current study evaluated latent tuberculosis infection (LTBI) positivity in a cohort of Indian subjects and the accuracy of IFN-gamma release assay (IGRA) in predicting tuberculosis (TB) reactivation. METHODS This cross-sectional, retrospective chart-based study considered patients diagnosed with autoimmune rheumatic diseases (AIRDs), especially those who received treatment with biologics or targeted synthetic (ts)DMARDs. The patients had undergone LTBI screening and IGRA test. The study excluded patients with inadequate information and those who had undergone test exclusively for diagnostic purpose. Statistical analyses were carried out for descriptive, demographic and clinical variables. Accuracy and error rate in predicting the absence of TB reactivation were calculated for IGRA test. RESULTS The study selected 943 patients who had undergone IGRA pre-screening prior to the initiation of biologics or tsDMARDs with a mean age of 42.93 ± 14.01 years and male-to-female ratio of 1:2.08. RA was the most common primary diagnosis (43.16%). The proportion of subjects who received single, double and triple or more DMARDs or immune suppressants were 54.35%, 33.33% and 7.69%, respectively. Among the selected subjects, 125 patients were LTBI positive and 816 were negative. All patients, except one who tested positive at baseline, received antitubercular prophylaxis. Accuracy of IGRA in predicting the absence of TB reactivation was 99.6%, with an error rate of 0.46. CONCLUSION LTBI screening is beneficial in AIRDs patients prior to the prescription of biologics or tsDMARDs. IGRA is ideal for identifying patients with increased likelihood of developing TB upon receiving biologics or tsDMARDs with reasonable accuracy.
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Affiliation(s)
- S Chandrashekara
- ChanRe Rheumatology and Immunology Center and Research, Bengaluru, India
| | | | - Yogitha Chennupati
- ChanRe Rheumatology and Immunology Center and Research, Bengaluru, India
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10
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Mak JWY, Ho AHY, Ng SC. IBD barriers across the continents - East Asia. Therap Adv Gastroenterol 2023; 16:17562848231212089. [PMID: 38026101 PMCID: PMC10666695 DOI: 10.1177/17562848231212089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic illnesses with significant morbidities and impact on patients' quality of life. There has been a rapid increase in the incidence of IBD in East Asia in recent decades. However, there is a huge unmet need in the diagnosis and management of IBD in this region. With the increasing awareness of IBD in East Asia and a persistently high rate of tuberculosis in this region, this poses a significant challenge in the diagnosis and management of IBD. In this review, we will explore the barriers to the diagnosis and management of IBD in the East Asia, hoping to provide an insight on how to improve the healthcare system in the management of this complex disease.
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Affiliation(s)
- Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Agnes Hiu Yan Ho
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Microbiota I-Center (MagIC), Center for Gut Microbiota Research, The Chinese University of Hong Kong, Shatin, Hong Kong
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11
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Govind N, Romanini T, Winchow LL. Probable endometrial tuberculosis in a patient with rhupus. S Afr J Infect Dis 2023; 38:543. [PMID: 37927913 PMCID: PMC10623593 DOI: 10.4102/sajid.v38i1.543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Accepted: 08/07/2023] [Indexed: 11/07/2023] Open
Abstract
Endometrial tuberculosis (TB) is an uncommon manifestation of disseminated TB. Rhupus is the coexistence of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We describe a case of endometrial TB in rhupus patient an immunosuppressed. Contribution We describe an uncommon presentation of disseminated TB, endometrial TB, in a rare rheumatic disease, rhupus. A high index of suspicion for TB is imperative in immunocompromised patients presenting with chronic urogenital symptoms especially in an endemic area.
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Affiliation(s)
- Nimmisha Govind
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Tamara Romanini
- Department of Internal Medicine, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
| | - Lai Ling Winchow
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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12
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MASTORINO L, DAPAVO P, TRUNFIO M, AVALLONE G, RUBATTO M, CALCAGNO A, RIBERO S, QUAGLINO P. Risk of Reactivation of Latent Tuberculosis in Psoriasis Patients on Biologic Therapies: A Retrospective Cohort from a Tertiary Care Centre in Northern Italy. Acta Derm Venereol 2022; 102:adv00821. [PMID: 36065745 PMCID: PMC9811291 DOI: 10.2340/actadv.v102.1982] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Psoriatic patients with latent tuberculosis infection and properly treated active tuberculosis need careful management when prescribing modern biological drugs. Although data and guidelines regarding tumour necrosis factor-α inhibitors advise caution and initiation of prophylactic therapy in patients with latent tuberculosis infection, the same indications do not seem to find equal force for interleukin (IL)-23 and IL-17 inhibitors. In order to evaluate the risk of reactivation in patients with latent tuberculosis infection or properly treated active tuberculosis, an observational retrospective study was conducted on the population referred to our centre at Dermatologic Clinic of University of Turin, Italy. In the last 10 years at the clinic 19 psoriatic patients were found to be at risk of tuberculosis reactivation: 10 patients were QuantiFERON- TB-positive at baseline, 2 became positive during treatment, 6 reported prior tuberculous infection, and 1 was QuantiFERON-TB-negative at baseline and developed disseminated tuberculosis during treatment with anti-tumour necrosis factor-α. Overall, 10.5% of this group of patients developed active tuberculosis; however, stratifying by biologic therapy, zero cases were observed among patients treated with anti-IL-17, -23, or -12/23 over a relatively long follow-up (48.1 months) A review of the available literature following our experience confirms the increased risk of tuberculosis reactivation with tumour necrosis factor-α inhibitors. Concerning anti-IL-23 and IL-17 drugs, available data showed high safety in patients at risk of tuberculosis reactivation. Screening of patients who should be taking IL-17 and IL-23 inhibitors is recommended for public health purposes. In case of a positive result with these therapies, consulting with an infectious diseases specialist is suggested in order to weigh up the risks and benefits of prophylactic treatment.
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Affiliation(s)
| | - Paolo DAPAVO
- Dermatology Clinic, Department of Medical Sciences
| | - Mattia TRUNFIO
- Unit of Infectious Diseases, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy
| | | | | | - Andrea CALCAGNO
- Unit of Infectious Diseases, Amedeo di Savoia Hospital, Department of Medical Sciences, University of Turin, Turin, Italy
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13
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Nasonov EL, Feist E. The prospects of interleukin-6 inhibition in rheumatoid arthritis: Olokizumab (novel monoclonal antibodies to IL-6). RHEUMATOLOGY SCIENCE AND PRACTICE 2022. [DOI: 10.47360/1995-4484-2022-505-518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Rheumatoid arthritis (RA) is a chronic immune-mediated rheumatic diseases (IMRDs) manifested with progressive destruction of joints, systemic inflammation of visceral organs and a wide range of co-morbidities associated with chronic inflammation. Among the cytokines involved in the pathogenesis of RA and certain other IMRDs, the role of interleukin (IL) 6 is of special interest. The introduction of mAbs tocilizumab (TCZ) and later sarilumab (SAR), both blocking the receptor of this cytokine, into clinical practice was an important achievement in the treatment of IIRDs at the beginning of the 21st century. As a novel approach in the treatment of RA, the humanized mAb against IL-6 olokizumab (OKZ) is in development by the Russian company R-PHARM under the license agreement with UCB Pharma. The review examines new data on efficacy and safety of OKZ in RA and the prospects of its use in rheumatology
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Affiliation(s)
- E. L. Nasonov
- V.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russian Federation (Sechenov University)
| | - Eugen Feist
- Department of Rheumatology, Helios Clinic VogelsangGommern, cooperation partner of the Otto-vonGuericke University Magdeburg
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14
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Aletaha D, Kerschbaumer A, Kastrati K, Dejaco C, Dougados M, McInnes IB, Sattar N, Stamm TA, Takeuchi T, Trauner M, van der Heijde D, Voshaar M, Winthrop KL, Ravelli A, Betteridge N, Burmester GRR, Bijlsma JW, Bykerk V, Caporali R, Choy EH, Codreanu C, Combe B, Crow MK, de Wit M, Emery P, Fleischmann RM, Gabay C, Hetland ML, Hyrich KL, Iagnocco A, Isaacs JD, Kremer JM, Mariette X, Merkel PA, Mysler EF, Nash P, Nurmohamed MT, Pavelka K, Poor G, Rubbert-Roth A, Schulze-Koops H, Strangfeld A, Tanaka Y, Smolen JS. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update. Ann Rheum Dis 2022; 82:773-787. [PMID: 35953263 DOI: 10.1136/ard-2022-222784] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/18/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.
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Affiliation(s)
- Daniel Aletaha
- Division of Rheumatology, Medical University of Vienna, Wien, Austria
| | | | - Kastriot Kastrati
- Division of Rheumatology, Medical University of Vienna, Wien, Austria
| | - Christian Dejaco
- Rheumatology, Medical University of Graz, Graz, Austria.,Rheumatology, Brunico Hospital, Brunico, Italy
| | - Maxime Dougados
- Rheumatology, Universite Paris Descartes Faculte de Medecine Site Cochin, Paris, France
| | - Iain B McInnes
- Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow, UK
| | - Tanja A Stamm
- Section for Outcomes Research, Medical University of Vienna, Wien, Austria
| | - Tsutomu Takeuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine Graduate School of Medicine, Shinjuku-ku, Japan
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Medical University of Vienna, Wien, Austria
| | - Désirée van der Heijde
- Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.,Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
| | - Marieke Voshaar
- Department of Psychology, Health and Technology, Enschede, Netherlands and Stichting Tools Patient Empowerment, University of Twente, Enschede, The Netherlands
| | - Kevin L Winthrop
- Schools of Medicine and Public Health, Division of Infectious Diseases, Oregon Health & Science University, Portland, Oregon, USA
| | - Angelo Ravelli
- UO Pediatria II-Reumatologia, IRCCS Istituto Giannina Gaslini, Genova, Italy
| | | | | | - Johannes Wj Bijlsma
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Vivian Bykerk
- Rheumatology, University of Toronto, Toronto, Ontario, Canada
| | - Roberto Caporali
- Department of Clinical Sciences and Community Health, ASS G. Pini, University of Milan, Milano, Italy
| | - Ernest H Choy
- CREATE Centre, Section of Rheumatology, School of Medicine, Division of Infection and Immunity, Cardiff University, Cardiff, UK
| | - Catalin Codreanu
- Rheumatology, Carol Davila University of Medicine and Pharmacy, Bucuresti, Romania
| | - Bernard Combe
- Immunorhumatologie, CHU Lapeyronie, Montpellier, France
| | - Mary K Crow
- Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York City, New York, USA
| | - Maarten de Wit
- Medical Humanities, Amsterdam University Medical Centres, Duivendrecht, The Netherlands
| | - Paul Emery
- University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.,Leeds Teaching Hospitals NHS Trust, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK
| | - Roy M Fleischmann
- Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Cem Gabay
- Division of Rheumatology, Geneva University Hospitals, Geneve, Switzerland
| | - Merete Lund Hetland
- Department of Clinical Medicine, Copenhagen University Hospital, Kobenhavn, Denmark.,Department of Clinical Medicine, University of Copenhagen, Kobenhavn, Denmark
| | - Kimme L Hyrich
- Centre for Epidemiology Versus Arthritis, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Annamaria Iagnocco
- Scienze Cliniche e Biologiche, Università degli Studi di Torino, Torino, Italy
| | - John D Isaacs
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Joel M Kremer
- Medicine Rheumatology, Albany Medical College, Albany, New York, USA
| | - Xavier Mariette
- Rheumatology, Assistance Publique-Hôpitaux de Paris, Paris, France.,Center for Immunology of Viral Infections and Auto-immune Diseases, Université Paris-Sud, Gif-sur-Yvette, France
| | - Peter A Merkel
- Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Eduardo F Mysler
- Organización Médica de Investigación SA, Buenos Aires, Argentina
| | - Peter Nash
- Griffith University School of Medicine, Gold Coast, Queensland, Australia
| | | | - Karel Pavelka
- Rheumatology Department, Charles University, Praha, Czech Republic
| | - Gyula Poor
- National Institute of Rheumatology & Physiology, Semmelweis University, Budapest, Hungary
| | - Andrea Rubbert-Roth
- Division of Rheumatology, Kantonsspital Sankt Gallen, Sankt Gallen, Switzerland
| | - Hendrik Schulze-Koops
- Division of Rheumatology and Clinical Immunology, Internal Medicine IV, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany
| | - Anja Strangfeld
- Forschungsbereich Epidemiologie, Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany
| | - Yoshiya Tanaka
- First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Josef S Smolen
- Division of Rheumatology, Medical University of Vienna, Wien, Austria
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15
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Tuberculin skin test before biologic and targeted therapies: does the same rule apply for all? Rheumatol Int 2022; 42:1797-1806. [PMID: 35486197 DOI: 10.1007/s00296-022-05134-z] [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: 01/09/2022] [Accepted: 04/05/2022] [Indexed: 10/18/2022]
Abstract
This study aimed to compare Tuberculin Skin Test (TST) and QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients scheduled for biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) in a Bacillus Calmette-Guérin-vaccinated population. Adult RA (n = 206) and SpA (n = 392) patients from the TReasure database who had both TST and QFT-GIT prior to initiation of biological and targeted synthetic DMARDs were included in the study. Demographic and disease characteristics along with pre-biologic DMARD and steroid use were recorded. The distribution of TST and performance with respect to QFT-GIT were compared between RA and SpA groups. Pre-biologic conventional DMARD and steroid use was higher in the RA group. TST positivity rates were 44.2% in RA and 69.1% in SpA for a 5 mm cutoff (p < 0.001). Only 8.9% and 15% of the patients with RA and SpA, respectively, tested positive by QFT-GIT. The two tests poorly agreed in both groups at a TST cutoff of 5 mm and increasing the TST cutoff only slightly increased the agreement. Among age, sex, education and smoking status, pre-biologic steroid and conventional DMARD use, disease group, and QFT-GIT positivity, which were associated with a 5 mm or higher TST, only disease group (SpA) and QFT-GIT positivity remained significant in multiple logistic regression. TST positivity was more pronounced in SpA compared to that in RA and this was not explainable by pre-biologic DMARD and steroid use. The agreement of TST with QFT-GIT was poor in both groups. Using a 5 mm TST cutoff for both diseases could result in overestimating LTBI in SpA.
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16
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Aachari I, Tahiri L, Elolemy G, Taik FZ, Afilal S, Fellous S, Berkchi JM, Rkain H, Bahiri R, Majjad A, Achemlal L, Ousehal S, Nassar K, Mkinsi O, Mahha FZ, El Aissaoui A, Chaoui I, Harzy T, Youssoufi T, Hassikou H, Kherrab A, Niamane R, Eddarami J, Ichchou L, Ghozlani I, El Bouchti I, Abourazzak FZ, Razine R, Allali F. Active tuberculosis infection in moroccan patients with rheumatic diseases under biologic therapy: A multicenter national study. Int J Mycobacteriol 2022; 11:175-182. [PMID: 35775550 DOI: 10.4103/ijmy.ijmy_153_20] [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: 11/04/2022] Open
Abstract
Background The aim of this study was to evaluate the prevalence of active tuberculosis (TB) infection in Moroccan patients with rheumatic diseases under biologic therapy, and to describe the demographic characteristics of these patients as well as to explore potential risk factors. Methods This 14-year nationally representative multicenter study enrolled Moroccan patients with rheumatic diseases who had been treated with biologic therapy. Patient medical records were reviewed retrospectively for demographic characteristics, underlying rheumatic diseases, associated comorbidities, and TB-related data. Results In total, 1407 eligible patients were studied, detailed records were obtained for only 130 patients; 33 cases with active TB were identified at an estimated prevalence rate of 2.3%. The mean age was 42.9 ± 12 years and 75.8% were males. Ankylosing spondylitis accounted for 84.8% of active TB cases, and the majority of the cases (31/33) occurred among antitumor necrosis factor-alpha (TNF-α) users. A total of 8 out of 33 patients were positive at initial latent TB infection (LTBI) screening by tuberculin skin test and/or interferon-gamma release assay. Consumption of unpasteurized dairy products (odds ratio [OR], 34.841; 95% confidence interval [CI], 3.1-389.7; P = 0.04), diabetes (OR, 38.468; 95% CI, 1.6-878.3; P = 0,022), smoking (OR, 3.941; 95% CI, 1-159.9; P = 0.047), and long biologic therapy duration (OR, 1.991; 95% CI, 1.4-16.3; P = 0.001) were identified as risk factors for developing active TB. Conclusion Moroccan patients with rheumatic diseases under anti-TNF-α agents are at an increased TB risk, especially when risk factors are present. Strict initial screening and regular monitoring of LTBI is recommended for patients living in high TB prevalence areas.
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Affiliation(s)
- Ilham Aachari
- Department of Rheumatology B, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Latifa Tahiri
- Department of Rheumatology B, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Gehan Elolemy
- Department of Rheumatology, Faculty of Medicine, Benha University, Banha, Egypt
| | - Fatima Z Taik
- Department of Rheumatology B, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Saloua Afilal
- Department of Rheumatology B, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Safaa Fellous
- Department of Rheumatology B, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Jihad M Berkchi
- Department of Rheumatology B, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Hanan Rkain
- Department of Rheumatology B, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University; Laboratory of Physiology, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Rachid Bahiri
- Department of Rheumatology A, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Abderrahim Majjad
- Department of Rheumatology, Mohammed V Military Hospital, Rabat, Morocco
| | - Lahsen Achemlal
- Department of Rheumatology, Mohammed V Military Hospital, Rabat, Morocco
| | - Soumaya Ousehal
- Department of Rheumatology, CHU Ibn Rochd, Casablanca, Morocco
| | - Kawtar Nassar
- Department of Rheumatology, CHU Ibn Rochd, Casablanca, Morocco
| | - Ouafa Mkinsi
- Department of Rheumatology, CHU Ibn Rochd, Casablanca, Morocco
| | | | | | - Imane Chaoui
- Department of Rheumatology, CHU Hassan II, Fez, Morocco
| | - Taoufik Harzy
- Department of Rheumatology, CHU Hassan II, Fez, Morocco
| | - Tarik Youssoufi
- Department of Rheumatology, Moulay Ismail Military Hospital, Meknes, Morocco
| | - Hasna Hassikou
- Department of Rheumatology, Moulay Ismail Military Hospital, Meknes, Morocco
| | - Anass Kherrab
- Department of Rheumatology, Avicenne Military Hospital, Marrakech, Morocco
| | - Radouane Niamane
- Department of Rheumatology, Avicenne Military Hospital, Marrakech, Morocco
| | | | | | - Imad Ghozlani
- Department of Rheumatology, First Medical and Surgical Center, Agadir, Morocco
| | - Imane El Bouchti
- Department of Rheumatology, Arrazi Hospital, CHU Mohammed VI, Marrakech, Morocco
| | | | - Rachid Razine
- Department of Public Health Laboratory, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Fadoua Allali
- Department of Rheumatology B, El Ayachi Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
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17
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Brito ACD, Oliveira CMMD, Unger DAA, Bittencourt MDJS. Cutaneous tuberculosis: epidemiological, clinical, diagnostic and therapeutic update. An Bras Dermatol 2022; 97:129-144. [PMID: 34996655 PMCID: PMC9073256 DOI: 10.1016/j.abd.2021.07.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 07/19/2021] [Accepted: 07/26/2021] [Indexed: 12/23/2022] Open
Abstract
Tuberculosis is certainly one of the diseases considered to be ancient on planet Earth. The etiological agent of tuberculosis is Mycobacterium tuberculosis. This terrible bacterial infection still results in severe socioeconomic consequences to date, and its complete eradication represents a great challenge. It constitutes one of the most important public health problems in developing countries. According to the World Health Organization, this infection results in more than 4,000 deaths daily worldwide, with 10.4 million being affected annually and 1.5 million deaths from TB every year. With the emergence of the HIV/AIDS pandemic, the disease became the main cause of morbidity and mortality in patients infected with the human immunodeficiency virus. Cutaneous tuberculosis is a rare infection that represents 1% to 1.5% of extrapulmonary tuberculosis, whose etiological agents are Mycobacterium tuberculosis, Mycobacterium bovis, and the attenuated form of the bacillus Calmette-Guérin (BCG vaccine). Cutaneous tuberculosis can be exogenous; endogenous: caused by contiguity or autoinoculation and by hematogenous spread; induced by the Calmette-Guérin bacillus and manifest as a tuberculid. The diagnosis of the infection is carried out through the direct test, culture, histopathology, tuberculin skin test, polymerase chain reaction, interferon-gamma release assay, and genotyping. Drugs used comprise isoniazid, rifampicin, pyrazinamide and ethambutol.
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18
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[What should specialist in internal medicine be aware of in patients treated with biologics? : Infections and autoimmune phenomena]. Internist (Berl) 2022; 63:165-170. [PMID: 35089363 DOI: 10.1007/s00108-021-01259-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/22/2021] [Indexed: 10/19/2022]
Abstract
Biologics that influence the immune system play a crucial role in the treatment of autoimmune and malignant diseases. Overall these drugs have revolutionized treatment as they demonstrate high efficacy and a relatively low amount of side effects. This leads to longer treatment of patients with a high quality of life. Side effects, especially longer-term side effects, become ever more important as patients are simultaneously seen by different physicians due to comorbidities. Infections, mainly of the upper airway or urogenital tract, represent the main side effect of immunosuppressive biologics, but atypical infections by fungi or mycobacteria may also occur. Biologics that enhance the immune response such as checkpoint inhibitors lead to autoimmune phenomena necessitating the interruption of treatment or immunosuppressive treatment.
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19
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Redeker I, Albrecht K, Kekow J, Burmester GR, Braun J, Schäfer M, Zink A, Strangfeld A. Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register. Ann Rheum Dis 2022; 81:41-47. [PMID: 34321218 PMCID: PMC8762036 DOI: 10.1136/annrheumdis-2021-220651] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 07/05/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To compare event and incidence rates of herpes zoster (HZ), also known as shingles, in patients with rheumatoid arthritis under treatment with conventional synthetic (cs), targeted synthetic (ts) or biologic (b) disease-modifying antirheumatic drugs (DMARDs). METHODS Patients were prospectively enrolled from 2007 until October 2020. Reported HZ events were assigned to ongoing treatments or those terminated within 1 month prior to the HZ event. Exposure-adjusted event rates (EAERs) of HZ were calculated per 1000 patient years (py) and adjusted HRs with 95% CIs computed. Inverse probability weights (IPW) were used to adjust for confounding by indication. RESULTS Data of 13 991 patients (62 958 py) were analysed, with 559 HZ events reported in 533 patients. The EAER of HZ was highest for tsDMARDs (21.5, 95% CI 16.4 to 27.9), followed by B cell targeted therapy (10.3, 95% CI 8.0 to 13.0), monoclonal antitumour necrosis factor (anti-TNF) antibodies (9.3, 95% CI 7.7 to 11.2), interleukin 6 inhibitors (8.8, 95% CI 6.9 to 11.0), soluble TNF receptor fusion protein (8.6, 95% CI 6.8 to 10.8), T cell costimulation modulator (8.4, 95% CI 5.9 to 11.8) and csDMARDs (7.1, 95% CI 6.0 to 8.3). Adjusted for age, sex and glucocorticoids and weighted with IPW, tsDMARDs (HR 3.66, 95% CI 2.38 to 5.63), monoclonal anti-TNF antibodies (HR 1.63, 95% CI 1.17 to 2.28) and B cell targeted therapy (HR 1.57, 95% CI 1.03 to 2.40) showed a significantly higher risk compared with csDMARDs. CONCLUSION Our results provide evidence for a 3.6-fold increased risk of HZ associated with tsDMARDs and an increased risk of HZ under bDMARDs compared with csDMARDs.
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Grants
- RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Hexal, Lilly, MSD, Viatris, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis and UCB
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Affiliation(s)
- Imke Redeker
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
| | - Katinka Albrecht
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
| | - Joern Kekow
- Clinic of Rheumatology and Orthopaedics, Helios Clinic for Rheumatolog, Vogelsang-Gommern, Germany
| | | | | | - Martin Schäfer
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
| | - Angela Zink
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
| | - Anja Strangfeld
- Epidemiology and Health Services Research, German Rheumatism Research Centre, Berlin, Germany
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20
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Multifocal Mycobacterium kansasii osteomyelitis in a patient on ruxolitinib. CLINICAL INFECTION IN PRACTICE 2022. [DOI: 10.1016/j.clinpr.2021.100124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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21
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Syal G, Serrano M, Jain A, Cohen BL, Rieder F, Stone C, Abraham B, Hudesman D, Malter L, McCabe R, Holubar S, Afzali A, Cheifetz AS, Gaidos JKJ, Moss AC. Health Maintenance Consensus for Adults With Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:1552-1563. [PMID: 34279600 PMCID: PMC8861367 DOI: 10.1093/ibd/izab155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND With the management of inflammatory bowel disease (IBD) becoming increasingly complex, incorporating preventive care health maintenance measures can be challenging. The aim of developing these updated recommendations is to provide more specific details to facilitate their use into a busy clinical practice setting. METHOD Fifteen statements were formulated with recommendations regarding the target, timing, and frequency of the health maintenance interventions in patients with IBD. We used a modified Delphi method and a literature review to establish a consensus among the panel of experts. The appropriateness of each health maintenance statement was rated on a scale of 1 to 5 (1-2 as inappropriate, and 4-5 as appropriate) by each panelist. Interventions were considered appropriate, and statements were accepted if ≥80% of the panelists agreed with a score ≥4. RESULTS The panel approved 15 health maintenance recommendations for adults with IBD based on the current literature and expert opinion. These recommendations include explicit details regarding specific screening tools, timing of screening, and vaccinations for adults with IBD. CONCLUSIONS Patients with IBD are at an increased risk for infections, malignancies, and other comorbidities. Given the complexity of caring for patients with IBD, this focused list of recommendations can be easily incorporated in to clinical care to help eliminate the gap in preventative care for patients with IBD.
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Affiliation(s)
- Gaurav Syal
- Cedars-Sinai Medical Center, Los Angeles, California, USA
| | | | - Animesh Jain
- University of North Carolina, Chapel Hill, North Carolina, USA
| | | | | | - Christian Stone
- Comprehensive Digestive Institute of Nevada, Las Vegas, Nevada, USA
| | | | - David Hudesman
- New York University Langone Medical Center, New York, New York, USA
| | - Lisa Malter
- NYU Grossman School of Medicine, Bellevue Hospital Center, New York, New York, USA
| | | | | | - Anita Afzali
- Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Adam S Cheifetz
- Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | | | - Alan C Moss
- Boston University School of Medicine, Boston, Massachusetts, USA
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22
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Cardoso da Silva DI, Santos BHDO, Renosto FL, Watanabe EM, Herrerias GSP, Saad-Hossne R, Baima JP, Sassaki LY. Pulmonary Tuberculosis After Therapy with Anti-Tumor Necrosis Factor (TNF) for Crohn Disease: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2021; 22:e932963. [PMID: 34564689 PMCID: PMC8483059 DOI: 10.12659/ajcr.932963] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Patient: Male, 38-year-old
Final Diagnosis: Crohn’s disease • pulmonary tuberculosis
Symptoms: Abdominal pain • bloody bowel movements • diarrhea • dry cough • fever • hyporexia • malaise • weight loss
Medication: —
Clinical Procedure: —
Specialty: Gastroenterology and Hepatology
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Affiliation(s)
| | | | - Fernanda Lofiego Renosto
- Department of Internal Medicine, São Paulo State University (Unesp), Medical School, Botucatu, SP, Brazil
| | - Erika Mayumi Watanabe
- Department of Radiology, São Paulo State University (Unesp), Medical School, Botucatu, SP, Brazil
| | | | - Rogerio Saad-Hossne
- Department of Surgery, São Paulo State University (Unesp), Medical School, Botucatu, SP, Brazil
| | - Julio Pinheiro Baima
- Department of Internal Medicine, São Paulo State University (Unesp), Medical School, Botucatu, SP, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, São Paulo State University (Unesp), Medical School, Botucatu, SP, Brazil
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23
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Liu JM, Jin QX, Fujimoto M, Li FF, Jin LB, Yu R, Yan GH, Zhu LH, Meng FP, Zhang QG, Jin GH. Dihydroartemisinin Alleviates Imiquimod-Induced Psoriasis-like Skin Lesion in Mice Involving Modulation of IL-23/Th17 Axis. Front Pharmacol 2021; 12:704481. [PMID: 34483908 PMCID: PMC8415163 DOI: 10.3389/fphar.2021.704481] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 07/09/2021] [Indexed: 12/25/2022] Open
Abstract
Background: Psoriasis is a T help 17 (Th17) cell-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells. Objective: To verify whether DHA can improve the symptoms of psoriasis and to further explore the possible mechanism. Methods: The efficiency of DHA was preliminary detected on human keratinocytes (HaCaT) cells in psoriatic condition. Then, imiquimod-induced psoriasis-like model in BALB/c mice was established to evaluate the effects of DHA in vivo. Results: Under the stimulation of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), DHA inhibited the proliferation of HaCaT cells and significantly affected the mRNA expression levels of IFN-γ, interleukin (IL), IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-γ, IL-17A, and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17+CD4+T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-γt) in vitro. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23/Th17 axis plays a pivotal role. Conclusion: DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.
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Affiliation(s)
- Jiang-Min Liu
- Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China
| | - Quan-Xin Jin
- Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China
| | - Manabu Fujimoto
- Department of Dermatology, Graduate School of Medicine, Osaka University; Laboratory of Cutaneous Immunology, Osaka University Immunology Frontier Research Center, Osaka, Japan
| | - Fang-Fang Li
- Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China
| | - Lin-Bo Jin
- Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China
| | - Ran Yu
- Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China
| | - Guang-Hai Yan
- Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University Medical College, Yanji, China
| | - Lian-Hua Zhu
- Department of Dermatology, Yanbian University Hospital, Yanji, China
| | - Fan-Ping Meng
- Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China
| | - Qing-Gao Zhang
- Chronic Disease Research Center, Dalian University, Dalian, China
| | - Gui-Hua Jin
- Department of Immunology and Pathogenic Biology, Yanbian University Medical College, Yanji, China
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24
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Ebina K. Drug efficacy and safety of biologics and Janus kinase inhibitors in elderly patients with rheumatoid arthritis. Mod Rheumatol 2021; 32:256-262. [PMID: 34894239 DOI: 10.1093/mr/roab003] [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: 02/24/2021] [Revised: 04/21/2021] [Accepted: 05/24/2021] [Indexed: 11/14/2022]
Abstract
Elderly patients with rheumatoid arthritis (RA) are frequently associated with higher disease activity and impaired physical function, although they show intolerance for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, because of their comorbidities. However, the present treatment recommendation based on randomized controlled trials is not distinguished by age or comorbidities. Therefore, this review aimed to investigate the efficacy and safety of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) in elderly patients. Present bDMARDs, including tumor necrosis factor inhibitors (TNFi), cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (abatacept), interleukin (IL)-6 receptor antibody (tocilizumab and salirumab), and anti-CD20 antibody (rituximab), may be similarly or slightly less effective or safe in elderly patients compared with younger patients. Oral glucocorticoid use, prolonged disease duration, and very old patients appear to be associated with an increased risk of adverse events, such as serious infection. Some recent cohort studies demonstrated that non-TNFi showed better retention than TNFi in elderly patients. Both TNFi and non-TNFi agents may not strongly influence the risk of adverse events such as cardiovascular events and malignancy in elderly patients. Regarding JAKi, the efficacy appears to be similar, although the safety (particularly for serious infections, including herpes zoster) may be attenuated by aging.
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Affiliation(s)
- Kosuke Ebina
- Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, Osaka 565-0871, Japan
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25
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Abstract
Biologic therapies have revolutionized the treatment of immune-mediated inflammatory diseases but are associated with an increased risk of serious and opportunistic infections, including tuberculosis and nontuberculous mycobacterial disease. Despite this increased risk, the overall risk-benefit ratio remains favorable with appropriate screening and risk assessment. Further population-based studies are needed to establish the risk of tuberculosis and nontuberculous mycobacterial disease with the new biologics. This article highlights the incidence and drug-specific risk of tuberculous and nontuberculous mycobacterial infection in the setting of biologics, screening and prevention, and treatment of latent tuberculosis in this setting.
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Affiliation(s)
- Cassandra Calabrese
- Department of Rheumatologic & Immunologic Disease, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A50, Cleveland, OH 44195, USA.
| | - Kevin L Winthrop
- Division of Infectious Diseases, Schools of Medicine and Public Health, Oregon Health and Science University, OHSU, 3181 Sam Jackson Road, Mail Code: Gaines Hall, Portland, OR 97239, USA
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26
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Shoor S. Risk of Serious Infection Associated with Agents that Target T-Cell Activation and Interleukin-17 and Interleukin-23 Cytokines. Infect Dis Clin North Am 2021; 34:179-189. [PMID: 32444009 DOI: 10.1016/j.idc.2020.02.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Co-stimulatory T-cell inhibitors are used in the treatment of rheumatoid arthritis and to prevent rejection of renal transplants. Inhibitors of the intereukin (IL-17) cytokine are indicated for psoriasis, psoriatic arthritis and ankylosing spondylitis and anti- IL-23 drugs for psoriasis. Serious infections occur in 4.2% to 25.0% of co-stimulatory inhibitors and 1.0% to 2.0% with IL-17 or IL-23 inhibitors. Underlying disease, steroid dose greater than 7.5 to 10.0 mg, and comorbidities influence risk in individual patients. Opportunistic infections or reactivation of tuberculosis are rare.
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Affiliation(s)
- Stanford Shoor
- Stanford University, 1000 Welch Road Suite 203, Palo Alto, CA 94304, USA.
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27
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Lasa JS, Olivera PA, Bonovas S, Danese S, Peyrin-Biroulet L. Safety of S1P Modulators in Patients with Immune-Mediated Diseases: A Systematic Review and Meta-Analysis. Drug Saf 2021; 44:645-660. [PMID: 33666900 DOI: 10.1007/s40264-021-01057-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/15/2021] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Sphingosine-1-phosphate modulators are approved for the treatment of multiple sclerosis and are under development for other immune-mediated conditions; however, safety concerns have arisen. OBJECTIVE The objective of this systematic review was to investigate the safety profile of S1P modulators in patients with multiple sclerosis, ulcerative colitis, Crohn's disease, psoriasis, and systemic lupus erythematosus. METHODS We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1 January, 1990 through 1 April, 2020. We also performed a manual review of conference databases from 2017 through 2020. The primary outcome was the occurrence of adverse events and serious adverse events. We also estimated the occurrence of serious infections, herpes zoster infection, malignancy, bradycardia, atrio-ventricular block, and macular edema. We performed a meta-analysis of controlled studies to assess the risks of such events. RESULTS We identified 3843 citations; of these, 26 studies were finally included, comprising 9604 patients who were exposed to a sphingosine-1-phosphate modulator. A meta-analysis of randomized controlled trials showed an increased risk in herpes zoster infection [risk ratio, 1.75 (95% confidence interval 1.09-2.80)], bradycardia [2.64 (1.77-3.96)], and atrio-ventricular block [1.73 (1.03-2.91)] among subjects exposed to sphingosine-1-phosphate modulators as compared with a placebo or an active comparator. CONCLUSIONS We found an increased risk of herpes zoster infection, and transient cardiovascular events among patients treated with sphingosine-1-phosphate modulators. CLINICAL TRIAL REGISTRATION PROSPERO CRD42020172575.
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Affiliation(s)
- Juan S Lasa
- IBD Unit, Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigación Clínica (CEMIC), Buenos Aires, Argentina.,Gastroenterology Department, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
| | - Pablo A Olivera
- IBD Unit, Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigación Clínica (CEMIC), Buenos Aires, Argentina
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Unit, Humanitas Clinical and Research Center-IRCCS, Milan, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Unit, Humanitas Clinical and Research Center-IRCCS, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Hepatogastroenterology, INSERM NGERE, Nancy University Hospital, Lorraine University, Allée du Morvan, 54511, Vandoeuvre-lès-Nancy, France.
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28
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Álvaro-Gracia JM, García-Llorente JF, Valderrama M, Gomez S, Montoro M. Update on the Safety Profile of Tofacitinib in Rheumatoid Arthritis from Clinical Trials to Real-World Studies: A Narrative Review. Rheumatol Ther 2021; 8:17-40. [PMID: 33245555 PMCID: PMC7991042 DOI: 10.1007/s40744-020-00258-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 11/11/2020] [Indexed: 12/11/2022] Open
Abstract
Tofacitinib is approved for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who do not respond adequately or are intolerant to one or more disease-modifying anti-rheumatic drugs. The tofacitinib RA clinical development program included randomized controlled trials of 6-24-month duration and long-term extension studies with > 7061 patients and 22,875 patient-years of exposure. To date, there are no data from other randomized studies in patients with cardiovascular risk factors comparing the long-term safety of a JAK inhibitor versus an anti-TNF. Real-world studies are necessary to complete the body of evidence supporting the effectiveness and safety of a therapeutic agent. In the case of tofacitinib, real-world data derive from health insurance claims databases, registries (US Corrona Registry, Swiss Registry, and others), national pharmacovigilance programs, and hospital databases (case series). The present article provides complete and up-to-date information on the safety profile of tofacitinib in RA, from clinical trials to real-world studies. Tofacitinib has demonstrated a consistent safety profile during up to 9.5 years of experience in randomized controlled trials and long-term extension studies. Real-world evidence has not added new safety issues with respect to those found in the clinical program. In general, the safety profile of tofacitinib is consistent with that of biologic disease-modifying anti-rheumatic drugs, with an increased risk of herpes zoster that seems to be a class effect of Janus kinase inhibitors. The continuous follow-up of therapeutic agents to treat rheumatoid arthritis is needed to adequately establish the safety profile for new mechanisms of action and potential risks associated with their longer term use.
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Affiliation(s)
- Jose María Álvaro-Gracia
- Rheumatology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
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29
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Diel R, Schaberg T, Nienhaus A, Otto-Knapp R, Kneitz C, Krause A, Fabri M, Mrowietz U, Bauer T, Häcker B. Joint Statement (DZK, DGRh, DDG) on the Tuberculosis Risk with Treatment Using Novel Non-TNF-Alpha Biologicals. Pneumologie 2021; 75:293-303. [PMID: 33598901 DOI: 10.1055/a-1294-1580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
BACKGROUND While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed. METHODS We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019. Of interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria. RESULTS 677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63 %, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68 %) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33 %, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment. CONCLUSIONS The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future.
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Affiliation(s)
- R Diel
- Institute for Epidemiology, University Medical Hospital Schleswig-Holstein, Campus Kiel, Germany. Member of the German Center for Lung Research (ARCN).,LungClinic Grosshansdorf, Germany. Airway Research Center North (ARCN), German Center for Lung Research (DZL).,German Central Committee against Tuberculosis, Berlin, Germany
| | - T Schaberg
- German Central Committee against Tuberculosis, Berlin, Germany
| | - A Nienhaus
- Institution for Statutory Accident Insurance and Prevention in the Health and Welfare Services (BGW), Hamburg, Germany.,Institute for Health Service Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - R Otto-Knapp
- German Central Committee against Tuberculosis, Berlin, Germany
| | - C Kneitz
- Medicine, Rheumatology, rheumatological main practice Schwerin, Germany
| | - A Krause
- Department of Rheumatology, Clinical Immunology and Osteology, Immanuel Hospital Berlin, Germany
| | - M Fabri
- Department of Dermatology, University of Cologne, Germany
| | - U Mrowietz
- Psoriasis Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany
| | - T Bauer
- German Central Committee against Tuberculosis, Berlin, Germany
| | - B Häcker
- German Central Committee against Tuberculosis, Berlin, Germany
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30
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Tseng IL, Yang CC, Lai ECC, Lee CN. Psoriasis in the geriatric population: A retrospective study in Asians. J Dermatol 2021; 48:818-824. [PMID: 33458884 DOI: 10.1111/1346-8138.15737] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/17/2020] [Accepted: 12/03/2020] [Indexed: 11/30/2022]
Abstract
There is a paucity of data focusing on geriatric psoriatic patients. The clinical features were different among those with early-onset psoriasis and elderly-onset psoriasis among the geriatric population. From 2014 to 2018, a total of 290 geriatric psoriatic patients were retrospectively enrolled in our study. They were subclassified into two groups, early-onset (aged <60 years, n = 154) and elderly-onset (aged ≥60 years, n = 136). The characteristics and treatment course of these two groups were reviewed. Psoriasis of the elderly-onset group was generally milder than the early-onset groups (P < 0.05). Less nail involvement and arthritis were noted among the elderly-onset group (P < 0.05). There were four cases of erythrodermic psoriasis in the early-onset group and three cases of palmoplantar psoriasis in the elderly-onset group. Oral medication and biologics for treatment of psoriasis appeared to be safe among the geriatric psoriatic patients. Elderly-onset psoriasis has features which are distinct from early-onset psoriasis and may be a particular subtype, which needs further evaluation.
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Affiliation(s)
- I-Lun Tseng
- Department of Dermatology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Chao-Chun Yang
- Department of Dermatology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.,International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan
| | - Edward Chia-Cheng Lai
- School of Pharmacy, College of Medicine, Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
| | - Chaw-Ning Lee
- Department of Dermatology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.,School of Pharmacy, College of Medicine, Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
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31
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Lortholary O, Fernandez-Ruiz M, Baddley JW, Manuel O, Mariette X, Winthrop KL. Infectious complications of rheumatoid arthritis and psoriatic arthritis during targeted and biological therapies: a viewpoint in 2020. Ann Rheum Dis 2020; 79:1532-1543. [PMID: 32963049 DOI: 10.1136/annrheumdis-2020-217092] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 05/28/2020] [Accepted: 06/16/2020] [Indexed: 12/13/2022]
Abstract
Biological therapies have improved the outcomes of several major inflammatory, autoimmune and also neoplastic disorders. Those directed towards cytokines or other soluble mediators, cell-surface molecules or receptors or various components of intracellular signalling pathways may be associated with the occurrence of infections whose diversity depends on the particular immune target. In this context and following a keynote lecture given by one of us at the European League Against Rheumatism meeting on June 2018, a multidisciplinary group of experts deeply involved in the use of targeted and biological therapies in rheumatoid and psoriatic arthritis decided to summarise their recent vision of the immunological basis and epidemiology of infections occurring during targeted and biological therapies, and provide useful indications for their management and prevention.
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Affiliation(s)
- Olivier Lortholary
- Paris University, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, IHU Imagine, Necker Enfants malades University Hospital, APHP, Paris, France
- Institut Pasteur, National Reference Center for Invasive Mycoses and Antifungals, Molecular Mycology Unit, CNRS UMR 2000, Paris, France
| | - Mario Fernandez-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - John W Baddley
- University of Maryland School of Medicine, Division of Infectious Diseases, Baltimore, Maryland, USA
| | - Oriol Manuel
- Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Xavier Mariette
- Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux universitaires Paris-Sud - Hôpital Bicêtre, Le Kremlin Bicêtre, France
- Université Paris-Sud, Center for Immunology of Viral Infections and Auto-immune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin Bicêtre, France
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Atzeni F, Gerratana E, Giallanza M, La Corte L, Nucera V, Miceli G, Sangari D, Masala IF. The effect of drugs used in rheumatology for treating SARS-CoV2 infection. Expert Opin Biol Ther 2020; 21:219-228. [PMID: 32866053 DOI: 10.1080/14712598.2020.1817372] [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] [Indexed: 02/07/2023]
Abstract
INTRODUCTION SARS-CoV-2 is a novel coronavirus that was first isolated from a group of patients hospitalized with pneumonia in China at the end of 2019, and, in February 2020, the syndrome it caused was named coronavirus disease 2019 (COVID-19) by the World Health Organization. In the absence of specific antiviral treatments capable of neutralizing the etiological agent, one therapeutic approach is to control the cytokine storm responsible for the most severe forms of the disease. The characteristic cytokine profile of severely affected patients is increased levels of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor alpha (TNF-α). AREAS COVERED This article discusses the pathogenesis of COVID-19 as a rationale for using the biological and targeted synthetic drugs used in rheumatology (anti-TNF, anti-IL-1 and anti-IL-6 agents and baricitinib) to treat the disease, and provides key information concerning their potential benefits and adverse effects. EXPERT OPINION Interleukin inhibition seems to be a promising means of treating COVID-19 patients when respiratory function declines (or even earlier) if there are laboratory data indicating the presence of a cytokine storm because the interleukins are key drivers of inflammation. However, it is important to consider the risks and benefits of biological agents carefully, and critically analyze the evidence concerning their use in COVID-19 patients.
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Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina , Messina, Italy.,Trauma and Orthopedic Unit, Santissima Trinità Hospital , Cagliari, Italy
| | - Elisabetta Gerratana
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina , Messina, Italy.,Trauma and Orthopedic Unit, Santissima Trinità Hospital , Cagliari, Italy
| | - Manuela Giallanza
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina , Messina, Italy.,Trauma and Orthopedic Unit, Santissima Trinità Hospital , Cagliari, Italy
| | - Laura La Corte
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina , Messina, Italy.,Trauma and Orthopedic Unit, Santissima Trinità Hospital , Cagliari, Italy
| | - Valeria Nucera
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina , Messina, Italy.,Trauma and Orthopedic Unit, Santissima Trinità Hospital , Cagliari, Italy
| | - Gianfranco Miceli
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina , Messina, Italy.,Trauma and Orthopedic Unit, Santissima Trinità Hospital , Cagliari, Italy
| | - Donatella Sangari
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina , Messina, Italy.,Trauma and Orthopedic Unit, Santissima Trinità Hospital , Cagliari, Italy
| | - Ignazio Francesco Masala
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina , Messina, Italy.,Trauma and Orthopedic Unit, Santissima Trinità Hospital , Cagliari, Italy
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Nogueira M, Warren RB, Torres T. Risk of tuberculosis reactivation with interleukin (IL)-17 and IL-23 inhibitors in psoriasis - time for a paradigm change. J Eur Acad Dermatol Venereol 2020; 35:824-834. [PMID: 32790003 DOI: 10.1111/jdv.16866] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 07/28/2020] [Indexed: 12/20/2022]
Abstract
Tuberculosis is an infectious disease with a major global impact, ranked in the top 10 mortality causes worldwide. In an immunocompetent individual, the host defence mechanisms control Mycobacterium tuberculosis infection and induce the latent form of the disease. However, in the presence of diseases or therapies, which exert an immunosuppressive effect, latent tuberculosis can be re-activated. Psoriasis is an immune-mediated, inflammatory disease, and its treatment has rapidly evolved over the last few years. It has long been recognized that the tumour necrosis factor (TNF)-α inhibitors are associated with increased risk of reactivation of latent tuberculosis infection. Thus, international guidelines have been suggesting tuberculosis screening before starting the treatment with all biological agents since then. In addition, the institution of chemoprophylaxis in the presence of latent tuberculosis and the annual screening for tuberculosis thereafter have also been indicated. However, anti-tuberculosis treatments can have significant side-effects and there are currently several contraindications to their use. The risk benefit of starting anti-tuberculous treatment should be carefully weighed up. The emergence of new biological drugs for the treatment of psoriasis, such as interleukin (IL)-17 and IL-23 inhibitors, has reignited the subject of tuberculosis reactivation as it is possible that IL-17 and 23 blockade do not carry the same risk of TB reactivation as TNF-α inhibitors. Although preclinical studies have shown that cytokines IL-17 and IL-23 have a possible role against infection with M. tuberculosis, data from clinical trials and post-marketing surveillance with drugs that inhibit these cytokines appear to suggest that they are not crucial to this response. In this article, we review the available data on tuberculosis reactivation after the treatment of psoriasis with IL-17 and IL-23 inhibitors, and its possible impact on the way we currently manage latent tuberculosis infection before or after starting treatment with these new drugs.
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Affiliation(s)
- M Nogueira
- Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - R B Warren
- The Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK
| | - T Torres
- Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal.,Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
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Michaut A, Varin S. [Biotherapies in elderly patients]. Rev Med Interne 2020; 41:591-597. [PMID: 32674900 DOI: 10.1016/j.revmed.2020.04.011] [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: 12/17/2019] [Revised: 03/27/2020] [Accepted: 04/09/2020] [Indexed: 11/29/2022]
Abstract
The ageing of the population leads health professionals to question the tolerance and the effectiveness of the different biotherapies used in autoimmune diseases. Due to the exponential increase of biotherapies and their indications, several studies have been carried out to evaluate their impact on elderly patients suffering from autoimmune disease. However, these studies are still too few to take into account all the different specificities of elderly patients and their comorbidities; prescribers are therefore hesitant with their introduction after 75 years or even 65. More than the age of patients, it is necessary to evaluate the comorbidities before introducing this kind of treatments. Every biotherapy has different indications and contraindications, which must be known to adapt each treatment to each patient. This focus aims to remind of the adaptations and contraindications of the different biological disease-modifying anti-rheumatic drugs for geriatric population, and improve their uses since the treatments for these patients are sometimes not enough. Here we resume the methods allowing supervisors to identify errors of clinical reasoning in medical students and interns and we explain remediation techniques adapted to the types of error identified. Access to short illustrative videos of a MOOC (Massive Open On line Course) devoted to the supervision of clinical reasoning constitutes practical help for supervisors who are not expert in the complexity of medical pedagogy at the bedside.
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Affiliation(s)
- A Michaut
- Service de Rhumatologie, Centre Hospitalier Départemental de Vendée, Boulevard Stéphane Moreau, 85000 La Roche-sur-Yon, France.
| | - S Varin
- Service de Rhumatologie, Centre Hospitalier Départemental de Vendée, Boulevard Stéphane Moreau, 85000 La Roche-sur-Yon, France
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Segueni N, Jacobs M, Ryffel B. Innate type 1 immune response, but not IL-17 cells control tuberculosis infection. Biomed J 2020; 44:165-171. [PMID: 32798210 PMCID: PMC8178558 DOI: 10.1016/j.bj.2020.06.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/16/2020] [Accepted: 06/29/2020] [Indexed: 01/22/2023] Open
Abstract
The role of the innate immune response and host resistance to Mycobacterium tuberculosis infection (TB) is reviewed. Based on our data and the abundant literature, an early type 1 immune response is critical for infection control, while ILC3 and Th17 cells seem to be dispensable. Indeed, in M. tuberculosis infected mice, transcriptomic levels of Il17, Il17ra, Il22 and Il23a were not significantly modified as compared to controls, suggesting a limited role of IL-17 and IL-22 pathways in TB infection control. Neutralization of IL-17A or IL-17F did not affect infection control either. Ongoing clinical studies with IL-17 neutralizing antibodies show high efficacy in patients with psoriasis without increased incidence of TB infection or reactivation. Therefore, both experimental studies in mice and clinical trials in human patients suggest no risk of TB infection or reactivation by therapeutic IL-17 antibodies, unlike by TNF.
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Affiliation(s)
- Noria Segueni
- Molecular and Experimental Immunology and Neurogenetics, UMR 7355, INEM, CNRS-University of Orleans, Orleans, France
| | - Muazzam Jacobs
- Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa; National Health Laboratory Service, Johannesburg, South Africa; Immunology of Infectious Disease Research Unit, University of Cape Town, South Africa
| | - Bernhard Ryffel
- Molecular and Experimental Immunology and Neurogenetics, UMR 7355, INEM, CNRS-University of Orleans, Orleans, France.
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Evangelatos G, Koulouri V, Iliopoulos A, Fragoulis GE. Tuberculosis and targeted synthetic or biologic DMARDs, beyond tumor necrosis factor inhibitors. Ther Adv Musculoskelet Dis 2020; 12:1759720X20930116. [PMID: 32612710 PMCID: PMC7309385 DOI: 10.1177/1759720x20930116] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 05/07/2020] [Indexed: 12/12/2022] Open
Abstract
Patients with autoimmune rheumatic diseases (ARD) have an increased risk for tuberculosis (TB). The use of tumor necrosis factor inhibitors (TNFi) and glucocorticoids in these patients has been associated with an increased prevalence of latent TB reactivation. Over the last few years, several biologic disease-modifying anti-rheumatic drugs (bDMARDs), other than TNFi (e.g. rituximab, abatacept, tocilizumab, secukinumab) and targeted synthetic DMARDs (tsDMARDs) [e.g. apremilast, Janus kinase (JAK) inhibitors] have been used for the treatment of patients with ARD. For many of these drugs, especially the newer ones like JAK inhibitors or antibodies against interleukin (IL)-23, most data stem from randomized clinical trials and few are available from real life clinical experience. We sought to review the current evidence for TB risk in patients with ARD treated with tsDMARDs or bDMARDs, other than TNFi. It seems that some of these drugs are associated with a lower TB risk, indirectly compared with TNFi treatment. In fact, it appears that rituximab, apremilast and inhibitors of IL-17 and IL-23 might be safer, while more data are needed for JAK inhibitors. As seen in TNFi, risk for TB is more pronounced in TB-endemic areas. Screening for latent TB must precede initiation of any tsDMARDs or bDMARDs. The growing use of non-TNFi agents has raised the need for more real-life studies that would compare the risk for TB between TNFi and other treatment modalities for ARD. Knowledge about the TB-safety profile of these drugs could help in the decision of drug choice in patients with confirmed latent TB infection or in TB endemic areas.
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Affiliation(s)
- Gerasimos Evangelatos
- Rheumatology Department, 417 Army Share Fund Hospital (NIMTS), Monis Petraki 10-12, Athens, 11521, Greece
| | - Vasiliki Koulouri
- Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexios Iliopoulos
- Rheumatology Department, 417 Army Share Fund Hospital (NIMTS), Athens, Greece
| | - George E Fragoulis
- Rheumatology Unit, First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
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Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies. Clin Microbiol Rev 2020; 33:e00035-19. [PMID: 32522746 PMCID: PMC7289788 DOI: 10.1128/cmr.00035-19] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
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Affiliation(s)
- Joshua S Davis
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David Ferreira
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Emma Paige
- Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia
| | - Craig Gedye
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia
| | - Michael Boyle
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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Atzeni F, Nucera V, Gerratana E, Cirillo M, Marino F, Miceli G, Sangari D, Boccassini L, Masala IF. Concerns about the safety of anti-TNF agents when treating rheumatic diseases. Expert Opin Drug Saf 2020; 19:695-705. [DOI: 10.1080/14740338.2020.1763299] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, University of Messina, Messina, Italy
| | - Valeria Nucera
- Rheumatology Unit, University of Messina, Messina, Italy
| | | | | | | | | | | | - Laura Boccassini
- Department of Rheumatology, ASST Fatebenefratelli-Sacco, Milan, Italy
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Olivera PA, Lasa JS, Bonovas S, Danese S, Peyrin-Biroulet L. Safety of Janus Kinase Inhibitors in Patients With Inflammatory Bowel Diseases or Other Immune-mediated Diseases: A Systematic Review and Meta-Analysis. Gastroenterology 2020; 158:1554-1573.e12. [PMID: 31926171 DOI: 10.1053/j.gastro.2020.01.001] [Citation(s) in RCA: 217] [Impact Index Per Article: 43.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 12/15/2019] [Accepted: 01/02/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, or ankylosing spondylitis. METHODS We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990, through July 1, 2019. We performed a manual review of conference databases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous thromboembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events. RESULTS We identified 973 studies; of these, 82 were included in the final analysis, comprising 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 person-years, 2.67 per 100 person-years, 0.89 per 100 person-years, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared with patients given placebo or active comparator (relative risk 0.72; 95% confidence interval 0.40-1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% confidence interval 1.04-2.37). CONCLUSIONS In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors.
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Affiliation(s)
- Pablo A Olivera
- Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina
| | - Juan S Lasa
- Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina; Gastroenterology Department, Hospital Británico de Buenos Aires, Argentina
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy
| | - Laurent Peyrin-Biroulet
- INSERM NGERE and Department of Hepatogastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre-lés-Nancy, France.
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Infectious Implications of Interleukin-1, Interleukin-6, and T Helper Type 2 Inhibition. Infect Dis Clin North Am 2020; 34:211-234. [PMID: 32334983 DOI: 10.1016/j.idc.2020.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Targeting interleukins that drive innate inflammation has expanded treatments of autoinflammatory and autoimmune disorders. Interleukin (IL)-1 inhibition has proven useful for monogenic autoinflammatory syndromes, and IL-6 inhibition for autoimmune arthritides. Biological therapies impeding these pathways impair detection and containment of pathogens, particularly invasive bacteria, reflecting the importance of IL-1 and IL-6 in communicating danger throughout the immune system. Biologics targeting T helper type 2 inflammation are used to treat specific allergic, atopic, and eosinophilic diseases. They may impair protections against local herpesvirus reactivations while augmenting antiviral responses to respiratory viruses. Their risks with helminth exposures have yet to be defined.
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Kordzadeh-Kermani E, Khalili H, Karimzadeh I, Salehi M. Prevention Strategies to Minimize the Infection Risk Associated with Biologic and Targeted Immunomodulators. Infect Drug Resist 2020; 13:513-532. [PMID: 32110062 PMCID: PMC7035951 DOI: 10.2147/idr.s233137] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 01/29/2020] [Indexed: 12/18/2022] Open
Abstract
The introduction of biologic and targeted immunomodulators is a significant breakthrough in the therapeutic area of various fields of medicine. The occurrence of serious infections, a complication of secondary immunosuppression associated with these agents, leads to increased morbidity and mortality. Implementing preventive strategies could minimize infection-related complications and improve therapeutic outcomes. The purpose of this review is to focus on current evident approaches regarding screening, monitoring, preventing (immunization and chemoprophylaxis), and management of infections in patients who are candidates for about 70 biologic and targeted immunomodulators. Recommendations are based on relevant guidelines, especially the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document series published in 2018.
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Affiliation(s)
- Elaheh Kordzadeh-Kermani
- Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Khalili
- Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Iman Karimzadeh
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammadreza Salehi
- Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Chang S, Hudesman D. First-Line Biologics or Small Molecules in Inflammatory Bowel Disease: a Practical Guide for the Clinician. Curr Gastroenterol Rep 2020; 22:7. [PMID: 32002688 DOI: 10.1007/s11894-020-0745-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW Treating moderate-to-severe inflammatory bowel disease has become increasingly complex as the array of available biologics increases. Moreover, tofacitinib, the first small molecule approved for IBD, is available for use in ulcerative colitis. Choosing the right biologic, for the right patient, at the right time, can be a confusing and daunting task for clinicians. RECENT FINDINGS In this review, we summarize the evidence for first-line use of the available biologics by disease state. Special circumstances for consideration including rapidity of action, safety, comparative effectiveness, postoperative Crohn's disease, fertility and pregnancy, and extraintestinal manifestations are discussed. In the moderate-to-severe UC patient, vedolizumab and infliximab are preferred first-line options. In the moderate-to-severe CD patient with a penetrating phenotype or with multiple EIMs, infliximab or adalimumab are the preferred first-line agents. In the moderate-to-severe CD patient with an inflammatory phenotype, anti-TNF, vedolizumab, and ustekinumab are all reasonable options.
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Affiliation(s)
- Shannon Chang
- Inflammatory Bowel Disease Center, Division of Gastroenterology, NYU Langone Health, 240 East 38th Street, 23rd Floor, New York, NY, 10016, USA
| | - David Hudesman
- Inflammatory Bowel Disease Center, Division of Gastroenterology, NYU Langone Health, 240 East 38th Street, 23rd Floor, New York, NY, 10016, USA.
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Chiu YM, Chen DY. Infection risk in patients undergoing treatment for inflammatory arthritis: non-biologics versus biologics. Expert Rev Clin Immunol 2020; 16:207-228. [PMID: 31852268 DOI: 10.1080/1744666x.2019.1705785] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Despite the therapeutic effectiveness of biologics targeting immune cells or cytokines in patients with inflammatory arthritis, which reflects their pathogenic roles, an increased infection risk is observed in those undergoing biological treatment. However, there are limited data regarding the comparison of infection risks in inflammatory arthritis patients treated with non-biologics (csDMARDs), biologics (bDMARDs), including tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors, or targeted synthetic (ts)DMARDs.Areas covered: Through a review of English-language literature as of 30 June 2019, we focus on the existing evidence on the risk of infections caused by bacteria, Mycobacterium tuberculosis, and hepatitis virus in inflammatory arthritis patients undergoing treatment with csDMARDs, bDMARDs, or tsDMARDs.Expert opinion: While the risks of bacterial and mycobacterial infection are increased in arthritis patients treated with csDMARDs, the risks are further higher in those receiving bDMARDs therapy, particularly TNF inhibitors. Regarding HBV infection, antiviral therapy may effectively prevent HBV reactivation in patients receiving bDMARDs, especially rituximab. However, more data are needed to establish effective preventive strategies for HBsAg-negative/HBcAb-positive patients. It seems safe to use cyclosporine and TNF inhibitors in patients with HCV infection, while those undergoing rituximab therapies should be frequently monitored for HCV activity.Abbreviations: ABT: abatacept; ADA: adalimumab; AS: ankylosing spondylitis; bDMARDs: biologic disease-modifying anti-rheumatic drugs; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; CS: corticosteroids; CsA: cyclosporine A; csDMARDs: conventional synthetic disease-modifying anti-rheumatic drugs; CZP: certolizumab; DAAs: direct-acting antiviral agents; DM: diabetes mellitus; DOT: directly observed therapy; EIN: Emerging Infections Network; ETN: etanercept; GOL: golimumab; GPRD: General Practice Research Database; HBV: hepatitis B virus; HBVr: HBV reactivation; HBsAg+: HBsAg-positive; HBsAg-/anti-HBc+: HBsAg-negative anti-HBc antibodies-positive; HCV: hepatitis C virus; HCQ: hydroxychloroquine: IFX: infliximab; IL-6: interleukin-6; JAK: Janus kinase; LEF: leflunomide; LTBI: latent tuberculosis infection; mAb: monoclonal antibody; MTX: methotrexate; OR: odds ratio; PsA: psoriatic arthritis; PMS: post-marketing surveillance; RA: rheumatoid arthritis; TNF: tumor necrosis factor; TNFi: tumor necrosis factor inhibitor; SCK: secukinumab; SSZ: sulfasalazine; TOZ: tocilizumab; RCT: randomized controlled trial; RR: relative risk; RTX: rituximab; 3HP: 3-month once-weekly isoniazid plus rifapentine; TB: tuberculosis; tsDMARDs: targeted synthetic disease-modifying anti-rheumatic drugs; UTK: ustekinumab; WHO: World Health Organization.
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Affiliation(s)
- Ying-Ming Chiu
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Der-Yuan Chen
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan.,Translational Medicine Laboratory, Rheumatic Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.,Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.,Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
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Kim HW, Kwon OC, Han SH, Park MC. Positive conversion of interferon-γ release assay in patients with rheumatic diseases treated with biologics. Rheumatol Int 2020; 40:471-479. [PMID: 31919575 DOI: 10.1007/s00296-019-04510-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 12/30/2019] [Indexed: 12/19/2022]
Abstract
The objective of this study is to investigate whether the type of biologics (TNFi or others) or type of rheumatic diseases (RA or AS) influence the conversion rate of initially negative tuberculosis (TB) screening test results. A total of 119 patients with RA or AS who had negative baseline interferon-γ release assay (IGRA) results assessed by QuantiFERON-TB Gold in tube (QTF-GIT) were included. All patients received biologic agents, and rescreening with QTF-GIT was performed after a median of 25.9 months from the baseline test. Clinical characteristics and IFN-γ levels were compared between converters and non-converters. Logistic regression analysis was performed to identify factors associated with positive conversion. IGRA conversion was found in 14 of 119 patients (11.8%). The converters were older (53.4 ± 14.2 vs 44.4 ± 15.5 years, p = 0.040), had higher baseline TB-specific IFN-γ responses (0.105 [0.018-0.205] vs 0.010 [0.000-0.035] IU/ml, p = 0.001) and higher incidence of active TB (14.3% vs 0.0%, p = 0.013). The number of patients with RA or AS was 9 (64.3%) or 5 (35.7%) in converters, and 45 (42.9%) or 60 (57.1%) in non-converters. In terms of use of biologics, TNFi of monoclonal antibody form was less commonly used in the converters (p = 0.024). In the logistic regression analysis, type of disease and type of biologics used were not associated with IGRA conversion, whereas baseline TB-specific IFN-γ response was significantly associated with IGRA conversion (OR 1.083, 95% CI 1.019-1.151, p = 0.011). Serial monitoring of LTBI with IGRA retesting is needed during biologic treatment, regardless of the type of rheumatic diseases or type biologics used.
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Affiliation(s)
- Hye Won Kim
- Department of Medicine, The Graduate School, Yonsei University, Seoul, South Korea
- Division of General Internal Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Oh Chan Kwon
- Division of Rheumatology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul, 06273, South Korea
| | - Sang Hoon Han
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Min-Chan Park
- Division of Rheumatology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul, 06273, South Korea.
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Revisiting John Snow to Meet the Challenge of Nontuberculous Mycobacterial Lung Disease. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16214250. [PMID: 31683836 PMCID: PMC6862550 DOI: 10.3390/ijerph16214250] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 10/25/2019] [Accepted: 10/28/2019] [Indexed: 01/09/2023]
Abstract
Nontuberculous mycobacteria (NTM) are ubiquitous components of the soil and surface water microbiome. Disparities by sex, age, and geography demonstrate that both host and environmental factors are key determinants of NTM disease in populations, which predominates in the form of chronic pulmonary disease. As the incidence of NTM pulmonary disease rises across the United States, it becomes increasingly evident that addressing this emerging human health issue requires a bold, multi-disciplinary research framework that incorporates host risk factors for NTM pulmonary disease alongside the determinants of NTM residence in the environment. Such a framework should include the assessment of environmental characteristics promoting NTM growth in soil and surface water, detailed evaluations of water distribution systems, direct sampling of water sources for NTM contamination and species diversity, and studies of host and bacterial factors involved in NTM pathogenesis. This comprehensive approach can identify intervention points to interrupt the transmission of pathogenic NTM species from the environment to the susceptible host and to reduce NTM pulmonary disease incidence.
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Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, Haroon N, Borenstein D, Wang R, Biehl A, Fang MA, Louie G, Majithia V, Ng B, Bigham R, Pianin M, Shah AA, Sullivan N, Turgunbaev M, Oristaglio J, Turner A, Maksymowych WP, Caplan L. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Care Res (Hoboken) 2019; 71:1285-1299. [PMID: 31436026 PMCID: PMC6764857 DOI: 10.1002/acr.24025] [Citation(s) in RCA: 158] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 07/09/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.
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Affiliation(s)
- Michael M. Ward
- National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, Bethesda, Maryland
| | - Atul Deodhar
- Oregon Health & Science University, Portland, Oregon
| | | | | | - David Yu
- University of California, Los Angeles, Los Angeles, California
| | | | - Nigil Haroon
- Department of Medicine, University of Toronto, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada
| | | | - Runsheng Wang
- Columbia University Medical Center, New York, New York
| | - Ann Biehl
- National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, Bethesda, Maryland
| | - Meika A. Fang
- VA West Los Angeles Medical Center, Los Angeles, California
| | - Grant Louie
- Arthritis and Rheumatism Associates, Wheaton, Maryland
| | - Vikas Majithia
- University of Mississippi Medical Center, Jackson, Mississippi
| | - Bernard Ng
- University of Washington, Seattle, Washington
| | | | | | | | | | | | | | - Amy Turner
- American College of Rheumatology, Atlanta, Georgia
| | | | - Liron Caplan
- Rocky Mountain Regional VA Medical Center, Aurora, Colorado, and University of Colorado, Aurora, Colorado
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Herath K, Contis L, Aggarwal N, Birru Talabi M. A Case of Unremitting Fevers. Arthritis Care Res (Hoboken) 2019; 71:1310-1316. [DOI: 10.1002/acr.23800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 10/16/2018] [Indexed: 11/07/2022]
Affiliation(s)
| | - Lydia Contis
- University of Pittsburgh Pittsburgh Pennsylvania
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Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, Haroon N, Borenstein D, Wang R, Biehl A, Fang MA, Louie G, Majithia V, Ng B, Bigham R, Pianin M, Shah AA, Sullivan N, Turgunbaev M, Oristaglio J, Turner A, Maksymowych WP, Caplan L. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol 2019; 71:1599-1613. [PMID: 31436036 PMCID: PMC6764882 DOI: 10.1002/art.41042] [Citation(s) in RCA: 417] [Impact Index Per Article: 69.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 07/09/2019] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.
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Affiliation(s)
- Michael M. Ward
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland
| | - Atul Deodhar
- Oregon Health & Science University, Portland, Oregon
| | | | | | - David Yu
- University of California, Los Angeles
| | | | - Nigil Haroon
- University of Toronto, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada
| | | | - Runsheng Wang
- Columbia University Medical Center, New York, New York
| | - Ann Biehl
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland
| | - Meika A. Fang
- VA West Los Angeles Medical Center, Los Angeles, California
| | - Grant Louie
- Arthritis and Rheumatism Associates, Wheaton, Maryland
| | - Vikas Majithia
- University of Mississippi Medical Center, Jackson, Mississippi
| | | | | | | | | | | | | | | | - Amy Turner
- American College of Rheumatology, Atlanta, Georgia
| | | | - Liron Caplan
- Rocky Mountain Regional VA Medical Center and University of Colorado, Aurora
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Sonthalia S, Aggarwal P. Oral Tofacitinib: Contemporary Appraisal of Its Role in Dermatology. Indian Dermatol Online J 2019; 10:503-518. [PMID: 31544068 PMCID: PMC6743407 DOI: 10.4103/idoj.idoj_474_18] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Tofacitinib, an oral Janus kinase inhibitor (Jakinib), is an emerging treatment modality whose well-established efficacy in systemic inflammatory diseases is now being actively explored for cutaneous disorders (arising due to the patient's dysimmune responses) that are not responding to and/or sustaining intolerable adverse effects with the classical immunosuppressives and other targeted therapies such as the biologics. The most common dermatoses for which oral as well as topical Jakinibs such as tofacitinib have been evaluated and are being used albeit as an off-label indication include psoriasis, psoriatic arthritis, alopecia areata, vitiligo, and atopic dermatitis. This article provides a succinct review on the current status of oral tofacitinib in dermatology through literature search of PubMed database and stresses on the need for further evidence generation to define the drug's place in the therapeutic arsenal of dysimmune cutaneous disorders.
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Affiliation(s)
- Sidharth Sonthalia
- Medical Director and Senior Consultant Dermatologist, Department of Dermatology and Dermatosurgery, Skinnocence: The Skin Clinic and Research Center, Gurugram, Haryana, India
| | - Parul Aggarwal
- Consultant Dermatologist, Department of Dermatology and STD, Skinalive Clinic, New Delhi, India
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Bunte K, Beikler T. Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediated Inflammatory Diseases. Int J Mol Sci 2019; 20:ijms20143394. [PMID: 31295952 PMCID: PMC6679067 DOI: 10.3390/ijms20143394] [Citation(s) in RCA: 343] [Impact Index Per Article: 57.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 06/11/2019] [Accepted: 07/08/2019] [Indexed: 12/12/2022] Open
Abstract
Innate immunity represents the semi-specific first line of defense and provides the initial host response to tissue injury, trauma, and pathogens. Innate immunity activates the adaptive immunity, and both act highly regulated together to establish and maintain tissue homeostasis. Any dysregulation of this interaction can result in chronic inflammation and autoimmunity and is thought to be a major underlying cause in the initiation and progression of highly prevalent immune-mediated inflammatory diseases (IMIDs) such as psoriasis, rheumatoid arthritis, inflammatory bowel diseases among others, and periodontitis. Th1 and Th2 cells of the adaptive immune system are the major players in the pathogenesis of IMIDs. In addition, Th17 cells, their key cytokine IL-17, and IL-23 seem to play pivotal roles. This review aims to provide an overview of the current knowledge about the differentiation of Th17 cells and the role of the IL-17/IL-23 axis in the pathogenesis of IMIDs. Moreover, it aims to review the association of these IMIDs with periodontitis and briefly discusses the therapeutic potential of agents that modulate the IL-17/IL-23 axis.
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Affiliation(s)
- Kübra Bunte
- Department of Periodontics, Preventive and Restorative Dentistry, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Thomas Beikler
- Department of Periodontics, Preventive and Restorative Dentistry, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany.
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