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Isa M, Ramos MRR, Kamal S. Infection Risk in Biological Disease-Modifying Anti-rheumatic Drugs. Cureus 2025; 17:e80634. [PMID: 40236366 PMCID: PMC11998624 DOI: 10.7759/cureus.80634] [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: 03/14/2025] [Indexed: 04/17/2025] Open
Abstract
Rheumatology patients on biological disease-modifying anti-rheumatic drugs (bDMARDs) have been proposed to be at a higher risk of infections. Our review summarizes the current evidence behind this theory as well as explores which factors predispose patients to various infections, which agents are more likely to cause infections, and which infections are common in these patients. We also aim to explore updated guidelines on infection prevention in patients on bDMARDs.
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Affiliation(s)
- Mourushi Isa
- General Medicine, Northern Health, Melbourne, AUS
| | | | - Shahed Kamal
- General Medicine, Northern Health, Melbourne, AUS
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Bernardes TP, Paula TAF, Sales GTM, Calais PV, Foresto RD, Moura LA, Durão MDS, Pesquero JB, Kirsztajn GM. Collapsing glomerulopathy associated with parvovirus B19 and systemic lupus erythematosus in a patient with APOL1 high-risk variant for nephropathy. J Bras Nefrol 2025; 47:e20240104. [PMID: 39792859 PMCID: PMC11723606 DOI: 10.1590/2175-8239-jbn-2024-0104en] [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: 06/04/2024] [Accepted: 08/11/2024] [Indexed: 01/12/2025] Open
Abstract
Collapsing glomerulopathy (CG) has a severe course typically associated with viral infections, especially HIV and parvovirus B19, systemic lupus erythematosus (SLE), among other etiologies. A 35-year-old woman with recent use of a JAK inhibitor due to rheumatoid arthritis presented with a 2-week history of fever, cervical adenopathy, and facial erythema. After admission, anemia, hypoalbuminemia, proteinuria, and severe acute kidney injury were noted. SLE was diagnosed and parvovirus B19 DNA was detected in serum samples. Kidney biopsy showed CG without any typical features of lupus nephritis. The patient was treated with prednisone and presented marked improvement of anemia and kidney function after a few weeks. In this case, the patient with SLE presented CG possibly caused by parvovirus B19 infection associated with homozygous apolipoprotein 1 (APOL1) G1 genotype, which has been described as a determinant risk factor for this glomerulopathy. It is not clear whether SLE had a causal relationship with glomerular disease or was a concurrent cause. Treatment can be challenging in such a context, as no antiviral drug is efficient and immunosuppression has no discernable benefit, although steroid use was efficient in treating renal manifestations in this case.
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Affiliation(s)
| | | | | | - Patrícia Varela Calais
- Universidade Federal de São Paulo, Departamento de Biofísica, Centro de Pesquisa e Diagnóstico em Doenças Genéticas, São Paulo, SP, Brazil
| | | | - Luiz Antonio Moura
- Universidade Federal de São Paulo, Departamento de Medicina, São Paulo, SP, Brazil
- Fundação Oswaldo Ramos, Hospital do Rim, São Paulo, SP, Brazil
| | | | - João Bosco Pesquero
- Universidade Federal de São Paulo, Departamento de Biofísica, Centro de Pesquisa e Diagnóstico em Doenças Genéticas, São Paulo, SP, Brazil
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Haag C, Alexis A, Aoki V, Bissonnette R, Blauvelt A, Chovatiya R, Cork MJ, Danby SG, Eichenfield LF, Eyerich K, Gooderham M, Guttman-Yassky E, Hijnen DJ, Irvine AD, Katoh N, Murrell DF, Leshem YA, Levin AA, Vittrup I, Olydam JI, Orfali RL, Paller AS, Renert-Yuval Y, Rosmarin D, Silverberg JI, Thyssen JP, Ständer S, Stefanovic N, Todd G, Yu J, Simpson EL. A practical guide to using oral Janus kinase inhibitors for atopic dermatitis from the International Eczema Council. Br J Dermatol 2024; 192:135-143. [PMID: 39250758 DOI: 10.1093/bjd/ljae342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 08/05/2024] [Accepted: 08/27/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND Janus kinase inhibitors (JAKi) have the potential to alter the landscape of atopic dermatitis (AD) management dramatically, owing to promising efficacy results from phase III trials and their rapid onset of action. However, JAKi are not without risk, and their use is not appropriate for all patients with AD, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD. OBJECTIVES To provide a consensus expert opinion statement from the International Eczema Council (IEC) that provides a pragmatic approach to prescribing JAKi, including choosing appropriate patients and dosing, clinical and laboratory monitoring and advice about long-term use. METHODS An international cohort of authors from the IEC with expertise in JAKi selected topics of interest were placed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance and recommendations were reviewed by all authors, as well as the IEC Research Committee. RESULTS We recommend that JAKi be considered for patients with moderate-to-severe AD seeking the benefits of a rapid reduction in disease burden and itch, oral administration and the potential for flexible dosing. Baseline risk factors should be assessed prior to prescribing JAKi, including increasing age, venous thromboembolisms, malignancy, cardiovascular health, kidney/liver function, pregnancy and lactation, and immunocompetence. Patients being considered for JAKi treatment should be current on vaccinations and we provide a generalized framework for laboratory monitoring, although clinicians should consult individual product labels for recommendations as there are variations among the different JAKi. Patients who achieve disease control should be maintained on the lowest possible dose, as many of the observed AEs occurred in a dose-dependent manner. Future studies are needed in patients with AD to assess the durability and safety of continuous long-term JAKi use, combination medication regimens and the effects of flexible, episodic treatment over time. CONCLUSIONS The decision to initiate JAKi treatment should be shared between the patient and provider, accounting for AD severity and personal risk-benefit assessment, including consideration of baseline health risk factors, monitoring requirements and treatment costs.
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Affiliation(s)
- Carter Haag
- Department of Dermatology, Oregon Health and Science University, Portland, OR, USA
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Eric L Simpson
- Department of Dermatology, Oregon Health and Science University, Portland, OR, USA
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Wang C, Song X, Liu J, Song Y, Gao J. Analysis of Risk Factors and Development and Validation of a Dynamic Nomogram for Postherpetic Neuralgia: A Retrospective Study. J Pain Res 2024; 17:3935-3948. [PMID: 39583189 PMCID: PMC11585982 DOI: 10.2147/jpr.s483531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 11/06/2024] [Indexed: 11/26/2024] Open
Abstract
Purpose Postherpetic Neuralgia (PHN), recognized as the most common complication of Herpes Zoster, is experiencing an increasing trend in its occurrence. The goal of this study was to identify the independent risk factors for PHN and create a dynamic nomogram using routine clinical characteristics to predict PHN in patients with herpes zoster, for early identification and prevention of PHN. Patients and Methods A total of 2420 patients were retrospectively reviewed and divided into training (n=1696) and validation (n=724) cohort using a 7:3 random allocation. Univariable, LASSO and multivariable logistic regression analysis was performed to identified independent risk factors for PHN. A dynamic nomogram was assessed through the area under the receiver operating characteristic curve (AUC), calibration curves and Hosmer-Lemeshow test. The decision curve analysis (DCA) was used to evaluate its clinical validity. Results Multivariable logistic regression identified several independent risk factors for PHN, including age, female, diabetes mellitus, malignant tumors, and connective tissue diseases. The area under the curve was 0.698 (95% CI, 0.666-0.730) for training cohort and 0.713 (95% CI, 0.663-0.763) for the validation cohort. Calibration curve revealed a moderate consistency between actual observation and prediction. Decision curve analysis showed a risk threshold of 16% and demonstrated a clinically effective predictive model. Conclusion We have developed a user-friendly dynamic nomogram to predict PHN in patients with herpes zoster, which can assist in early identification and prevention of PHN.
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Affiliation(s)
- Cunjin Wang
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225001, People’s Republic of China
- Department of Anesthesiology, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China
- Department of Pain Treatment, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, 225001, People’s Republic of China
| | - Xiaowei Song
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225001, People’s Republic of China
- Department of Anesthesiology, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China
| | - Jing Liu
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225001, People’s Republic of China
- Department of Anesthesiology, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China
| | - Yinghao Song
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225001, People’s Republic of China
- Department of Pain Treatment, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, 225001, People’s Republic of China
| | - Ju Gao
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225001, People’s Republic of China
- Department of Anesthesiology, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China
- Department of Pain Treatment, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, 225001, People’s Republic of China
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Chang J, Wang G. A retrospective study of efficacy of tofacitinib combined with bDMARDs in the treatment of rheumatoid arthritis patients with inadequate response to bDMARDs. Int J Rheum Dis 2024; 27:e15311. [PMID: 39198040 DOI: 10.1111/1756-185x.15311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/12/2024] [Accepted: 08/15/2024] [Indexed: 09/01/2024]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation, joint swelling, and pain involving multiple joints. While biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are popular treatments for RA, there is limited research on their combined use. This study examined a cohort of RA patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib and bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach. METHODS In this study, we retrospectively collected the electronic medical records (EMR) of 62 adult patients with RA who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between August 2018 and December 2022. All patients had received at least one bDMARD treatment for more than 3 months and still exhibited moderate-to-high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment in 28 cases, and other 34 cases switched to another bDMARD or tsDMARD as control group. Treatment was continued for 24 weeks following the initiation of combination therapy. Changes in DAS28-ESR and ACR20, 50, 70 response rates at week 24 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, 12, 24 were also collected and analyzed. RESULTS After 24 weeks of treatment, the DAS28-ESR score in combined treatment group decreased significantly from a baseline of 5.26 ± 0.90 (3.87-8.31) to 2.67 ± 0.86 (1.41-5.11), with remission achieved by 19 patients (67.9%) and low disease activity achieved by five patients (17.9%). The DAS28-ESR in the control group exhibited a decrease from 5.20 ± 0.77 (3.87-7.23) at baseline to 3.25 ± 1.29 (1.54-5.69). In all, 13 patients (38.2%) achieved remission, while another 11 patients (32.4%) achieved low disease activity. The ACR20, 50, 70 response rates were 85.71%, 75%, and 39.29% in the combined treatment group, whereas it were 75.0%, 53.57%, 21.43% in the control group. Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation. CONCLUSION Our findings offer some evidence, supporting the effectiveness and safety of combining bDMARD with JAKi tofacitinib in RA patients who have an inadequate response to bDMARD monotherapy. This combination effectively manages disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.
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Affiliation(s)
- Jie Chang
- Department of Rheumatology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
| | - Gang Wang
- Department of Rheumatology, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China
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Guglielmo A, Deotto ML, Naldi L, Stinco G, Pileri A, Piraccini BM, Fortina AB, Sechi A. Biologics and small molecules treatment for moderate-to-severe atopic dermatitis patients with comorbid conditions and special populations: an Italian perspective. Dermatol Reports 2024; 16:9839. [PMID: 38957642 PMCID: PMC11216152 DOI: 10.4081/dr.2023.9839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 08/30/2023] [Indexed: 07/04/2024] Open
Abstract
This comprehensive review offers a detailed look at atopic dermatitis (AD) treatment in Italy, focusing primarily on the use of biologics and small molecules. In response to advancing knowledge of AD's causes and treatments, there's a global need for updated guidelines to provide physicians with a more comprehensive clinical perspective, facilitating personalized treatment strategies. Dupilumab, a groundbreaking biologic, gained approval as a significant milestone. Clinical trials demonstrated its ability to significantly reduce AD severity scores, with an impressive 37% of patients achieving clear or nearly clear skin within just 16 weeks of treatment. Real-world studies further support its efficacy across various age groups, including the elderly, with a safety profile akin to that of younger adults. Tralokinumab, a more recent approval, shows promise in clinical trials, particularly among younger populations. However, its real-world application, especially in older individuals, lacks comprehensive data. Janus Kinases inhibitors like Upadacitinib, Baricitinib, and Abrocitinib hold substantial potential for AD treatment. Nevertheless, data remains limited for patients over 75, with older adults perceived to carry a higher risk profile. Integrated safety analyses revealed individuals aged 60 and above experiencing major adverse cardiovascular events and malignancies, underscoring the need for cautious consideration. While these therapies offer promise, especially among younger patients, further research is essential to determine their safety and efficacy in various populations, including pediatric, geriatric, and those with comorbidities. Biologics and small molecules are improving AD treatment, as shown in this review.
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Affiliation(s)
- Alba Guglielmo
- Dermatology Unit, IRCCS University Hospital of Bologna, Policlinico S. Orsola-Malpighi, Bologna
- Institute of Dermatology, Azienda Sanitaria Universitaria Friuli Centrale, Udine
| | | | - Luigi Naldi
- Dermatology Unit, San Bortolo Hospital, Vicenza
| | - Giuseppe Stinco
- Institute of Dermatology, Azienda Sanitaria Universitaria Friuli Centrale, Udine
- Department of Medicine, University of Udine, Italy
| | - Alessandro Pileri
- Dermatology Unit, IRCCS University Hospital of Bologna, Policlinico S. Orsola-Malpighi, Bologna
| | - Bianca Maria Piraccini
- Dermatology Unit, IRCCS University Hospital of Bologna, Policlinico S. Orsola-Malpighi, Bologna
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Huang J, Tan Z, Tang Y, Shi W. Screening for latent infectious disease in patients with alopecia areata before initiating JAK inhibitors therapy: a single-center real-world retrospective study. Front Med (Lausanne) 2023; 10:1287139. [PMID: 37920596 PMCID: PMC10619649 DOI: 10.3389/fmed.2023.1287139] [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: 09/01/2023] [Accepted: 09/26/2023] [Indexed: 11/04/2023] Open
Abstract
Introduction Although there is growing evidence supporting the effectiveness of Janus kinase (JAK) inhibitors in treating alopecia areata, the high rate of recurrence following drug discontinuation has led to prolonged treatment courses and raised concerns about long-term safety. In clinical practice, caution should be exercised while using JAK inhibitors for various indications, and a comprehensive pre-treatment screening. Methods This study presents an analysis of screening data collected from real-world settings before the initiation of Janus kinase inhibitors in patients with alopecia areata. Investigators collected retrospective medical data characterizing patients' screening data. Data on demographic and clinical data, including age, sex, disease duration, severity of alopecia tool scale, history of prior treatment, and treatment regimen were recorded. Results In this cohort (N = 218), JAK inhibitors were initiated for 163 of 218 (74.8%) alopecia areata patients. The numbers of patients positive for antinuclear antibodies, hepatitis B surface antigen, hepatitis C virus antibodies, human immunodeficiency virus antibody, treponema pallidum hemagglutination assay, and thyroid-stimulating hormone were 32 (32/176), 10(10/218), 0 (0/218), 0 (0/218), 3 (3/218) and 9 (9/176), respectively. The number of patients with T-cell spot positive or imaging of the chest indicating tuberculosis was 37 (37/218). Disccusion Our data provide additional information on the safety profile of JAK inhibitors in patients with alopecia areata. As such, it is necessary and crucial to screen for JAK inhibitors before it is used, particularly for individuals with a high risk of tuberculosis, hepatitis B, and other infections.
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Affiliation(s)
| | | | | | - Wei Shi
- Department of Dermatology, Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
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Combe B, Besuyen R, Gómez-Centeno A, Matsubara T, Sancho Jimenez JJ, Yin Z, Buch MH. Geographic Analysis of the Safety and Efficacy of Filgotinib in Rheumatoid Arthritis. Rheumatol Ther 2023; 10:35-51. [PMID: 36205910 PMCID: PMC9931958 DOI: 10.1007/s40744-022-00494-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 09/14/2022] [Indexed: 10/10/2022] Open
Abstract
INTRODUCTION Global clinical trials in rheumatoid arthritis (RA) often do not recruit enough patients from diverse racial and ethnic backgrounds to identify any potential differences in treatment outcome across such groups. To overcome this limitation, using data from five previous clinical trials and two ongoing trial extensions, this study aimed to assess the efficacy and safety of filgotinib in patients with RA across geographic regions. METHODS This was a post hoc, exploratory analysis of data from male and female patients with RA meeting the 2010 RA criteria as defined by the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology. Data were analyzed from phase 2 (DARWIN 1-2) and phase 3 (FINCH 1-3) clinical trials, as well as two long-term extension studies (DARWIN 3, FINCH 4), of filgotinib. Efficacy endpoints included ACR 20%/50%/70% improvement (ACR20/50/70) responses, disease activity score in 28 joints using C-reactive protein [DAS28(CRP)], Clinical Disease Activity Index scores, Boolean remission, and change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety data were presented as exposure-adjusted incidence rates per 100 patient-years of exposure of treatment-emergent adverse events. RESULTS Compared with placebo, at week 12 a greater proportion of patients receiving filgotinib 200 mg (FIL200) or 100 mg (FIL100) achieved ACR20 (p < 0.01), with similar outcomes in most regions. Overall, the reduction in HAQ-DI with FIL200 or FIL100 was greater than with placebo (p < 0.05) at week 12. Compared with placebo, at week 24 the proportions of patients achieving DAS28(CRP) ≤ 3.2 were greater for both doses of FIL, as seen in most regions (p < 0.01). Safety outcomes did not indicate regional or ethnic differences in the safety profile of filgotinib. CONCLUSION Filgotinib efficacy and safety in patients with RA were generally consistent across geographic regions. CLINICALTRIALS GOV TRIAL REGISTRATION NUMBERS NCT02889796; NCT02873936; NCT02886728; NCT03025308; NCT01888874; NCT01894516; NCT02065700.
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Affiliation(s)
| | | | | | | | | | - Zhaoyu Yin
- Gilead Sciences, Inc., Foster City, CA, USA
| | - Maya H Buch
- NIHR Manchester Biomedical Research Centre, University of Manchester, AV Hill, Manchester, M13 9PT, UK.
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Winthrop K, Isaacs J, Calabrese L, Mittal D, Desai S, Barry J, Strengholt S, Galloway J. Opportunistic infections associated with Janus kinase inhibitor treatment for rheumatoid arthritis: A structured literature review. Semin Arthritis Rheum 2023; 58:152120. [PMID: 36347212 DOI: 10.1016/j.semarthrit.2022.152120] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 10/11/2022] [Accepted: 10/19/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND The availability of Janus kinase (JAK) inhibitors has transformed the management of rheumatoid arthritis (RA), helping patients achieve clinical remission. However, the emergence of opportunistic infections (OIs) associated with the use of JAK inhibitors has been reported. This structured literature review was conducted to summarize reports of OIs associated with JAK inhibitor treatment for RA in clinical trials. METHODS Structured searches were performed in MEDLINE® and Embase® to identify relevant clinical trial data through March 2021. Bibliographic searches of recent reviews were also conducted, and gray literature searches were used to supplement key gap areas. Publications were screened, extracted, and quality assessed. Data were narratively synthesized. RESULTS Following screening, 105 publications describing 62 unique clinical trials reporting the rates of OIs in RA patients treated with JAK inhibitors were included. Overall, the highest exposure-adjusted incidence rate was reported for herpes zoster (HZ) infection (any form), followed by OI (any) and tuberculosis based on limited data from clinical trials with approved doses of JAK inhibitors. Lack of head-to-head trials and differences in trial design preclude direct comparison across JAK inhibitors. Higher rates of OIs were noted in the Asian and Australian populations compared with the global population. Higher rates of OIs were also noted with increasing dose of JAK inhibitors in most clinical trial data. CONCLUSIONS HZ was the most common OI reported among RA patients using all currently approved JAK inhibitors in clinical trials, although tuberculosis and other OIs were also reported. More long-term safety studies in the real-world setting are needed to compare the risk of OIs between various JAK inhibitors.
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Affiliation(s)
- Kevin Winthrop
- Division of Infectious Diseases, Schools of Medicine and Public Health, Oregon Health and Sciences University, USA.
| | - John Isaacs
- Translational and Clinical Research Institute, Newcastle University and Musculoskeletal Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | | | | | | | - Jane Barry
- Galapagos, Zernikedreef 16, Leiden 2333 CL, the Netherlands
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Lin QX, Meng HJ, Pang YY, Qu Y. Recurrent herpes zoster in a rheumatoid arthritis patient treated with tofacitinib: A case report and review of the literature. World J Clin Cases 2022; 10:8703-8708. [PMID: 36157812 PMCID: PMC9453357 DOI: 10.12998/wjcc.v10.i24.8703] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 06/16/2022] [Accepted: 07/21/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Tofacitinib is an oral Janus kinase (JAK) inhibitor that is currently approved by the United States Food and Drug Administration for the treatment of rheumatoid arthritis (RA). Varicella zoster virus reactivation leading to herpes zoster (HZ) is an adverse effect of this drug; however, recurrent HZ at the same site is a rare clinical condition.
CASE SUMMARY A 70-year-old female RA patient had undergone 1-year of tofacitinib treatment (10 mg daily). About 1 mo after initiation of oral tofacitinib, she developed blisters on the left flank and abdomen and was diagnosed with HZ; antiviral therapy with acyclovir was resolutory. However, 5 d prior to presentation at our hospital, erythema and blisters with severe pain recurred at the same site. Small clustered blisters and bullous were visible on the left lumbar abdomen and perineum, with a pain score of 8 (visual analogue scale). Antiviral, nutritional supplement, analgesic and other treatments led to healing but over an atypically long period (approximately 26 d, vs approximately 1 wk). HZ is a common and serious adverse reaction of JAK inhibitors, but it rarely recurs. Our patient’s experience of HZ recurrence at the same site, with a wider affected area, more severe pain and longer healing period, is inconsistent with previous reports.
CONCLUSION Same-anatomical site HZ recurrence may occur during oral tofacitinib treatment, with more severe clinical manifestations than in the initial occurrence.
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Affiliation(s)
- Qing-Xia Lin
- Department of Dermatology, The Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
| | - Hui-Juan Meng
- Department of Dermatology, The Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
| | - Yun-Yan Pang
- Department of Dermatology, The Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
| | - Yan Qu
- Department of Dermatology, The Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
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Criptococosis diseminada por terapia biológica, se debe gestionar el riesgo. BIOMÉDICA 2022; 42:218-223. [PMID: 35867915 PMCID: PMC9296075 DOI: 10.7705/biomedica.6239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Indexed: 12/30/2022]
Abstract
Introducción. Se han descrito múltiples efectos adversos con el uso de la terapia biológica para enfermedades autoinmunitarias, muchos de ellos secundarios al estado de inmunosupresión, como las infecciones bacterianas, fúngicas o virales. Caso clínico. Se presenta el caso de una mujer de 64 años con diagnóstico comprobado de criptococosis diseminada secundaria al uso de tofacitinib. Se descartaron otras causas de inmunosupresión, como infección por el virus de la inmunodeficiencia humana (HIV). Tres años antes se le había diagnosticado artritis reumatoide y se encontraba en tratamiento farmacológico con un agente biológico que inhibe las enzimas JAK. Se han descrito muy pocos casos de criptococosis pulmonar y meníngea en este tipo de pacientes. Conclusión. Este reporte de caso es útil para que otros médicos tratantes tengan presente la posibilidad de este tipo de infección fúngica invasora asociada con la terapia biológica y el enfoque de gestión de riesgo.
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Tang J, Tao J, Luo G, Zhu J, Yao M. Analysis of Risk Factors and Construction of a Prediction Model of Motor Dysfunction Caused by Limb Herpes Zoster. J Pain Res 2022; 15:367-375. [PMID: 35153514 PMCID: PMC8827162 DOI: 10.2147/jpr.s346564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 01/28/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Jiayi Tang
- The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
- Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China
| | - Jiachun Tao
- Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China
| | - Ge Luo
- Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China
| | - Jianjun Zhu
- Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China
| | - Ming Yao
- Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China
- Correspondence: Ming Yao, Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, No. 1882 South Zhonghuan Road, Nanhu District, Jiaxing City, Zhejiang Province, People’s Republic of China, Tel +86 573 13456218632, Email
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Wu YL, Ke J, Zhang BY, Zhao D. Hepatitis B virus reactivation in rheumatoid arthritis. World J Clin Cases 2022; 10:12-22. [PMID: 35071501 PMCID: PMC8727249 DOI: 10.12998/wjcc.v10.i1.12] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 09/16/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovitis, which can cause cartilage and bone damage as well as functional limitations. Disease-modifying anti-rheumatic drugs have significantly improved the prognosis of RA patients. However, people with RA, when combined with hepatitis B virus (HBV) infection, may experience reactivation of HBV during treatment with anti-rheumatic drugs. The outcome of HBV reactivation (HBVr) varies from liver inflammation to liver failure, while insufficient HBV screening in RA patients has been reported in various countries. Therefore, it is necessary to identify patients at high risk before starting immunosuppressive therapy. The immune response plays an important role in anti-HBV infection. However, most anti-rheumatic drugs exert an inhibitory effect on the body's immune system, resulting in HBVr. Therefore, it is necessary to conduct a comprehensive evaluation based on host factors, viral factors, and drug factors. In this paper, we summarize the mechanism of HBVr, the risk of HBVr caused by anti-rheumatic drugs, and the appropriate diagnosis and treatment process for RA patients so that clinicians can have a more comprehensive understanding of HBVr in RA patients.
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Affiliation(s)
- Ya-Li Wu
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China
| | - Jing Ke
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China
| | - Bao-Yu Zhang
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China
| | - Dong Zhao
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China
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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: 48] [Impact Index Per Article: 16.0] [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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15
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Cantini F, Goletti D, Benucci M, Foti R, Damiani A, Niccoli L. Tailored first-line biologic and targeted synthetic disease modifying anti-rheumatic drugs therapy in patients with rheumatoid arthritis: 2021 updated ITABIO statements. Expert Opin Drug Saf 2021; 21:613-623. [PMID: 34937466 DOI: 10.1080/14740338.2022.2020247] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
INTRODUCTION In 2015, the Italian board for the TAilored BIOlogic therapy (ITABIO) proposed evidence-based decisional statements for first-line tailored biologic therapy in patients with rheumatoid arthritis (RA). Taking into account the new licensed drugs, the aim of the present review was to update the previous statements. AREAS COVERED A narrative review of the most recent evidence on the efficacy and safety of old and newly licensed drugs for the treatment of articular and extra-articular RA was performed. In addition, host-related variables potentially driving the therapy choice, such as the infection risk, the cardiovascular risk, the risk of deep vein thrombosis, thromboembolism, pregnancy, and obesity were analyzed. Consequently, several statements for personalized therapy were formulated, thus providing a decisional algorithm useful for proper personalized therapy of RA patients in clinical practice. EXPERT OPINION Several clinical variables related to specific drug and host characteristics may drive the choice toward anti-TNF and non-anti-TNF biologics, or anti-JAKs, thus allowing to personalize the therapy. Consequently, the right therapy for the right patient would ensure a successful therapeutic intervention.
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Affiliation(s)
| | - Delia Goletti
- Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Via,Portuense 292, 00149 Rome, Italy
| | - Maurizio Benucci
- Rheumatology Unit, Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy
| | - Rosario Foti
- Rheumatology Unit, Vittorio-Emanuele University Hospital of Catania, Catania, Italy
| | - Arianna Damiani
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Laura Niccoli
- Rheumatology Department, Hospital of Prato, Prato Italy
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Huang JX, Zhang LJ. Successful treatment of tofacitinib in a case with rheumatoid arthritis who experienced hepatitis B virus reactivation induced by tocilizumab and recovered from entecavir rescue therapy. Arch Rheumatol 2021; 36:458-460. [PMID: 34870178 PMCID: PMC8612488 DOI: 10.46497/archrheumatol.2021.8230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 07/22/2020] [Indexed: 12/17/2022] Open
Affiliation(s)
- Jin-Xian Huang
- Department of Rheumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Li-Jun Zhang
- Department of Rheumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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Takinib Inhibits Inflammation in Human Rheumatoid Arthritis Synovial Fibroblasts by Targeting the Janus Kinase-Signal Transducer and Activator of Transcription 3 (JAK/STAT3) Pathway. Int J Mol Sci 2021; 22:ijms222212580. [PMID: 34830460 PMCID: PMC8621335 DOI: 10.3390/ijms222212580] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/15/2021] [Accepted: 11/19/2021] [Indexed: 12/24/2022] Open
Abstract
TGF β-activated kinase 1 (TAK1) is an important participant in inflammatory pathogenesis for diseases such as rheumatoid arthritis (RA) and gouty arthritis. The central position it occupies between the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways makes it an attractive therapeutic target. As this field has developed in recent years, several novel inhibitors have been presented as having specific activity that reduces the TAK1 function either covalently as in the case of 5Z-7-oxozeanol (5Z7O) or reversibly (NG-25). However, the mechanism through which takinib elicits its anti-inflammatory activity remains elusive. While this inhibitor shows great promise, a thorough analysis of its inhibitor function and its potential off-target effects is necessary before addressing its clinical potential or its use in inflammatory conditions. An analysis through Western blot showed an unexpected increase in IL-1β-induced TAK1 phosphorylation—a prerequisite for and indicator of its functional potential—by takinib while simultaneously demonstrating the inhibition of the JAK/STAT pathway in human rheumatoid arthritis synovial fibroblasts (RASFs) in vitro. In THP-1 monocyte-derived macrophages, takinib again led to the lipopolysaccharide-induced phosphorylation of TAK1 without a marked inhibition of the TAK1 downstream effectors, namely, of c-Jun N-terminal kinase (JNK), phospho-c-Jun, NF-κB phospho-p65 or phospho-IκBα. Taken together, these findings indicate that takinib inhibits inflammation in these cells by targeting multiple signaling pathways, most notably the JAK/STAT pathway in human RASFs.
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Potera J, Kambhatla S, Gauto-Mariotti E, Manadan A. Incidence, mortality, and national costs of hospital admissions for potentially preventable infections in patients with rheumatoid arthritis. Clin Rheumatol 2021; 40:4845-4851. [PMID: 34254210 DOI: 10.1007/s10067-021-05836-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/13/2021] [Accepted: 06/20/2021] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) patients have high infection rates. Streptococcus pneumoniae, herpes zoster (HZV), and influenza are common and potentially preventable causes of morbidity and mortality. Vaccinations have been shown to reduce the rates of these infections. In this study, we aim to determine incidence, mortality, and national costs of hospital admissions for Streptococcus pneumoniae, HZV, and influenza infections in patients with RA. METHODS We conducted a retrospective analysis of the adult RA hospitalizations in 2016 from the National Inpatient Sample database. We limited the RA cases to hospitalizations with a principal discharge diagnosis of S. pneumoniae, HZV, and influenza infections. The total number of discharges, age, length of stay, mortality, and hospital charges were recorded. RESULTS In 2016, 552,230 adult hospitalizations had either a primary or secondary diagnosis of RA. Among this group, there were 1120 hospitalizations for influenza, 590 hospitalizations for herpes zoster, and 785 hospitalizations for S. pneumoniae. These infections constituted 0.5% of RA hospitalizations and were a more common cause of hospitalizations when compared to non-RA hospitalizations. Aggregate annual national hospital charges reached $124 million and an aggregate annual LOS of 13,750 days. CONCLUSION Infections, such as influenza, HZV, and S. pneumoniae, remain a common cause of inpatient morbidity and mortality among RA patients. Additionally, the economic burden of these infections is significant. Universal vaccination programs in RA patients, as well as other interventions aiming to improve quality of care of this susceptible population, should be further studied to reduce hospitalizations, cost, morbidity, and mortality. Key Points • Streptococcus pneumoniae, herpes zoster, and influenza infections remain an important preventable cause of hospitalizations among RA patients and carry significant economic burden.
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Affiliation(s)
- Joanna Potera
- Internal Medicine Department, John H Stroger, Jr. Hospital of Cook County, 1950 West Polk Street, Chicago, IL, 60612, USA.
| | - Soumyasri Kambhatla
- Division of Rheumatology, Rush University Medical Center, 1611 W Harrison St, Suite 510, Chicago, IL, 60612, USA
| | - Estefania Gauto-Mariotti
- Internal Medicine Department, John H Stroger, Jr. Hospital of Cook County, 1950 West Polk Street, Chicago, IL, 60612, USA
| | - Augustine Manadan
- Division of Rheumatology, Rush University Medical Center, 1611 W Harrison St, Suite 510, Chicago, IL, 60612, USA
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BİLGİN E, CEYLAN F, DURAN E, FARİSOĞULLARI B, BÖLEK EÇ, YARDIMCI GK, KILIÇ L, AKDOĞAN A, KARADAĞ Ö, BİLGEN ŞA, KİRAZ S, ERTENLİ Aİ, KALYONCU U. Efficacy, retention, and safety of tofacitinib in real-life: Hur-bio monocentric experience. Turk J Med Sci 2021; 51:297-308. [PMID: 32979899 PMCID: PMC7991862 DOI: 10.3906/sag-2007-123] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 09/26/2020] [Indexed: 12/11/2022] Open
Abstract
Background/aim To assess the real-life efficacy, retention rate, and safety data of tofacitinib in rheumatoid arthritis (RA) patients. Materials and methods We analyzed all patients registered in the HURBİO database who received at least 1 dose of tofacitinib. Patients who received at least one dose were included in retention analysis; patients with at least 1 control visit were included in efficacy and safety analysis. Factors predicting good response at the last follow-up visit were analyzed by logistic regression analysis. Drug retention rates were calculated using the Kaplan–Meier method and predictors of drug retention were determined by Cox proportional hazard model. Adverse events, reasons for switching, and discontinuation were also determined. Results Two hundred and forty-seven (210, 85.0% female) patients were included in the study. The median duration of tofacitinib treatment was 10.2 (20.2) [med, (IQR)] months. Two hundred and four (82.6%) patients were included in safety and efficacy analysis; 45.6% of patients were in low-disease activity (LDA) state (DAS28-CRP ≤ 3.2). Predictors of LDA were being biologic-naïve [aOR 2.53 (1.31–4.88); 95% CI] and RF negativity [aOR 2.14 (1.12–4.07); 95% CI]. At 1 year, the overall tofacitinib retention rate was 63.9% with no relevant predicting factor. Response and retention rates of tofacitinib were similar in patients with and without concomitant csDMARDs. Treatment failure was the most common cause of discontinuation. The most common infectious and laboratory adverse events were herpes zoster infection (3.9 per 100 patient-years) and elevation in ALT (x3UNL: 9.7 per 100 patient-years), respectively. Conclusion Tofacitinib is effective as monotherapy or in combination with csDMARDs. It is a well-tolerated treatment option in Turkish RA patients.
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Affiliation(s)
- Emre BİLGİN
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Furkan CEYLAN
- Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Emine DURAN
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Bayram FARİSOĞULLARI
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Ertuğrul Çağrı BÖLEK
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Gözde Kübra YARDIMCI
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Levent KILIÇ
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Ali AKDOĞAN
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Ömer KARADAĞ
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Şule Apraş BİLGEN
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Sedat KİRAZ
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Ali İhsan ERTENLİ
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
| | - Umut KALYONCU
- Division of Rheumatology, Department of Internal Medicine, Medical School of Hacettepe University, AnkaraTurkey
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Calvet X, Carpio D, Rodríguez-Lago I, García-Vicuña R, Barreiro-de-Acosta M, Juanola X, Aguas M, Castillo C, Gratacós J. Risk of infection associated with Janus Kinase (JAK) inhibitors and biological therapies in inflammatory intestinal disease and rheumatoid arthritis. Prevention strategies. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 44:587-598. [PMID: 33640469 DOI: 10.1016/j.gastrohep.2021.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 12/23/2020] [Accepted: 01/10/2021] [Indexed: 02/07/2023]
Abstract
Patients with certain immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), have an increased risk of severe infectious diseases than the general population, which are mainly associated with the immunosuppressive treatments that they receive. These treatments act on the immune system through different mechanisms, causing different degrees of immunosuppression and a variable risk depending on whether the pathogen is a virus, bacteria or fungus. This article reviews the most relevant literature on the subject, which was selected and discussed by a panel of experts. The aim of this article is to review the risk of infections in patients with IBD and RA, and the potential preventive measures.
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Affiliation(s)
- Xavier Calvet
- Servicio del Aparato Digestivo, Hospital Universitario Parc Taulí, Departamento de Medicina, Universidad Autónoma de Barcelona, CIBERehd, Instituto de Salud Carlos III. Parc Taulí, Sabadell, Barcelona, España.
| | - Daniel Carpio
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Complexo Hospitalario Universitario de Pontevedra, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Pontevedra, España
| | - Iago Rodríguez-Lago
- Servicio de Aparato Digestivo, Hospital de Galdakao-Usansolo, Instituto de Investigación Sanitaria Biocruces Bizkaia, Galdakao, Bizkaia, España
| | - Rosario García-Vicuña
- Servicio de Reumatología, Hospital Universitario de la Princesa, IIS-IP, Madrid, España
| | - Manuel Barreiro-de-Acosta
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Clínico Universitario, Santiago de Compostela, A Coruña, España
| | - Xavier Juanola
- Servicio de Reumatología, Hospital Universitario de Bellvitge, Universidad de Barcelona, IDIBELL, Hospitalet de Llobregat, Barcelona, España
| | - Mariam Aguas
- Departamento de Gastroenterología, Servicio de Medicina Digestiva, Hospital Universitario y Politécnico, CIBERehd, Valencia, España
| | - Concepción Castillo
- Sección de Reumatología, Hospital Universitario Torrecárdenas, Almería, España
| | - Jordi Gratacós
- Servicio de Reumatología, Hospital Universitario Parc Taulí, Departamento de Medicina, Universidad Autónoma de Barcelona, Sabadell, Barcelona, España
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Yamamoto-Furusho JK, Bosques-Padilla FJ, Martínez-Vázquez MA. Second Mexican consensus on biologic therapy and small-molecule inhibitors in inflammatory bowel disease. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2021; 86:70-85. [PMID: 33317930 DOI: 10.1016/j.rgmx.2020.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 09/30/2020] [Accepted: 10/04/2020] [Indexed: 06/12/2023]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic and incurable entity. Therapy with anti-TNF-α agents was the first biologic therapy approved in Mexico for IBD. New biologic agents, such as vedolizumab and ustekinumab, have recently been added, as have small-molecule inhibitors. AIM To update the biologic therapeutic approach to IBD in Mexico with new anti-TNF-α agents and novel biologics whose mechanisms of action induce and maintain remission of Crohn's disease and ulcerative colitis (UC). MATERIALS AND METHODS Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned to participate. The consensus was divided into 3 modules, with 49 statements. The Delphi method was applied, sending the statements to all participants to be analyzed and edited, before the face-to-face meeting. During said meeting, the clinical studies were shown, emphasizing the level of clinical evidence, and the final discussion and voting round on the level of agreement of all the statements was conducted. RESULTS In this second Mexican consensus, recommendations are made for new anti-TNF-α agents, such as golimumab, new biologics with other mechanisms of action, such as vedolizumab and ustekinumab, as well as for the small-molecule inhibitor, tofacitinib. CONCLUSIONS The updated recommendations focus on patient-reported outcomes, biologic therapy, small-molecule inhibitors, and the safety aspects of each of the drugs.
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Affiliation(s)
- J K Yamamoto-Furusho
- Clínica de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
| | - F J Bosques-Padilla
- Departamento de Gastroenterología, Hospital Universitario de la Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
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Second Mexican consensus on biologic therapy and small-molecule inhibitors in inflammatory bowel disease. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2021. [DOI: 10.1016/j.rgmxen.2020.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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23
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Tu Y, Wang K, Jia X, Tan L, Han B, Zhang Q, Li Y, He C. Isolation and Identification of Antiarthritic Constituents from Glycine tabacina and Network Pharmacology-Based Prediction of Their Protective Mechanisms against Rheumatoid Arthritis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:10664-10677. [PMID: 32530618 DOI: 10.1021/acs.jafc.0c00878] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Glycine tabacina (Labill.) Benth is an edible medicinal herb for rheumatoid arthritis (RA) treatment in folk medicine. Current phytochemical research on this dried herb led to the isolation of eight new coumestans, named glytabastan A-H (1-8), and twenty-three known compounds 9-31. Their structures were elucidated using spectroscopic methods. The antiarthritic activities of all isolates were evaluated, and the results showed that coumestans 1-6 and 8-10 could inhibit arthritic inflammation in vitro, while coumestans 1, 2, 9, and 10 significantly blocked the osteoclastogenesis induced by receptor activator of nuclear factor (NF) κB ligand (RANKL). Moreover, network pharmacological analysis revealed that the anti-RA effect of G. tabacina involved multitargets, multipathways such as PI3K/Akt and MAPK signaling pathways, and various biological processes such as inflammatory response and cytokine-mediated signaling pathways. These results suggested that this species and its novel coumestans could serve as potential antiarthritic agents for functional food or medicinal use.
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Affiliation(s)
- Yanbei Tu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China
| | - Kai Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China
| | - Xuejing Jia
- College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
| | - Lihua Tan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China
| | - Bing Han
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China
| | - Qingwen Zhang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China
| | - Yanfang Li
- School of Chemical Engineering, Sichuan University, Chengdu 610065, China
| | - Chengwei He
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR 999078, China
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Tu Y, Wang K, Tan L, Han B, Hu Y, Ding H, He C. Dolichosin A, a coumestan isolated from Glycine tabacina, inhibits IL-1β-induced inflammation in SW982 human synovial cells and suppresses RANKL-induced osteoclastogenesis: From network pharmacology to experimental pharmacology. JOURNAL OF ETHNOPHARMACOLOGY 2020; 258:112855. [PMID: 32376366 DOI: 10.1016/j.jep.2020.112855] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/05/2020] [Accepted: 04/05/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Glycine tabacina (Labill.) Benth has been used as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis (RA) and joint infection. It is also one of the sources of the renowned native herbal medicine 'I-Tiao-Gung' in Taiwan. AIM OF THE STUDY This study aimed to investigate anti-arthritic effects and underlying mechanisms of dolichosin A (DoA), a coumestan compound isolated from G. tabacina, by the integration of network pharmacology and experimental pharmacology. MATERIALS AND METHODS Putative therapeutic targets and potential pharmacological mechanisms of DoA for RA treatment were predicted by network pharmacology approach. The regulated network of DoA acting on RA was constructed using Cytoscape 3.7.1. Anti-arthritic effects of DoA and predicted mechanisms were further validated using IL-1β-induced SW982 human synovial cell model and RANKL-induced osteoclastogenesis model. RESULTS A regulatory network of DoA-targets-pathways-RA was successfully constructed using network pharmacology approach. In this network, 65 candidate targets of DoA related to its therapeutic effect on RA were identified and the functional enrichment analysis revealed that these candidate targets were significantly involved in 12 central signaling pathways such as PI3K/AKT pathway, MAPK pathway and osteoclast differentiation. Furthermore, we found that DoA could significantly inhibit IL-1β-induced inflammation in SW982 human synovial cells, as evidenced by the decreased levels of pro-inflammatory mediators (TNF-α, IL-6 and COX-2) and MMP-3. DoA also suppressed RANKL-induced osteoclastogenesis in vitro, as evidenced by decreased number of TRAP-positive multinucleated osteoclasts and reduced TRAP activity. Further experimental mechanism evidence confirmed the predicted results of network pharmacology that the blockade of PI3K/AKT and MAPK pathways activation was closely associated with these regulated processes of DoA. CONCLUSIONS Our results demonstrated that DoA exhibited strong anti-arthritic activity through suppressing PI3K/AKT and MAPK pathways activation in activated synovial cells and osteoclasts, suggesting its potential as a hopeful candidate for the development of novel agents for the prevention and treatment of RA.
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Affiliation(s)
- Yanbei Tu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, SAR, 999078, China
| | - Kai Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, SAR, 999078, China
| | - Lihua Tan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, SAR, 999078, China
| | - Bing Han
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, SAR, 999078, China
| | - Yuanjia Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, SAR, 999078, China
| | - Hang Ding
- Department of Biochemistry and Molecular Biology, Guangdong Medical University, Dongguan, Guangdong, 523808, China.
| | - Chengwei He
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, SAR, 999078, China.
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Tan L, Tu Y, Wang K, Han B, Peng H, He C. Exploring protective effect of Glycine tabacina aqueous extract against nephrotic syndrome by network pharmacology and experimental verification. Chin Med 2020; 15:79. [PMID: 32765640 PMCID: PMC7395350 DOI: 10.1186/s13020-020-00361-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 07/26/2020] [Indexed: 02/07/2023] Open
Abstract
Background Glycine tabacina (Labill.) Benth, one of the traditional Chinese herbal medicines, has been used for treatment of nephritis, osteoporosis, rheumatism, and menopausal syndrome. The aim of this study was to illuminate the therapeutic effect and mechanism of Glycine tabacina aqueous extract (GATE) in the treatment of nephrotic syndrome (NS). Methods UHPLC-DAD-MS/MS was used to analyze the chemical profile of GATE. Adriamycin (ADR)-induced NS mouse model and network pharmacology methods were conducted to explore the protective effect and mechanism of GATE on NS treatment. Results GATE administration significantly ameliorated symptoms of proteinuria and hyperlipidemia in NS mice, as evidenced by reduced excretion of urine protein and albumin, and decreased plasma levels of total cholesterol and triglyceride. Decreased blood urea nitrogen (BUN) and creatinine levels in NS mice suggested that GATE could prevent renal function decline caused by ADR. GATE treatment also inhibited ADR-induced pathological lesions of renal tissues as indicated by periodic acid Schiff staining. Six flavonoids of GATE were identified by using UHPLC-DAD-MS/MS. Network pharmacology analysis indicated that the protection of GATE in treating NS might be associated with the regulation of oxidative stress and inflammation. In addition, the in vivo experiment validated that treatment with GATE markedly decreased reactive oxygen species production, malonaldehyde level, and increased superoxide dismutase activity both in plasma and renal tissues. TNF-α level in plasma and protein expression in kidney were significantly decreased in GATE treatment groups. Conclusions Combination of network pharmacology analysis and experimental verification revealed that GATE exerts anti-NS effect possibly through modulating oxidative stress and inflammation, suggesting the potential application of GATE or its derivatives in the prevention and treatment of NS and other related kidney diseases.
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Affiliation(s)
- Lihua Tan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078 Macao SAR China
| | - Yanbei Tu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078 Macao SAR China
| | - Kai Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078 Macao SAR China
| | - Bing Han
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078 Macao SAR China
| | - Hongquan Peng
- Renal Division, Kiang Wu Hospital, Macao, 999078 Macao SAR China
| | - Chengwei He
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078 Macao SAR China
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Novais FO, Nguyen BT, Scott P. Granzyme B Inhibition by Tofacitinib Blocks the Pathology Induced by CD8 T Cells in Cutaneous Leishmaniasis. J Invest Dermatol 2020; 141:575-585. [PMID: 32738245 DOI: 10.1016/j.jid.2020.07.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 06/30/2020] [Accepted: 07/10/2020] [Indexed: 02/08/2023]
Abstract
In cutaneous leishmaniasis, the immune response is not only protective but also mediates immunopathology. We previously found that cytolytic CD8 T cells promote inflammatory responses that are difficult to treat with conventional therapies that target the parasite. Therefore, we hypothesized that inhibiting CD8 T-cell cytotoxicity would reduce disease severity in patients. IL-15 is a potential target for such a treatment because it is highly expressed in human patients with cutaneous leishmaniasis lesions and promotes granzyme B‒dependent CD8 T-cell cytotoxicity. Here we tested whether tofacitinib, which inhibits IL-15 signaling by blocking Jak3, might decrease CD8-dependent pathology. We found that tofacitinib reduced the expression of granzyme B by CD8 T cells in vitro and in vivo systemic and topical treatment, with tofacitinib protecting mice from developing severe cutaneous leishmaniasis lesions. Importantly, tofacitinib treatment did not alter T helper type 1 responses or parasite control. Collectively, our results suggest that host-directed therapies do not need to be limited to autoimmune disorders and that topical tofacitinib application should be considered a strategy for the treatment of cutaneous leishmaniasis disease in combination with antiparasitic drugs.
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Affiliation(s)
- Fernanda O Novais
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Current address: Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
| | - Ba T Nguyen
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Phillip Scott
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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Sunzini F, McInnes I, Siebert S. JAK inhibitors and infections risk: focus on herpes zoster. Ther Adv Musculoskelet Dis 2020; 12:1759720X20936059. [PMID: 32655703 PMCID: PMC7328488 DOI: 10.1177/1759720x20936059] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 05/27/2020] [Indexed: 12/22/2022] Open
Abstract
Currently, there is a growing interest in Janus kinase (JAK) intracellular
signalling since targeted inhibitors against these pathways are proving
effective in the treatment of a range of immune-mediated diseases, such as
rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), inflammatory
bowel disease and atopic dermatitis. In particular, post marketing experience
and the increasing development of new pharmacological inhibitors of broad and
increasingly selective JAK pathways provide new insights into the JAK pathway
role in viral infections as well as their pathogenic role in immune-mediated
inflammatory diseases. Herein we provide an overview of the biological role of
JAK signalling and its role in immunity against viruses, with particular regard
to herpes zoster reactivation. Thereafter, we will discuss the evidence
currently available on the principal JAK inhibitors and their association with
viral infections.
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Affiliation(s)
- Flavia Sunzini
- University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
| | - Iain McInnes
- University of Glasgow College of Medical Veterinary and Life Sciences, 120 University Place, Glasgow, G12 8TA, UK
| | - Stefan Siebert
- University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
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Cantini F, Blandizzi C, Niccoli L, Petrone L, Goletti D. Systematic review on tuberculosis risk in patients with rheumatoid arthritis receiving inhibitors of Janus Kinases. Expert Opin Drug Saf 2020; 19:861-872. [PMID: 32552289 DOI: 10.1080/14740338.2020.1774550] [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: 12/30/2022]
Abstract
INTRODUCTION Janus kinases inhibitors (anti-JAKs), including tofacitinib, baricitinib, upadacitinib, and filgotinib, represent a new class of synthetic targeted drugs for the treatment of rheumatoid arthritis (RA). In this review, the risk of active tuberculosis (TB) occurrence in patients receiving anti-JAKs was assessed. The literature on this topic, updated to 29 February 2020 was reviewed. Overall, 40 reports (22 tofacitinib, 10 baricitinib, 5 upadacitinib, 3 filgotinib) were examined. A low frequency, not exceeding 0.25%, of active TB cases in patients were exposed to anti-JAKs. Only 1 of 89 recorded cases in tofactinib and baricitinib exposure occurred in countries at intermediate or high TB risk, and most of the cases probably were due to first mycobacterium tuberculosis (Mtb) exposure. Although no cases were observed in patients receiving upadacitinib and filgotinib, long-term trials and data from real-life are required to more precisely address the TB risk associated with the two drugs. AREAS COVERED Discussion on the TB risk associated with anti-JAKs, and on the need for accurate evaluation of host-related risk factors in high risk countries. EXPERT OPINION Available data on anti-JAKs suggest a negligible risk of active TB occurrence in low endemic areas.
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Affiliation(s)
| | - Corrado Blandizzi
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa , Pisa, Italy
| | - Laura Niccoli
- Rheumatology Department, Hospital of Prato , Prato, Italy
| | - Linda Petrone
- Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS , Rome, Italy
| | - Delia Goletti
- Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS , Rome, Italy
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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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