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Background: Psoriatic arthritis (PsA) is a chronic arthritis affecting people with psoriasis. If untreated, it may lead to disability. Recommended drugs are non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), biologic DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). Tumour necrosis factor inhibitors (TNFi) are the first choice bDMARDs., Objectives: To assess the benefits and harms of TNFi in adults with psoriatic arthritis., Search Methods: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization trials portal up to 28 March 2024., Selection Criteria: We included randomized controlled trials (RCTs) in adults with PsA, comparing TNFi to placebo, physiotherapy, NSAIDs, corticosteroids, and cs/b/tsDMARDs. Major outcomes included clinical improvement, minimal disease activity, physical function, health-related quality of life, radiographic progression, serious adverse events, and withdrawals due to adverse events., Data Collection and Analysis: We used standard Cochrane methods. The primary comparison was TNFi versus placebo. The primary time point was 12 weeks for clinical improvement; 24 weeks for minimal disease activity, function, quality of life, and radiographic progression; and the end of the trial period for serious adverse events and withdrawals due to adverse events., Main Results: We included 25 RCTs randomizing 7857 participants. Four studies compared TNFi to methotrexate and one to ustekinumab in DMARD-naïve participants. In csDMARD-inadequate responders, 11 studies compared TNFi to placebo; four studies compared TNFi to placebo and ixekizumab, bimekizumab, tofacitinib, or upadacitinib; and three studies compared TNFi to ixekizumab, secukinumab, and ustekinumab. Two studies compared different TNFi. We found no studies with b/tsDMARD-inadequate responders (b/tsDMARD-IR). No studies compared TNFi to NSAIDs, corticosteroids, or physiotherapy. Performance (32%), detection (56%) and reporting (80%) biases were at high or unclear risk across studies. Only one study had a low risk of bias in all domains. We limit reporting to the primary comparison, TNFi versus placebo. DMARD-naïve We found no studies comparing TNFi with placebo in DMARD-naïve participants. csDMARD-inadequate responders TNFi probably result in a large clinical improvement compared to placebo. At 12 weeks, 149/1926 (8%) participants in the placebo group showed a clinical improvement (ACR50) compared to 784/2141 (37%) participants in the TNFi group (risk ratio (RR) 5.63, 95% confidence interval (CI) 3.98 to 7.96; I 2 = 65%; 14 studies, 4067 participants; moderate-certainty evidence). TNFi probably result in a higher proportion of participants in minimal disease activity. At 24 weeks, 95/1017 (9%) participants in the placebo group were in minimal disease activity compared to 428/1336 (32%) participants in the TNFi group (RR 3.76, 95% CI 2.39 to 5.92; I 2 = 72%; 5 studies, 2353 participants; moderate-certainty evidence). At 24 weeks, TNFi may improve function compared to placebo. The mean change in function from baseline (assessed with the Health Assessment Questionnaire; score from 0 to 3, 0 = no disability; minimal clinically important difference (MCID) = 0.35) was -0.14 points with placebo and 0.33 points lower (0.41 lower to 0.25 lower) with TNFi (I 2 = 72%; 8 studies, 2949 participants; low-certainty evidence). TNFi probably result in a clinically important improvement in health-related quality of life. The mean change in quality of life from baseline (assessed with the Short Form 36-item Mental Component Summary questionnaire; score from 0 to 100, 100 = best score; MCID = 1.7) was 2.4 points with placebo and 3.29 points higher (2.18 points higher to 4.40 points higher) with TNFi (I 2 = 52%; 8 studies, 2928 participants; moderate-certainty evidence). TNFi probably slightly reduce radiographic progression. The mean change in radiographic progression (assessed with the Sharp/Van der Heijde-PsA score; scale from 0 to 528, 0 = no damage) was 0.25 points with placebo and 0.37 points lower with TNFi (0.48 lower to 0.25 lower) (I 2 = 32%; 7 studies, 2478 participants; moderate-certainty evidence) at 24 weeks. We downgraded the evidence to moderate certainty for clinical improvement, minimal disease activity, quality of life, and radiographic progression due to risk of bias. For function, we downgraded the evidence to low certainty for risk of bias and imprecision. TNFi may result in little to no difference in serious adverse events, but may slightly increase withdrawals due to adverse events, compared to placebo. At the end of follow-up: 56/1826 participants (3%) given placebo and 69/1900 (4%) participants given TNFi experienced serious adverse events (RR 1.00, 95% CI 0.70 to 1.42; I 2 = 0%; 13 studies, 3866 participants; low-certainty evidence); and 35/1926 (2%) participants given placebo and 65/2140 (3%) given TNFi withdrew due to adverse events (RR 1.53, 95% CI 1.01 to 2.33; I 2 = 0%; 14 studies, 4066 participants; low-certainty evidence). We downgraded the evidence to low certainty for risk of bias and imprecision., Authors' Conclusions: In csDMARD-inadequate responders, moderate-certainty evidence showed that TNFi probably result in a large clinical improvement, lower disease activity, small decrease in radiographic progression, and better quality of life compared to placebo. Low-certainty evidence showed that TNFi may lead to a slight improvement in physical function compared to placebo. Low-certainty evidence suggested that TNFi may lead to a slight increase in withdrawals due to adverse events, whereas they may result in little to no difference in serious adverse events compared to placebo. No trials assessed TNFi compared to placebo in DMARD-naïve participants or in b/tsDMARD-IR., (Copyright © 2025 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA)., Methods: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment., Results: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75)., Conclusion: JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597)., Competing Interests: Conflicts of Interest. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, and there is no conflict of interest regarding the publication of this article., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the efficacy/safety of ivarmacitinib, a selective Janus kinase (JAK) 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)., Methods: Patients were randomised (1:1:1) to receive either placebo (n=188), ivarmacitinib 4 mg (n=189) or ivarmacitinib 8 mg (n=189) once daily, with background csDMARDs allowed. After 24 weeks, patients on placebo switched to ivarmacitinib 4 mg for an additional 28 weeks, while those on ivarmacitinib continued their initial dosage. The primary endpoint was the proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24., Results: At week 24, ACR20 response rates were significantly higher in the ivarmacitinib 4 mg (70.4%) and 8 mg (75.1%) groups compared with the placebo group (40.4%; both p<0.0001). Both ivarmacitinib doses achieved numerically higher Disease Activity Score 28-joint count C reactive protein of <2.6/≤3.2 response rates compared with placebo. Improvements in efficacy and patient-reported outcomes were sustained through 52 weeks and were noted in patients who switched from placebo after week 24. During the placebo-controlled period, treatment-emergent adverse events (TEAEs) occurred in 81.5% and 90.5% of patients in the ivarmacitinib 4 mg and 8 mg groups, versus 79.3% in the placebo group. Infection-related TEAEs were slightly higher in the ivarmacitinib groups., Conclusions: Ivarmacitinib may offer a potential therapeutic option for patients with RA who have an inadequate response to csDMARDs, with a safety profile that was generally manageable over 1 year of treatment and similar to other JAK inhibitors., Trial Registration Number: NCT04333771., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To evaluate the comparative risk of incident and recurrent acute anterior uveitis (AAU) across different biological DMARDs (bDMARDs) in patients with AS., Methods: A retrospective nationwide cohort study was conducted on 34 621 patients with AS without a previous history of AAU using a national claims database. Patients were followed-up from 2010 to 2021. The comparative risk of incident and recurrent AAU across different bDMARDs was examined using multivariable time-dependent Cox models and counting process (Anderson-Gill) models, respectively., Results: The adjusted hazard ratios (aHRs) and 95% CIs for incident AAU (bDMARDs non-exposure as reference) were: adalimumab 0.674 (0.581-0.891), etanercept 1.760 (1.540-2.012), golimumab 0.771 (0.620-0.959), infliximab 0.891 (0.741-1.071) and secukinumab 1.324 (0.794-2.209). Compared with adalimumab exposure, etanercept [aHR 2.553 (2.114-3.083)], infliximab [aHR 1.303 (1.039-1.634)] and secukinumab [aHR 2.173 (1.273-3.710)] exposures showed a higher risk of incident AAU. The aHRs and 95% CIs for recurrent AAU (bDMARDs non-exposure as reference) were: adalimumab 0.798 (0.659-0.968), etanercept 1.416 (1.185-1.693), golimumab 0.874 (0.645-1.185), infliximab 0.926 (0.729-1.177) and secukinumab 1.257 (0.670-2.359). Compared with adalimumab exposure, etanercept exposure [aHR 1.793 (1.403-2.292)] was associated with a higher risk of recurrent AAU., Conclusion: Our data suggest preference for bDMARDs in the following order: adalimumab/golimumab > infliximab > secukinumab > etanercept (for incident AAU prevention) and adalimumab > golimumab/infliximab/secukinumab > etanercept (for recurrent AAU prevention)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: The purpose of this review is to outline considerations for treating older adults with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) as it relates to infection, comorbidities, cancer, and quality of life., Recent Findings: The recent 2023 American College of Rheumatology/American College of Chest Physicians guideline conditionally recommended specific disease-modifying antirheumatic drugs (DMARDs), antifibrotics, and short-term glucocorticoids to treat RA-ILD. Since RA-ILD often affects older adults, we contextualize these pharmacologic options related to infection, gastrointestinal (GI) effects, cancer, cardiovascular disease, and quality of life. Nearly all DMARDs and glucocorticoids are immunosuppressive and increase infection risk. Rituximab, mycophenolate, cyclophosphamide, and glucocorticoids may have particularly high infection risk. Many therapies recommended for treating RA-ILD have potential GI side effects. Antifibrotics have a high rate of nausea and diarrhea. Janus kinase inhibitors may increase risk of cancer and cardiovascular disease in older people. In older individuals, decisions must weigh the risks and benefits of drug options while considering clinical and social factors such as polypharmacy, adherence, cost, convenience, and social support. Management of RA-ILD in older individuals is complex and should consider risks and benefits, while optimizing quality and quantity of life through a shared decision-making process., Competing Interests: Declarations. Funding: Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR080659, R01 AR077607, P30 AR070253, and P30 AR072577), National Heart, Lung, and Blood Institutes (grant number R01 HL155522), the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award funded by the Gordon and Llura Gund Foundation. Conflict of interest: J.A.S. has received research support from Boehringer Ingelheim, Bristol Myers Squibb, Janssen, and Sonoma Biotherapeutics unrelated to this work. He has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Johnson & Johnson, Merck, MustangBio, Optum, Pfizer, ReCor, Sana, Sobi, and UCB unrelated to this work. The funders had no role in the decision to publish or preparation of this manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard University, its affiliated academic health care centers, or the National Institutes of Health. All other authors report no conflicts of interest. Consent to participate: Not applicable; we did not prospectively enroll participants for this narrative review. Consent for publication: Not applicable; no patient data were obtained for this narrative review. Code availability: Not applicable; no statistical analyses were performed for this narrative review. Availability for data and material: Not applicable; no data or material were collected for this narrative review. Ethics approval: Not applicable; no ethics approval was required for this narrative review., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Tumor necrosis factor inhibitors (TNFi) are known to increase the risk of tuberculosis (TB) reactivation, though cases involving Mycobacterium bovis are rarely reported., Case Presentation/results: We describe a case of disseminated TB with M. bovis in a 78-year-old woman with a negative Interferon-Gamma-Release Assay (IGRA), taking adalimumab due to rheumatoid polyarthritis, which resulted in a fatal outcome. The atypical clinical and histopathological features were initially interpreted as sarcoidosis. The case occurred in Switzerland, an officially bovine tuberculosis-free country. The whole genome sequence of the patient's cultured M. bovis isolate was identified as belonging to the animal lineage La1.2, the main genotype in continental Europe, but showed significant genetic distance from previously sequenced Swiss cattle strains. In a literature review, four cases of bovine tuberculosis reactivation under TNFi treatment were identified, with pulmonal, oral and intestinal manifestations. Similar to our patient, two cases presented a negative IGRA before TNFi initiation, which later converted to positive upon symptomatic presentation of M. bovis infection., Conclusion: This case highlights the diagnostic challenges of TB in immunosuppressed patients, the limited sensitivity of IGRA, and the importance of considering TB reactivation even in regions declared free of bovine tuberculosis. Detailed patient histories, including potential exposure to unpasteurized dairy products, are essential for guiding preventive TB treatment before TNFi initiation., Competing Interests: Declarations. Ethical approval: Informed consent for participation in this case report was obtained from the patient’s close family members by the authors. Informed consent: Informed consent to publish this case report was obtained by the authors from the patient’s close family members. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Methotrexate (MTX) is a common medication used to treat rheumatoid arthritis (RA). MTX inhibits rapid cell turnover throughout the body which can lead to significant side effects. Patients who present with oral lesions may have suffered severe acute toxicity from MTX. Supportive pain treatment includes magic mouthwash solution and/or oral viscous lidocaine to manage pain and allow for healing. We report a case of MTX induced oral mucositis that did not respond to magic mouthwash but did improve with a morphine mouthwash solution. Case: A 67-year-old female with RA presented with worsening oral lesions over 2 weeks. She reported non-compliance with folic acid for 2 weeks while on MTX. Physical exam revealed ulcerating oral lesions on the mucous membranes consistent with mucositis. Pain treatment was initiated with magic mouthwash, but her pain was not well controlled after 24 hours, and still unable to swallow. An oral morphine mouthwash solution was initiated, and patient reported improved pain control over the next 48 hours. She was on the morphine mouthwash for 6 days during which improvement in the lesions was noted. Discussion: Pain management is imperative for oral mucositis. When traditional therapies do not provide adequate control, morphine mouthwash can be considered. It is a safer alternative to systemic opioids and topical opioids may influence cell proliferation and migration, which can positively impact healing of oral lesions. Conclusion: A morphine mouthwash solution can provide effective pain management for oral mucositis lesions in patients who do not respond adequately to magic mouthwash., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To examine how patients with rheumatoid arthritis (RA) perceive RA-related laboratory testing and the potential utility of a blood test to predict treatment response to a new RA medication., Methods: ArthritisPower members with RA were invited to participate in a cross-sectional survey on reasons for laboratory testing plus a choice-based conjoint analysis exercise to determine how patients value different attributes of a biomarker-based test to predict treatment response., Results: Most patients perceived that their doctors ordered laboratory tests to check for active inflammation (85.9%) or assess medication side effects (81.2%). The most commonly ordered blood tests used to monitor RA were complete blood counts, liver function tests, and those measuring C-reactive protein (CRP) and erythrocyte sedimentation rate. Patients felt CRP was most helpful in understanding their disease activity. Most worried their current RA medication would eventually stop working (91.4%) and they would waste time trying a new RA medication that may not work for them (81.7%). For patients who would require a future change in RA treatment, a majority (89.2%) reported that they would be very/extremely interested in a blood test that could help predict whether such new medication would be effective. Highly accurate test results (improving the chance RA medication will work from 50% to 85-95%) were more important to patients than low out-of-pocket cost (<$20) or minimal wait time (<7 days)., Conclusions: Patients consider RA-related blood work important for monitoring of inflammation and medication side effects. They worry about treatment effectiveness and would undergo testing to accurately predict treatment response., (© 2023 American College of Rheumatology.)

Background: Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease. Since it can lead to variable organ involvement, including life-threatening complications, and due to newly available therapeutic approaches, the German Society for Rheumatology and Clinical Immunology (Deutsche Gesellschaft für Rheumatologie und klinische Immunologie; DGRh) issued a newly developed S2e guideline in December 2022., Objective: This study aims to investigate the influence of the new guideline on the diagnosis, management, and outcomes of AOSD., Methods: Retrospective data from 168 patients diagnosed with AOSD between 2007 and 2023 (92 women and 76 men; average age 40.39 years) were captured at nine centers in Germany. Patient characteristics; results of laboratory, physical, and instrumental examinations; and therapeutic regimens were analyzed at three different timepoints., Results: After publication of the German AOSD guideline, the time to diagnosis was shorter (mean before: 18.56 months, mean after: 1.29 months) and fewer complications were recorded, especially with respect to macrophage activation syndrome. Although therapeutic approaches did not change over time, treatment side effects were lower in the recent observation periods. Of note, more patients have been diagnosed with cardiac (19% to 23.1%) and pulmonary (13.8% to 23.1%) manifestations of AOSD in recent years., Conclusion: The new AOSD guideline has contributed to increased disease awareness, with earlier diagnosis and identification of extra-articular organ manifestations. Treatment side effects were less frequent, especially those related to glucocorticoids. However, there is still a need to further improve the management of AOSD., Competing Interests: Declarations. Conflict of interest: R. Friedrich declares that there is no conflict of interest. The study was funded by a DGRh scholarship (Maja-Völkel-Promotionsstipendium). A. Kernder received consulting/speaker fees from Chugai Pharma and Novartis. E. Feist received consulting/speaker fees from Abbvie, BMS, Celgene, Galapagos, Lilly, Medac, Novartis, Roche, Sanofi, Sobi, Pfizer, and UCB. S. Vordenbäumen received speaker fees from Sobi. J. Henes received consulting/speaker fees from Abbvie, BMS, GSK, Novartis, Roche, Sobi, Pfizer, and UCB. J. Rech received consulting/speaker fees from Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, and UCB and a scientific grant from Novartis and Sobi. M. Krusche received consulting/speaker fees from Abbvie, BMS, Pfizer, Alphasigma, Lilly, Medac, Novartis, Roche, Sanofi, and Sobi. N. Blank, D. Ernst, G. Keyßer, P. Klemm, A. Meinecke, N. Schulz, and D. Schomburg declare that they have no competing interests. All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The prevalence of Pneumocystis jirovecii (PJ) pneumonia among rheumatic patients is rising. PJ colonization serves as a reservoir for transmission and precedes the development of PJ pneumonia. We aim to clarify the association of PJ colonization in patients of rheumatoid arthritis (RA) treated with biologics or Janus kinase inhibitors (JAKi)., Methods: A prospective cohort study was performed from March 2021 to July 2022 in the rheumatology outpatient department of National Cheng Kung University Hospital. We obtained oral-wash samples from asymptomatic RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and JAKi. A real-time quantitative polymerase chain reaction assay focusing on the mitochondrial large subunit ribosomal ribonucleic acid gene of PJ was applied to detect colonization., Results: One hundred and ten RA patients were enrolled. Adjusted odds ratios (ORs) of PJ colonization were 6.40 (95% CI 1.34-30.57, p-value =0.02) in patients receiving bDMARDs or JAKi. Specifically, in patients treated with bDMARDs the adjusted OR was 8.08 (95% CI 1.57-41.51, p-value=0.012), and a trend toward developing PJ colonization was further identified in patients receiving JAKi (adjusted OR: 4.79, 95% CI 0.89-25.91, p=0.069). Among patients treated with bDMARDs or JAKi, medication duration >3 years and age >60 y/o are risk factors for PJ colonization., Conclusion: RA patients on bDMARDs or JAK inhibitors have an approximately 6-fold higher risk of developing P. jirovecii colonization. Patients treated with bDMARDs had an 8-fold higher risk of P. jirovecii colonization. Risk factors of PJ colonization are medication duration >3 years and age > 60 y/o., Competing Interests: Declaration of competing interest All authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To evaluate the incidence and characteristics of severe infections in rheumatic patients receiving biologic disease-modifying anti-rheumatic drugs (bDMARDs) after kidney transplantation., Methods: This multicenter, retrospective study included 38 patients who had undergone kidney transplantation and received bDMARDs for rheumatic diseases. Demographic, clinical, and treatment data were collected. Severe infections were defined as those requiring hospitalization, and the incidence of severe infections was calculated per 100 patient years. Risk factors for severe infections were analyzed., Results: Of the 38 patients (median age 40.5 years), 52.6% experienced severe infections, with a total of 39 severe infection episodes. The incidence of severe infections was 26.2 per 100 patient-years. The most common infections were urinary tract infections (43.5%) and pneumonia (30.8%). Familial Mediterranean Fever (FMF) was the most common rheumatic disease (57.9%), and the median disease duration was 18.5 years. Most patients (68.4%) were using IL-1 inhibitors, and 31.6% were on anti-TNF therapy. There was no significant difference between patients with and without infections in terms of gender, pre-transplant biological therapy use, or type of biological therapy used. Four patients (11%) died from infection-related complications, including coronavirus disease-19 (COVID-19)., Conclusion: Rheumatic patients receiving bDMARDs post-kidney transplantation have a high risk of severe infections. The concurrent use of immunosuppressive therapy and bDMARDs may further increase this risk, necessitating close infection monitoring and management. Key Points • Rheumatic patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) following kidney transplantation face a heightened risk of severe infections. • The concurrent use of immunosuppressive therapy and bDMARDs may further increase this risk. • Individualized treatment strategies are essential to balance the benefits of bDMARDs with the potential for severe infectious complications., Competing Interests: Declarations. Authors’ declaration: The authors declare that the submitted work is their own and that copyright has not been breached in seeking its publication. They confirm that the article is an original work, has not been published before, and is not being considered for publication elsewhere in its final form, in either printed or electronic media. Competing interest: The authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: We investigated the effectiveness and safety of very-low-dose (<5 mg/day) glucocorticoids (GCs) in patients with RA treated with biologic and targeted synthetic DMARDs (b/tsDMARDs)., Methods: In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very-low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very-low-dose GCs on safety was also evaluated., Results: We enrolled 229 RA patients, of whom 68% were prescribed very-low-dose GCs and 32% received no GCs. After 3 years on b/tsDMARDs, 32% had never abandoned, 20% had gone on and off and 23% had permanently discontinued very-low-dose GCs, while 25% had never taken GCs. Shorter disease duration at b/tsDMARD initiation was the single modifiable predictor of very-low-dose GC cessation [odds ratio 1.1 (95% CI 1.03, 1.14) for any 1-year decrease; P = 0.001]. A significant association existed between ongoing utilization of very-low-dose GCs and persistent moderate disease activity. Use of very-low-dose GCs was associated with hypertension (20% vs 11%) and myocardial infarction (2.3% vs 0%)., Conclusion: A substantial proportion of RA patients treated with b/tsDMARDs continue to receive very-low-dose GCs without significantly improving disease control. However, this appears to increase cardiovascular morbidity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: No meta-analysis has holistically analyzed and summarized the efficacy and safety of tocilizumab in polymyalgia rheumatica (PMR). We undertook this meta-analysis to address this knowledge-gap., Methods: Electronic databases were searched for RCTs involving patients living with PMR receiving tocilizumab in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate percentage of patients able to achieve C-reactive protein PMR assessment score (CRP-PMR-AS) < 10 or prednisolone dose < 5 mg/day or > 10 mg/dL decline in prednisolone from baseline. Secondary outcomes were to determine percentage of patients able to totally stop prednisolone and adverse-events., Results: From initially screened 115 articles, data from 2 RCTs (136 patients) was analyzed. In addition, a descriptive analysis of 8 observational studies (356 patients) was also done. After 24-weeks of clinical use, patients with PMR receiving tocilizumab had significantly higher chances of achieving composite primary end-point defined as CRP-PMR-AS < 10 and either prednisone dosage < 5 mg/day or decrease in prednisolone dosage by > 10 mg/day compared to baseline [odds ratio (OR) 4.89 (95% CI: 2.34-10.23); p < 0.001; I 2  = 0%], compared to placebo. Patients with PMR receiving tocilizumab also had significantly higher chances of being able to stop prednisolone compared to placebo [OR 4.45 (95% CI: 2.06-9.61); p < 0.001; I 2  = 0%]. Occurrence of total adverse-events [risk ratio (RR) 1.24 (95% CI: 0.50-3.12); p = 0.64; I 2  = 0%], adverse-events leading to treatment discontinuation [RR 0.45 (95% CI: 0.10-2.02); p = 0.29; I 2  = 17%], and infections [RR 1.71 (95% CI: 0.83-3.52); p = 0.14; I 2  = 6%] were comparable in patients receiving tocilizumab as compared to placebo. Observational studies have noted lung infections, neutropenia and increased cholesterol with tocilizumab use., Conclusion: Tocilizumab is well tolerated and is effective for managing PMR. Tocilizumab is an effective glucocorticoid sparing agent in PMR., (© 2025 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Notwithstanding progress in conventional medicine (CM), the management of rheumatoid arthritis (RA) continues to be problematic due to factors such as limited patient response to treatment and restricted medication access. This study aimed to evaluate the extent to which East Asian herbal medicine with CM combination therapy (EACM) provides additional benefits in effectiveness and safety., Methods: We conducted a comprehensive search across 11 databases in English, Chinese, Korean, and Japanese for randomized controlled trials. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the American College of Rheumatology (ACR) 20/50/70 Response Criteria and the incidence of adverse events (AEI) as primary outcomes. This meta-analysis was performed using a random-effects model. The quality of each study was assessed according to the RoB 2. Of the 1036 full-text articles screened, 415 were included in the review., Results: This review included data from 37,839 participants. EACM was associated with higher ACR responses: ACR 20 (RR: 1.2332; 95 % CI: 1.1852-1.2831, p < 0.0001), ACR 50 (RR: 1.3782; 95 % CI: 1.2936-1.4684, p < 0.0001), and ACR 70 (RR: 1.7084; 95 % CI: 1.5555-1.8762, p < 0.0001), as well as a favorable AEI (OR: 0.3977; 95 % CI: 0.3476-0.4551, p < 0.0001), indicating both better efficacy and safety compared to CM alone. These patterns were consistent across eight secondary outcomes measuring pain, inflammation, and disease activity in RA. Subgroup analyses showed that EACM's effects were independent of the control CM type. Through a comprehensive analysis of a polyherbal prescription dataset, we identified 18 key herbs and 16 significant combination rules, further supported by relevant preclinical evidence. These herbs and synergistic herbal combinations were anticipated to be the most pharmacologically influential in contributing to the meta-analysis outcomes, as substantiated by analytical metrics including network topology and intricate association pattern evaluations., Conclusions: The findings suggest that EACM may serve as a valuable complementary strategy for RA patients insufficiently managed by CM alone. In particular, given that the ACR index integrates multiple aspects of RA patients, the results are expected to provide valuable complementary decision support for the management of RA patients who do not respond well to CM therapy, both for medical and economic reasons. Additionally, the key herbs derived through the multifaceted analysis, which actively reflect clinicians' implicit preferences for prescribing EACMs, may serve as important hypotheses for further research and clinical application. However, additional qualitative and quantitative improvements in research are needed for more definitive conclusions. Further analysis of the herbal prescriptions presented in this study will provide valuable direction for future research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Our goal was to assess the efficacy and safety of intravenous (IV) secukinumab for the treatment of adults with active axial spondyloarthritis (axSpA) in INVIGORATE-1., Methods: INVIGORATE-1 (NCT04156620) was a randomized, double-blind, parallel-group, phase 3 trial in patients with active axSpA (either radiographic or nonradiographic). Patients were randomized one to one to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every four weeks) or IV placebo for 16 weeks. After week 16, patients randomized to placebo were switched to IV secukinumab (3 mg/kg every four weeks), and patients randomized to secukinumab continued treatment through week 52. The primary endpoint was the Assessment of SpondyloArthritis International Society (ASAS40) response at week 16. Safety was evaluated through week 60., Results: Among patients initially randomized to IV secukinumab (n = 264) or placebo (n = 262), 86.0% and 88.9% completed the entire 60-week study period, respectively. A higher proportion of patients receiving secukinumab versus placebo met the primary endpoint (ASAS40 response) at week 16 (40.9% vs 22.9%; P < 0.0001). By week 24, patients who switched from placebo to secukinumab at week 16 achieved ASAS40 response rates comparable to those in patients originally randomized to secukinumab. All secondary efficacy endpoints were met at week 16, and responses were sustained through week 52. No new or unexpected safety signals were observed with IV secukinumab., Conclusion: IV secukinumab was effective for the treatment of adults with active axSpA over 52 weeks. The safety profile was consistent with that in previous reports on subcutaneous secukinumab., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

On October 6, 2023, the US Food and Drug Administration (FDA) approved an intravenous (IV) formulation and dosage of Cosentyx® (secukinumab), for the treatment of adult patients with active psoriatic arthritis (PsA), active ankylosing spondylitis (AS), and active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation. Clinical pharmacokinetics (PK), efficacy, and short-term placebo-controlled safety data were available from clinical studies (NCT04156620 and NCT04209205) with the to-be-marketed IV formulation using a maintenance dosage 3 mg/kg every 4 weeks (q4w), which was different from the dose approved (1.75 mg/kg q4w). The IV dosage of 3 mg/kg utilized in these two trials resulted in exposures (C max,ss ) significantly higher than those for the approved subcutaneous (SC) regimens. Further, there is limited long-term safety information available for this 3 mg/kg q4w IV dose. To address this important limitation, a model-informed drug development (MIDD) approach was employed to leverage available clinical PK, efficacy, and safety data from the secukinumab development program to identify a maintenance IV dosing regimen, 1.75 mg/kg IV q4w, that better approximated the relevant SC secukinumab exposures for which efficacy and safety have been established. The MIDD analyses were used to support approval of this IV dosing regimen not directly studied in the indications sought for licensure, PsA, AS, and nr-AxSpA., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Objective: Assess long-term safety, tolerability and efficacy of bimekizumab in ankylosing spondylitis (radiographic axial spondyloarthritis (r-axSpA))., Methods: Patients with active r-axSpA completing the dose-ranging 48-week randomised controlled trial could enrol in the open-label extension, where patients received bimekizumab 160 mg every 4 weeks. Safety (exposure-adjusted incidence rates/100 patient-years (EAIRs)) and efficacy outcomes (binary: non-responder imputation (NRI) and observed case (OC); continuous: multiple imputation (MI)) are presented through 256 weeks., Results: From Weeks 0-256, 289/303 (95.4%) patients had ≥1 treatment-emergent adverse event (TEAE); most frequent were nasopharyngitis (21.8%) and upper respiratory tract infection (14.5%). The EAIR of fungal infections was 7.4 ( Candida infections: 2.6; oral candidiasis: 2.2); none systemic. EAIR of serious infections was 1.4; no active tuberculosis was reported. Active inflammatory bowel disease and anterior uveitis EAIRs were 0.8 and 0.7, respectively. 202/303 (66.7%) patients completed Week 256. 42 (13.9%) patients discontinued treatment due to TEAEs.Efficacy at Week 48 was maintained for 5 years. At Week 256, NRI analysis showed 49.7% (OC: 73.1%) and 41.6% (OC: 71.1%) of patients achieved Assessment of SpondyloArthritis International Society 40% (ASAS40) response and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity, respectively. Mean (SE; MI) ASDAS improved from 3.9 (0.1) at baseline to 2.1 (0.1) at Week 48, which was maintained to Week 256. Improvements in pain, fatigue, physical function and health-related quality of life were sustained., Conclusions: The safety profile of bimekizumab after 5 years of treatment remained consistent with previous reports, with no new safety signals identified. 5-year efficacy was sustained in this r-axSpA population following robust disease control achieved at Week 48., Trial Registration Numbers: NCT02963506; NCT03355573., Competing Interests: Competing interests: AD: Speakers bureau for Eli Lilly, Janssen, Novartis, Pfizer and UCB; consultant for BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB; grant/research support from BMS, Celgene, Eli Lilly, Novartis, Pfizer, and UCB; VNC: Speakers bureau for AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer, and UCB; consultant for AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer, and UCB; grant/research support from AbbVie and Novartis; DP: Speaker for AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, and UCB; consultant for AbbVie, Biocad, Eli Lilly, Gilead, GSK, MSD, MoonLake, Novartis, Pfizer, Samsung Bioepis, and UCB; grant/research support from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer; LSG: Grants from Novartis and UCB paid to institution; consulting fees from AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, and UCB; SR: Grants from AbbVie, Galapagos, MSD, Novartis, Pfizer, and UCB; consulting fees from AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, Sanofi, and UCB; TT: Consulting fees from AbbVie, Eli Lilly, Gilead, Novartis, and Pfizer; speaker fees from AbbVie, Astellas, BMS, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis, and Pfizer; HMO: Research grants from Janssen, Novartis, Pfizer and UCB; speaking honoraria and/or consulting fees from AbbVie, Amgen, Biogen, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, Takeda, and UCB; HMO is supported by the NIHR Leeds Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the UK National Health Service (NHS), the NIHR, or the UK Department of Health; DvdH: Consulting fees from AbbVie, Argenx, Bayer, BMS, Galapagos, Gilead, GSK, Janssen, Eli Lilly, Novartis, Pfizer, Takeda, and UCB, and is the director of Imaging Rheumatology BV; CF, TV: Employees and shareholders of UCB; UM, NdP: Employees of UCB; XB: Speaker, paid instructor, and consultant for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Novartis, Pfizer, and UCB; speaker and paid instructor for MSD; consultant for Gilead; grant/research support from Novartis and UCB., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objectives: DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials., Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol. Patients received filgotinib 200 mg/day, except 15 men who received filgotinib 100 mg/day. The primary endpoints were safety and tolerability, which were assessed by the incidence of treatment-emergent adverse events (TEAEs). Safety and efficacy analyses included all enrolled patients who received ≥1 dose of filgotinib in DARWIN 3., Results: 739 patients entered the LTE. The total patient-years of exposure (PYE) to filgotinib was 3706.3 years; the mean exposure duration was 259.8 weeks. 497 patients (67.3%) discontinued prematurely (including 266 TEAEs and 172 withdrawals due to the patient's decision or 'sponsor request'). Overall exposure-adjusted incidence rate (EAIR) was 67 (95% CI 62 to 72.2)/100 PYE for TEAEs and 3.8 (95% CI 3.2 to 4.5)/100 PYE for serious TEAEs. EAIR of infections was 23.3 (95% CI 21.2 to 25.6)/100 PYE, 1.3 (95% CI 0.9 to 1.7)/100 PYE for serious infections and 1.3 (95% CI 0.9 to 1.7)/100 PYE for herpes zoster. EAIRs of major adverse cardiovascular events (0.19 (95% CI 0.8 to 0.39)/100 PYE) and malignancies (0.6 (95% CI 0.4 to 0.9)/100 PYE) were low. Disease response assessed using non-responder imputation plateaued at LTE week 12 before slowly declining over time, with overall American College of Rheumatology (ACR)20/50/70 response rates of 26.9%/20.2%/14.7% at week 396., Conclusion: Filgotinib was well tolerated in patients with RA for up to 8 years. Safety and efficacy profiles were maintained in patients previously receiving either filgotinib plus methotrexate or filgotinib monotherapy., Competing Interests: Competing interests: RW reports consultancy fees and speaker fees from Celltrion, Galapagos and Gilead. KLW reports consultancy fees from AbbVie, AstraZeneca, BMS, Galapagos, Gilead, GSK, Lilly, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB; and grant/research support from BMS and Pfizer. AK reports consultancy fees from Amgen, AbbVie, BMS, Janssen, Novartis, Pfizer and UCB. MG reports grant/research support from AbbVie, Aclaris, Galapagos, Janssen, Lilly and Nimbus. LD reports consultancy fees from AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, BMS, Celltrion, Galapagos, GSK, Janssen, Kiniksa Pharmaceuticals, Lilly, Novartis, Pfizer, Roche, Sanofi-Genzyme, Sobi and Takeda; and grant/research support from AbbVie, BMS, Celgene, GSK, Janssen, Kiniksa Pharmaceuticals, MSD, Mundipharma, Novartis, Pfizer, Roche, Sanofi-Genzyme and Sobi. RC none declared. RB and DdV were employees of, and shareholders in, Galapagos at the time of the study. VM is an employee of, and shareholder in, Galapagos. LHL is an employee of Alfasigma S.p.A. MCG was an employee of, and shareholder in, Gilead at the time of the analysis. PE reports consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Galapagos, Gilead, Lilly and Novartis; speaker fees from AbbVie, BMS, Boehringer Ingelheim, Galapagos, Gilead, Lilly, Novartis and Samsung; and grant/research support from AbbVie, BMS, Lilly, Novartis, Roche and Samsung. PV reports consultancy fees from Alfasigma S.p.A., Boehringer Ingelheim, Cytryl, Galapagos, Lilly, Pfizer and Sidekick Health; speaker fees from AbbVie, Galapagos, Lilly, Medicongress and Roularta; and grant/research support from Galapagos and Pfizer. RA reports consultancy fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, UCB and Viatris., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and haemophagocytic lymphohistiocytosis (HLH) are rare but severe immune-mediated diseases with overlapping clinical manifestations. We present a case of a woman in her late 40s with rheumatoid arthritis who developed DRESS/HLH overlap syndrome after starting hydroxychloroquine and leflunomide therapy. Despite corticosteroid treatment, her condition worsened, necessitating etoposide therapy. The persistent pancytopenia required supportive measures, including transfusions of blood products and administration of growth factors. Tofacitinib was successfully used as a steroid-sparing agent and resulted in the resolution of symptoms without relapse during a 2 month follow-up. This case emphasises the diagnostic and therapeutic challenges posed by the co-occurrence of DRESS and HLH and highlights the importance of tailoring treatment strategies to achieve good outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objective: To compare work loss after starting tumour necrosis factor inhibitors (TNFi), rituximab, abatacept or tocilizumab in patients with rheumatoid arthritis (RA)., Methods: We used data from the Swedish Rheumatology Quality Register to identify patients aged 19-62 years who were treated with TNFi (n=15 093), rituximab (n=2123), abatacept (n=1877) or tocilizumab (n=1720) between 2007 and 2020. Data on work loss (0-365 days per year) from sick leave and disability pension were retrieved from linkage to the Social Insurance Agency. Patients in the different treatment arms were balanced regarding baseline covariates using inverse probability weighting (IPTW)., Results: Work loss increased for patients with RA until drug treatment initiation, reached a peak in the month after treatment initiation and then levelled off. Following IPTW, at 3 years before starting the treatment, there were no statistically significant differences in the mean annual adjusted work loss days between rituximab, abatacept or tocilizumab vs TNFi (mean difference vs TNFi: rituximab 1.1 days, 95% CI -4.5 to 6.7; abatacept 3.3, 95% CI -2.6 to 9.2; tocilizumab 1.2, 95% CI -4.9 to 7.3). At 3 years after starting the treatment (latest January 2021), there were also no statistically significant differences in the mean annual adjusted work loss days (mean difference: rituximab -4.8 days, 95% CI -11.3 to 1.7; abatacept 5.3, 95% CI -1.8 to 12.3; tocilizumab -0.6, 95% CI -7.7 to 6.5)., Conclusions: Taking channelling into account, patients with RA treated with TNFi, rituximab, abatacept or tocilizumab had similar trajectories of work loss from sick leave and disability pension until treatment initiation, and similar trend breaks and plateau 3 years thereafter., Competing Interests: Competing interests: ‘C.T. has received consulting fees from Abbvie and Boehringer-Ingelheim, and speaker fees from Abbvie, Bristol-Myers Squibb, Nordic Drugs, Pfizer, and Roche. J.A. has acted as principal investigator in agreements between Karolinska Institutet and the following entities, mainly for the safety monitoring of rheumatology immunomodulators via the national ARTIS programme: Abbvie, BMS, Eli Lilly, Janssen, Merck, Pfizer, Roche, Samsung Bioepis, and Sanofi.‘, (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Background: Adalimumab is an effective treatment for juvenile idiopathic arthritis-associated uveitis. Data are scarce on the effects of discontinuing adalimumab after control of the disease had been reached. We aimed to assess efficacy and safety of discontinuing treatment in patients with juvenile idiopathic arthritis-associated uveitis., Methods: We conducted a multicentre, double-masked, randomised, placebo-controlled trial at 20 ophthalmology and rheumatology clinics across the USA, the UK, and Australia. Patients aged at least 2 years who had controlled arthritis and uveitis for at least 1 year on adalimumab were randomly assigned in a 1:1 ratio using a web-based system to receive adalimumab or placebo, administered subcutaneously every 2 weeks until the 48-week visit or treatment failure. The primary outcome was the time to treatment failure, defined by recurrence of uveitis or arthritis; all participants were included in the primary and safety analysis. Unmasking occurred at treatment failure, and patients were offered open-label adalimumab through 48 weeks of follow-up. This trial was registered with ClinicalTrials.gov (NCT03816397)., Findings: 87 patients were enrolled from March 3, 2020, to Feb 14, 2024, whereafter the prespecified interim stopping criteria were met and enrolment was stopped. One patient in each group dropped out but data were included in analyses. Six (14%) of 43 patients in the adalimumab group and 30 (68%) of 44 patients in the placebo group had treatment failure (hazard ratio 8·7, 95% CI 3·6-21·2; p<0·0001). The median time to treatment failure in the placebo group was 119 days (IQR 84-243). The median time to re-establishing sustained control of inflammation in the placebo group after restarting adalimumab was 105 days (63-196). 226 non-serious adverse events occurred in the adalimumab group (7·5 events per person-year, 95% CI 6·5-8·5), and 115 non-serious adverse events occurred in the placebo group (6·8 events per person-year, 5·6-8·1). Four serious adverse events were reported, all in the adalimumab group., Interpretation: Discontinuing adalimumab led to higher rates of recurrence of uveitis, arthritis, or both in patients with previously controlled juvenile idiopathic arthritis-associated uveitis. However, all patients who had treatment failure successfully regained control of inflammation by the end of the 48-week study period after restarting adalimumab., Funding: US National Institutes of Health (National Eye Institute)., Competing Interests: Declaration of interests NRA declares receiving research funding from the National Eye Institute, under the National Institutes of Health, and a donation of study medication from AbbVie for the present study; consulting fees from Roche; and participation on an Advisory Board for the TURTLE trial. AVR declares speaker fees, honoraria, and consultancy work for AbbVie, Eli Lilly, Novartis, Roche, Swedish Orphan Biovitrum, AstraZeneca, and Union Chimique Belge; and participation on a Data Safety Monitoring Board or Advisory Board for Eli Lilly and AstraZeneca. CMG declares participation on a Data Safety Monitoring Board or Advisory Board for the TURTLE trial; and performs unpaid manuscript writing for the JUVE BRIGHT study sponsored by Eli Lilly. BFA declares receiving research funding from the National Eye Institute, under the National Institutes of Health; participation on a Data Safety Monitoring Board for the COAST Trial; and support for travel and accommodation expenses from the Bill & Melinda Gates Foundation. The University of California San Francisco Department of Ophthalmology is supported by a core grant from the National Eye Institute (EY06190) and an unrestricted grant from the Research to Prevent Blindness Foundation. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

This study investigated severity, course and patterns of fatigue surrounding subcutaneous biological disease-modifying antirheumatic drug (bDMARD) injection in inflammatory rheumatic disease (IRD) patients using ecological momentary assessments and investigated self-reported adverse drug reactions (ADRs). In this prospective cohort study, IRD patients completed fatigue severity numeric rating scales (0-10) in web-based ecological momentary assessments in three waves of five days surrounding bDMARD injection. The course of fatigue was measured by the change in fatigue from pre-dosing to post-dosing scores and was classified as: worsening, improving or no clinically relevant change. A pattern was defined as a course of worsening, improving or no clinically relevant change in fatigue in at least two out of three waves for patients completing assessments across all three waves. ADRs could be reported on day five of each wave. In total 609 participants completed ecological momentary assessments surrounding 1541 bDMARD injections. Overall average fatigue severity across all three waves was 4.5 (± SD 2.4) and 78% experienced severe fatigue in at least one assessment. Of 398 patients completing all three waves, 61% had no clinically relevant change in fatigue in at least two out of three waves, 13% had a pattern of worsening fatigue and 18% had a pattern of improving fatigue. Of 398 patients, 36% had a consistent pattern in all three waves. IRD patients using a bDMARD may consistently experience specific fatigue patterns surrounding bDMARD administration. These patterns provide insights for clinical practice and could be used to inform patients properly., Competing Interests: Declarations. Ethical approval: The Dutch Medical Research Committee of East Netherlands (METC Oost-Nederland) exempted ethical approval on May 3 2022 because this study was not subject to the Medical Research Involving Human Subjects Act (file number 2022–13752). This study was approved by the institutional review board of the Sint Maartenskliniek and all participants signed digital informed consent prior to participation. The study was conducted in accordance with the principles of the Declaration of Helsinki. Competing interests: JvL, JV, NJ, AdB, BvdB and VH have no conflicts of interest to declare., (© 2025. The Author(s).)

Objective: This systematic review and meta-analysis assess the efficacy and safety of rituximab (RTX) in treating idiopathic inflammatory myositis (IIM)., Methods: PubMed and Embase were systematically searched for trials and observational studies involving RTX use in IIM. Data were analyzed using a random-effects model to generate pooled estimates for overall response, complete remission, partial response, and adverse events, with subgroup analyses by myositis type and RTX dosage (PROSPERO registered number CRD42022353740). Risk of bias assessments were done using the Newcastle-Ottawa Scale for observational studies and risk of bias 1 tool for trials., Results: Seventeen studies (1 randomized controlled trial and 16 observational studies), encompassing 362 patients, were included. The overall pooled response rate was 70% (95% confidence interval [CI]: 57%-82%; I2 = 74%, p < 0.001). Complete remission occurred in 13% (95% CI: 3%-25%; I2 = 79%, p < 0.001) and partial response in 48% (95% CI: 30%-67%; I2 = 87%, p < 0.001), both with significant heterogeneity. Subgroup analysis revealed high response rates across all myositis types: polymyositis 69%, dermatomyositis 67%, antisynthetase syndrome 70%, juvenile dermatomyositis 60%, and immune-mediated necrotizing myopathy 86%. Response rates were similar between RTX induction doses of 1 g IV on days 0 and 14 (68%) and 375 mg/m 2 weekly for 4 weeks (71%). Reported adverse events totaled 120, including infusion reactions (18.5%) and infections (12.4%)., Conclusions: RTX shows a favorable clinical response in IIM treatment, though response rates vary. There was a significant heterogeneity in treatment effect estimates that are based on a small number of patients. The incidence of infusion reactions and infections highlights the need for careful monitoring. Further controlled trials are essential to refine treatment protocols and evaluate long-term outcomes for RTX's role in IIM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA)., Methods: This population-based cohort study utilized Swedish nationwide registers and included all singleton births (2006-2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling ≥1 HCQ prescription during the first trimester. The outcome was infant MCM within 1 year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes and corticosteroids). Modified Poisson regression models with robust variance were used to estimate risk ratios (RR) and 95% CI., Results: We included 1007 births (453 exposed) and 2500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed and unexposed groups were 3.6%, 3.7% and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6% and 4.3%, respectively. The adjusted RRs (95% CI) were 1.29 (0.65, 2.56) in the SLE cohort, 1.32 (0.56, 3.13) in the RA cohort and 1.30 (0.76, 2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings., Conclusion: First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ's benefits may outweigh the risks in managing SLE or RA during pregnancy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Still's disease is a rare autoinflammatory disorder characterized by systemic inflammation, fever, rash and arthritis. The term 'Still's disease' covers the paediatric subtype systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which affects adults. Biologic drugs, including the anti-IL-1 agents anakinra, canakinumab and rilonacept and the IL-6 antagonist tocilizumab, are used in the management of Still's disease., Methods: We conducted a systematic review and network meta-analysis of randomized controlled trials, and the study protocol was registered in PROSPERO (CRD42023450442). MEDLINE, EMBASE and CENTRAL were screened from inception until 17 September 2023. We included patients with Still's disease who received placebo or biologic drugs: anakinra, canakinumab, rilonacept or tocilizumab. The primary efficacy and safety outcomes were achievement of ACR50 response and occurrence of serious adverse events, respectively. The interventions were ranked using rankograms and SUCRA values., Results: Nine trials with 430 patients were included. All biologic drugs were associated with greater odds of ACR50 response compared with placebo. There was no statistically significant association between biologic drugs and serious adverse events. The multivariate meta-analysis found no difference between biologic drugs. As per SUCRA rankings, anakinra was the most effective and safe option with respect to ACR50 response and occurrence of serious adverse events., Conclusion: This is the first systematic review and meta-analysis to assess the efficacy and safety of biologic drugs in paediatric and adult patients with Still's disease. Biologic drugs were effective in achieving ACR response and demonstrated a low adverse event profile in the management of Still's disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

About 25-50% of patients with primary Sjögren's disease (SjD) take hydroxychloroquine (HCQ). Although it is widely prescribed, and recommended in international guidelines, its use is mostly based on expert opinion and personal experience. Our aim was to provide a comprehensive overview of the pathogenic mechanisms of HCQ, the current clinical evidence for its use, and its safety in primary SjD. HCQ plays an immunomodulatory and anti-inflammatory role, mainly by regulating some interferon proteins, chemokines, BAFF levels, and by modifying gut microbiota. It decreases immunoglobulins and ESR levels. In a Latin-American cohort, the main indications were arthritis, parotid gland enlargement and sicca-only symptoms. In the clinical setting, most studies showing a positive effect of HQC are open trials or retrospective cohorts. Some of these studies may be biased due to the use of non-validated outcomes, and a placebo response effect. To date, only 3 RCTs have investigated the benefits of HCQ, the JOQUER being the pivotal one. This study failed to improve oral/ocular symptoms or ESSDAI score. However, a re-analysis by symptomatology subgroups detected some differences in the ESSPRI. Recently, promising data from a small phase II RCT of the combination of HCQ/leflunomide was reported, but results should be replicated. Currently, the NECESSITY study is investigating treatment combinations that will provide new insights. In the meantime, HCQ plays a central role in the treatment of SjD due to its excellent benefit-risk profile. Data on damage accrual, quality of life, mortality and prevention of cardiovascular risks are also still lacking., (Copyright © 2024 Sociýtý Franýaise de Rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: This analysis reported the incidence of safety endpoints across five phase 3 randomized controlled clinical trials in patients with rheumatoid arthritis (RA), Crohn's disease (CD), and chronic plaque psoriasis (PsO) who received ≥ 1 dose of adalimumab-adbm or adalimumab reference product (RP)., Methods: Exposure-adjusted incidence rates for safety endpoints were calculated per 100 patient-years and reported by disease indication and treatment arm. Subgroup analyses by patient age and sex were also conducted., Results: The mean length of follow-up was 62 weeks, 48 weeks, and 32 weeks for patients with RA, CD, and PsO, respectively. Rates of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) were similar among patients with RA and PsO, but slightly higher among those with CD. Incidence rates of all safety endpoints were consistent between the adalimumab-adbm and adalimumab RP treatment arms within each indication Subgroup analyses of patients with RA, CD, and PsO showed no between-group differences by age and sex., Conclusions: In patients with RA, CD, and PsO, there were no differences between biosimilar adalimumab-adbm or the adalimumab RP regarding the rate of AEs, SAEs, discontinuations due to AEs, deaths, or any AEs of special interest.

Background: Monitoring biologic drug therapy during pregnancy in women with immune-mediated inflammatory diseases (IMIDs) is crucial to ensure treatments align with evidence-based practices., Research Design and Methods: A retrospective cohort study based on healthcare claims data from eight Italian regions was conducted, analyzing deliveries between 2009 and 2021. The study included women receiving biologic drugs within nine months before their last menstruation. Exposures to biologics, conventional disease-modifying anti-rheumatic drugs (DMARDs) and symptom-relieving medications were assessed in the trimesters (T) before, during and after pregnancy. Factors influencing biologic treatment persistence during pregnancy were analyzed., Results: A cohort of 1,763 deliveries was considered. Biologic drugs were prescribed for rheumatic (33.6%), dermatological (32.6%), and gastrointestinal diseases (28.4%). Biologic use declined during pregnancy (TI = 37.3%; TII = 17.6%; TIII = 11.3%), increasing again postpartum. During pregnancy, there was increased use of symptom-relieving medications for rheumatic diseases and DMARDs for gastrointestinal diseases. Factors associated with continued biologic treatment included being older than 35 years and the region of delivery., Conclusions: This study found a decrease in biologics drug use during pregnancy and highlights the necessity for personalized therapeutic approaches. Geographic variations in biologic drug use emphasize the need for educational initiatives about the risk-benefit profiles of these therapies during pregnancy.

Objectives: The usefulness of methotrexate-polyglutamates (MTX-PGs) concentration for management of rheumatoid arthritis has been debated. We aimed to clarify the association of MTX-PGs concentration with efficacy and safety in MTX-naïve patients initiating MTX in a prospective interventional clinical trial., Methods: The MIRACLE trial enrolled 300 MTX-naïve patients. Oral MTX was initiated and increased to the maximum tolerated dose by week 12. Patients who did not achieve remission according to the Simplified Disease Activity Index at week 24 were randomised to either the continued dose or reduced dose group and were started on subcutaneous adalimumab. We measured the concentrations of MTX-PGs in erythrocytes using liquid chromatography-tandem mass spectrometry and analysed the association of these concentrations with efficacy and safety., Results: The mean concentration of total MTX-PGs increased with an increasing dose of MTX and continued to elevate for another 12 weeks after the dose was fixed. At week 24, the total MTX-PGs concentration was 110.5 (SD 43.8) nmol/L with MTX dose of 12.6 (3.0) mg/week (0.23 (0.07) mg/kg/week). During MTX monotherapy, the higher MTX-PGs concentration was an independent factor for lower disease activity; however, this association disappeared after adalimumab initiation in patients with continued MTX dose. Hepatotoxicity was related to the higher MTX-PGs concentration regardless of adalimumab use. The total MTX-PGs concentration was significantly elevated by lower estimated glomerular filtration rate, serum albumin and body mass index., Conclusions: The MIRACLE trial demonstrated that higher total MTX-PGs concentration in erythrocytes is related to the higher efficacy and lower safety of MTX., Trial Registration Number: NCT03505008., (Copyright © 2024 European Alliance of Associations for Rheumatology (EULAR). Published by Elsevier B.V. All rights reserved.)

Objective: This study investigates the efficacy and safety of baricitinib, an oral targeted synthetic disease-modifying antirheumatic drugs (DMARDs), in patients with difficult-to-treat rheumatoid arthritis (D2T RA) compared to those without, aiming to determine its potential as an alternative treatment for D2T RA., Subject and Methods: A total of 78 patients participated in this retrospective cohort study, with 33 meeting the D2T RA criteria and 45 in the non-D2T RA group. Various clinical and laboratory parameters, adverse events, and disease activity indices were assessed, alongside drug efficacy and survival rates., Results: Patients with D2T RA exhibited higher seronegativity, prior use of b-DMARDs and c-DMARDs, and longer disease duration. Both groups experienced reductions in VAS and DAS28 scores, as well as SDAI, CDAI, HAQ, CRP, and ESR levels at baseline and 3, 6, and 12 months post-baricitinib initiation, with sustained efficacy observed over 12 months. The most prevalent adverse event was infection (28.21%). Although initial drug survival rates were similar between groups, the non-D2T RA group demonstrated higher rates at 24 months (46.70% vs. 59.40%). Subgroup analyses showed comparable survival rates between D2T RA and non-D2T RA groups, whether treated with baricitinib alone or in combination with methotrexate or leflunomide., Conclusion: Despite potential treatment resistance, patients meeting the D2T RA criteria shared similar safety and efficacy profiles with those non-D2T RA. Baricitinib emerges as a promising treatment option for D2T RA patients, offering effectiveness and safety comparable to the non-D2T RA group., Objective: This study investigates the efficacy and safety of baricitinib, an oral targeted synthetic disease-modifying antirheumatic drugs (DMARDs), in patients with difficult-to-treat rheumatoid arthritis (D2T RA) compared to those without, aiming to determine its potential as an alternative treatment for D2T RA., Subject and Methods: A total of 78 patients participated in this retrospective cohort study, with 33 meeting the D2T RA criteria and 45 in the non-D2T RA group. Various clinical and laboratory parameters, adverse events, and disease activity indices were assessed, alongside drug efficacy and survival rates., Results: Patients with D2T RA exhibited higher seronegativity, prior use of b-DMARDs and c-DMARDs, and longer disease duration. Both groups experienced reductions in VAS and DAS28 scores, as well as SDAI, CDAI, HAQ, CRP, and ESR levels at baseline and 3, 6, and 12 months post-baricitinib initiation, with sustained efficacy observed over 12 months. The most prevalent adverse event was infection (28.21%). Although initial drug survival rates were similar between groups, the non-D2T RA group demonstrated higher rates at 24 months (46.70% vs. 59.40%). Subgroup analyses showed comparable survival rates between D2T RA and non-D2T RA groups, whether treated with baricitinib alone or in combination with methotrexate or leflunomide., Conclusion: Despite potential treatment resistance, patients meeting the D2T RA criteria shared similar safety and efficacy profiles with those non-D2T RA. Baricitinib emerges as a promising treatment option for D2T RA patients, offering effectiveness and safety comparable to the non-D2T RA group., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Key Messages: What is known • Hydroxychloroquine (HCQ) is widely used for autoimmune disorders but is associated with the risk of retinal toxicity. • Early detection of retinal structural changes due to HCQ toxicity remains challenging, and cumulative HCQ dose as a risk factor has conflicting clinical relevance. What Is New • Higher cumulative HCQ doses are significantly associated with thinner outer retinal layers (foveal, parafoveal, and perifoveal regions). • No significant associations were found between HCQ cumulative dose and inner retinal thickness or age., Competing Interests: Declarations. Conflict of interest: None related to this manuscript., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aimed to evaluate the cost-effectiveness of introducing tofacitinib in second-line therapies after methotrexate failure for rheumatoid arthritis in France., Methods: Using a Markov model, we simulated a cohort of 10,000 patients based on literature data to compare various treatment strategies. The reference strategy included the four classes of biologics commonly used in France (TNFi, tocilizumab, abatacept, rituximab). The trial strategies additionally included tofacitinib at different introduction positions. The cycle duration was set at 6 months, and the time horizon was a lifetime. The data for severe adverse effects were sourced from the ORAL Surveillance study., Results: Compared to the reference strategy, introducing tofacitinib is a dominant strategy, regardless of its introduction position. Introducing it as the first-line treatment results in the greatest cost savings (€1,679 per patient) while increasing quality-adjusted life years (QALYs) by 0.29. According to the one-way sensitivity analysis, the discount rate and the cost of TNFi were the two variables that most influenced costs, while the change in HAQ score and the discount rate were the two variables that most influenced QALYs., Conclusions: Our study represents the first assessment of the cost-effectiveness of tofacitinib in France and incorporates the latest adverse effects reported in the literature. It reinforces previously obtained results from other countries. Our study has some limitations, mainly related to the use of data from clinical trials. Our analysis is limited to severe adverse effects, and their cost is extrapolated from the average hospitalisation cost. The estimated costs are therefore underestimated for chronic diseases such as cancer.

Aim: Uncontrolled chronic inflammatory diseases (CIDs) before, during, and after pregnancy, as well as some CID medications, can increase the risk of impaired fertility in addition to adverse maternal/pregnancy outcomes in women of childbearing age. We report pregnancy outcomes from prospectively reported pregnancies in Japanese women treated with certolizumab pegol (CZP)., Methods: Data from July 2001 to November 2020 on CZP-exposed pregnancies from the CZP Pharmacovigilance safety database were reviewed. Pregnancy outcomes analyzed included live birth, ectopic pregnancy, abortion (miscarriage or medically indicated/elective), and stillbirth. Congenital anomalies (major and minor), preterm delivery, and low birth weight were also examined., Results: Among 149 prospective pregnancies with maternal CZP exposure and known outcomes identified in Japanese women, 111/149 (74.5%) involved at least first-trimester exposure and 53/149 (35.6%) were exposed in all trimesters; 135/149 (90.6%) live births, 12/149 (8.1%) abortions (11 miscarriages, one elective termination), 2/149 (1.3%) stillbirths, no ectopic pregnancies reported. One (0.7%) infant, whose mother had first-trimester exposure, manifested a minor congenital anomaly (accessory auricle). There were no major congenital anomalies. Among live births, 3/135 (2.2%) were preterm and 10/135 (7.4%) had low birth weight., Conclusion: The safety profile of CZP in pregnant Japanese women was consistent with published global data., (© 2025 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: Patients with ankylosing spondylitis (AS) have a higher risk of cardiovascular events than controls. Although biological disease-modifying anti-rheumatic drugs (bDMARDs) are efficacious in treating AS, their effect on cardiovascular risk remains unclear. This study evaluated the effect of tumour necrosis factor inhibitors (TNFis) and interleukin-17 inhibitors (IL-17is) on cardiovascular risk in patients with AS., Methods: Data of 43,502 patients diagnosed with AS from 2010 onwards and without prior history of cardiovascular events were extracted from the Korean nationwide database. Cardiovascular events were defined as incident myocardial infarctions or strokes. Patients were followed-up through 2021. The risk of cardiovascular events was compared between TNFis exposure (vs. bDMARDs non-exposure), IL-17is exposure (vs. bDMARDs non-exposure), and IL-17is exposure (vs. TNFis exposure), using time-dependent Cox models., Results: The incidence rates of cardiovascular events during bDMARDs non-exposure, TNFis exposure, and IL-17is exposure were 18.66, 8.92, and 12.87 per 10,000 person-years, respectively. TNFis exposure (vs. bDMARDs non-exposure) was significantly associated with a lower risk of cardiovascular events (adjusted hazard ratio [aHR] = 0.697, 95% confidence interval [CI] = 0.499-0.973), whereas IL-17is exposure (vs. bDMARDs non-exposure) was not (aHR = 0.962, 95% CI = 0.134-6.920). The risk of cardiovascular events did not differ between IL-17is and TNFis exposures (aHR = 1.381, 95% CI = 0.189-10.087)., Conclusions: TNFis exposure (vs. bDMARDs non-exposure) was associated with approximately 30% lower risk of cardiovascular events in patients with AS. IL-17is exposure had no significant association with the risk of cardiovascular events compared with bDMARDs non-exposure or TNFis exposure. Key Points • TNFis exposure was associated with a 30% lower cardiovascular risk in patients with AS. • IL-17is exposure had no significant association with cardiovascular risk in patients with AS. • TNFis could be the preferred bDMARD with regard to cardiovascular risk in patients with AS., Competing Interests: Declarations. Disclosures: None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: Despite significant savings with biosimilars, their negative perception can lead to the occurrence of a nocebo effect (NE), therefore we aimed to quantify the NE in inflammatory rheumatism after switching from adalimumab or etanercept originators to biosimilars., Methods: This retrospective study was conducted in 4 hospitals in Normandy, France between January 2018 and July 2022. The study included patients with rheumatoid arthritis or spondyloarthritis in remission under adalimumab or etanercept originators before switching to biosimilars. The occurrence of a NE was considered in patients who did not maintain biosimilars at 12 months and who presented a subjective adverse event (AE). A comparative analysis of the quantitative data collected before and after switching was performed. The AE that led to biosimilar discontinuation was identified. Additional analyses were performed to identify potential risk factors for the occurrence of a NE., Results: Among 183 patients included,13.1% presented a NE. Objective AEs were observed, including rheumatism reactivation (15.3%), intolerance (8.2%), infection (1.6%) and allergic reactions (0.5%). Morning stiffness duration was significantly different before and after the switch in the spondyloarthritis group (p=0.01). No risk factors were associated with the occurrence of a NE within the limits of the studied parameters., Conclusions: The occurrence of a NE after switching to a biosimilar remains acceptable. It appears less frequent when the switch is supervised by the practitioner rather than being systematic (up to 33% in some countries). A shared medical decision seems to be essential in a subset of patients, which remains to be defined.

Introduction: Biosimilars are biologic medications designed to closely replicate the properties of previously approved biologic disease-modifying anti-rheumatic drugs (bDMARDs). They offer a cost-effective alternative once the original product's patent has expired., Areas Covered: In pediatric rheumatology, the use of biosimilars began in 2013 with the launch of the infliximab biosimilar. Since then, more biosimilars, including etanercept, rituximab, and adalimumab, have been introduced, providing additional treatment options for children with rheumatic diseases. This article explores the role of biosimilars in pediatric rheumatology, particularly in juvenile idiopathic arthritis, focusing on their development, safety, and efficacy, as well as the challenges associated with their clinical adoption. It also addresses the importance of education in improving understanding of biosimilars., Expert Opinion: The article provides insights into their safety, effectiveness, and economic impact by reviewing current literature to help healthcare professionals make informed decisions for treating pediatric rheumatic diseases. Education for both patients and healthcare providers, effective communication, and expectation management play a critical role in ensuring appropriate treatment continuity.

Importance: Immunocompromised status is a risk factor for severe SARS-CoV-2 infection. Little is known about how systemic corticosteroid dose and concurrent use of immunosuppressants are associated with COVID-19 outcomes., Objective: To assess the association between corticosteroid dose/duration and concurrent immunosuppressant use on COVID-19 hospitalisation and death in the era of COVID-19 vaccinations., Design: This is a retrospective cohort study using a deidentified insurance claims database from 1 July 2020 to 30 June 30, 2022, with the risk period starting on 1 July 2021. Impact of corticosteroid exposures and concurrent use of other immunosuppressants was assessed with attributable risk analysis and Cox regression that included COVID-19 vaccination status and time-updated dichotomous immunosuppressive medication exposures., Participants: There were 10 109 596 eligible patients enrolled during the risk period, each with at least 365 days of continuous enrolment prior to 1 July 2021., Exposures: Systemic corticosteroids, disease-modifying antirheumatic drugs (DMARDs), tumour necrosis factor-alpha inhibitors (TNFis) and other immunosuppressive drug categories., Main Outcomes: Incidence rate ratios and hazard ratios for COVID-19 hospitalisation and death., Results: Corticosteroids were prescribed to 1 379 049 (13.6%) of 10 109 596 individuals. After adjustment, corticosteroids were associated with an increased risk of COVID-19 hospitalisation (HR: 5.40; 95% CI 5.27 to 5.53; p<0.0001) and death (HR: 5.90; 95% CI 5.59 to 6.22; p<0.0001). Among individuals exposed to corticosteroids without a record of COVID-19 vaccination, risks for COVID-19 hospitalisation and death were increased by 3- and 14.5-fold. The population attributable risk of corticosteroid use for COVID-19 hospitalisations was 13.9% (95% CI 13.5 to 14.3%). There was a significantly increased risk of COVID-19 hospitalisation associated with the use of corticosteroids plus DMARDs (HR: 1.55; 95% CI 1.42 to 1.70; p<0.0001) or plus TNFis (HR: 1.60; 95% CI 1.15 to 2.22; p=0.005)., Conclusions: Corticosteroids are associated with greater risk of COVID-19 hospitalisation and death, especially among unvaccinated individuals. Concurrent use of DMARDs and TNFis with corticosteroids confers greater risk., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organization for the submitted work; Dr Acharya: AbbVie (drug donation for NIH-funded trial), Roche (consultant); Dr Arnold: none declared; Dr Sechrist: none declared; Tang: none declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objectives: This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA)., Methods: Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual of Minds for observational studies., Results: One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 [95% confidence interval (CI): 0.94-1.79]/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection, and malignancy caused by TNF inhibitors was 0-4%., Conclusions: Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, especially well-designed RCTs, are needed to accumulate clinical data., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: This study aimed to assess the efficacy and safety of sarilumab in older patients with active rheumatoid arthritis (RA)., Methods: This is a post hoc analysis of KAKEHASI (NCT02293902) and HARUKA (NCT02373202) trials with stratification by age (<65 and ≥65 years). Patients with moderately to severely active RA were treated with sarilumab in combination with methotrexate or with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy. The primary end points in KAKEHASI and HARUKA trials were the American College of Rheumatology 20% improvement criteria (ACR20) responses at Week 24 and safety, respectively. Secondary end points were other RA disease activity measures, including Clinical Disease Activity Index (CDAI)., Results: Approximately 20% of patients were aged ≥65 years in treatment arms across both trials, except the sarilumab + csDMARD arm (40%, 12/30). ACR20 response rates were similar between age groups across sarilumab treatment arms, and similar results were obtained for the CDAI scores. Safety profiles were similar between age groups except for a higher incidence of serious adverse events in patients aged ≥65 years in the sarilumab + methotrexate arm., Conclusions: In Japanese patients with RA enrolled in Phase 3 studies for sarilumab, no clear difference in efficacy or safety was observed between patients aged <65 and ≥65 years., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: Hydroxychloroquine (HCQ) is recommended at a target dose of 5 mg/kg per actual body weight to reduce the risk of retinopathy in systemic lupus erythematosus (SLE). However, the efficacy of HCQ has been established at doses of 6.5 mg/kg per ideal body weight. This study aimed to clarify the effects of the HCQ dose on the continuation rate in Japanese patients, who generally have a lower body mass index than Western patients., Methods: This retrospective single-centre observational study enrolled patients with SLE on HCQ therapy. Patients were divided into two groups with a dose per actual body weight [the low-dose (<5 mg/kg) group and the high-dose (≥5 mg/kg) group], and continuation rates were compared. The efficacy of 1-year HCQ therapy was assessed in patients without additional immunosuppressive agents and biologics., Results: Of the 231 patients enrolled, 48 (20.8%) discontinued HCQ. The HCQ dose per actual body weight was identified as an independent risk factor for discontinuation. The low-dose group showed a significantly higher 1-year HCQ continuation rate than the high-dose group (83.2% vs. 72.8%, respectively). Both groups showed reductions in glucocorticoid requirement and serological activity after 1-year HCQ therapy., Conclusions: HCQ <5 mg/kg per actual body weight may facilitate greater continuation., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: Using data from a postmarketing surveillance, this interim subgroup analysis investigated the safety of sarilumab in younger (<65 years) and older patients (≥65 and ≥75 years) with rheumatoid arthritis., Methods: During this interim analysis, patients who were treated with sarilumab in Japan were enrolled between June 2018 and 2021. Data collected by 12 January 2022 were analysed, with adverse drug events monitored over 52 weeks., Results: Of 972 patients with available data, the proportion of patients aged <65 years, ≥65 years, and ≥75 years was 40.8%, 59.2%, and 27.8%, respectively. Most patients (95.5%) received the standard 200 mg dose of sarilumab as the initial dose. Adverse drug reactions were reported in 24.6% of patients, with serious events accounting for 6.4% of cases. No malignancy and low incidences of adverse drug reactions of special interest were reported across all age groups (<65 years, 7.8%; ≥65 years, 8.2%; ≥75 years, 8.5%). When stratified by absolute neutrophil count above and below the lower limit of normal, there were no numerical differences in incidences of serious and non-serious infections between age groups., Conclusions: Regardless of age, sarilumab therapy was well tolerated by patients with rheumatoid arthritis, with no new safety signals reported in this study., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA)., Methods: Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan., Results: Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6, and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9%, and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms, and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases., Conclusions: Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL-6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients., Methods: The Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as a historical, weighted control group. The primary end point for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years., Results: Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% [95% confidence interval (CI) 34.7-46.2%] and 28.9% (95% CI 9.9-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years., Conclusions: This study confirmed the 3-year effectiveness and safety and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Introduction: Annual screening for hydroxychloroquine (HCQ) retinopathy is recommended, and electroretinography (ERG) is considered a gold-standard test, but there are screening shortfalls and standard ERG is burdensome and has limited availability. Newer, portable ERG devices using skin-based electrodes may increase screening capacity but need validation. This study aims to determine initial device accuracies and feasibility of further research., Methods and Analysis: Prospective diagnostic device accuracy and feasibility study comparing novel ERG devices to standard screening tests. Three groups of 35 participants on HCQ, categorised by HCQ retinopathy (definite, possible and no retinopathy), and 35 healthy control participants, recruited by consecutive sampling, will have full field and multifocal ERG index tests, delivered using skin-contact electrodes by two devices-RETEval full-field and UTAS multifocal ERG, both manufactured by LKC Technologies (Gaithersburg, Maryland, USA), compared with spectral-domain optical coherence tomography and autofluorescence reference tests graded by two masked, independent retinal specialists. Eligible HCQ participants will either have diagnosed HCQ retinopathy or be eligible for screening per UK guidelines. Healthy control participants will have no prior HCQ exposure and be of similar age and sex to HCQ participants. Primary outcome is device-specific sensitivity and specificity. Secondary outcomes include the effect of dilation on device outputs, analysis of discriminatory waveforms, device acceptability and recruitment rate. Safety outcomes include adverse and serious adverse events and device events., Ethics and Dissemination: Cambridge East ethics committee gave a favourable opinion (24/EE/0011, 23/02/2024). Results will be published in a peer-reviewed ophthalmology journal., Trial Registration Number: ClinicalTrials.gov NCT06035887., Competing Interests: Competing interests: The devices are subject to a cost-free loan agreement between LKC Technologies and the Sponsor. The grants above cover part of CNL’s time on the project, as well as publication costs and conference fees in relation to this project. CNL and GM’s employer receives payments for commercial research trial work in retinal and glaucomatous diseases. TLJ is a consultant/advisor to 2CTech; Alcon; Dutch Ophthalmic Research Centre; iLumen; Opthea; Outlook Therapeutics; Oxurion; Regeneron, and has received conference support from Roche. OM has participated on an advisory board for Janssen 21 Pharmaceuticals. None of the authors hold any stocks, nor receive any royalties or consulting fees from LKC Technologies., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess immunogenicity and safety in patients with active rheumatoid arthritis (RA) transitioning from rituximab [US-licensed rituximab: Reference Product (RP); EU-approved rituximab: Reference Medicinal Product (RMP)] to DRL&#95;RI (proposed rituximab biosimilar), in comparison to those continuing on RP/RMP., Methods: This double-blind, randomized, Phase 3 study included 140 RA patients having prior exposure to RP/RMP; transitioned to DRL&#95;RI (n = 70) or continued with RP/RMP (n = 70) for two 1000 mg infusions on Days 1 and 15. Assessments included Time-matched Rituximab Concentration (TMRC), anti-drug antibodies (ADAs), neutralizing antibodies (NAbs) and ADA titre over 12 weeks, and safety follow-up till 26 weeks., Results: The mean age of subjects was 59.8 years (range: 24, 86) and the mean BMI was 27.76 kg/m 2 (range: 17.5, 52.0). Incidence of ADA after dosing was low in both groups: 1.4% in DRL&#95;RI group on Day 15, Week 8, and Week 12; and 2.9% in RP/RMP group at Week 12. Only 1 patient in DRL&#95;RI group was positive for NAbs at Week 8. ADA titre values did not significantly differ between the two groups. The time-matched rituximab concentration was comparable between groups, indicating no interference for immunogenicity assessment. Treatment-emergent adverse events (TEAEs) were reported by 34.3% and 38.6% patients, respectively, in DRL&#95;RI and RP/RMP groups. Incidences of TEAEs that were drug-related, leading to treatment discontinuation, grade ≥ 3, or serious, were also comparable., Conclusion: Immunogenicity was low and comparable in RA patients transitioning to DRL&#95;RI or continuing on RP/RMP. The overall safety profile in patients transitioning to DRL&#95;RI did not appear to differ in frequency, severity, or quality from patients continuing on RP/RMP and was in line with the known safety profile of rituximab., Trial Registration: ClinicalTrials.gov identifier NCT0426877 EudraCT:2019-002810-37 US IND 112766., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The study protocol was reviewed and approved by the respective regulatory agencies, and ethics committees at each participating centre. All participating patients provided written informed consent prior to entering the study and before initiation of any study-related procedure. Consent for publication: Not applicable. Competing interests: DU, NR, PR, and NM are current employers of Dr.Reddy’s Laboratories Ltd.,, (© 2024. The Author(s).)

Rheumatoid arthritis (RA), a condition characterized by joint deterioration through the action of matrix metalloproteinases (MMPs), is prevalent worldwide. Bee venom (BV) has traditionally been used in Chinese medicine for pain, arthritis, rheumatism, skin diseases, etc. BV is enriched with active substances, notably melittin and phospholipase A2 (PLA2), offering significant therapeutic potential. Hence, the review summarizes current insights into BV's composition, antiarthritic mechanism and pharmacological benefits, focusing on melittin. Constituting 50-60% of BV, melittin notably downregulates nuclear factor Kappa B (NF-κB) activity, inhibits MMP-1 and MMP-8, and diminishes tumor necrosis factor (TNF-α), all of which contribute to the mitigation of type 2 collagen degradation. Despite its potential, melittin exhibits hemolytic activity and can significantly affect cell membranes, limiting its application, which poses a challenge to its therapeutic use. To overcome these challenges, delivery techniques utilizing nanocarriers and modifications in amino acid sequencing have been developed. Recent advancements in delivery systems, including nanocarriers, transdermal patches, and nanoemulsions, aim to minimize toxicity, expanding its therapeutic utility for RA. This article explores these novel strategies, underlining the evolving role of melittin in RA management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pareek, Mehlawat, Tripathi, Pareek, Chaudhary, Ratan, Apostolopoulos and Chuturgoon.)

Background: Data on treatment switching directly from tumor necrosis factor inhibitors to tofacitinib in psoriatic arthritis (PsA) are limited. This post hoc analysis assessed efficacy and safety outcomes in patients with PsA who directly switched to tofacitinib in a long-term extension (LTE) study after receiving adalimumab (ADA) in a Phase 3 study, compared with those who continued to receive tofacitinib., Methods: Patients with active PsA received tofacitinib 5 mg twice daily (BID) or ADA 40 mg once every 2 weeks in a 12-month, randomized, double-blind study (OPAL Broaden) and then continued or switched to tofacitinib 5 mg BID and maintained this dose in an open-label LTE study (OPAL Balance). Efficacy was assessed 3 months before the last visit and at the last visit in the Phase 3 study, and at month 3 (or month 6 for select outcomes) in the LTE study and included rates of ≥ 20/50/70% improvement in American College of Rheumatology response criteria, Psoriasis Area and Severity Index ≥ 75% improvement, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (decrease from baseline ≥ 0.35 for patients with baseline HAQ-DI ≥ 0.35), Psoriatic Arthritis Disease Activity Score ≤ 3.2, and minimal disease activity; and change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue score. Safety was assessed at months 3 and 12 in both studies via incidence rates (patients with first events/100 patient-years)., Results: Overall, 180 patients were included (ADA→tofacitinib 5 mg BID: n = 91; continuing tofacitinib 5 mg BID: n = 89). At Phase 3 baseline, patients in the ADA→tofacitinib 5 mg BID group tended to be younger and have less active disease compared with those continuing tofacitinib. Efficacy was similar between groups in the Phase 3 study, and was maintained to month 3 or 6 in the LTE study. Treatment-emergent adverse events (AEs), serious AEs, and serious infections were generally similar in the Phase 3 and LTE studies, and between groups within each study., Conclusion: Tofacitinib efficacy and safety were similar in patients with PsA who directly switched from ADA to tofacitinib and those who continued tofacitinib, suggesting that patients can be directly switched from ADA to tofacitinib without any washout period., Trial Registration: NCT01877668; NCT01976364., Competing Interests: Declarations. Ethics approval and consent to participate: Both studies were conducted in accordance with the Good Clinical Practice guidelines of the International Council for Harmonisation and with the principles of the Declaration of Helsinki. All patients provided written informed consent and the protocols were approved by the institutional review board or independent ethics committee at each investigational site. Consent for publication: Not applicable. Competing interests: DDG has received grants and/or research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB, and has acted as a consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc, and UCB. PN has received grants and/or research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer Inc, and UCB, and has received speaker fees/honoraria from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, and Pfizer Inc. PJM has received grants and/or research support from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc, Sun, and UCB, has acted as a consultant for AbbVie, Acelyrin, Aclaris, Alumis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, Inmagene, Janssen, MoonLake, Novartis, Pfizer Inc, Sun, UCB, and Ventyx, and has received speaker fees/honoraria from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB. OF has received grants and/or research support from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB, has acted as a consultant for Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and Pfizer Inc, and has received speaker fees/honoraria from AbbVie, Janssen, Novartis, and Pfizer Inc. SD and MJC are employees and stockholders of Pfizer Inc. KRM is a stockholder of Pfizer Inc and was an employee of Pfizer Inc at the time of the analysis., (© 2024. The Author(s).)

Objectives: Describe tofacitinib safety from an integrated analysis of randomized controlled trials (RCTs) in patients with ankylosing spondylitis (AS)., Method: Pooled data from Phase 2 (NCT01786668; 04/2013-03/2015)/Phase 3 (NCT03502616; 06/2018-08/2020) RCTs in AS patients were analyzed (3 overlapping cohorts): 16-week placebo-controlled (tofacitinib 5 mg twice daily [BID] [n = 185]; placebo [n = 187]); 48-week only-tofacitinib 5 mg BID (n = 316); 48-week all-tofacitinib (≥ 1 dose of tofacitinib 2, 5, or 10 mg BID; n = 420). Baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk was determined in patients without history of ASCVD (48-week cohorts). Adverse events (AEs)/AEs of special interest were evaluated/compared with findings from other tofacitinib programs (16 Phase 2/Phase 3 rheumatoid arthritis [RA]; 2 Phase 3 psoriatic arthritis [PsA] RCTs) and a real-world cohort of AS patients initiating biologic disease-modifying antirheumatic drugs (US MarketScan)., Results: Most patients (> 75%; 48-week cohorts) without history of ASCVD had low baseline 10-year ASCVD risk. One patient (tofacitinib 5 mg BID; in all 3 cohorts) had a serious infection (aseptic meningitis). Herpes zoster (non-serious) occurred in the 48-week only-tofacitinib 5 mg BID (n = 5 [1.6%]) and all-tofacitinib (n = 7 [1.7%]; one multi-dermatomal [tofacitinib 10 mg BID]) cohorts. No deaths, opportunistic infections, tuberculosis, malignancies, major adverse cardiovascular events, thromboembolic events, gastrointestinal perforations occurred., Limitations: short RCT durations/low patient numbers within cohorts., Conclusion: Tofacitinib 5 mg BID was well tolerated to 48 weeks in AS patients; safety profile was consistent with RA/PsA clinical programs and a cohort of AS patients from US routine clinical practice., Clinical Trial Registration Numbers: NCT01786668 (2013-02-06); NCT03502616 (2018-04-11)., Competing Interests: Declarations. Ethics approval and consent to participate: Trials were conducted according to the Declaration of Helsinki/Good Clinical Practice Guidelines of the International Council for Harmonisation, and approved by the Institutional Review Board and/or Independent Ethics Committee of the investigational centers. Patients provided written informed consent. Consent for publication: Not applicable. Competing interests: AD has received grant/research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer Inc, and UCB, and has been a consultant for AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer Inc, and UCB. SA has received grant/research support from Pfizer Inc and has been a consultant for, and participated in speaker bureaus for, AbbVie, Amgen, Eli Lilly, MSD, Novartis, Pfizer Inc, and UCB. JRC has received grant/research support from, and has been a consultant for, AbbVie, Amgen, Bristol Myers Squibb, CorEvitas, LLC (formerly Corrona, LLC), Eli Lilly, Janssen, Myriad, Novartis, Pfizer Inc, Sanofi, and UCB. BE-Z has received grant/research support from, and has been a consultant for, AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Eva, Hekma, Janssen, MSD, New Bridge, Novartis, Pfizer Inc, Roche, Sandoz, Sanofi-Aventis, and Servier. MM has received grant/research support from AbbVie, Bristol Myers Squibb, and UCB, and has been a consultant for AbbVie, Eli Lilly, Novartis, Pfizer Inc, and UCB. CW, JW, SBM, IV, SM, DLF, AMD, LF, and AY are employees and stockholders of Pfizer Inc. RBML has been a consultant for AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos NV, Gilead Sciences, Janssen, Novartis, Pfizer Inc, and UCB., (© 2024. The Author(s).)

The safety of tumor necrosis factor (TNF) inhibitors has been demonstrated for over two decades. However, their effects on cardiovascular function in patients with rheumatic diseases remain controversial, and conclusions are additionally hampered by the cardiovascular complications inherent in such diseases. We present two 15-year-old patients diagnosed with ankylosing spondylitis and juvenile idiopathic arthritis classified as polyarthritis with positive rheumatoid factor, respectively. Soon after treatment onset with adalimumab and etanercept, respectively, they developed myocardial inflammation leading to heart failure. Their condition improved upon treatment discontinuation and onset of secukinumab and tocilizumab, respectively. A thorough literature search revealed that these are the only cases of heart failure reported to date after anti-TNF treatment in adolescents with rheumatic diseases. Although cardiovascular adverse effects seem to be very rare in this population, even atypical symptoms of cardiac failure should not be ignored, and cardiac function should be closely monitored when administering anti-TNF-α., Competing Interests: Declarations. Ethical approval: All procedures followed ethical standards in accordance with the 1964 Helsinki declaration and its amendments. Informed consent: Informed consent was obtained from the guardians of both patients for the purpose of publishing this article. Conflict of interest: The authors declare no relevant conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Little is known about how various treatments impact the progression of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Here, we compared ILD progression in RA patients treated with Janus kinase inhibitors (JAKi) or biological disease-modifying anti-rheumatic drugs (bDMARDs). In vitro experiments were also performed to evaluate the potential effects of the drugs on epithelial-mesenchymal transition (EMT), a key event in pulmonary fibrosis., Methods: This retrospective study included 93 RA-ILD patients who initiated treatment with JAKi, tumour necrosis factor inhibitors (TNFi), or abatacept between 2017 and 2020. Worsening ILD was quantified by changes in chest computed tomography (CT) scans between baseline and follow-up (mean 14 months, range 6-51 months). Response to treatment was evaluated using Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Expression of the EMT marker N-cadherin in A549 lung cells was assessed by western blotting., Results and Discussion: Worsening ILD was detected in 19.4% (7/36), 16.7% (5/30), and 22.2% (6/27) of patients treated with JAKi, abatacept, and TNFi, respectively. Multivariate analysis identified female gender (P=0.043) and >10% fibrotic lesions (P=0.015) as significant predictors of worsening ILD. DAS28-ESR-based non-responder status was also significantly associated with worsening ILD (P=0.0085). In vitro, combination treatment with methotrexate and baricitinib significantly impeded EMT progression. Worsening ILD was associated with more extensive fibrotic lesions at baseline and female gender in RA patients treated with JAKi or bDMARDs. JAKi and methotrexate co-treatment may prove beneficial in modifying key events underlying the pathogenesis of RA-ILD., Competing Interests: TK and AK received honoraria for speaking engagements from Eli Lilly, Japan. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Kurushima, Koga, Umeda, Iwamoto, Miyashita, Tokito, Okuno, Yura, Ishimoto, Kido, Sakamoto, Ueki, Mukae and Kawakami.)