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Background: Efficacy of tumour necrosis factor inhibitors (TNFi) for peripheral arthritis in patients with psoriatic arthritis (PsA) has been established in randomized clinical trials that have used improvement in summated joint counts as an outcome. Whether joints at different anatomical locations might respond differentially to TNFi remains unknown. The aim of the study was to investigate potential variations in the responsiveness to a first tumour necrosis factor inhibitor (TNFi) among joints at distinct locations in patients with psoriatic arthritis (PsA) treated in routine clinical care., Methods: Bionaive PsA patients from nine European countries were included in this observational cohort study if ≥ 1 joint was swollen at the initiation of a first TNFi as monotherapy or added to methotrexate. Only the 28-joint count was available without imaging data confirming the presence of synovitis. The primary outcome was time to first resolution of joint swelling at each joint level. Hazard ratios (HR) for resolution comparing different joint locations were estimated using interval-censored mixed-effects Cox proportional hazards models, including a random effect for country and patient, adjusted for age and sex., Results: A total of 1729 patients with 8397 swollen joints at the start of TNFi were included. Considering the upper extremity, a higher rate of resolution of joint swelling (HR, 95% CI) was observed for the shoulder (1.65, 1.16-2.35) and elbow (1.90, 1.38-2.61), while a lower rate was found for the wrist (0.72, 0.62-0.83) compared to the joints of digit 3. Within fingers, and using the same reference, joint swelling resolved fastest in digit 4 (1.77, 1.49-2.11) and digit 5 (1.88, 1.53-2.31). A lower rate of resolution of joint swelling was found for the knee in comparison to the elbow, the corresponding joint on the upper limb (0.56, 0.40-0.78)., Conclusion: The time to resolution of joint swelling upon treatment with TNFi in patients with PsA seems to depend on the localisation of the affected joints., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the respective national data protection agencies and research ethical committees according to legal regulatory requirements in the participating countries (online supplemental table S6). Consent for publication: Not required. Competing interests: AG reports a grant from Novartis (paid to employer). AGL reports a research grant from Novartis; speaking and/or consulting fees from Abbvie, Janssen, Eli Lilly, MSD, Novartis, Pfizer, and UCB; and being a paid instructor for Pfizer. BeG reports a grant from Novartis (paid to institution); grants from Abbvie, BMS, and Sandoz paid to the institution, outside the submitted work. BrM reports a research grant from Novartis paid to the employer (outside the submitted work); speaker fees from Novartis; grants from the Research Council of Norway to the Centre for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY). CC reports speaking and consulting fees from Abbvie, Amgen, Boehringer-Ingelheim, Ewopharma, Eli Lilly, Novartis, and Pfizer. FI reports a provision from Abbvie for article processing; consulting fees from Abbvie, Janssen, and UCB; payments or honoraria from Abbvie, Eli Lilly, Galapagos, Janssen, and UCB; support for attending meetings from Abbvie, Astra-Zeneca, Eli Lilly, Galapagos, Janssen, and UCB. GTJ reports a research grant from Amgen paid to the employer; speaker fees from Janssen. IC reports speaker and/or consulting fees form BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, MSD, Pfizer, and GSK. IvdHB reports payment for lecture from UCB and support for attending a meeting from Pfizer. JMD reports grants from the Portuguese Society of Rheumatology (RheumaPlus grant); consulting fees from Abbvie, Bial, Merck Sharp & Dohme, and Pfizer; payments or honoraria from Abbvie, Bial, Merck Sharp & Dohme, Novartis, Pfizer, and UCB; JKW reports speaking fees from Abbvie, and Amgen (paid to institution); research support from Abbvie, Amgen, Eli Lilly, Novartis, and Pfizer (unrelated to the present study and paid to institution); he acts as co-chair of the Swedish Society for Rheumatology’s working group which is annually updating the Swedish treatment recommendations for axial spondyloarthritis and psoriatic arthritis. JZ reports speaking fees from Abbvie, Akord, Astra Zeneca, Celltrion, Eli Lilly, Pfizer, and Sobi; consulting fees from Abbvie, and Astra Zeneca; support for attending meetings from Abbvie, and Pfizer; participation in advisory boards for Abbvie, and Astra Zeneca. KP reports consulting fees from Abbvie, UCB, Pfizer, Eli Lilly, Celltrion, MSD, and Novartis. LMØ reports a research grant from Novartis paid to the employer. MJN reports a research grant from Novartis paid to the institution; consulting fees from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, and Pfizer paid to the institution; speaking fees from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, and Pfizer paid to the institution; support for attending meetings from Janssen and UCB; participation in advisory boards from Eli Lilly, Janssen, Novartis and Pfizer paid to the institution; he is a scientific member of the SCQM registry and of the EuroSpA collaboration and an ASAS-EULAR taskforce member. MØ reports grants from Abbvie, Amgen, BMS, Celgene, Eli Lilly, Merck, Novartis, and UCB, outside the submitted work; consulting fees from Abbvie, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novatis, Pfizer, and UCB; payments or honoraria from Abbvie, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pifzer, and UCB. MLH reports consulting fees from Abbvie paid to institution; research grants from Abbvie, BMS, Eli Lilly, Lundbeck Fondation, MSD, Pfizer, Sandoz, Novartis, and Nordforsk, all paid to institution; speaking fees from Pfizer, Medac, Sandoz paid to the institution and a personal honorarium from Novartis; participation in an advisory board of Abbvie paid to the institution; being the previous chair of the steering committee of the Danish Rheumatology Quality Registers, which receive public funding from the hospital owners and from pharmaceutical companies; she co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis. MS reports consulting fees from Janssen-Cilag, Boehringer-Ingelheim, and Pfizer; payments or honoraria from BMS, Boehringer-Ingelheim, and GSK. RM reports payments or honoraria from Abbvie, Amgen, Eli Lilly, and Janssen Biotech. RP reports consulting fees from Boehringer Ingelheim and Celltrion, speaking fees from Boehringer Ingelheim, Eli Lilly, Janssen, and UCB; participation in advisory boards for Boehringer Ingelheim, Eli Lilly, and UCB. SHR reports a research grant from Novartis. SK reports a grant from Novartis (paid to employer). VR reports personal grants for the expenses of the research group from the competitive State Research Financing of the Expert Responsibility Area of Kanta-Häme Central Hospital and of Tampere University Hospital, as well as from the Wilhelm and Else Stockmann’s Foundation; payments or honoraria from Abbvie, Novartis, and Viatris. ZR reports payment or honoraria from Abbvie, Amgen, AstraZeneca, Boehringer, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Roche, and Sandoz Lek; payments for expert testimony from Abbvie, Amgen, AstraZeneca, Boehringer, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Roche, and Sandoz Lek; being president of the section of rheumatology of the Slovenian Medical Association. AC, AS, BM, BT, BjG, BuM, CM, CO, GJM, OD, OP, PV, and RB declare they have no conflicts of interests., (© 2025. The Author(s).)

Background: Randomized clinical trials have demonstrated the efficacy of secukinumab (SECU) in reducing disease activity in psoriatic arthritis (PsA), while real-world studies prove a broader perspective on SECU's usefulness in everyday clinical practice., Objectives: To assess the effectiveness of SECU by evaluating drug survival and identifying potential predictors of clinical response and treatment discontinuation in patients with moderate-to-severe PsA, using real-world data from the Italian Group for the Study of Early Arthritis (GISEA) registry., Design: This longitudinal retrospective study included PsA patients treated with SECU, spanning from May 2016 to November 2023., Methods: Data from 1045 PsA patients, including 783 with peripheral-only PsA (perPsA) and 262 with peripheral and axial involvement (mixed PsA) were analyzed. Drug survival was estimated by Kaplan-Meier analysis. Clinical outcomes, including Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriasis Area Severity Index (PASI), Ankylosing Spondylitis Disease Activity Score (ASDAS, C-Reactive Protein (CRP)-based), and Visual Analogue Scale (VAS) measures, were evaluated at baseline and at 6, 12, and 24 months. Adjusted hazard ratios (aHRs) for discontinuing SECU were determined using multivariate Cox regression models., Results: SECU survival at 24 months was 63.24%, significantly higher in mixed PsA compared to perPsA ( p  = 0.036). In the overall PsA population, DAPSA scores decreased significantly at 6 months, and further at 24 months (all p  < 0.0001). In mixed PsA, ASDAS-CRP scores were significantly reduced at 6 months and remained stable through 24 months (all p  < 0.0001). VAS pain scores also improved already at 6 months and continued to improve at 24 months (all p  < 0.0001). Higher age (aHR = 0.98, 95% confidence interval (CI): 0.96-0.99, p  = 0.007) and lower baseline DAPSA scores (aHR = 1.02, 95% CI: 1.01-1.03, p  = 0.014) were associated with greater persistence of SECU treatment. SECU was well tolerated, with no serious adverse events., Conclusion: SECU showed sustained clinical improvements in both peripheral and axial involvement of PsA patients over 24 months, with higher persistence observed in mixed PsA patients. Our findings highlight the favorable clinical and safety profile of SECU in real world., Competing Interests: F.I. and G.Lopalco received speaker honoraria from Novartis. The remaining 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., (© The Author(s), 2025.)

Objective: Some concerns remain about the safety of nintedanib in patients with rheumatoid arthritis-related interstitial lung disease (RA-ILD), such as in the presence of comorbidities or in combination with biologic, targeted synthetic, and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). In this multicenter study, we retrospectively evaluated the safety of nintedanib in a real-world population of patients with RA-ILD from the Italian Group for the Study of Early Arthritis (GISEA) registry and the possible role of comorbidities and DMARDs on drug safety and withdrawal. Our secondary aim was to investigate the causes of nintedanib discontinuation., Methods: Sixty-five patients treated with nintedanib in accordance with the current therapeutic indications were enrolled in the study. Nintedanib was prescribed in combination with DMARDs and/or steroids in 62 patients (95.4%)., Results: The 12-month retention rate of nintedanib was 76.7% and the drug was effective in about 80% of patients with ≥ 6 months of follow-up. Adverse events (AEs) were recorded in 36 subjects (55.3%), and these were mainly gastroenteric. Thirty-one subjects required a reduction of the nintedanib dose; among them, a transient or permanent reduction of the daily dose of nintedanib allowed the continuation of the treatment in 22, whereas 15 (23.1%) withdrew from the drug. All reductions and discontinuations were owing to treatment-related AEs. Comorbidities were significantly associated with side effects in multivariate analysis, whereas AEs due to nintedanib were the main cause of discontinuation., Conclusion: Combination therapy with DMARDs did not reduce the safety and effectiveness of nintedanib, and AEs were the main cause of drug withdrawal or dose reduction, mainly owing to comorbidities.

Introduction: Hepatitis B reactivation and administration of prophylactic antiviral treatment are considered in patients with autoimmune inflammatory rheumatic diseases (AIIRD) undergoing immunosuppressive/immunomodulatory treatment. Data are more robust for rheumatoid arthritis patients receiving bDMARDs but are limited for other AIIRD and drug categories., Methods: Adult patients with AIIRD (inflammatory arthritis [IA] or connective tissue diseases [CTD]) and documented chronic or resolved HBV infection (defined as serum HBsAg positivity or anti-HBcAb positivity in the case of HBsAg non-detection respectively), followed-up in six rheumatology centers in Greece and Italy, were included. Data collected included demographic characteristics, AIIRD medications prior and after HBV screening [cs-DMARDs, (b-ts)- DMARDs, other immunosuppressants initiated and mean glucocorticoid dose], HBV prophylactic treatment, and possible HBV-reactivation (defined as increase in HBV-DNA or HBsAg seroconversion) within one year of HBV screening. Frequency of HBV reactivation and possible association with recorded parameters were examined., Results: During one year of follow-up, HBV reactivation occurred in 5.6% and 7.9% of IA and CTD patients, respectively. In patients with chronic hepatitis B, reactivation rates were 14.8% for IA and 22.2% for CTD, while in patients with resolved hepatitis B were 3.7% and 6%, respectively. In patients with resolved hepatitis B no association was found between HBV reactivation and antiviral prophylactic treatment, or the use of csDMARDs, bDMARDS, or other immunosuppressants., Conclusion: The risk of HBV reactivation was similar between IA and CTD patients and was significantly higher in chronic compared to resolved hepatitis B infection. For the latter, prophylactic treatment was not associated with lower reactivation risk., Competing Interests: Declarations. Ethical approval: Ethical approval was obtained from the Institutional Board of “Laiko” Hospital Scientific Council (Protocol No. 19/968, July 2019), and all participants provided written informed consent according to the Declaration of Helsinki. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Interstitial lung disease (ILD) is a relevant cause of morbidity and mortality in patients with autoimmune rheumatic diseases (ARDs). In the last years, an acute exacerbation (AE) - defined as an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality - has been reported to occur in virtually all ILD types, including ARD-ILD. The aim of this review is to describe the available and investigational treatments in patients affected by AE-ARD-ILD in light of the very low quality of evidence available. Currently, management consists of efforts to identify reversible triggers of respiratory decline, such as drugs effective in ARDs and infections, including opportunistic infections, together with supportive treatments. AE-ILD, AE-ARD-ILD and acute respiratory distress syndrome share histopathologically similar findings of diffuse alveolar damage in most cases. Identification of triggers and risk factors might contribute to early diagnosis and treatment of AE-ILD, before the alveolar damage becomes irreversible. In patients with acute respiratory distress syndrome, the role of steroids and immunosuppressants remains controversial. Also, many uncertainties characterize the management of AE-ARD-ILD because of the lack of evidence and of an unquestionable effective therapy. At this time, no effective evidence-based therapeutic strategies for AE-ARD-ILD are available. In clinical practice, AE-ARD-ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. Randomized controlled trials are needed to better understand the efficacy of current and future drugs for the treatment of this clinical relevant condition., Competing Interests: Declaration of competing interest The Authors have no Conflict of Interest related to this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Progressive pulmonary fibrosis (PPF) has been associated with a worse prognosis, even when interstitial lung disease (ILD) is related to rheumatic diseases. Since many differences are detectable among rheumatic diseases in prevalence and features of ILD, we aimed to investigate features of PPF in different rheumatic diseases, namely rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS). Methods: In an Italian multicentre cross-sectional study, consecutive pSS or RA patients with a diagnosis of ILD from at least two years were enrolled. For each patient, demographic, clinical, and serological data, other than chest high-resolution computed tomography and lung function tests, were recorded at the enrolment and after 2 years. Results : Among 232 patients, namely 156 RA-ILD and 76 pSS-ILD, a PPF was recorded in 38.8% of cases, without differences between the two diseases. Analysing patients with a PPF, usual interstitial pneumonia was significantly more frequent in RA than pSS (71.4% and 44.4%, respectively; p = 0.019), while ILD preceded the diagnosis of the rheumatic disease in 29.1% of RA and 89.5% of pSS ( p < 0.001). Finally, RA patients were significantly younger than pSS at the diagnosis of the rheumatic disease ( p < 0.001). Conclusions: In conclusion, although there is a similar prevalence of PPF in RA-ILD and pSS-ILD, we demonstrated for the first time that the two conditions differ in terms of radiological patterns and demographic and clinical features, suggesting that specific factors related to such diseases might influence the lung involvement over time. Prospective studies could investigate if these specificities could induce different responses to the treatment.

Objective: Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD., Methods: We used a large, international, multicenter "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both patients with ASSD and controls with mimicking conditions, namely, SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort., Results: Our analysis included 948 patients with ASSD and 1,077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in patients with ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/magnetic resonance imaging/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between patients with ASSD and controls or were inversely associated with ASSD., Conclusion: We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)