Effectiveness and tolerability of antifibrotics in rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVE: Our aim was to investigate the effectiveness and tolerability of antifibrotics in a real-world cohort of patients with rheumatoid arthritis-associated interstitial lung diseases (RA-ILD). METHODS: In this retrospective cohort study, we identified RA-ILD patients initiating antifibrotics at Mass General Brigham Integrated Health Care System, a large multi-hospital healthcare system in Boston, MA, USA. We used electronic query to identify all patients with at least 2 RA diagnosis codes and a prescription for either nintedanib or pirfenidone (2014-2023). All analyzed patients met 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for RA and had definite RA-ILD according to Bongartz criteria. Data regarding pulmonary function test (PFT) results, adverse events (AEs), tolerability, and clinical data were collected. A linear mixed model with random intercept was used to compare the within-patient trajectory of the percent predicted forced vital capacity (FVCpp) within 18-months before to 18-months after antifibrotic initiation among those with these PFT data. Lung transplant-free survival and drug retention was estimated in a Kaplan-Meier analysis and a Cox regression analysis was performed to identify independent baseline factors associated with lung transplant or mortality. RESULTS: We analyzed 74 patients with RA-ILD that initiated antifibrotics (mean age 67.8 years, 53 % male); 40 patients initiated nintedanib and 34 initiated pirfenidone. Median follow-up was 89 weeks (min 4, max 387). There was a significant improvement in the estimated slope of FVCpp after antifibrotic initiation (-0.3 % per year after initiation compared to -6.2 % per year before antifibrotic initiation, p = 0.03). Nintedanib and pirfenidone had similar FVCpp trajectory. Twenty-six patients (35 %) died and 4 (5 %) had undergone lung transplantation during follow-up. Male sex and heavy smoking were each associated with the composite outcome of lung transplant or mortality. AEs were reported in 41 (55 %) patients, with gastrointestinal (GI) AEs being most common (n = 30). The initial antifibrotic was discontinued in 34 (46 %) patients mostly due to GI AEs (n = 19). The median drug retention time was 142 weeks (95 %CI 56, 262) with no difference between nintedanib and pirfenidone (p = 0.68). CONCLUSION: In this first real-world study of antifibrotic use dedicated to RA-ILD, antifibrotic initiation was associated with a modestly improved trajectory of FVCpp. AEs were frequently reported, particularly GI, and discontinuation was common. However, lung transplant and mortality rates were still high, emphasizing the need for further therapeutic strategies in patients with severe RA-ILD. These real-world data complement previous trial data that investigated efficacy and safety.

Rheumatic and musculoskeletal features of Whipple disease: a report of 29 cases.

OBJECTIVE: Whipple disease is a rare infection caused by Tropheryma whipplei. Although patients commonly complain of osteoarticular involvement, musculoskeletal manifestations have been poorly described. We report cases of Whipple disease with rheumatic symptoms and describe their clinical presentation, modes of diagnosis, and outcomes. METHODS: This retrospective multicenter study included patients with Whipple disease diagnosed and referenced between 1977 and 2011 in 10 rheumatology centers in France and Italy. RESULTS: Twenty-nine patients were included. The median age was 55 years. The median time to diagnosis from first symptoms was 5 years. Polyarthritis was the most frequent presentation (20/29), and was most often chronic, intermittent (19/29), seronegative (22/23), and nonerosive (22/29). In all cases, the symptoms had led to incorrect diagnosis of inflammatory rheumatic disease and immunosuppressants, including biotherapy, were prescribed in most cases (24/29) without success. The diagnosis of Whipple disease was made by histological analysis, molecular biology tests, or both in 21%, 36%, and 43% of the cases, respectively. Duodenal biopsies were performed in most cases (86%). Synovial biopsies were performed in 18% of cases, but all contributed to diagnosis. The clinical outcomes after antibiotic therapy were good for all patients. CONCLUSION: Polyarthritis is the main feature observed in cases of Whipple disease; it is seronegative and associated with general and gastrointestinal symptoms. The molecular analysis of duodenal tissue and/or other tissues remains the method of choice to confirm the diagnosis. Reducing the time to diagnosis is important because severe late systemic and fatal forms of the disease may occur.