Sebastiani Marco, Lepri Gemma, Iannone Claudia, Cassione Emanuele Bozzalla, Guggino Giuliana, Lo Monaco Andrea, Foti Roberta, Fornaro Marco, Chimenti Maria Sole, Fassio Angelo, Truglia Simona, Cozzini Francesca, Carletto Antonio, Giollo Alessandro, Corrado Addolorata, Bazzani Chiara, Guiducci Serena, Favalli Ennio, Bugatti Serena, Iannone Florenzo, Caporali Roberto, Manfredi Andreina
M. Sebastiani, MD, Rheumatology Unit, Azienda Unità Sanitaria Locale di Piacenza, Piacenza, and Department of Medicine and Surgery, University of Parma, Parma;
G. Lepri, MD, S. Guiducci, MD, Division of Rheumatology, AOU Careggi, Department of Experimental and Clinical Medicine, University of Florence, Florence.
J Rheumatol. 2025 May 1;52(5):420-425. doi: 10.3899/jrheum.2024-0976.
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.
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%).
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.
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.
对于尼达尼布在类风湿关节炎相关间质性肺病（RA-ILD）患者中的安全性仍存在一些担忧，例如存在合并症时，或与生物制剂、靶向合成和/或传统合成抗风湿药物（DMARDs）联合使用时。在这项多中心研究中，我们回顾性评估了尼达尼布在来自意大利早期关节炎研究组（GISEA）登记处的真实世界RA-ILD患者群体中的安全性，以及合并症和DMARDs对药物安全性和停药的可能影响。我们的次要目的是调查尼达尼布停药的原因。
65例按照当前治疗指征接受尼达尼布治疗的患者纳入研究。62例患者（95.4%）的尼达尼布与DMARDs和/或类固醇联合使用。
尼达尼布的12个月保留率为76.7%，在随访≥6个月的患者中，约80%的患者药物有效。36例受试者（55.3%）记录到不良事件（AE），主要为胃肠道不良事件。31例受试者需要降低尼达尼布剂量；其中，尼达尼布每日剂量的短暂或永久降低使22例患者能够继续治疗，而15例（23.1%）患者停药。所有减量和停药均归因于治疗相关的AE。在多变量分析中，合并症与副作用显著相关，而尼达尼布引起的AE是停药的主要原因。
DMARDs联合治疗并未降低尼达尼布的安全性和有效性，AE是药物停药或减量的主要原因，主要是由于合并症。
