OBJECTIVE Some concerns remain about the safety of nintedanib in patients with interstitial lung disease (ILD) related to rheumatoid arthritis (RA-ILD), such as in presence of comorbidities or in combination with biologic, targeted synthetic and/or conventional synthetic disease modifying antirheumatic drugs (DMARDs). In this multicentre study, we retrospectively evaluated the safety of nintedanib in a real-world population of RA-ILD patients from Italian GISEA registry and the possible role of comorbidities and DMARDs on drug safety and withdrawal. Secondary aim was to investigate the causes of nintedanib discontinuation. METHODS Sixty-five patients treated with nintedanib according to 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 Twelve-month retention rate of nintedanib was 76.7% and the drug was effective on about 80% of patients with at least 6 months of follow-up. Adverse events were recorded in 36 subjects (55.3%), 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 to continue the treatment in 22, while 15 (23.1%) withdrew the drug, in all cases for treatment-related adverse events. Comorbidities were significantly associated to side effects at multivariate analysis, while adverse events of nintedanib were the main cause of discontinuation. CONCLUSION Combination therapy with DMARDs didn't reduce safety and effectiveness of nintedanib, while adverse events were the main cause of drug withdrawal or reduction of the dose of drug, mainly due to comorbidities.

中文翻译：

---

尼达尼布治疗类风湿性关节炎相关的间质性肺病：真实世界的安全性和副作用和停药风险。


目的 对于尼达尼布在类风湿性关节炎相关间质性肺病 （ILD） 患者中的安全性仍然存在一些担忧，例如存在合并症或与生物制剂、靶向合成和/或常规合成疾病缓解抗风湿药 （DMARDs） 联合使用。在这项多中心研究中，我们回顾性评估了尼达尼布在意大利 GISEA 登记处真实世界 RA-ILD 患者人群中的安全性，以及合并症和 DMARD 对药物安全性和戒断的可能作用。次要目的是调查尼达尼布停药的原因。方法 根据目前的治疗适应症，65 例接受尼达尼布治疗的患者被纳入研究。尼达尼布与 DMARD 和/或类固醇联合用于 62 例患者 （95.4%）。结果 尼达尼布的 12 个月保留率为 76.7%，该药物对约 80% 的患者有效，随访至少 6 个月。36 例受试者 （55.3%） 记录了不良事件，主要是胃肠病。31 名受试者需要减少尼达尼布剂量;其中，尼达尼布每日剂量的短暂或永久减少允许在 22 人中继续治疗，而 15 人 （23.1%） 撤药，在所有情况下都是与治疗相关的不良事件。在多变量分析中，合并症与副作用显著相关，而尼达尼布的不良事件是停药的主要原因。结论 与 DMARDs 联合治疗并未降低尼达尼布的安全性和有效性，而不良事件是停药或减少药物剂量的主要原因，主要是由于合并症。