Seibold James R, Maher Toby M, Highland Kristin B, Assassi Shervin, Azuma Arata, Hummers Laura Kathleen, Costabel Ulrich, von Wangenheim Ute, Kohlbrenner Veronika, Gahlemann Martina, Alves Margarida, Distler Oliver
Scleroderma Research Consultants, LLC, Aiken, South Carolina, USA
National Heart and Lung Institute, Imperial College London, London, UK.
Ann Rheum Dis. 2020 Nov;79(11):1478-1484. doi: 10.1136/annrheumdis-2020-217331. Epub 2020 Aug 5.
To characterise the safety and tolerability of nintedanib and the dose adjustments used to manage adverse events in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).
In the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib 150 mg two times per day or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg two times per day. We assessed adverse events and dose adjustments over 52 weeks.
A total of 576 patients received nintedanib (n=288) or placebo (n=288). The most common adverse event was diarrhoea, reported in 75.7% of patients in the nintedanib group and 31.6% in the placebo group; diarrhoea led to permanent treatment discontinuation in 6.9% and 0.3% of patients in the nintedanib and placebo groups, respectively. In the nintedanib and placebo groups, respectively, 48.3% and 12.2% of patients had ≥1 dose reduction and/or treatment interruption, and adverse events led to permanent discontinuation of the trial drug in 16.0% and 8.7% of patients. The adverse events associated with nintedanib were similar across subgroups defined by age, sex, race and weight. The rate of decline in forced vital capacity in patients treated with nintedanib was similar irrespective of dose adjustments.
The adverse event profile of nintedanib in patients with SSc-ILD is consistent with its established safety and tolerability profile in patients with idiopathic pulmonary fibrosis. Dose adjustment is important to minimise the impact of adverse events and help patients remain on therapy.
描述尼达尼布在系统性硬化症相关间质性肺病（SSc-ILD）患者中的安全性和耐受性，以及用于处理不良事件的剂量调整情况。
在SENSCIS试验中，SSc-ILD患者被随机分配接受每日两次150毫克尼达尼布或安慰剂治疗。为处理不良事件，治疗可中断或剂量减至每日两次100毫克。我们评估了52周内的不良事件和剂量调整情况。
共有576例患者接受了尼达尼布（n = 288）或安慰剂（n = 288）治疗。最常见的不良事件是腹泻，尼达尼布组75.7%的患者和安慰剂组31.6%的患者报告有腹泻；腹泻导致尼达尼布组和安慰剂组分别有6.9%和0.3%的患者永久停药。在尼达尼布组和安慰剂组中，分别有48.3%和12.2%的患者进行了≥1次剂量减少和/或治疗中断，不良事件导致16.0%和8.7%的患者永久停用试验药物。在按年龄、性别、种族和体重定义的亚组中，与尼达尼布相关的不良事件相似。无论剂量调整如何，接受尼达尼布治疗的患者用力肺活量下降率相似。
尼达尼布在SSc-ILD患者中的不良事件谱与其在特发性肺纤维化患者中已确立的安全性和耐受性谱一致。剂量调整对于将不良事件的影响降至最低并帮助患者持续接受治疗很重要。
