Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial

Abstract

ObjectivesTo 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).MethodsIn 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.ResultsA 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.ConclusionsThe 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.

Nintedanib: A Review in Fibrotic Interstitial Lung Diseases

“…Oral nintedanib had a manageable tolerability profile in clinical trials in patients with fibrotic ILDs [9,11,12,36,52,53] and in real-world studies in patients with IPF (e.g. [13][14][15][16]).…”

SnapshotDx Quiz: April 2021

“…Although numerous medications have been used off label for patients with SS (e.g., methotrexate, mycophenolate, cyclophosphamide), there are currently no FDAapproved treatments for dcSS. Of note, nintedanib, a tyrosine kinase inhibitor, is currently the only FDAapproved medication for SS-associated interstitial lung disease (Seibold et al, 2020).…”

The Treatment of Lung Involvement in Systemic Sclerosis

“…This beneficial effect on FVC preservation was seen both in MMF and non-MMF co-treated patients, with a numerically lower decline in patients receiving the combination treatment [ 58 ]. In the SENSCIS study, Nintedanib showed a safety profile similar to the side effects seen in IPF, particularly affecting the gastrointestinal tract (75.7% of treated patients manifested diarrhea) and requiring dose-adjustment/temporary interruption in almost half of the treated patients [ 59 ]. Interestingly, the safety profile was similar in patients receiving or not receiving co-treatment with MMF, which itself carries a gastro-intestinal burden in terms of adverse events [ 58 ].…”