Data from the SENSCIS trial demonstrate that the adverse event profile of nintedanib for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is consistent with its established safety and tolerability profile in idiopathic pulmonary fibrosis, according to study results published in Annals of the Rheumatic Diseases.
In the SENSCIS trial (ClinicalTrials.gov Identifier: NCT02597933), patients with SSc-ILD were randomly assigned to receive nintedanib 150 mg twice daily or placebo, for 52 weeks. Treatment interruptions and dose reductions to 100 mg twice daily enabled the management of adverse events. Treatment interruptions were ≤4 weeks duration for adverse events related to nintedanib and ≤8 weeks duration for other adverse events. Adverse events were monitored throughout the 52-week study period. Forced vital capacity (FVC) was measured at baseline and 52 weeks. Annual rate of decline in FVC was compared between the placebo and nintedanib group.
A total of 576 patients received nintedanib (n=288) or placebo (n=288). The majority of patients were women (75.2%); 67.2% were White and 24.8% were Asian. Mean age at baseline was 54.0±12.2 years. Most patients (97.7%) were taking ≥1 medication at baseline. Over 52 weeks, 16.0% of the nintedanib group and 8.7% of the placebo group prematurely discontinued their medication course due to adverse events. In addition, 48.3% of the nintedanib group and 12.2% of the placebo group had ≥1 dose reduction and/or treatment interruption.
The percentage of patients with any adverse events was comparable between the nintedanib and placebo groups (98.3% and 95.8%, respectively). The most common adverse event was diarrhea, reported by 75.7% and 31.6% of the nintedanib and placebo groups, respectively. Most drug discontinuations were due to gastrointestinal symptoms. Serious adverse events occurred at similar rates in the nintedanib and placebo groups (24.0% and 21.5%, respectively). Adverse events in the nintedanib group occurred at similar rates across strata defined by age, sex, race, and weight. Nintedanib vs placebo also reduced the annual rate of decline in FVC, regardless of dose reductions or treatment interruptions.
Overall, adverse events in the nintedanib group were not different from those previously reported in the literature. Nintedanib slowed the decline of FVC in patients with SSc-ILD, even among those with reduced dose or interrupted treatment. The dose adjustments used in this trial may be an important tool to increase tolerability and maintain compliance among patients with SSc-ILD.
Study limitations included incomplete information on the procedures used for the management of gastrointestinal adverse events and the differences among the patient populations between the trials.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Seibold JR, Maher TM, Highland KB, et al. Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial. Published online August 5, 2020. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-217331