Nintedanib may slow the decline in lung function among patients with limited cutaneous systemic sclerosis (lcSSc) and interstitial lung disease (ILD) by targeting pulmonary fibrosis, as these patients may develop progressive fibrosing ILD, according to study results published in Rheumatology (Oxford).
The randomized controlled SENSCIS trial (ClinicalTrials.gov Identifier: NCT02597933), included patients diagnosed with systemic sclerosis (SSc)-ILD who were randomly assigned to be given either nintedanib 150 mg twice daily or placebo. Patients continued receiving blinded treatment for 100 weeks, until the last patient reached week 52.
Patients who finished the SENSCIS trial and completed follow-up 28 days later or finished a study on the interaction between nintedanib and oral contraceptives could enter the open-label SENSCIS-ON study (ClinicalTrials.gov Identifier: NCT03313180), where all participants received nintedanib.
Using data from both trials, investigators assessed the change in lung function (measured in forced vital capacity [FVC]) from study baseline to week 52 among patients with lcSSc. They further assessed the percentages of patients with relative declines in FVC greater than 5% and 10%, as well as absolute declines in FVC greater than 5% and 10%, predicted at week 52.
Overall, patients with lcSSc experienced a decline in FVC over 52 weeks. The decline rate was -74.5 (standard error [SE], 19.2) mL/year among those who received placebo and -49.1 (SE, 19.8) mL/year among those who were given nintedanib. The between-group difference was 25.3 (95% CI, -28.9 to 79.6) mL/year.
At week 52, the average change in FVC was -39.1 (SE, 22.2) mL among those taking nintedanib and -86.4 (SE, 21.1) mL among those taking placebo. This suggested a continuous positive effect in slowing down the progression of SSc-ILD with the use of nintedanib.
Additionally, patients who received nintedanib had similar or lower proportions of both relative and absolute declines in FVC greater than 5% and 10% predicted at week 52, compared with those who received placebo.
During the 52 weeks, diarrhea was the most common adverse event reported, occurring in 77.0% of those taking nintedanib and 30.3% of those taking placebo.
The mean change in FVC from baseline to week 52 was -41.5 (SE, 24.0) mL among patients given placebo in the SENSCIS trial who started taking nintedanib in SENSCIS-ON. Among patients who took nintedanib in the SENSCIS trial and continued treatment in SENSCIS-ON, the mean change in FVC was -45.1 (SE, 19.1) mL.
Diarrhea was the most commonly reported adverse event in the SENSCIS-ON trial, occurring in 71.4%, of patients who took nintedanib continuously and 70.1% of patients who initiated it.
Study limitations include that the SENSCIS and SENSCIS-ON trials were not specifically designed to measure results among patients with lcSSc, and SENSCIS-ON did not have a placebo comparison group. Additionally, not all patients from SENSCIS continued into SENSCIS-ON.
Study authors concluded, “These findings support the screening of patients with lcSSc for ILD and the importance of prompt initiation of treatment in patients with lcSSc-ILD to preserve lung function.”
Allanore Y, Khanna D, Smith V, et al. Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease. Rheumatol (Oxford). Published online June 9, 2023. doi:10.1093/rheumatology/kead280