In patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), treatment with nintedanib has a clinically relevant benefit on disease progression, according to results of an analysis published in Arthritis & Rheumatology.
In the current post hoc analyses of the SENSCIS trial (ClinicalTrials.gov Identifier: NCT02597933), the study authors sought to explore the effects of nintedanib on categorical changes in forced vital capacity (FVC) and other measures of ILD progression. They evaluated the percentage of participants with categorical changes in FVC % predicted at week 52 and the time to absolute decline in FVC 5% or more predicted or death and absolute decline in FVC 10% or more predicted or death.
All participants were randomly assigned 1:1 to receive nintedanib 150 mg twice daily (n=288) or placebo (n=288), stratified by the presence of antitopoisomerase I antibody. Participants continued to receive blinded treatment until the last person in the study had reached week 52, but for 100 weeks or less. Mean participant age was 54.0 (SD, 12.2) years, with 75.2% of the participants being women and 67.2% White. Mean FVC was 2500 (SD, 777) mL and 72.5 (SD, 16.7) % predicted and mean diffusion capacity of the lung for carbon monoxide (DLCO) was 53.0 (SD, 15.1) % predicted.
Overall, 16.0% (n=46) of participants in the nintedanib group and 10.8% (n=31) of those in the placebo group had missing FVC data at week 52. At week 52, 55.7% of participants in the nintedanib group and 66.3% of those in the placebo group showed a decline in FVC % predicted. The percentage of participants in the nintedanib and placebo groups with absolute FVC declines of less than 5% to 10% or less predicted and greater than 10% to 15% or less predicted at week 52 were 13.6% vs 20.1%, respectively, and 3.5% vs 5.2%, respectively.
Further, in the nintedanib and placebo groups, 34.5% and 43.8% of participants, respectively, exhibited an absolute decrease in FVC of 3.3% or more predicted at week 52 (the proposed minimally clinically important differences [MCID] for worsening of FVC), whereas 23.0% vs 14.9%, respectively, had an absolute increase in FVC of 3% or more predicted at week 52 (the proposed MCID for improvement in FVC).
During the 52-week period, the hazard ratio (HR) for an absolute decline in FVC 5% or more predicted or death with nintedanib vs placebo was 0.83 (95% CI, 0.66-1.06: P =.14). In addition, the HR for absolute decline in FVC 10% or more predicted was 0.64 (95% CI, 0.43-0.95; P =.029).
Limitations of the analysis included its design (post hoc analysis), the fact that study authors did not assess whether categorical changes in FVC led to improvements or declines in patient-reported outcomes, the lack of adjusting for confounding factors, and the inability to form associations between FVC decline and mortality because of the small number of deaths.
Study authors concluded, “… these further analyses of FVC decline in the SENSCIS trial support a clinically meaningful effect of nintedanib on slowing the progression of SSc-ILD.”
Disclosure: The SENSCIS trial was supported by Boehringer Ingelheim. Please see the original reference for a full list of authors’ disclosures.
Maher TM, Mayes MD, Kreuter M, et al. Effect of nintedanib on lung function in patients with systemic sclerosis-associated interstitial lung disease: further analyses of the SENSCIS trial. Arthritis Rheumatol. Published online November 3, 2020. doi:10.1002/art.41576