Nintedanib Benefits FVC Decline in Systemic Sclerosis Plus ILD

Kristin B. Highland, MD

Nintedanib is associated with a reduced annual rate of forced vital capacity (FVC) decline in patients with systemic sclerosis-associated interstitial lung disease (ILD), according to the results of the one-year Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial.

Trial results presented at the American Thoracic Society (ATS) 2019 International Conference in Dallas, TX, show the intracellular tyrosine kinases inhibitor nintedanib has a similar benefit for patients with the rare, heterogenous associated form of ILD as it does for patients with idiopathic pulmonary fibrosis.

Investigators—led by Oliver Distler, MD, of the Department of Rheumatology at the University Hospital of Zurich, and Kristin B. Highland, MD, of the Respiratory Institute at the Cleveland Clinic—sought to understand whether anitfibrotic, anti-inflammatory therapy nintedanib could provide efficacious, safe disease progression reduction in patients with systemic sclerosis-associated ILD.

For the Boehringer Ingelheim-funded trial, the team conducted a randomized, double-blind, placebo-controlled assessment of patients with systemic sclerosis and an onset of first non-Raynaud’s symptom in the past 7 years. Qualified patients also had a computed tomographic scan showing fibrosis affecting at least 10% of their lungs.

Patients were assigned 1:1 to either 150 mg twice-daily oral nintedanib, or placebo. Primary study endpoint was annual rate of FVC decline over 52 weeks, and key secondary endpoints were overall changes in modified Rodnan skin score and St. George’s Respiratory Questionnaire (SGRQ) from baseline at week 52.

The trial included 576 patients; of which more than half (51.9%) had diffuse cutaneous systemic sclerosis, and almost half (48.8%) were receiving mycophenolate at baseline. Mean patient age was 54±12.2 years, and median time to first non-Raynaud’s symptom was 3.4 years.

Adjusted annual rate of FVC change was -52.4 ml per year for patients on nintedanib—a reduced rate compared to the -93.3 ml average change in patients on placebo (41 ml; 95% CI: 2.9 — 79; P= .04). Modified Rodnan skin score and total SGRQ score from baseline to week 52 did not differ significantly across treatment groups.

Investigators concluded that nintedanib’s clinical benefit was solely reserved for ILD patients with associated systemic sclerosis, albeit with an adverse-event profile similar to that observed in patients with idiopathic pulmonary fibrosis and still no existing assessment of the therapy in patients with clinically significant pulmonary hypertension—such patients were excluded from the trial.

The split patient population who were previously administered mycophenolate may be the best candidates for daily nintedanib.

“Despite the large variability associated with the adjusted annual rates of decline in FVC observed in the current trial and the limitations inherent in comparing groups of patients who had not undergone randomization according to mycophenolate use, these data suggest a potential benefit of mycophenolate on lung function,” the team wrote.

Though the clinical benefit in FVC decline was singular to systemic sclerosis-associated ILD patients over 1 year, an ongoing, uncontrolled open-label extension study is hoping to provide clinicians more evidence of benefit.

The study, “Nintedanib for Systemic Sclerosis-Association Interstitial Lung Disease,” was published online in the New England Journal of Medicine.