The long-term extension SENSCIS-ON trial shows patients receiving nintedanib over 3 years were not at significantly greater risk of serious adverse events or outcomes.
A majority of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) adhered to a ≥3-year regimen of nintedanib without a serious adverse event and with opportunity to reduce their dosage while maintaining forced vital capacity (FVC) management, according to findings from an open-label extension trial.1
In data from the SENSCIS-ON study extension, presented at the Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting in Destin, FL, this week, a multinational team of investigators reported that the 148-week safety profile associated with nintedanib was consistent with the phase 3, 52-week SENSCIS trial. Along with tolerability and sustained efficacy outcomes, the data support a long-term use of the tyrosine kinase (TK) inhibitor for SSc-ILD.
Led by Yannick Allanore, MD, PhD, of the department of rheumatology at Descartes University, Cochin Hospital in Paris, investigators conducted the open-label extension of SENSCIS to further investigate adverse events and FVC decline in patients with SSc-ILD treated with nintedanib over the period of a few years. As they noted, the original 52-week trial showed 150 mg twice-daily oral nintedanib was associated with a 44%, or 40.9 mL, improvement in adjusted annual FVC change versus placebo (-52.4 ml vs -93.3 ml).2
The trial additionally showed adverse events were “manageable in most patients.”
The SENSCIS-ON extension trial was comprised of original trial participants who completed the ≥52-week regimen, plus participants from a drug-drug interaction (DDI) trial of nintedanib and oral contraception; the latter trial included female patients with SSc-ILD who received nintedanib for ≥14 – 28 days. Allanore and colleagues assessed adverse events and changes in FVC from baseline to ≤148 weeks among 197 patients patients who received nintedanib in the SENSCIS trial, as well as in the 247 patients who received placebo in the trial or who received nintedanib in the DDI trial.
Mean baseline FVC was 2379 mL and 70.4% predicted among the continued nintedanib arm, and 2443 mL and 70.8% predicted in the initiated nintedanib arm. Investigators observed that 64.0% and 50.6% of the trials’ arms were still receiving treatment at 148 weeks, respectively.
Significant adverse events across each treatment arm included diarrhea (77.2% and 74.1%, respectively), nausea (21.8% and 29.6%, respectively), and skin ulcers (24.4% and 21.9%, respectively), among others. Approximately one-third (38.6% and 38.5%) of patients reported a serious adverse event; another 14.7% and 29.1%, respectively, reported an adverse event leading to treatment discontinuation.
Investigators observed that 26.9% and 59.9% of patients, respectively, achieved a ≥1-dose reduction by 148 weeks; another 36.5% and 53.0% had ≥1 treatment interruption.
Mean FVC change was -189.1 mL in the continued nintedanib arm and -126.4 mL in the initiated nintedanib arm, respectively, from baseline to week 148.
In a 2019 interview with HCPLive regarding the original SENSCIS trial findings, study author Kristin Highland, MD, stressed the importance of ensuring benefit in FVC decline reduction among patients with SSc-ILD.3
“So forced vital capacity is really our best surrogate for overall lung function and it does track with what we see on chest CT; it does track with survival,” Highland said at the time. “This is an orphan disease—it would be a little difficult to power design the study to be a mortality study. So first vital capacity, at this point in time, is probably our best surrogate in in all comers with interstitial lung disease.”
In the current SENSCIS-ON trial findings, Allanore and colleagues concluded nintedanib may remain viable for patients through 3 years.
“The safety profile of nintedanib over 148 weeks of SENSCIS-ON was consistent with that reported in the SENSCIS trial, characterized mainly by gastrointestinal events that were manageable for most patients,” they wrote. “These results support the potential use of nintedanib in the long-term treatment of patients with SSc-ILD.”