Ofev effectiveness, safety seen over 3-year SENSCIS extension trial
Sustained slowing of lung function decline shown for SSc-ILD patients
Treatment with Ofev (nintedanib) for up to four years was associated with a sustained slowing of lung function decline in people with systemic sclerosis (SSc) associated with interstitial lung disease (SSc-ILD).
That’s according to new results from the open-label study SENSCIS-ON (NCT03313180), a three-year extension of the SENSCIS Phase 3 trial that formed the basis for the therapy’s regulatory approvals. In the long-term extension, Ofev also had a safety profile consistent with previous studies, the new data show.
“These findings suggest that [Ofev] can be used over the long term to slow the progression of SSc-ILD and so improve patient outcomes,” the researchers wrote.
Their study, “Continued nintedanib in patients with systemic sclerosis-associated interstitial lung disease: 3-year data from SENSCIS-ON,” was published as a brief report in the journal RMD Open Rheumatic & Musculoskeletal Disorders.
SENSCIS-ON tracked SSc-ILD patients across up to 4 years
Systemic sclerosis, also known as scleroderma, is characterized by inflammation and fibrosis, or the accumulation of scar tissue, in the skin and internal organs, including the lungs. People with SSc may develop interstitial lung disease (ILD), a complication in which the lungs become scarred, impairing their ability to transfer oxygen to the bloodstream.
Ofev, an oral therapy by Boehringer Ingelheim, is approved in the U.S. and the European Union to slow lung function decline in people with SSc-ILD. It works by blocking a group of growth factor receptors involved in lung inflammation and fibrosis.
Its approval was based on data from the Phase 3 SENSCIS trial (NCT02597933), showing that after one year of treatment, Ofev slowed lung function decline by 44%, compared with a placebo. Lung health was assessed using forced vital capacity, or FVC, a measure of how much air a person can forcibly exhale after taking a deep breath. FVC is an important indicator of the progression of iILD.
Now, researchers described Ofev’s safety and efficacy over 148 weeks, or about 2.8 years, in 197 patients who received Ofev in the SENSCIS study and continued the treatment in the extension part, as well as 247 patients who started on Ofev in SENSCIS-ON. The latter group mainly comprised patients — 231 in total — given the placebo in the SENSCIS trial, who switched to Ofev in the extension study.
At enrollment in the extension study, participants had a mean age of 55. The majority were white individuals (69.4%) and females (75.5%). The mean percent predicted FVC was 70.6%. Treatment was administered at the same dose used in the SENSCIS trial, 150 mg twice daily, unless a dose reduction to 100 mg twice daily was necessary.
The median duration of Ofev treatment was 35.8 months, or approximately three years, for patients who continued the treatment. In total, the median cumulative treatment time across the SENSCIS and SENSCIS-ON trials was nearly four years. For those who started treatment during the study, the median duration was 31.4 months, or about 2.6 years.
More patients who started Ofev in SENSCIS-ON had at least one treatment dose reduction (59.9% vs. 26.9%), and also had at least one treatment interruption (53% vs. 36.5%), than those who continued treatment.
Overall, 64% of the patients in the continued treatment group and 50.6% of those in the initiated group were still receiving treatment at week 148.
Ofev effectiveness, safety similar for patients in study and extension
The most commonly reported adverse event was diarrhea, reported in 77.2% of those who continued Ofev and 74.1% of those who initiated treatment. Other reported side effects included nausea, skin ulcers, vomiting, and liver test abnormalities.
Adverse events leading to Ofev discontinuation occurred in 14.7% of patients on continued treatment and 29.1% of those who initiated Ofev, with diarrhea as the most common cause. Serious adverse events were reported in about 39% of the patients in both groups, the data showed.
According to the researchers, “the rates of dose reductions, treatment interruptions, and discontinuations of [Ofev] over the first 52 weeks were similar in patients who initiated [Ofev] in SENSCIS-ON as in patients who initiated [treatment] in the SENSCIS trial.”
Changes in FVC [forced vital capacity] during SENSCIS and SENSCIS-ON supported a continued effect of [Ofev] on slowing the decline in lung function in patients with SSc-ILD, [though] lung function continued to decline.
A total of 102 patients (51.8%) in the continued nintedanib group and 88 patients (35.6%) in the initiated nintedanib group had available FVC data at both the beginning of the study and week 148. The mean decline in FVC between baseline and week 148 was 160 mL in all patients, with a higher decline observed in patients in the continued treatment group (189.1 vs. 126.5 mL).
“Changes in FVC during SENSCIS and SENSCIS-ON supported a continued effect of [Ofev] on slowing the decline in lung function in patients with SSc-ILD, [though] lung function continued to decline,” the researchers concluded.
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