Ofev Seen to Slow Lung Function Decline Across SSc-ILD Subgroups

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Clinical trial results are shown with a bar graph, with a stethoscope, pills and hands surrounding the graph.

Ofev (nintedanib) effectively slowed lung function decline in adults with interstitial lung disease (ILD) associated with systemic sclerosis (SSc-ILD) across patient groups based on autoantibody status and skin involvement severity, according to an analysis of the SENSCIS trial.

These findings add to the trial’s top-line results, which showed that one year of treatment with Ofev was superior to a placebo at reducing the rate of ILD progression in SSc patients, and supported the therapy’s benefits across a broad population of people with SSc-ILD.

Analysis results were described in the study, “Nintedanib in patients with systemic sclerosis-associated interstitial lung disease: subgroup analyses by autoantibody status and skin score,” published in the journal Arthritis & Rheumatology.

Systemic sclerosis, also known as scleroderma, is characterized by tissue scarring (fibrosis) that may affect multiple organs, such as the lungs.

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Interstitial lung disease, the leading cause of death among SSc patients, comprises a group of lung disorders in which the tissue in and around the air sacs becomes inflamed and scarred, impairing the lungs’ ability to transfer oxygen to the bloodstream.

Ofev, an oral treatment by Boehringer Ingelheim, was the first therapy approved to slow lung function decline in people with SSc-ILD. It works by blocking a group of growth factor receptors involved in lung fibrosis.

Its approval in several countries was based on top-line data from the global Phase 3 SENSCIS trial (NCT02597933), which evaluated Ofev’s safety and effectiveness against a placebo in 576 adults with SSc-ILD. Half were treated with Ofev, while the other half were given a placebo, both taken twice daily for up to one year.

The study met its main goal, with one year of Ofev’s use slowing a decline in patients’ lung function by 44% relative to a placebo. Lung health was assessed through forced vital capacity (FVC), representing how much air can be forcibly exhaled after taking a deep breath.

No significant differences were evident between the groups in terms of skin thickness, as assessed with the modified Rodnan skin score (mRSS).

An international team of researchers involved in the SENSCIS study now conducted a post-hoc analysis to assess whether Ofev was effective across distinct subgroups of patients, based on features previously associated with SSc-ILD progression. (A post-hoc trial analysis is done after a study has finished, often to focus on a particular subject of interest.)

These features included the presence of anti-topoisomerase I antibodies (ATAs) — self-reactive antibodies often found in SSc patients — SSc subtype (limited cutaneous SSc or lcSSc, and diffuse cutaneous SSc or dcSSc), and mRSS scores (low scores vs. 18 or higher scores).

ATA antibodies and the dcSSc subtype have been associated with a higher risk of ILD, and mRSS scores of 18–25 were previously shown to include patients with progressive skin fibrosis. Ranging from 0 to 51, higher mRSS scores indicate thicker skin.

Of the 576 patients who participated in SENSCIS, 60.8% were positive for ATAs and 51.9% had dcSSc at the start of the study (baseline). Most patients with available mRSS data at baseline — 77.5% of 574 people — had a score lower than 18.

Ofev was superior to placebo at slowing lung function decline across all subgroups, with each having a greater proportion of Ofev-treated patients maintaining or showing clinically meaningful improvements in lung health relative to those on a placebo.

Compared with a placebo, Ofev’s effect on FVC decline was also numerically more pronounced among ATA-negative patients, those with mRSS scores of 18 or higher, and dcSSc patients, relative to their respective counterparts.

However, these differences did not reach statistical significance, meaning the possibility exists, mathematically, that they are due to random chance. The team noted that this post-hoc subgroup analysis was not powered for statistical testing, and should be considered exploratory.

Consistent with SENSCIS’ findings in the overall patient population, Ofev had no effect on skin thickness across all subgroups, relative to placebo.

Among placebo group patients, the annual rate of lung decline was similar between those ATA-positive and ATA-negative, but greater among those with an mRSS score of 18 or higher (vs. lower scores), and in those with dcSSc (relative to lcSSc patients).

“These findings support a clinically meaningful benefit of [Ofev] in reducing the rate of ILD progression across a broad population of patients with SSc-ILD,” the researchers wrote.

Combined data from SENSCIS and its extension study SENSCIS-ON (NCT03313180) showed that up to two years of Ofev treatment continued to be safe and to effectively slow lung function decline in SSc-ILD patients.