Trial results were discussed at the 2019 Annual European Congress of Rheumatology (EULAR) in Madrid, during an oral presentation titled “Efficacy of Pirfenidone in Systemic Sclerosis Related Interstitial Lung Disease — a Randomised Controlled Trial.”
Pirfenidone, marketed under the brand name Esbriet by Genentech, is an approved therapy for the treatment of idiopathic pulmonary fibrosis (IPF). The therapy can effectively help slow the progression of IPF, and delay loss of lung function in these patients.
Studies have shown that the underlying biological mechanisms of IPF are similar to those contributing to tissue scarring (fibrosis) in people with SSc. This has led researchers to explore the impact of pirfenidone as a potential treatment for SSc-ILD in a clinical trial (CTRI/2018/01/011449).
The study enrolled 34 adults with confirmed SSc-ILD, who had more than 50% of predicted forced vital capacity (FVC, a measure of lung function), and more than 30% of diffusing capacity of lung for carbon monoxide (a measure of oxygen uptake).
Participants were randomly assigned to take pirfenidone or a placebo for 6 months (17 patients per group). The treatment started with a dose of 600 mg per day of pirfenidone, which was increased to 2,400 mg per day within the first month, and continued for the duration of the trial.
By the end of the trial, 16 (94.1%) patients who had been treated with pirfenidone showed stabilization of lung function, compared to 13 (76.5%) in the placebo-treated group.
The treatment, however, failed to improve patients’ FVC, with a median change of 0.55% reduced FVC, compared to 1% improvement in the placebo group.
Further evaluations showed that the 6-month treatment with pirfenidone did not have a positive effect on the patient’s physical capacity (as determined by the 6-minute walking distance exercise), nor did it prevent skin scarring (measured by the modified Rodnan skin score).
Also, pirfenidone failed to effectively reduce the levels of TNF-alpha and TGF-beta in the blood. These are well-known contributors for tissue scarring and inflammation in SSc.
“We failed to demonstrate a beneficial effect of pirfenidone over placebo in stabilizing FVC, functional status, or skin disease after six months of therapy,” researchers said.
Although IPF and SSc-ILD share some disease-associated mechanisms, IPF only affects the lungs. SSc-ILD can affect a variety of organs, including the skin, lungs, heart, gastrointestinal tract, and kidneys. So it is crucial to evaluate the overall impact of the therapy.
Regarding safety, treatment with pirfenidone was in general well-tolerated, with most of the adverse events reported — gastrointestinal symptoms and skin rashes among them — being mild. Only one serious gastrointestinal adverse effect was reported.
Despite the disappointing efficacy results, the team suggested that further studies with larger groups of patients and longer follow-up could provide more detailed information on the real potential of pirfenidone for people with SSc-ILD.