Poor Lung Function Before Starting Ofev Seen as Main Reason for Halting Use in UK Real-world Study

A greater decline in lung function prior to treatment start may lead idiopathic pulmonary fibrosis (IPF) patients to stop using Ofev (nintedanib), as might older age, a real-world study from the United Kingdom found.

“No predominant reason for discontinuation was identified in this group,” its researchers wrote, but it’s possible “the preceding longer duration of disease burden limits tolerance to any side-effects and so increases the likelihood of discontinuation.”

The study, “Safety and tolerability of nintedanib for the treatment of idiopathic pulmonary fibrosis in routine UK clinical practice,” was published in the journal ERJ Open Research.

It investigated the safety and tolerability of Ofev, an approved IPF treatment marketed by Boehringer Ingelheim, in routine practice.

Researchers reviewed the clinical records of 154 IPF patients treated with Ofev, who were followed for at least 12 months at one of six National Health Service (NHS) hospital trusts in the U.K. The study included patients who started treatment between October 2014 and July 2015, when Ofev was provided through a company-funded compassionate-use program.

Patients were 71 years old on average, and 50 of them (32.5%) had previously been treated with Esbriet (pirfenidone; by Genentech).

In this group, 17 had more severely affected pulmonary function (a predicted forced vital capacity, or FVC, below 50%), while 81 had FVC scores between 50% and 80%, and 56 had less impaired respiratory function (FVC above 80%) before starting treatment with Ofev.

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The treatment was largely well-tolerated. In total, 77% of the patients reported at least one adverse event, with the most common  being gastrointestinal symptoms, including diarrhea, nausea, and reduced appetite. Weight loss was reported by 14.3% of patients, and 3.9% had altered liver function, as determined by a more than three times increase in liver enzyme activity.

Slightly less than half — 69 (44.8%) patients — discontinued treatment during the 12-month period that followed initiation, and 34 of them reduced their regular dose before stopping to use Ofev. Nearly half of the patients who discontinued, 32 people or 46.8% of this group, did so within three months of starting.

Those who discontinued were older, had poorer FVC scores before starting the treatment, and were using oxygen at home (a 76.5% discontinuation rate was seen among those with FVC under 50% predicted). Further analysis confirmed that increasing age and declining FVC at treatment initiation were associated with a greater likelihood of stopping Ofev. (The study, however, did not give an age range here.)

Most patients who continued with Ofev after one year of use had an initial FVC of greater than 80% predicted (39 people or  69.6%). In the middle FVC range, between 50% and 80% predicted, 42 patients or 51.8%  continued the treatment, but only four people among the 17 whose initial FVC was less than 50% predicted.

The researchers noted that Ofev is not offered within the U.K.’s public health system for the group of IPF patients with better lung function who did best at adhering to the treatment.

Discontinuation rates seen in this routine practice study were higher (around 44.8%) than those reported in clinical trials, which were about 25% in the INPULSIS Phase 3 trials (NCT01335464 and NCT01335477).

“This could be related partly to the current cohort, which included 50 patients not tolerating pirfenidone and may therefore be enriched for patients with a propensity towards drug induced side-effects,” the team wrote. “[I]ncreasing age and decreasing pre-treatment FVC are associated with increased probability of [Ofev] discontinuation during 52 weeks of treatment.”

Additional studies are warranted to “further investigate these real-world findings that suggest that commencement of antifibrotic therapy in patients with preserved lung volume (FVC higher than 80% predicted) may increase the duration of therapy for an individual patient,” the researchers added.

If these findings are confirmed, initiating treatment with Ofev earlier, while patients still retain their respiratory function, may be advised to help preserve  quality of life and reduced IPF-associated mortality rates, they concluded.