Ofev Effective in Elderly Patients, Those With Comorbidities

Treatment with Ofev (nintedanib) is safe and can preserve lung function in people with idiopathic pulmonary fibrosis (IPF) who are elderly or have several other health conditions, a new study indicates.

The study, “Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities,” was published in Respiratory Research and funded by Boehringer Ingelheim, which markets Ofev.

Ofev is an approved anti-fibrotic treatment for IPF that can improve patients’ lung function. IPF typically affects elderly people (older than 60), and it is fairly common for them to have comorbidities (co-occurring health conditions other than IPF).

“Some clinicians may be reluctant to use anti-fibrotic therapies [such as Ofev] in elderly patients with IPF due to concerns over side effects, or a belief that elderly patients will receive less of a benefit from therapy,” Ian Glaspole, MD, professor at Monash University in Australia and co-author of the study, said in a Boehringer Ingelheim podcast.

An international team of researchers from Boehringer Ingelheim and other institutions performed an analysis of clinical trial data in order to better understand the effectiveness of Ofev treatment in IPF patients who are elderly or have multiple comorbidities — including cardiovascular diseases, diabetes, liver disease, kidney disease, and cancer, among others.

In total, the investigators analyzed data for 1,690 IPF patients who were given either Ofev (150 mg twice daily) or a placebo in five clinical trials:  NCT00514683, NCT01335464, NCT01335477, NCT02788474, and NCT01979952.

Among the patients, 326 were 75 or older upon starting the trial. Compared to younger patients, these elderly patients included a higher percentage of females (25.5% vs. 21.6%), and had lower average body weights.

Among individuals younger than 75, treatment with Ofev for 52 weeks slowed the rate of decline in forced vital capacity (FVC) by 125.2 mL/year on average, compared to values for patients given placebo. FVC is a standard measurement of lung function.

Similar results were seen among elderly patients, in whom the rate of FVC decline slowed by 105.3 mL/year compared to the placebo group.

Additional statistical analyses showed that Ofev treatment had similar effects at preventing exacerbations and extending lifespan in elderly patients as it did in younger patients.

In other analyses, the researchers divided patients into two groups based on the number of comorbidities: fewer than five (843 patients) or five or more (847 patients). The group with more comorbidities had a higher percentage of females and whites, was older on average, and had higher average body weight and BMI (body mass index). Common comorbidities included high blood pressure, high cholesterol, and gastroesophageal reflux disease.

Ofev treatment slowed the rate in FVC decline similarly in individuals with less than five (107.9 mL/year) or more than five (139.3 mL/year) comorbidities. Additional analyses generally indicated no difference in the effect of Ofev in the two groups, including the effect on exacerbations and lifespan.

Other analyses based on a measurement called the Charlson Comorbidity Index, to assess comorbidity severity, found generally consistent results — that is, the benefits of Ofev treatment were similar in people with more or fewer comorbidities.

The safety profile of Ofev was generally consistent in elderly and younger patients, and it also was largely consistent for people with more or fewer comorbidities. Most common side effects of Ofev reported were gastrointestinal effects (related to the digestive tract), such as diarrhea.

Notably, while rates of side effects were similar between subgroups, patients who were older or had more comorbidities were more likely to discontinue treatment due to side effects — likely because these frailer patients were less able to tolerate them, the researchers noted.

“This highlights the importance of managing any side effects of [Ofev] through symptom relief or dose-adjustment, to help patients remain on therapy,” Glaspole said in the podcast.

Also, elderly patients more frequently reported weight loss as an adverse event (side effect), and elderly patients also tended to weigh less at the start of treatment.

“This suggests that in the most elderly patients, clinicians need to be particularly mindful of weight loss as an adverse event and ensure that gastrointestinal events are managed effectively and nutritional interventions provided where needed,” the researchers wrote.

Overall, the team concluded that the therapeutic effects of Ofev in reducing lung function decline are “consistent across subgroups based on age and comorbidity burden,” they wrote.