HONOLULU, Hawaii — There’s new evidence to support a practice that many pulmonologists have been doing empirically anyway: namely, reducing the dose of the antifibrotic medication nintedanib (Ofev) for patients with idiopathic pulmonary fibrosis (IPF) who can’t tolerate the full 150 mg twice-daily dose.
An analysis of data from a large administrative claims database showed that there were no significant differences in either all-cause mortality or hospitalization rates between patients with IPF treated at the full 150 mg twice-daily dose and those treated with a reduced twice-daily dose of 100 mg nintedanib.
Although the results need to be confirmed by additional prospective and registry studies, they suggest that patients with IPF can still fare just as well with a reduced-dose nintedanib regimen, ideally with fewer gastrointestinal side effects such as diarrhea, reported Andrew Limper, MD, from the Mayo Clinic in Rochester, Minnesota.
“At least on this preliminary data you could…rest assured,” Limper told his colleagues in an oral abstract session here at the American College of Chest Physicians (CHEST) 2023 annual meeting.
“This is not definitive proof, I’m not making more out of this than it is, but we all put people on 100 mg twice daily because their guts don’t tolerate it; they live in the bathroom and they don’t want to live that way,” Limper said.
Hard to Take
Nintedanib is approved in the US for the treatment of IPF, chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype, and systemic sclerosis-associated ILD. For IPF, the standard dose established in randomized clinical trials is 150 mg twice daily.
However, nintedanib is associated with a number of side effects, including hepatic and other gastrointestinal toxicities, arterial thromboembolic events, and proteinuria within the nephrotic range. As a result, clinicians often reduce the dose to 100 mg twice daily, but there is a lack of data to indicate whether it’s safe to do so or if efficacy will be compromised.
To see whether dose reductions might result in poorer outcomes for patients with IPF, Limper and colleagues analyzed data from the OptumLabs Data Warehouse, a large administrative claims database, to compare outcomes for patients treated with IPF at either the 150 mg or 100 mg twice-daily doses.
They used propensity-score matching to account for differences among individuals according to age, sex, race/ethnicity, residence, insurance type, additional medication use, oxygen use, smoking status, healthcare use, and comorbidities. The final cohort included 346 patients in each dosing group.
There was no difference between the dosing groups for the primary outcome of all-cause mortality at 18 months, with a nonsignificant hazard ratio of 0.65 (P = .313), and no significant difference over 24 months in risk of hospitalization, with a hazard ratio of 0.98 (P = .899).
“This is not randomized controlled data; I doubt that [nintedanib maker Boehringer Ingelheim] is ever going to do a 150 vs 100 milligram head-to-head trial, but it does give us some ground to start to look at this,” Limper said.
Not So Sure
Session co-moderator Misbah Baqir, MBBS, who is also from the Mayo Clinic but was not involved in the study, told Medscape Medical News that she would need to see more data from prospective studies using endpoints other than mortality before she could be convinced that nintedanib dose reductions do not adversely affect efficacy.
“I feel that the endpoint should be different, either it should be forced vital capacity change, quality of life, or something else. The problem with a database study is that you don’t have everything in it. You have to play with what you have, and you don’t have forced vital capacity. You have to go into the charts to get it,” she said.
It would be more helpful to objectively compare, for example, diarrhea episodes or other adverse events to see whether they were significantly reduced with the 100 mg dose, she added.
In an interview with Medscape, Limper said that he and his colleagues plan to gather additional observational data including the newly available Medicare fee-for-service data set, registry data, and other sources.
“If we get all of that, and it really still looks compelling — and that’s an if — then I think that would be the foothold to go back to the manufacturer and say, ‘Hey, maybe you ought to think about doing a prospective trial to prove it with lung function and other endpoints such as 6-minute walks,'” he said.
The study was supported by a grant from Three Lakes Foundation. Limper and Baqir have disclosed no relevant financial relationships.
American College of Chest Physicians (CHEST) 2023 Annual Meeting: The Impact of Nintedanib Dosing on Clinical Outcomes: An Analysis of Real World Data. Presented October 8, 2023.
Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.
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