HONOLULU — A reduced-dose regimen of the antifibrotic medication nintedanib (Ofev) held up in real-world clinical practice, an observational study found.
Approved for the treatment of idiopathic pulmonary fibrosis (IPF), nintedanib at the standard dose of 150 mg twice daily was not significantly better than 100 mg twice daily for the outcomes of all-cause mortality at 18 months (HR 0.65, 95% CI 0.29-1.49) and hospitalization at 24 months (HR 0.98, 95% CI 0.71-1.35).
“At least on this preliminary data, you can be a little rest assured,” said Andrew Limper, MD, of Mayo Clinic in Rochester, Minnesota, here at the CHEST annual meeting hosted by the American College of Chest Physicians.
“This is not definitive, I’m not trying to make more out of this study than it is, but we all put people on 100 mg twice daily because their guts don’t tolerate it and they’re living in the bathroom. They don’t want to live that way,” he added.
Nintedanib works by inhibiting a variety of tyrosine kinase receptors that drive the pathogenesis of IPF. The drug has been around for nearly a decade since the FDA approved it, alongside another antifibrotic drug pirfenidone (Esbriet). Approval was supported by evidence that nintedanib slows the progression of IPF, demonstrated by a reduced decline in forced vital capacity in the INPULSIS trials.
The standard dose of nintedanib thus went to market, though the reduced dose came into practice because many patients encountered upset stomach, weight loss, diarrhea, and other side effects.
“Empirically, clinically, all of us, anybody in this room ever reduce the dose from 150 to 100 twice a day?” Limper asked the room at CHEST. A smattering of hands were raised from the audience. “What data were you basing that on? Anybody have good data? Well, the data doesn’t really exist. That’s why we did this stuff.”
Limper said his group is currently working to identify risk factors that might identify people more prone to getting side effects on nintedanib.
Whether slowly or quickly, the progression of IPF leads to scarring in the lungs and may cause acute exacerbations. No cure for IPF exists, though recent data showed that an investigational oral PDE4 inhibitor halted disease progression even when used on top of existing antifibrotic drugs.
Real-world observational studies have shown that antifibrotic agents reduce mortality and rates of hospitalization for about 2 years and that goes away as the disease progresses, Limper said, adding that effects are considered equivalent between pirfenidone and nintedanib.
In the present report, Limper’s group had performed a retrospective analysis based on administrative claims from the OptumLabs Data Warehouse. The speaker noted that this dataset covers diverse practice settings nationwide and links insurance records — mostly private insurance and Medicare Advantage from UnitedHealth.
The investigators identified and compared IPF patients treated with nintedanib 150 versus 100 mg twice daily using a 1:1 propensity score-matched cohort of 346 individuals in each dosing group.
Limper said an extended version of the analysis is underway with additional Medicare fee-for-service data. He said he doubted that the manufacturer of nintedanib is ever going to do 150 versus 100 mg head-to-head trials and that his team’s findings should be confirmed with other studies.
For now, best practice is still to start IPF patients on the traditional dose of nintedanib and see if side effects occur, Limper suggested.
“I always start at 150 mg twice a day,” he stressed. “I always start at the full dose because that’s what was studied.”
Limper disclosed a grant from Three Lakes Foundation for research.
Source Reference: Limper A, et al “The impact of nintedanib dosing on clinical outcomes: an analysis of real world data” CHEST 2023.