Treatment with Ofev (nintedanib) offers less clinical benefit to patients with severe idiopathic pulmonary fibrosis (IPF) than to those with mild-to-moderate disease, but does improve outcomes if these patients are able to continue on treatment over the longer term, a new study shows.
Controlling the therapy’s side effects will be essential in this more vulnerable patient group, its researchers said.
The study, “Utility of nintedanib for severe idiopathic pulmonary fibrosis: a single-center retrospective study,” was published in the journal Drug Design, Development and Therapy.
The severity of IPF can be determined using tests to assess pulmonary function, which help measure parameters such as forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). FVC measures the total amount of air exhaled, while DLCO evaluates the extent to which oxygen passes from the air sacs of the lungs into the blood.
Results from the Phase 2 TOMORROW (NCT00514683), and Phase 3 INPULSIS-1/2 (NCT01335464/NCT01335477) clinical trials showed that Ofev treatment was associated with less decline in lung function and with fewer acute exacerbations.
However, the inclusion criteria for these clinical trials favored patients who had mild to moderate disease severity.
The INPULSIS-ON trial (NCT01619085), an open-label extension of the INPULSIS trial, included IPF patients with more severe disease. Results showed that Ofev, marketed by Boehringer Ingelheim, decreased FVC decline in both advanced and non-advanced patients. However, further studies on this topic are needed.
So, researchers in Japan undertook a study to evaluate the effectiveness and safety of Ofev in patients with severe IPF in real-world conditions. They conducted a single-center, retrospective study, with patients with mild or moderate IPF (34 patients), as well as severe IPF (17 patients). All patients were treated with an initial dose of 150 mg twice daily.
Results indicated that among patients with severe IPF, the mean decline in FVC after one year of treatment was reduced by using Ofev, compared to one year before treatment (decline of minus 143 mL of lung capacity versus minus 459 ml before treatment). This was similar to that found in the mild-to-moderate IPF group (minus 106 mL versus minus 273 mL before treatment).
Regarding safety, results indicated that the main adverse side effects — including diarrhea, nausea, liver disease, and acute exacerbation — tended to occur more often in patients with severe IPF. However, the difference was not statistically significant compared to the mild-to-moderate IPF group.
The continuation rates of Ofev treatment over 12 months were significantly higher in the mild-to-moderate group (77%), compared to the severe IPF group (44%).
Finally, the prognosis was significantly better for patients in the mild-to-moderate group than in those in the severe group. However, among patients with severe IPF, those who were able to continue Ofev treatment for more than three months had a significantly better prognosis compared to those who could not.
Overall, the team concluded: “survival benefit from nintedanib [Ofev] is reduced in patients with severe IPF when compared to those with mild to moderate IPF; however, an improvement in prognosis may be expected when side effects are controlled and the drug is administered over long-term. Hence, controlling side effects in severe [IPF] group is very important.”