Ofev May Be Less Tolerable Over Long Term in IPF Patients in Poorer Health

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by Joana Carvalho |

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Ofev study

People with idiopathic pulmonary fibrosis (IPF) in poorer health are less likely than healthier patients to tolerate more than one year of treatment with Ofev (nintedanib), and benefit less from the therapy than those able to continue with its use, a small real-world study reports.

Side effects that included nausea, and disease progression were the main reasons IPF patients being followed at two hospitals in Japan stopped the treatment after 12 months, its researchers noted.

But benefits in lung health and survival were evident in those who continued with Ofev, suggesting this treatment is best started before IPF progresses and overall health declines.

The study, “Clinical Significance of Continuable Treatment with Nintedanib Over 12 Months for Idiopathic Pulmonary Fibrosis in a Real-World Setting,” was published in the journal Drug Design, Development and Therapy.

Marketed by Boehringer Ingelheim, Ofev is an oral anti-fibrotic therapy approved in the U.S. and Europe to treat IPF. It works by interfering with several signaling cascades, including the PDGF and FGF signaling pathways that are known to be overly active in people with lung tissue scarring (fibrosis).

Its approval in both regions was supported by data from two replicate Phase 3 trials — INPULSIS-1 (NCT01335464) and INPULSIS-2 (NCT01335477) — which showed Ofev to be effective at slowing lung function decline in patients, as well as at reducing the frequency of disease exacerbations (flares).

Two subsequent extension studies — INPULSIS-ON (NCT01619085) and TOMORROW (NCT01170065) — also showed Ofev to be safe and well-tolerated when used long term to treat IPF (up to around five years).

However, no real-world studies have focused on the long-term safety and efficacy of Ofev in this patient population.

Investigators in Japan analyzed data covering 104 IPF patients — 90 men and 14 women with a median age of 73 — treated with Ofev between October 2015 and December 2018, and followed at hospitals in that country.

Patients were divided into two groups, depending on the total amount of time they had been taking Ofev. The “P” group comprised 51 patients who found it possible to continue taking Ofev for more than one year. In the “I” group were the remaining 53 patients who found it impossible to take the medication for more than one year or stopped within one year.

All treatment safety and efficacy analyses were performed comparing these two patient groups.

Of the 53 patients in the I group, 29 stopped taking Ofev due to side effects, which included diarrhea, nausea and/or anorexia (loss of appetite). Another 19 stopped treatment due to IPF progression, four due to an overall deterioration in health. One person in this group died suddenly.

Cases of nausea were significantly higher among those in the I group (49.06%) than the P group (25.49%), as were incidences of collapsed lung or pneumothorax ( 13.21% for the I group and 1.96% for the P group), analyses showed.

No significant differences in incidences of other side effects, including diarrhea, were found between the two groups.

The benefits of continued treatment were evident in analyses. P group patients lived longer compared with those in I group — a median survival of 35 vs. 12 months. And P group patients showed slower lung function decline, or a  loss of 0.35%  each year vs. 4.99% annual decline among people in the I group.

Poor overall health at the time of treatment initiation was identified in statistical analyses as the only significant risk factor for discontinuing Ofev’s use over or after one year of treatment.

Additional survival analyses confirmed that patients in overall better health lived longer than those in poorer overall health, 27 vs. 13 months.

“Our findings propose that a poor PS [performance status; roughly, overall health] was the only risk factor for discontinuation of nintedanib treatment after 12 months,” the researchers wrote.

Based on the findings, the team proposed that IPF patients should start taking Ofev before their overall health deteriorates, in order to maximize potential treatment benefits that include a better survival rate.