New and Effective Treatments for Idiopathic Pulmonary Fibrosis

Nicholas Gross, MD, PhD


July 11, 2014

Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis

Richeldi L, du Bois RM, Raghu G, et al; INPULSIS Trial Investigators
N Engl J Med. 2014;370:2071-2082

A Phase 3 Trial of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis

King TE Jr, Bradford WZ, Castro-Bernardini S, et al; ASCEND Study Group
N Engl J Med. 2014;370:2083-2092


Idiopathic pulmonary fibrosis (IPF) has been an untreatable condition since its description nearly a century ago. Its progression from diagnosis to death from respiratory failure is, on average, more rapid than that of lung cancer. At last, 2 new agents have now been reported to provide meaningful benefits.

Nintedanib, an inhibitor of tyrosine kinases, was studied in a pair of phase 3 randomized, double-blind trials involving a total of 1066 patients with early IPF, who received either placebo or active drug for 52 weeks. The primary outcome was rate of decline of forced vital capacity (FVC).

The annual rate of decline of FVC was decreased by more than 50% in both treatment groups compared with the placebo groups -- a highly significant difference. Among secondary outcomes, time to first acute exacerbation, a relatively rare event in IPF, was reduced in only one trial. Both the St. George's Respiratory Questionnaire (SGRQ), a measure of respiratory-related health status, and mortality were trending toward benefit but were not statistically improved.

A second phase 3 controlled trial was conducted on pirfenidone, an antifibrotic agent. It was done in 555 patients over 52 weeks, with annual decline in FVC or death being the joint primary outcome. In the active-drug group, this endpoint was reduced by 48% overall (P < .001). Progression-free survival and distance walked in 6 minutes were also substantially and significantly better in the active-drug group.

Both treatments were associated with adverse effects. In both nintedanib trials, a majority of patients in the active-drug groups experienced diarrhea, often associated with nausea, vomiting, and weight loss. However, less than 5% of those patients withdrew from the study. Liver enzymes were elevated in 5% of treatment group participants vs 0.5% of control participants. In the pirfenidone study, nausea was the most common adverse event (36% in the treatment group vs 13% in the placebo group). Rash was also more common in the active-treatment group. Liver enzymes were elevated in 3% of active-treatment recipients vs 0.7% of placebo recipients.


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