Phase 3 Antifibrotic-Directed Therapy Outcomes in Idiopathic Pulmonary Fibrosis: Beyond FVC Decline.
Fumihiro Kashizaki, Shohei Watanabe, Ryusuke Orii et al.
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In 30 seconds
This systematic review compared phase 3 randomized, placebo-controlled trials of antifibrotic-directed therapies in idiopathic pulmonary fibrosis (IPF), examining FVC decline, treatment discontinuation, and mortality. Ten trials involving 5,386 participants were included. Pirfenidone and nintedanib consistently reduced FVC decline versus placebo; inhaled treprostinil showed a favorable FVC signal, largely when added to background antifibrotic therapy. Nintedanib and inhaled treprostinil were associated with higher odds of treatment discontinuation (both OR 1.39). Pirfenidone was the only therapy associated with lower odds of all-cause mortality (OR 0.50; 95% CI, 0.31-0.83).
Key findings
- Pirfenidone and nintedanib consistently reduced FVC decline versus placebo across the reviewed trials.
- Inhaled treprostinil showed a favorable FVC signal in combined TETON-1/2 evidence, largely as add-on therapy with background antifibrotic treatment.
- Treatment discontinuation odds were higher with nintedanib and inhaled treprostinil versus placebo: OR 1.39 (95% CI, 1.02-1.88) and OR 1.39 (95% CI, 1.08-1.78), respectively.
- Pirfenidone was associated with lower all-cause mortality odds: OR 0.50 (95% CI, 0.31-0.83).
Why it matters
FVC decline is an important trial outcome, but it may not capture differences in treatment continuation or mortality. Considering these outcomes alongside background therapy can help clinicians interpret the evidence without assuming that therapies are equivalent or directly comparable, particularly because head-to-head trials are lacking.
What to keep in mind
Direct head-to-head trials were lacking, and some findings were based on pooled published mortality data. Several FVC effects without background antifibrotic therapy were imprecise and did not establish equivalence.