Evidence base is limited and mostly observational. There is no RCT of pirfenidone specifically in anti-MDA5-positive NSIP-ILD. The best available data come from a prospective cohort by Li et al. (referenced in a 2024 MDA5-DM review), where pirfenidone (titrated up to a target dose of 1800 mg/day: 200 mg tid, escalated to 600 mg tid over 2 weeks) was added to standard immunosuppression in rapidly progressive ILD (RP-ILD), predominantly anti-MDA5-positive. Benefit was seen mainly in subacute disease (ILD duration 3-6 months), not in acute disease (<3 months), where it showed no clear benefit. That study does not report a defined treatment endpoint - it was used as ongoing background therapy.

First-line therapy for anti-MDA5 RP-ILD is combination immunosuppression (glucocorticoids + calcineurin inhibitor, or triple therapy with IV cyclophosphamide, with JAK inhibitors like tofacitinib emerging as an option). Pirfenidone is used as an adjunct antifibrotic, not a substitute for immunosuppression.

General antifibrotic-in-ILD principle (extrapolated from IPF/PPF data - Washington Manual of Medical Therapeutics, Fishman's Pulmonary Diseases): Pirfenidone and nintedanib are continued long-term/indefinitely in fibrosing ILD as long as:

In connective-tissue-disease-associated ILD trials generally (e.g., the RELIEF trial in progressive fibrosing non-IPF ILD), the study duration was 52 weeks, but that reflects trial design, not a recommended clinical stopping point - real-world use continues beyond that if the patient benefits.