Antifibrotic dose cuts were common, and progression frequent whatever the dose

Design

Retrospective cohort study in two US data sources

Population

1,572 patients with IPF starting nintedanib or pirfenidone

Primary outcome

Composite progression: ≥10% FVC decline, hospitalisation, transplant or death

Effect

Registry: reduction HR 1.17 (0.90–1.52), stopping HR 1.51 (1.04–2.18); EHR: 0.87 and 0.94 (both NS)

This retrospective study used a US multicentre registry (545 patients) and one health system's records (1,027 patients) to follow people with IPF after starting nintedanib or pirfenidone. Dose was classed over time as full, reduced for at least three months, or stopped for at least three months.

Only 64% and 59% stayed on full dose. Progression — a 10% fall in FVC, hospital admission, transplant or death — was frequent in every group. In the registry, stopping was associated with more progression (HR 1.51, 1.04–2.18) while dose reduction was not clearly different (HR 1.17). In the health system data, neither reduction nor stopping was associated with a difference.

The inconsistency between the two sources and the observational design mean this cannot say whether a reduced dose works as well as full dose. It does support keeping patients on some dose where tolerability allows, rather than stopping, and shows how poorly current antifibrotics are tolerated in routine care.

• Manage antifibrotic side effects actively — diet, timing with food, antidiarrhoeals — before reducing or stopping.
• Consider a dose reduction rather than stopping when side effects are limiting.
• Monitor FVC and symptoms after any dose change.
• Expect progression despite treatment; plan advance care and transplant referral early where relevant.

Why it matters

Dose reduction is how most real patients stay on antifibrotics, and its effect has been largely unknown.

Don't overread it

The two data sources disagreed, and observational data cannot show that a reduced dose is as effective as full dose.

The statistics, in plain English

In the registry, stopping antifibrotics had a hazard ratio of 1.51 (1.04–2.18), meaning progression came about 50% faster; in the health system data the same comparison gave 0.94 (0.66–1.36), meaning no difference. When two data sets disagree like this, neither result should be taken alone.

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