Pirfenidone vs nintedanib in progressive fibrosing ILD beyond IPF: real-world treatment selection? | tachyDx

2 Answers

Accepted Answer

As a pulmonologist who manages a large ILD clinic at Apollo, this is a case type I see weekly. My approach:

1. Nintedanib is my first choice for RA-ILD with UIP pattern. Rationale:

INBUILD trial specifically included RA-ILD patients and showed consistent benefit across all subgroups
The UIP pattern subgroup in INBUILD showed the largest treatment effect (FVC decline reduction of 128 mL/year vs placebo)
Pirfenidone evidence in non-IPF progressive fibrosing ILDs is weaker (RELIEF trial: n=127, stopped early for futility at interim, though post-hoc analysis suggested benefit)
GI side effects are comparable between the two; hepatotoxicity monitoring is similar

2. Mycophenolate decision: I would continue mycophenolate at the current dose even without active joint disease. The rationale:

RA-ILD has an inflammatory component that may not be visible on HRCT (subclinical inflammation can drive fibrosis)
The INBUILD trial allowed background immunosuppression, so the nintedanib efficacy data was generated WITH ongoing treatment
Stopping mycophenolate risks both RA flare and potential acceleration of ILD (removing the anti-inflammatory "brake")

3. Monitoring protocol: I use a composite approach:

FVC every 3 months (absolute change > 5% over 6 months = progression despite treatment)
6-minute walk distance every 3 months (more sensitive to functional change than FVC)
Annual HRCT (looking for new honeycombing or fibrotic changes)
Patient-reported outcomes: King's Brief Interstitial Lung Disease questionnaire (K-BILD) every 3 months
DLCO every 6 months (though DLCO has high test-to-test variability)

If FVC continues to decline > 5% over 6 months on nintedanib, I would consider adding pirfenidone (dual antifibrotic therapy). The INJOURNEY trial showed tolerability of the combination, though efficacy data is still emerging.

Dr. Suresh Kumar

Thank you Dr. Kumar. Sharing the French perspective from our ILD referral center:

In France, we have access to both nintedanib and pirfenidone for progressive fibrosing ILDs (both reimbursed since 2020 for non-IPF indications following INBUILD).

Our institutional protocol differs in one key aspect: We use a trial of pirfenidone first in patients with connective tissue disease-associated ILD (CTD-ILD). The reasoning:

Pirfenidone has anti-inflammatory properties in addition to antifibrotic effects (demonstrated in vitro and in animal models)
For CTD-ILD specifically, this dual mechanism may be advantageous over nintedanib (which is purely antifibrotic via tyrosine kinase inhibition)
Our retrospective cohort (n=42 CTD-ILD patients on pirfenidone) showed FVC stabilization in 71% over 12 months

However: If the patient has significant GI comorbidity or is on methotrexate (hepatotoxicity overlap with pirfenidone), I default to nintedanib.

On the mycophenolate question: I agree strongly with continuing it. We conducted a chart review of 18 RA-ILD patients who stopped immunosuppression when starting antifibrotics: 6/18 had RA flares, and 3/18 had accelerated ILD progression requiring ICU admission. The lesson was clear.

Monitoring addition: We have started using home spirometry (hand-held devices connected to apps). Patients perform FVC measurements weekly. This captures subtle decline trends that 3-monthly clinic visits miss. Early data from our center suggests it detects progression 2 months earlier than clinic-based monitoring.