A 48-year-old woman with progressive exertional dyspnoea, bibasilar crackles, and clubbing undergoes HRCT showing bilateral subpleural, basal-predominant reticulation with honeycombing and traction bronchiectasis with no ground glass. Surgical lung biopsy shows usual interstitial pneumonia (UIP) pattern. Which antifibrotic agent's mechanism involves inhibition of TGF-β, PDGF, and VEGF receptor tyrosine kinases?

• A Nintedanib ✓
• B Pirfenidone
• C N-acetylcysteine
• D Sildenafil for associated pulmonary hypertension

Explanation

Nintedanib (approved for IPF based on INPULSIS trials) is an intracellular kinase inhibitor that blocks multiple receptor tyrosine kinases — PDGFR-α and -β, VEGFR-1/2/3, and FGFR-1/2/3 — thereby blocking profibrotic pathways including TGF-β signalling. Pirfenidone, used for IPF (ASCEND, CAPACITY trials), has a different mechanism: it inhibits TGF-β-stimulated collagen production, reduces fibroblast proliferation, and attenuates oxidative stress, but is not a tyrosine kinase inhibitor. N-acetylcysteine failed to show benefit as monotherapy in the PANTHER-IPF trial.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.