A 55-year-old woman with moderate-to-severe atopic dermatitis has failed topical steroids and two immunosuppressants. She is started on abrocitinib. What is the mechanism of action of this drug?
- A Pan-JAK inhibitor blocking all four JAK isoforms
- B Selective JAK1 inhibitor blocking IL-4, IL-13, IL-31, and TSLP signalling ✓
- C Phosphodiesterase-4 (PDE4) inhibitor increasing intracellular cAMP
- D Calcineurin inhibitor blocking T-cell activation
Correct answer: B. Selective JAK1 inhibitor blocking IL-4, IL-13, IL-31, and TSLP signalling
Explanation
Abrocitinib (and upadacitinib) are selective JAK1 inhibitors approved for moderate-to-severe atopic dermatitis. JAK1 is the key signalling kinase for IL-4, IL-13, IL-31, TSLP, and IL-33 — the central Th2 and pruritic cytokines in AD. Selective JAK1 inhibition thus blocks the itch-inflammation axis. Baricitinib targets JAK1/JAK2. PDE4 inhibitors (crisaborole, roflumilast) prevent cAMP degradation. Tacrolimus and pimecrolimus are calcineurin inhibitors. The oral route and rapid onset of JAK inhibitors offer a distinct advantage over injectable biologics.
Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.