Topical Tofacitinib for Atopic Dermatitis - Outcomes from Randomized Phase 3 Clinical Trial: First Approval

The Janus kinase (JAK) enzyme plays a crucial role in the pathophysiology of atopic dermatitis (AD). The United States Food and Drug Administration (USFDA) has recently granted approval for three JAK inhibitors intended for AD treatment. These comprise topical Ruxolitinib, oral Abrocitinib, and Upadacitinib. In alignment with these advancements, we developed a topical formulation of Tofacitinib, a JAK inhibitor, and evaluated its potential in mild-to-moderate AD, which has been recently approved on the basis of a phase 3 clinical trial.

The present trial was conducted to evaluate the efficacy and safety of tofacitinib ointment 2% w/w (Tof-O) versus pimecrolimus cream 1% w/w (Pim-C) in adult patients with mild-to-moderate AD.

In this prospective, open-label, multicenter phase 3 trial, 184 patients with mild-to-moderate AD were randomized (1:1) to receive either Tof-O or Pim-C for 4 weeks. The efficacy evaluations included percent change in Eczema Area and Severity Index (EASI) score, percentage of patients achieving EASI 50, 75, and 90% improvement, change in validated Investigator Global Assessment (vIGA-AD) score, change in affected percentage body surface area (BSA), and change in pruritus using numeric scale. Safety and tolerability were assessed by laboratory parameters, physical examination, and adverse events (AEs).

Tof-O significantly (P < 0.05, mean: 1.9709, CI: -4.3327, 8.2745) improved EASI score from baseline after 4 weeks of treatment; the improvement was comparable to Pim-C. Both treatment groups also demonstrated a significant (P < 0.05) increase in the percentage of patients achieving EASI 50, 75, and 90, along with significant (P < 0.05) improvements in vIGA-AD scores, affected BSA, and pruritus from baseline after 4 weeks of treatment. There were no significant changes observed in laboratory values and other safety parameters in both groups.

Tof-O demonstrated favourable safety and efficacy in mild-to-moderate AD patients following 4 weeks of treatment.

Clinical Trial Registry-India (CTRI). CTRI/2022/07/044136 [Registered on: 19/07/2022] Trial Registered Prospectively.

https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=71771&EncHid=&userName=tofacitinib%20ointment.

Interventional.