Just Keep Applying: Topical JAK Inhibitors for Atopic Dermatitis

Original Article: Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies.

What are the key takeaways of this article?

The purpose of this study was to evaluate the long-term safety (LTS) and disease control of ruxolitinib cream in the treatment of atopic dermatitis (AD). Standard topical treatments for AD include corticosteroids, calcineurin inhibitors, and crisaborole (a phosphodiesterase 4 inhibitor). However, these are associated with local adverse events (AEs), tolerability concerns, or anatomic limitations, particularly with regards to long term usage.

Ruxolitinib is a Janus kinases (JAKs) inhibitor. JAK inhibitors modulate inflammatory cytokines involved in the pathogenesis of AD and directly mediate pruritus. In two double-blind AD studies, the investigators found that ruxolitinib cream (at either 0.75% or 1.5% strength) demonstrated anti-inflammatory activity with antipruritic action, as compared to control, and was well tolerated during the 8-week period. However, long-term usage remained a concern. Therefore this article aimed to understand the LTS of ruxolitinib.

Participants from North America and Europe over the age of 12 years with known AD were recruited. Key inclusion criteria included AD duration ≥2 years, Investigator’s Global Assessment (IGA) score of 2 or 3, and 3% to 20% affected body surface area (BSA) involvement (excluding scalp). Participants in the vehicle group were rerandomized to either ruxolitinib cream strength after week 8, and all participants continued treatment for 44 weeks (LTS period). Overall, 1072 participants continued from the 8-week period into the LTS period and of those, 831 (77.5%) completed the LTS period. Participants were instructed to only treat areas with active AD, stop treatment 3 days after clearance of lesions, and restart treatment at the first signs of recurrence. Other treatments were not permitted, except bland emollients.

Over 52 weeks, treatment-emergent adverse events (TEAEs) were reported in 287 (67.4%) and 279 (62.6%) participants on 0.75% and 1.5% ruxolitinib cream, respectively. Among those who switched from vehicle to 0.75% and 1.5% ruxolitinib cream, TEAEs were reported in 54 (53.5%) and 57 (57.6%) participants, respectively. The most common TEAEs were upper respiratory tract infection (occurring slightly more frequently in those continuing on treatment vs those who switched from vehicle) and nasopharyngitis (occurring at similar rates across all groups). Treatment-related adverse events (TRAEs) were reported in 37 (8.7%) and 33 (7.4%) participants on 0.75% and 1.5% ruxolitinib cream, respectively. TRAEs were slightly less frequent among those who switched from vehicle to 0.75% and 1.5% ruxolitinib cream. In this group, TRAEs were reported in 2 (2.0%) and 6 (6.1%) participants, respectively. The most common TRAEs were neutropenia, application site pain, and application site pruritus. Serious AEs were reported in 12 (2.8%) and 8 (1.8%) participants on 0.75% and 1.5% ruxolitinib cream, respectively, and 5 (5.0%) and 1 (1.0%) participants who switched from vehicle to 0.75% and 1.5% ruxolitinib cream.

Both strengths of ruxolitinib cream monotherapy demonstrated effective disease control and were well tolerated in the long-term setting. With as-needed application, participants spent a median of 38% and 44% of the 44-week LTS period off treatment due to lesion clearance for 0.75% and 1.5% ruxolitinib cream, respectively. Disease control was achieved throughout the LTS; 74.1%-77.8% of participants had Investigator’s Global Assessment 0/1 at week 52 and mean affected body surface area was low (1.4%-1.8%).

Overall, ruxolitinib cream had low bioavailability and was well tolerated when used as needed for 44 weeks following 8 weeks of continuous application. Long-term safety events mostly reflected known risk factors in the population. Alongside low plasma ruxolitinib concentrations, this suggests that physiologically meaningful systemic JAK inhibition is highly unlikely with topical application. Ultimately, ruxolitinib cream demonstrated effective treatment of AD over 52 weeks.

Publication Date: June 9, 2023

Reference: Papp K, Szepietowski JC, Kircik L, et al. Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies. J Am Acad Dermatol. 2023;88(5):1008-1016. doi:10.1016/j.jaad.2022.09.060

Summary By: Marina Guirguis