JAK Inhibitor Updates: Ruxolitinib Cream for Pediatric, Adolescent Eczema

The state of dermatology drug development has been accelerating at an unprecedented rate for the last half-decade, with a myriad of targeted and novel therapy breakthroughs achieved in both common chronic diseases—like atopic dermatitis and psoriasis—and previously under-treated and psychosocially-affecting skin disorders—like alopecia areata and vitiligo. Drug options are becoming more robust, more versatile, and more efficacious in in dermatology, and there’s little indication the pipeline will slow any time soon.

At the center of this incredible trend is the Janus kinase (JAK) inhibitor drug class—a selection of targeted agents already in development and US Food and Drug Administration (FDA)-approved for oral and topical use in a variety of dermatologic conditions, including each of the ones mentioned above.

In a recent interview with HCPLive, Editorial Advisory Board members Raj Chovatiya, MD, PhD, MSCI, assistant professor of dermatology at Nortwestern University Feinberg School of Medicine, and Lawrence E. Eichenfield, MD, vice chair of the department of dermatology at the University of California, San Diego School of Medicine and chief of pediatric and adolescent dermatology at Rady Children’s Hospital, provided a review on a handful of JAK inhibitors at the forefront of dermatology research, development, and real-world care.

The first agent they reviewed was ruxolitinib cream (Opzelura).

HCPLive: The first subject is on ruxolitinib cream, with which there are ongoing clinical trials assessing an open-label, one-year regimen in adolescents with atopic dermatitis,¹ as well as another assessing the overall efficacy and safety of the agent in children ≥2 to <12 years old.²

What could be the utility of ruxolitinib cream in the management of pediatric and adolescent atopic dermatitis, relative to standard care for such eligible patients?

Eichenfield: I’ll start with my just clinical experiences and then the new data. So, we have topical ruxolitinib approved for ages 12 and older for both vitiligo and atopic dermatitis.³ It's incredibly helpful in clinical practice. And I use those phase 2 trials that did a head-to-head with triamcinolone cream over 4 weeks that showed it was a little bit stronger in our major outcome of measures, as compared to triamcinolone cream, which is really nice for giving a sense of how strong it is.⁴ I think it performs like that in clinical practice, where it's really useful.

Now we know they've completed the core studies, for atopic dermatitis down to age 2, with very similar robust efficacy results, with good tolerance, and after some peak trials that didn't show that much systemic absorption—with the caveat of being limited to 20% body surface area, which is how they did the phase 3 trials as well. So, I think with expanded indication for age, it'll be a useful adjunct. I think expanded non-steroidals are really important.

Chovatiya: You know, especially in that younger age group, this is where we start to run into those problems with topical steroids— whether it's actual fear, chronic use, limitations in terms of potency based on where you're going to be applying it. And thus, it's one of the reasons why we've all been after non-steroidals that can work fast, effectively and mimic what we want from a topical steroid. So, the fact that you're thinking about potency in the class of a topical steroid that doesn't necessarily have some of the limitations as far as application goes repetitively in certain sites—plus with good absorption data suggesting that some of the JAK side effects we'd worry about perhaps are not going to be a major issue—is sort of a win-win-win on all accounts when thinking about a drug that could work for this population.

Eichenfield: Lastly, I'll say that I think in the general dermatology community, what happened to be the first JAK which was approved for atopic dermatitis was our topical ruxolitinib. And there was a lot of hand-wringing about the class warning label. And most of us don't really deal with that too much when we're prescribing topical JAKs on-label for atopic dermatitis, because we don't really see big risks for that in clinical practice, or really in the expanded safety data set with topical ruxolitinib.

Chovatiya: It's been a pretty easy counseling point. It's not one that's really stopped use of the topical in the real world the way that which perhaps with the oral (option), there's a bit more discussion.

References

1. ^{Smith T. Ruxolitinib Cream Shows Long-Term Disease Control, Efficacy Among Adolescents with Eczema. HCPLive. Published May 9, 2024. https://www.hcplive.com/view/ruxolitinib-cream-shows-long-term-disease-control-efficacy-among-adolescents-with-eczema}
2. ^{Smith T. Ruxolitinib Consistent in Safety, Tolerability Over 52-Weeks in Children with Extensive Atopic Dermatitis. HCPLive. Published June 10, 2024. https://www.hcplive.com/view/ruxolitinib-consistent-safety-tolerability-over-52-weeks-children-with-extensive-atopic-dermatitis}
3. ^{Butera A. FDA Approves Ruxolitinib Cream 1.5% for Nonsegmental Vitiligo. HCPLive. Published July 18, 2022. https://www.hcplive.com/view/fda-approves-ruxolitinib-cream-for-nonsegmental-vitiligo}
4. ^{Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020;145(2):572-582. doi:10.1016/j.jaci.2019.08.042}