JAK Inhibitors Could Fill AD, Vitiligo, and AA Treatment Gaps

Although Janus kinase (JAK) inhibitors in the FDA approval pipeline have made headlines as potential treatments for atopic dermatitis (AD), they also show promise for patients with vitiligo and alopecia areata (AA), said James Q Del Rosso, DO, Research Director of JDR Dermatology Research in Las Vegas, Nevada and Senior Vice President of Clinical Research and Strategic Development at Advanced Dermatology & Cosmetic Surgery in Maitland, Florida, in a presentation at the 2021 Fall Clinical Dermatology Conference for PAs & NPs held November 12 to 14, 2021 in Orlando, Florida, and virtual.¹ Other Phase 2 and 3 studies indicate longer term safety and disease control in ruxolitinib cream in atopic dermatitis, he added.²

Del Rosso drilled down on the role this new drug class may in play in addressing dermatologic disease and offered pointers on best-practice strategies for integrating them into treatment plans for specific patients.

In September, the FDA approved topical ruxolitinib cream (Opzelura, Incyte) as the first JAK inhibitor to treat AD. Del Rosso noted its list of indications could expand in the near future. Recently released Phase 3 clinical trial program data shows positive outcomes for this JAK inhibitor in treating vitiligo and AA.³ “We are seeing some good results for this topical combined with phototherapy for treating vitiligo,” Rosso said.

Clinicians should not expect immediate improvement. "Vitiligo is not going to change in 1, 2, or 3 months. This is something that is going to require several months of treatment,” he said.

In addition, Del Rosso pointed to expert opinions published in the current literature that recommended tofacitinib (Xeljanz, Pfizer) , ruxolitinib, baricitinib (Olumiant, Eli Lilly and Company), and other JAK inhibitors to treat AA. The discovery of JAK inhibition represents a “major breakthrough” in the treatment of AA, the authors noted.⁴

While some practitioners are concerned about serious adverse effects (AEs) outlined in the black box warning mandated by the FDA for some oral JAK inhibitors as well as ruxolitinib, Del Rosso shared research showing that AEs are generally few.⁵ The review on which the black box warning is based was done on oral tofacitinib and did not include topical JAK inhibitors.⁶ Del Rosso noted that because ruxolitinib is a topical, systemic absorption would be much lower than with an oral medication.

However, “There may be some warnings or precautions that you as a clinician should evaluate,” Del Rosso said.

Ruxolitinib can be used for short-term and non-continuous use of mild to moderate atopic dermatitis, not moderate to severe cases, he noted.

Del Rosso cited a study evaluating ruxolitinib 1.5% cream for atopic dermatitis over 8 weeks in patients 12 years and older. “Regardless of the parameter that you looked at…both of the groups worked much better…certainly in regards to itching….than the placebo cream,” Del Rosso noted.

Oral JAK inhibitors baricitinib, upadacitinib (Rinvoq, AbbVie) and abrocitinib (Pfizer) still await their FDA approvals for AD, though baricitinib and upadacitinib are approved for other indications. JAK inhibitors have shown promise in AA treatment and treatment for alopecia universalis (AU) and associated nail dystrophy.⁷ Oral JAK inhibitors show superior efficacy compared to topical JAK inhibitors for this indication, according to Del Rosso.

Disclosures

Del Rosso serves as research investigator for Almirall, Aclaris, Amgen, Anaptys Bio, Arcutis, Athenex, Bausch, BioPharmx, Biorasi, Botanix, Brickell, Cara Therapeutics, Cassiopea, Dermavant, Dermira, Eli Lilly and Company, Epi Health, Foamix, Galderma, Genentech, Incyte, Leo Pharma, Novan, Ralexar, Regeneron, Solgel, Sun Pharma, UCB and Vyne a consultant/advisor for Almirall, Amgen, Aclaris, Arcutis, Bausch, Biofrontera, Biopharmx, Blue Creek, Bristol Myers Squibb, Cassiopea, Dermata, Dermavant, Dermira, Eli Lilly and Company, Encore, Epi Health, Evommune,Ferndale, Foamix, Galderma, Incyte,Jem Health Leo Pharma, La Roche Posay, MC2, Novan, Pfizer, Regeneron, Sanofi-Genzyme, Sente, Solgel, Sonoma (Intraderm), Sun Pharma, UCB, Verrica and Vyne and a speaker for AbbVie, Almirall ,Amgen, Aclaris,Bausch, Biofrontera, Celgene, Eli Lilly and Company, Encore, Epi Health, Ferndale, Galderma, Genentech, Jem Health, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, UCB, Verrica and Vyne.

References

1.Del Rosso, J. JAK Inhibitors in Dermatologic Disease. 2021Fall Clinical Dermatology Conference for PAs & NPs, held November 12-14, 2021 in Orlando, Florida, and virtual.

2.Incyte announces U. S. FDA approval of Opzelura™(Ruxolitinib) cream, a topical JAK inhibitor, for the treatment of atopic dermatitis(Ad). Published September 21, 2021. Accessed November 13, 2021.

3.Fathima Ferial Ismail & Rodney Sinclair (2019): JAK inhibition in the treatment of alopecia areata – a promising new dawn?, Expert Review of Clinical Pharmacology, doi: 10.1080/17512433.2020.1702878 https://doi.org/10.1080/17512433.2020.1702878

4.Incyte announces full results from phase 3 true-v program evaluating ruxolitinib cream (Opzelura) in patients with vitiligo. Incyte. Press release. Published October 2, 2021. Accessed November 11, 2021. https://investor.incyte.com/press-releases/press-releases/2021/Incyte-Announces-Full-Results-From-Phase-3-TRuE-V-Program-Evaluating-Ruxolitinib-Cream-Opzelura-in-Patients-With-Vitiligo/default.aspx

5.Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85(4):863-872. doi:10.1016/j.jaad.2021.04.085

6. FDA.gov. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Published February 4, 2021. Updated September 16, 2021. Accessed November 13, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death

7. Dillon KL. A Comprehensive Literature Review of JAK Inhibitors in Treatment of Alopecia Areata. Clin Cosmet Investig Dermatol. 2021;14:691-714
https://doi.org/10.2147/CCID.S309215