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JAKs, an Exciting Potential for Derms in Clinical Trials

Dermatologists and researchers alike continue to explore different biological pathways in the hopes of discovering more effective and tolerable therapies for dermatologic diseases. In particular, Janus kinase (JAK) inhibitors show great promise in a variety of areas: atopic dermatitis, psoriasis, alopecia areata, vitiligo, among others. At Winter Clinical, “JAKinibs” were the subject of several sessions, including

  • “Managing Autoimmune Diseases of Skin and Hair” with Seemal R. Desai, MD
  • “What’s New and Coming With JAKs” with Brett King, MD, PhD
  • “JAK Stat Family: The Next Frontier in the Management of Atopic Dermatitis, Vitiligo, and Inflammatory Diseases - Part 1” with Dr Desai
  • “JAK Stat Family: The Next Frontier in the Management of Atopic Dermatitis, Vitiligo, and Inflammatory Diseases - Part 2” with Dr King

Dr Margitta Worm discussed the potential of a novel JAK inhibitor in the treatment of chronic hand eczema—read her interview here!


Several autoimmune diseases, such as atopic dermatitis, are known to be affected by interleukins, which signal through JAK-STAT (signal transducer and activator of transcription) pathways. This novel class of therapeutics acts by inhibiting the activity of JAK enzymes (JAK1, JAK2, JAK3, and tyrosine kinase [TYK] 2).

In the session “Managing Autoimmune Disease of Skin and Hair,” Dr Desai discussed how JAK inhibitors may be agents to treat diseases such as vitiligo and alopecia areata, both of which lack a variety of therapeutic options. “We have new, novel small molecules, both in topical and oral formulations, which are being developed and could really help us at a molecular level to target these devastating skin conditions,” he said in a post-presentation video interview.1

JAK inhibitors with FDA approval include tofacitnib (rheumatoid arthritis [RA], psoriatic arthritis, ulcerative colitis), ruxolitinib (polycythemia vera, myelofibrosis), upadacitinib (RA), and fedratinib (myelofibrosis). Additional JAKinibs currently in clinical trials for dermatologic use include deucravacitinib (psoriasis,2,3 psoriatic arthritis4), abrocitinib (atopic dermatitis5), baricitinib (alopecia areata,6,7 atopic dermatitis8), delgocitinib (hand eczema9-11), and CTP-543 (alopecia areata12,13).

In his JAK-STAT part two session, Dr King covered various other potential avenues for JAKs in dermatology. In particular, he highlighted successful treatment of erosive lichen planus and granulomatous diseases with JAK inhibitors. Dr King and colleagues14 reviewed tofacitinib within cutaneous granulomatous disorders in a recent prospective study of three patients with recalcitrant cutaneous sarcoidosis and one with generalized granulomatous annulare. The group found tofacitinib resulted in significant improvement in all four patients, recommending more study is needed to better understand the effect the JAK inhibitor has on these diseases. His group has also found success with tofacitinib for severe lichen planus15 and necrobiosis lipoidica.16


References
1. WC21 - Managing Autoimmune Diseases of Skin and Hair | Seemal R. Desai, MD. FC TV. Accessed January 21, 2021. https://www.youtube.com/watch?v=FwZWQfFH5as&feature=youtu.be

2. An investigational study to evaluate experimental medication BMS-986165 compared to placebo and a currently available treatment in participants with moderate to severe plaque psoriasis (POETYK-PSO-1). NCT03624127. Updated September 1, 2020. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03624127?recrs=ad&intr=BMS-986165&draw=2&rank=10

3. An investigational study to evaluate experimental medication BMS-986165 compared to placebo and a currently available treatment in participants with moderate-to-severe plaque psoriasis (POETYK-PSO-2). NCT03611751. Updated August 28, 2020. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03611751?recrs=ad&intr=BMS-986165&draw=3&rank=11

4. Efficacy and safety of BMS-986165 compared with placebo in participants with active psoriatic arthritis (PsA). NCT03881059. Updated June 16, 2020. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03881059?recrs=ad&intr=BMS-986165&draw=3&rank=12

5. Study of abrocitinib compared with dupilumab in adults with moderate to severe atopic dermatitis on background topical therapy. NCT04345367. Updated January 13, 2021. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT04345367?intr=Abrocitinib&draw=2&rank=1

6. A study of baricitinib (LY3009104) in adults with severe or very severe alopecia areata (BRAVE-AA2). NCT03899259. Updated January 20, 2021. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03899259?cond=Alopecia&intr=Baricitinib&cntry=US&draw=2&rank=1

7. A study of baricitinib (LY3009104) in participants with severe or very severe alopecia areata (BRAVE-AA1). Updated January 20, 2021. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03570749?cond=Alopecia&intr=Baricitinib&cntry=US&draw=2&rank=2

8. A study of baricitinib (LY3009104) in adult participants with moderate to severe atopic dermatitis (BREEZE-AD5). NCT03435081. Updated January 3, 2020. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03435081?cond=Atopic+Dermatitis&intr=Baricitinib&cntry=US&draw=2&rank=2

9. Dose-ranging trial to evaluate delgocitinib cream 1, 3, 8, and 20 mg/g compared to delgocitinib cream vehicle over an 8-week treatment period in adult subjects with atopic dermatitis. NCT03725722. Update June 30, 2020. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03725722?intr=Delgocitinib&cntry=US&draw=2&rank=2

10. Dose-ranging trial to evaluate delgocitinib cream 1, 3, 8, and 20 mg/g compared to delgocitinib cream vehicle over an 8-week treatment period in adult subjects with atopic dermatitis. NCT03725722. Updated June 30, 2020. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03725722?intr=Delgocitinib&cntry=US&draw=2&rank=2

11. Delgocitinib cream for the treatment of moderate to severe atopic dermatitis during 8 weeks in adults, adolescents, and children. NCT03826901. Updated December 2, 2020. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03826901?intr=Delgocitinib&cntry=US&draw=2&rank=3

12. A phase 3 study to evaluate the efficacy and safety of CTP-543 in adult patients with moderate to severe alopecia areata (THRIVE-AA1). NCT04518995. Updated January 7, 2021. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT04518995?intr=ctp-543&cntry=US&draw=2&rank=8

13. Extension study to evaluate safety and efficacy of CTP-543 in adults with alopecia areata. NCT03898479. Updated January 19, 2021. Accessed January 21, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03898479?intr=ctp-543&cntry=US&draw=2&rank=5

14. Damsky W, Thakral D, McGeary MK, Leventhal J Glaan A, King B. Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare. J Am Acad Dermatol. 2020;82(3):612-621. doi:10.1016/j.jaad.2019.05.098

15. Damsky W, Wang A, Olamiju B, Peterson D, Galan A, King B. Treatment of severe lichen planus with the JAK inhibitor tofacitnib. J Allergy Clin Immunol. 2020;145(6):1708-1710.e2. doi:10.1016/j.jaci.2020.01.031

16. Damsky W, Singh K, Galan A, King B. Treatment of necrobiosis lipoidica with combination Janus kinase inhibition and intralesional corticosteroid. JAAD Case Rep. 2020;6(2):133-135. doi:10.1016/j.jdcr.2019.11.016

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