Various Applications of Tofacitinib and Ruxolitinib (Janus Kinase Inhibitors) in Dermatology and Rheumatology:  A Review of Current Evidence and Future Perspective

Sara Sadeghi; Azadeh Goodarzi

doi:10.5826/dpc.1204a178

Various Applications of Tofacitinib and Ruxolitinib (Janus Kinase Inhibitors) in Dermatology and Rheumatology: A Review of Current Evidence and Future Perspective

Authors

Sara Sadeghi Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), Iran University of Medical Sciences, Tehran, Iran
Azadeh Goodarzi Iran University of Medical Sciences (IUMS), RasoolAkram hospital, Department of Dermatology

Keywords:

Tofacitinib, Ruxolitinib, Janus Kinase Inhibitors, Skin, Mucosa, Review

Abstract

Backgrounds: Janus kinase inhibitors (JAKi) are anti-inflammatory medications suppressing Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by inhibiting various cytokines receptors on the membrane of cells. Mutations and polymorphisms on JAK and STAT proteins can cause dysregulation in the balance of immune system, and ultimately result in autoimmune disorders.

Objectives: to record and summarize the overall efficacy and safety of JAKi in various autoimmune conditions such as alopecia areata (AA), psoriasis vulgaris (PV), psoriatic arthritis (PsA), atopic dermatitis (AD), vitiligo, hidradenitis suppurative (HS), lichen planus (LP), and pyoderma gangrenosum (PG).

Methods: A thorough review of articles was performed across PubMed and Google Scholar on meta-analyses, systematic reviews, clinical trials and case studies evaluating the treatment of autoimmune disorders such as AA, PV, PsA, AD, vitiligo, LP, HS, and PG with JAKi. Duplicated data and animal experiments or in vitro/ex vivo studies were excluded.

Results: all the reviewed articles reported beneficial effects of tofacitinib and ruxolitinib application in the treatment of disorders mentioned above with the autoimmune predisposition.

Conclusion: tofacitinib and ruxolitinib showed potential efficacy in treating several autoimmune disorders. Based on records in the reviewed studies, both medications had acceptable safety profiles; however, physicians are recommended to outweigh the risks and benefits of such treatments for each specific condition.

References

Choy EH. Clinical significance of Janus Kinase inhibitor selectivity. Rheumatology. 2019;58(6):953-62.

Damsky W, King BA. JAK inhibitors in dermatology: the promise of a new drug class. Journal of the American Academy of Dermatology. 2017;76(4):736-44.

O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013;72 Suppl 2(0 2):ii111-5.

Cinats A, Heck E, Robertson L. Janus kinase inhibitors: a review of their emerging applications in dermatology. Skin therapy letter. 2018;23(3):5-9.

Elli EM, Baratè C, Mendicino F, Palandri F, Palumbo GA. Mechanisms underlying the anti-inflammatory and immunosuppressive activity of ruxolitinib. Frontiers in oncology. 2019;9:1186.

Hodge JA, Kawabata TT, Krishnaswami S, Clark JD, Telliez J-B, Dowty ME, et al. The mechanism of action of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016;34(2):318-28.

Agrawal M, Kim ES, Colombel J-F. JAK Inhibitors Safety in Ulcerative Colitis: Practical Implications. Journal of Crohn's and Colitis. 2020;14(Supplement_2):S755-S60.

Bewersdorf JP, Jaszczur SM, Afifi S, Zhao JC, Zeidan AM. Beyond Ruxolitinib: Fedratinib and Other Emergent Treatment Options for Myelofibrosis. Cancer Manag Res. 2019;11:10777-90.

Pratt CH, King LE, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nature Reviews Disease Primers. 2017;3(1):17011.

Dillon KL. A Comprehensive Literature Review of JAK Inhibitors in Treatment of Alopecia Areata. Clin Cosmet Investig Dermatol. 2021;14:691-714.

Hordinsky MK. Overview of Alopecia Areata. Journal of Investigative Dermatology Symposium Proceedings. 2013;16(1):S13-S5.

Yu D-A, Kim YE, Kwon O, Park H. Treatment outcome of oral tofacitinib and ruxolitinib in patients with alopecia areata: A systematic review and meta-analysis. Indian Journal of Dermatology, Venereology and Leprology. 2021:1-7.

Hamilton CE, Craiglow BG. JAK Inhibitors for the Treatment of Pediatric Alopecia Areata. Journal of Investigative Dermatology Symposium Proceedings. 2020;20(1):S31-S6.

Guo L, Feng S, Sun B, Jiang X, Liu Y. Benefit and risk profile of tofacitinib for the treatment of alopecia areata: a systemic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology. 2020;34(1):192-201.

He H, Guttman-Yassky E. JAK inhibitors for atopic dermatitis: an update. American journal of clinical dermatology. 2019;20(2):181-92.

Rendon A, Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019;20(6).

Kvist-Hansen A, Hansen PR, Skov L. Systemic treatment of psoriasis with JAK inhibitors: a review. Dermatology and therapy. 2020;10(1):29-42.

Tian F, Chen Z, Xu T. Efficacy and safety of tofacitinib for the treatment of chronic plaque psoriasis: a systematic review and meta-analysis. Journal of International Medical Research. 2019;47(6):2342-50.

Su YJ. Early diagnosis of psoriatic arthritis among psoriasis patients: clinical experience sharing. Clin Rheumatol. 2020;39(12):3677-84.

Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, et al. Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors. N Engl J Med. 2017;377(16):1525-36.

Campanaro F, Batticciotto A, Zaffaroni A, Cappelli A, Donadini MP, Squizzato A. JAK inhibitors and psoriatic arthritis: A systematic review and meta-analysis. Autoimmunity Reviews. 2021;20(10):102902.

Paik J, Deeks ED. Tofacitinib: a review in psoriatic arthritis. Drugs. 2019;79(6):655-63.

Rodrigues MA, Torres T. JAK/STAT inhibitors for the treatment of atopic dermatitis. Journal of Dermatological Treatment. 2020;31(1):33-40.

Tsai HR, Lu JW, Chen LY, Chen TL. Application of Janus Kinase Inhibitors in Atopic Dermatitis: An Updated Systematic Review and Meta-Analysis of Clinical Trials. J Pers Med. 2021;11(4).

Rothstein B, Joshipura D, Saraiya A, Abdat R, Ashkar H, Turkowski Y, et al. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib. J Am Acad Dermatol. 2017;76(6):1054-60 e1.

Wang Y, Li S, Li C. Clinical Features, Immunopathogenesis, and Therapeutic Strategies in Vitiligo. Clin Rev Allergy Immunol. 2021.

Phan K, Phan S, Shumack S, Gupta M. Repigmentation in vitiligo using janus kinase (JAK) inhibitors with phototherapy: systematic review and Meta-analysis. Journal of Dermatological Treatment. 2020:1-5.

Komnitski M, Komnitski A, Komnitski Junior A, Silva de Castro CC. Partial repigmentation of vitiligo with tofacitinib, without exposure to ultraviolet radiation. An Bras Dermatol. 2020;95(4):473-6.

Mutalik SD, Belgaumkar VA, Rasal YD. Current perspectives in the treatment of childhood lichen planus. Indian Journal of Paediatric Dermatology. 2021;22(4):316.

Shao S, Tsoi LC, Sarkar MK, Xing X, Xue K, Uppala R, et al. IFN-gamma enhances cell-mediated cytotoxicity against keratinocytes via JAK2/STAT1 in lichen planus. Sci Transl Med. 2019;11(511).

Damsky W, Wang A, Olamiju B, Peterson D, Galan A, King B. Treatment of severe lichen planus with the JAK inhibitor tofacitinib. J Allergy Clin Immunol. 2020;145(6):1708-10 e2.

Yang CC, Khanna T, Sallee B, Christiano AM, Bordone LA. Tofacitinib for the treatment of lichen planopilaris: A case series. Dermatol Ther. 2018;31(6):e12656.

Scala E, Cacciapuoti S, Garzorz-Stark N, Megna M, Marasca C, Seiringer P, et al. Hidradenitis Suppurativa: Where We Are and Where We Are Going. Cells. 2021;10(8):2094.

Sabat R, Jemec GBE, Matusiak Ł, Kimball AB, Prens E, Wolk K. Hidradenitis suppurativa. Nature Reviews Disease Primers. 2020;6(1):18.

Savage KT, Santillan MR, Flood KS, Charrow A, Porter ML, Kimball AB. Tofacitinib shows benefit in conjunction with other therapies in recalcitrant hidradenitis suppurativa patients. JAAD Case Rep. 2020;6(2):99-102.

Zouboulis CC, Frew JW, Giamarellos-Bourboulis EJ, Jemec GBE, del Marmol V, Marzano AV, et al. Target molecules for future hidradenitis suppurativa treatment. Experimental Dermatology. 2021;30(S1):8-17.

Miller J, Yentzer BA, Clark A, Jorizzo JL, Feldman SR. Pyoderma gangrenosum: a review and update on new therapies. J Am Acad Dermatol. 2010;62(4):646-54.

Crowson AN, Mihm MC, Jr., Magro C. Pyoderma gangrenosum: a review. J Cutan Pathol. 2003;30(2):97-107.

Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G. Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol. 2009;23(9):1008-17.

Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of pyoderma gangrenosum (PG): an updated review. Journal of the American Academy of Dermatology. 2015;73(4):691-8.

Alavi A, French LE, Davis MD, Brassard A, Kirsner RS. Pyoderma gangrenosum: an update on pathophysiology, diagnosis and treatment. American journal of clinical dermatology. 2017;18(3):355-72.

Choi AW, Abuav R, Rabizadeh SM, Ansari R, Marsch AF. Recalcitrant and severe pyoderma gangrenosum attributable to levamisole-adulterated cocaine and treated successfully with oral tofacitinib. JAAD Case Rep. 2020;6(9):939-41.

Kochar B, Herfarth N, Mamie C, Navarini AA, Scharl M, Herfarth HH. Tofacitinib for the treatment of pyoderma gangrenosum. Clinical Gastroenterology and Hepatology. 2019;17(5):991-3.