Tofacitinib
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Refractory Alopecia Areata and Vitiligo Responding to Tofacitinib Monotherapy

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INTRODUCTION

Tofacitinib is a Janus kinase (JAK) 1-3 inhibitor first U.S. Food and Drug Administration (FDA) approved in 2012 for rheumatoid arthritis, with subsequent approval for psoriatic arthritis, ulcerative colitis, polyarticular course juvenile idiopathic arthritis, and ankylosing spondylitis in 2017, 2018, 2020, and 2021, respectively.1,2 In the last several years, oral tofacitinib has become an increasingly utilized treatment option for immune-mediated skin conditions such as alopecia areata (AA), vitiligo, plaque psoriasis, and atopic dermatitis; however, it is not FDA approved for these diseases.3,4 These conditions’ pathophysiology involves an interplay of cytokines and interleukins in which the JAK-signal transducer and activation of transcription (STAT) signaling pathway has a role.5

AA and vitiligo are largely TH1 and interferon-gamma driven diseases.6 In AA, CD8+ T cells produce interferon-gamma which leads to collapse of immune privilege and increased production of IL-15, propagating autoimmune destruction of the hair follicle.6 In vitiligo, an autoimmune disease in which melanocytes are destroyed resulting in de-pigmentation, interferon-gamma induces expression of the C-X-C motif in chemokine-10 (CXCL10) in immune cells, leading to melanocyte destruction and depigmentation.7 Notably, interferon-gamma mediates its effects through the JAK-STAT pathway.5,8 Due to the relationship between AA and vitiligo with interferon gamma and the JAK-STAT pathway, JAK inhibitors, such as tofacitinib, are an appropriate choice for targeted therapy of these conditions. In this case report, we present a patient with concomitant AA and non-segmental vitiligo who was treated with oral tofacitinib. The autoimmune components of both diseases and similar pathophysiology cause AA and vitiligo to occur together more often than one would expect by chance; with approximately 3-8% of patients with AA having concomitant vitiligo.9 The patient in this report attempted multiple different treatment regimens with minimal improvement, however, upon initiation with tofacitinib, had moderate to significant improvement in both her AA and vitiligo, with no reported side effects.

CASE REPORT

A 49 year-old female presented to the clinic with a diagnosis of alopecia areata affecting her scalp, eyebrows, eyelashes, and body hair; as well as vitiligo affecting her left peri-oral area, left malar area, midline chest, bilateral forearms, and bilateral dorsal hands (approximately 10% BSA). She developed AA at the age of 21 and by the age of 32 had complete hair loss on her scalp. Since that time, she had cyclical flares of regrowth and complete hair loss, every two years. At her initial visit, hydrocortisone 2.5% cream daily, triamcinolone 0.1% cream daily, and narrow-band UVB phototherapy three times a week were prescribed for vitiligo. This regimen resulted in mild repigmentation of her face and chest, but her hands were resistant to treatment. Narrow-band UVB phototherapy was discontinued after 6 months of treatment due to logistical challenges of coming into clinic three times a week; however, she remained on topical corticosteroids. While her vitiligo remained stable with topical corticosteroids, no further improvement was obtained. For the patient’s AA, methotrexate 5 milligrams (mg) weekly with folic acid 1 mg/day were initially prescribed with minimal improvement. Methotrexate was subsequently increased to 10 mg weekly but the patient developed elevations in her liver function tests, which prompted discontinuation of methotrexate. Topical 5% minoxidil, fluocinonide 0.05% solution, clobetasol 0.05% solution, and Kenalog injections to the scalp were subsequently attempted with minimal improvement in her AA. A short course of prednisone was prescribed but minimal improvement was observed and she reported several side effects. Due to her refractory AA and vitiligo over a period of 1-2 years, she was prescribed tofacitinib 5 mg twice daily (BID) PO. Two months after initiating tofacitinib, the patient had noticeable scalp hair re-growth and small patches of re-pigmentation in all affected areas of vitiligo. The most improvement occurred in her hands, which were previously resistant to therapy. At eight months after starting tofacitinib, she had continued scalp hair re-growth, complete eyebrow hair re-growth, and moderate re-pigmentation of her hands. Over the next 2 years, she had continued improvement and no reported side effects (Figures 1-6).
tofacitinib
FIGURE 1. Scalp affected by alopecia areata prior to treatment with
tofacitinib.

 

 

 

 

 

 

 

tofacitinib
FIGURE 2. Scalp after 2 years of treatment with tofacitinib illustrating hair re-growth in areas of previous alopecia areata.

 

 

 

 

 

 

 

 

tofacitinib
FIGURE 3. Bilateral dorsal hands and wrists affected by vitiligo prior to treatment with tofacitinib.

 

 

 

 

 

 

tofacitinib
FIGURE 4. Bilateral dorsal hands and wrists after 2 years of treatment
with tofacitinib illustrating re-pigmentation.

 

 

 

 

 

 

tofacitinib
FIGURE 5. Eyebrows affected by alopecia areata prior to treatment
with tofacitinib.

 

 

 

 

tofacitinib
FIGURE 6. Eyebrows after 2 years of treatment with tofacitinib illustrating hair re-growth.

DISCUSSION

Only two case reports exist in the literature of patients with concomitant alopecia areata and vitiligo who were treated with tofacitinib.1,3 Of those cases, one patient additionally had inverse plaque psoriasis, while the other patient additionally had atopic dermatitis. In both of these cases, tofacitinib was effective; however, it was utilized as adjunctive therapy rather than monotherapy. In our case report, we present a patient treated with low-dose tofacitinib monotherapy. Our patient’s response to tofacitinib monotherapy is similar to that of other patients on multiple treatments, where clinical response was observed as quickly as 2 months with significant improvement reached around 6-8 months of treatment.1

Tofacitinib is well studied in AA with improvement rates of >50% in 30-60% of patients on tofacitinib 5 mg BID.10-12 In vitiligo, the use of tofacitinib is less studied with some patients reporting marginal improvement and others reporting near complete repigmentation.1,7,13-16 In these reports, tofacitinib is commonly used concordantly with ultraviolet B phototherapy. In general, patients have greater improvement in areas of sun exposure or those additionally treated with phototherapy. Nonetheless, our patient had good improvement in her hand vitiligo, with minimal reported sun exposure and no additional phototherapy.

Patients with AA and vitiligo often need combination therapy, with both topical and systemic medications. However, monotherapeutic treatment regimens have increased adherence versus multiple medication regimens; thus JAK inhibitors, which can target a common pathway of both autoimmune diseases, may be particularly practical for patients with simultaneous autoimmune skin disorders.17

 

The use of JAK inhibitors off-label has become increasingly utilized and is effective for the treatment of AA, vitiligo, and other immune-mediated diseases. While JAK inhibitors are associated with several Black Box warnings and require careful monitoring, they may be a suitable alternative for patients refractory to previous treatments. In particular, in the few patients in the literature who have concomitant AA and vitiligo, tofacitinib appears to be an effective treatment option.

DISCLOSURES

Patrick O. Perche, Caitlin G. Purvis, and Rita O. Pichardo have no conflicts of interest to report.

 

REFERENCES

1. Vu M, Heyes C, Robertson SJ, et al. Oral tofacitinib: a promising treatment in atopic dermatitis, alopecia areata, and vitiligo. Clin Exp Dermatol. 2017;42(8):942-944. doi:10.1111/ced.13290
2. Pfizer. Xeljanz (Tofacitinib) [package insert]. U.S. Food and Drug Administration website. www.accessdata.fda.gov/drugsatfda_docs/lab el/2021/203214s028,208246s013,213082s003lbl.pdf#page=66. Revised December 2021. Accessed December 16, 2021.
3. Tajalli M, Kabir S, Vance TM, et al. Effective use of oral tofacitinib and phototherapy in a patient with concomitant alopecia areata, vitiligo, and plaque and inverse psoriasis. Clin Case Rep. 2020;8(5):819-822. doi:10.1002/ ccr3.2759
4. Shreberk-Hassidim R, Ramot Y, Zlotogorski A. Janus kinase inhibitors in dermatology: A systematic review. J Am Acad Dermatol. 2017;76(4):745-753. e19. doi:10.1016/j.jaad.2016.12.004
5. Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017;76(4):736-744. doi:10.1016/j. jaad.2016.12.005
6. Harris JE. Vitiligo and alopecia areata: apples and oranges? Exp Dermatol. 2013;22(12):785-9. doi:10.1111/exd.12264
7. Craiglow BG, King BA. Tofacitinib citrate for the treatment of vitiligo: a pathogenesis-directed therapy. JAMA Dermatol. 2015;151(10):1110-2. doi:10.1001/jamadermatol.2015.1520
8. Horvath CM. The Jak-STAT pathway stimulated by interferon gamma. Sci STKE. 2004;2004(260):tr8. doi:10.1126/stke.2602004tr8
9. Rork JF, Rashighi M, Harris JE. Understanding autoimmunity of vitiligo and alopecia areata. Curr Opin Pediatr. 2016;28(4):463-469. doi:10.1097/ MOP.0000000000000375
10. Ibrahim O, Bayart CB, Hogan S, et al. Treatment of alopecia areata with tofacitinib. JAMA Dermatol. 2017;153(6):600-602. doi:10.1001/ jamadermatol.2017.0001
11. Liu LY, Craiglow BG, Dai F, et al. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017;76(1):22-28. doi:10.1016/j.jaad.2016.09.007
12. Kennedy Crispin M, Ko JM, Craiglow BG, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1(15):e89776. doi:10.1172/jci.insight.89776
13. Joshipura D, Plotnikova N, Goldminz A, et al. Importance of light in the treatment of vitiligo with JAK-inhibitors. J Dermatolog Treat. 2018;29(1):98- 99. doi:10.1080/09546634.2017.1339013
14. Gianfaldoni S, Tchernev G, Wollina U, et al. Micro – Focused phototherapy associated to janus kinase inhibitor: a promising valid therapeutic option for patients with localized vitiligo. Open Access Maced J Med Sci. 2018;6(1):46- 48. doi:10.3889/oamjms.2018.042
15. Liu LY, Strassner JP, Refat MA, et al. Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure. J Am Acad Dermatol. 2017;77(4):675-682.e1. doi:10.1016/j.jaad.2017.05.043
16. Relke N, Gooderham M. The Use of Janus Kinase Inhibitors in Vitiligo: A Review of the Literature. J Cutan Med Surg. 2019;23(3):298-306. doi:10.1177/1203475419833609
17. Ahn CS, Culp L, Huang WW, et al. Adherence in dermatology. J Dermatolog Treat. 2017;28(2):94-103. doi:10.1080/09546634.2016.1181256

 

SOURCE

Perche, Patrick, Caitlin Purvis, and Rita Pichardo. “Refractory Alopecia Areata and Vitiligo Responding to Tofacitinib Monotherapy.” Journal of Drugs in Dermatology: JDD 21.12 (2022): 1366-1368.

Content and images used with permission from the Journal of Drugs in Dermatology.

Adapted from original article for length and style.

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