Alopecia Universalis Treated With Tofacitinib: The Role of JAK/STAT Inhibitors in Hair Regrowth
Alopecia universalis is alopecia areata (AA) with total-body involvement of hair loss. The disease progression is due to autoimmune T cells. We present a case of a patient with alopecia universalis who was successfully treated with tofacitinib.
Practice Points
- Janus kinase inhibitors target one of the cellular pathogeneses of alopecia areata.
- Janus kinase inhibitors may be an option for patients who have exhausted other treatment modalities for alopecia.
A recent retrospective study assessing response to tofacitinib in adults with AA (>40% hair loss), alopecia totalis, alopecia universalis, and stable or progressive diseases for at least 6 months determined a clinical response in 50 of 65 (77%) patients, with 13 patients exhibiting a complete response.10 Patients in this study were started on tofacitinib 5 mg twice daily with the addition of adjuvant pulsed prednisone (300 mg once monthly for 3 doses) with or without doubled dosing of tofacitinib if they had a halt in hair regrowth. This study demonstrated some benefit when pulsed prednisone was combined with the daily tofacitinib therapy. However, the study emphasized the importance of maintenance therapy, as 8 patients experienced hair loss with discontinuation after previously having hair regrowth; 5 (63%) of these patients experienced regrowth with augmentation of dosing or addition of adjuvant therapy.10
Another group of investigators assessed the efficacy of tofacitinib 5 mg in 13 adolescents aged 12 to 17 years, most with alopecia universalis (46% [6/13]); 10 of 13 (77%) patients responded to treatment with a mean duration of 6.5 months. The patients who had alopecia totalis and alopecia universalis for more than 10 years were poor responders to tofacitinib, and in fact, 1 of 13 (33%) patients in the study who did not respond to therapy had disease for 12 years.11 Therefore, starting tofacitinib either long-term or intermittently should be considered in children diagnosed early with severe AA, alopecia totalis, or alopecia universalis to prevent irreversible hair loss or progressive disease12,13; however, further data are required to assess efficacy and long-term benefits of this type of regimen.
Safety Profile—Widespread use of a medication is determined not only by its efficacy profile but also its safety profile. With any medication that exhibits immunosuppressive effects, adverse events must be considered and thoroughly discussed with patients and their primary care physicians. A prospective, open-label, single-arm trial examined the efficacy and safety of tofacitinib 5 mg twice daily in the treatment of AA and its more severe forms over 3 months.12 Of the 66 patients who completed the trial, 64% (42/66) exhibited a positive response to tofacitinib. Relapse was noted in 8.5 weeks after discontinuation of tofacitinib, reiterating the potential need for a maintenance regimen. In this study, 25.8% (17/66) of patients experienced infections as adverse events including (in decreasing order) upper respiratory tract infections, urinary tract infections, herpes zoster, conjunctivitis, bronchitis, mononucleosis, and paronychia. No reports of new or recurrent malignancy were noted. Other more constitutional adverse events were noted including headaches, abdominal pain, acne, diarrhea, fatigue, nausea, pruritus, hot flashes, cough, folliculitis, weight gain, dry eyes, and amenorrhea. One patient with a pre-existing liver condition experienced transaminitis that resolved with weight loss. There also were noted increases in low- and high-density lipoprotein levels.12 Our patient with baseline thrombocytopenia had mild drops in platelet count that subsequently stabilized and did not result in any bleeding abnormalities.
Duration of Therapy—Tofacitinib has demonstrated some preliminary success in the management of AA, but the appropriate duration of treatment requires further investigation. Our patient has been on tofacitinib for more than 5 years. She started at a total dosage of 10 mg/d, which increased to 16 mg/d. Initial dosing with maintenance regimens needs to be established for further widespread use to maximize benefit and minimize harm.
At what point do we decide to continue or stop treatment in patients who do not respond as expected or plateau? This is another critical question; our patient had periods of slowed growth and plateauing, but knowing the risks and benefits, she continued the medication and eventually experienced improved regrowth again.
Conclusion
Throughout the literature and in our patient, tofacitinib has demonstrated efficacy in treating AA. When other conventional therapies have failed, use of tofacitinib should be considered.
