Alopecia

Long-Term Treatment for Severe Alopecia Areata with Oral Tofacitinib Citrate

Tofacitinib citrate is a Janus kinase 1/3 inhibitor that is FDA-approved for the treatment of rheumatoid arthritis and that has recently been shown to be effective in treating alopecia areata (AA). The Department of Dermatology conducted a retrospective chart review of 31 AA patients presenting from March 2015 to June 2017, including 27 with alopecia totalis or universalis, with a mean pretreatment scalp hair loss of 88.7% calculated using the Severity of Alopecia Tool (SALT) score. Twelve patients had nail involvement, defined as pitting, ridging, or onychodystrophy.

All other AA therapies were discontinued, and patients were started on an initial dose of tofacitinib citrate 5 mg orally twice daily. Doses were increased monthly as tolerated and maintained after the treating physician noted the first signs of hair regrowth. Patients returned to the clinic every 3 to 4 months. In addition, they underwent monthly laboratory tests, including a complete blood count (CBC), a comprehensive metabolic panel (CMP), and a lipid panel during drug titration and every 3 to 4 months after they had reached maintenance dose. Standardized photos were taken with each clinic visit. Mean SALT scores at follow-up visits were estimated using mixed effect models. A Kaplan-Meier analysis was used to produce estimates of time until hair regrowth and nail improvement.

Twenty-one patients were treated, of which 13 patients have taken tofacitinib for ≥ 12 months. SALT scores decreased over time, and scores at 3, 9, and 12 months were significantly lower than baseline (P = 0.005; P = 0.004; P < 0.001, respectively). In addition, the mean score at 12 months was lower than at 6 months (P = 0.015). At 9 and 12 months, the estimated regrowth was 94%. Improvement of nail involvement of AA was not as notable, with 23% of patients having improvement at ≥ 6 months. Lab values were generally stable over time. Of 10 adverse events, 6 were lab abnormalities.

Among the 20 patients treated, 47% experienced regrowth of hair by 12 months. The extent of regrowth varied greatly, however, ranging from minimal regrowth to complete regrowth.

Mean SALT Score by Time Point in Treatment (N = 20)

March 2015 – June 2017

Kaplan Meier Estimates of Time to Hair Regrowth (N = 20)

March 2015 – June 2017

Outcome Time (Months) % (95% CI)
Regrowth 3 70 (49.9, 90.1)
6 76 (56.8, 95.2)
9 94 (82.7, 100)
12 94 (82.7, 100)
Kaplan Meier Estimates of Time to Nail Improvement (N = 12)

March 2015 – June 2017

Outcome Time (Months) % (95% CI)
Nail Improvement 3 10.0 (0.0, 23.1)
6 22.9 (2.9, 42.8)
9 22.9 (2.9, 42.8)
12 22.9 (2.9, 42.8)
Adverse Effects on Tofacitinib (N = 20)

March 2015 ¬ June 2017

Patient # Sex Age at Treatment Initiation Disease Duration (Years Since Diagnosis of AA) Months Until First Signs of Hair Growth Duration of Therapy (Months) Holding Dose (mg/day) Twice Daily Adverse Events and Associated Dose (Clinical or Laboratory) Outcome
1 F 57 25 3 12 20 Herpes zoster at month 6; 20 mg (clinical) Dose held for 10 days then restarted
2 F 43 19 3 15 20
3 F 22 16 3 17 15
4 F 55 26 7 28 15 AKI and elevated total cholesterol at month 4; 15 mg (laboratory) Medication discontinued
5 F 39 13 0 0.5 10 Rash and peripheral edema, 10 mg (clinical) Medication discontinued
6 F 56 16 10 26 20
7 F 62 7 3 7 30
8 F 46 36 3 1 10
9 F 57 15 3 12 20
10 F 37 9 4 15 10 AST/ALT elevation at month 6; 35 mg (laboratory) Dose decreased to 10 mg and AST/ALT normalized
11 F 57 9 8 24 20 Elevated cholesterol (211) at month 6; 20 mg (laboratory) Medication continued; cholesterol normalized by month 24
12 F 50 31 3 6 10 Chest palpitations at month 6; 10 mg (clinical) Medication discontinued
13 F 50 1 6 20 10
14 F 38 7 1 12 20 Leukopenia at Month 12 (laboratory) Medication continued
15 F 56 11 2 25 25 Scant growth on face noted at month 3. Lost to follow-up
16 F 25 5 3 4 10
17 F 54 3 2 12 20 Elevated total cholesterol, LDL and total bilirubin at month 3; 10 mg (laboratory) Dose decreased to 10 mg. LDL and total cholesterol normalized by month 6, then dose increased to 20 mg.
18 F 56 16 2 5 0 Recurrent URIs from initiation through Month 5; 15 mg (clinical) Medication stopped then restarted at month 7 at 10 mg.
19 F 49 17 8 13 10 Elevated AST/ALT at month 10; 10 mg (laboratory) Medication continued
20 F 61 44 3 4 10 Growth of scant hairs noted

AKI = acute kidney injury; ALT = alanine transaminase; AST = acetate aminotransferase; LDL = low-density lipoprotein; URI = upper respiratory infection

Alopecia areata treated with tofacitinib
Patient 1 at baseline. Alopecia areata treated with tofacitinib
Patient 1 at month 16. Alopecia areata treated with tofacitinib
Patient 1 at month 16. Alopecia areata treated with tofacitinib
Patient 1 at month 22. Alopecia areata treated with tofacitinib
Patient 1 at month 22. Alopecia areata treated with tofacitinib
Patient 1 at month 30. Alopecia areata treated with tofacitinib
Patient 1 at month 30. Alopecia areata treated with tofacitinib
Patient 15 at baseline. Alopecia areata treated with tofacitinib
Patient 15 at baseline. Alopecia areata treated with tofacitinib
Patient 15 at month 9. Alopecia areata treated with tofacitinib
Patient 15 at month 9. Alopecia areata treated with tofacitinib
Patient 15 at month 12. Alopecia areata treated with tofacitinib
Patient 15 at month 12. Alopecia areata treated with tofacitinib
Patient 15 at month 20. DPSI Alopecia areata treated with tofacitinib
Patient 15 at month 20. DPSI Alopecia areata treated with tofacitinib