Encyclopedia · immunomodulator
Tofacitinib
The first JAK inhibitor used off-label for alopecia areata; about a third to two thirds of patients regrow hair in open-label studies, but most relapse within months of stopping.
What it is
Tofacitinib is an oral JAK inhibitor approved for rheumatoid arthritis and other inflammatory diseases. It is used off-label for alopecia areata and is not approved for it anywhere we found. It is prescription-only and is not a treatment for pattern hair loss: a search for tofacitinib in pattern hair loss returned only alopecia areata studies.
How it works
It blocks JAK signalling that carries interferon-gamma and related cytokines driving the T-cell attack on the follicle (Xing 2014).
What the studies show
- In an open-label study of 66 people on 5 mg twice daily for 3 months, 32% improved by at least 50%, and relapse came about 8.5 weeks after stopping (Kennedy Crispin 2016).
- A meta-analysis of 12 mostly observational studies (288 on tofacitinib, 58 on ruxolitinib) found at least 50% improvement in 66%, and 74% relapsed within 3 months of stopping (Yu 2021).
- A meta-analysis of 7 RCTs of JAK inhibitors (1,710 people) found oral ones beat placebo (odds ratio 8.15 for 90% improvement) while topical ones did not (Liu 2023).
- A Cochrane review found no tofacitinib trial contributing high-certainty evidence, while baricitinib did (Mateos-Haro 2023).
- The evidence is open-label or retrospective, with varying doses and likely publication bias. No placebo-controlled RCT in alopecia areata exists.
How it's used in studies
- 5 mg twice daily for at least 3 months in the main prospective study (Kennedy Crispin 2016).
Side effects and safety
- Infections and laboratory abnormalities, more common with longer treatment (24% versus 7% beyond 6 months) (Yu 2021).
- The JAK class warning (infection, cancer, cardiovascular events, clots) originated from the tofacitinib ORAL Surveillance trial in older people with rheumatoid arthritis (Ytterberg 2022); see baricitinib.
Bottom line
Tofacitinib is historically important and still used where approved drugs are unavailable or unaffordable, but baricitinib, ritlecitinib and deuruxolitinib have randomised evidence behind them. Relapse after stopping is the norm. Discuss with a doctor.
Studies 6
Kennedy Crispin M et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016
Tested: tofacitinib 5 mg twice daily, open-label
Result: 32% improved by at least 50%; relapse came about 8.5 weeks after stopping.
Read the study ↗Yu DA et al. Treatment outcome of oral tofacitinib and ruxolitinib in patients with alopecia areata. Indian J Dermatol Venereol Leprol. 2021
Tested: oral tofacitinib or ruxolitinib
Result: At least 50% improvement in 66%; 74% relapsed within 3 months of stopping; infections and lab abnormalities were the commonest problems.
Read the study ↗Liu M et al. Janus kinase inhibitors for alopecia areata: a systematic review and meta-analysis. JAMA Netw Open. 2023
Tested: oral and topical JAK inhibitors vs placebo
Result: Oral JAK inhibitors beat placebo (odds ratio 8.15 for 90% improvement); topical ones did not.
Read the study ↗Mateos-Haro M et al. Treatments for alopecia areata: a network meta-analysis. Cochrane Database Syst Rev. 2023
Tested: all studied treatments
Result: Baricitinib was the only treatment with high-certainty evidence of benefit; for oral prednisolone or cyclosporine versus placebo the evidence was very uncertain.
Read the study ↗Xing L et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014
Tested: JAK inhibitors, including oral ruxolitinib
Result: Systemic JAK inhibitors prevented disease in mice, topical ones reversed it, and three patients on ruxolitinib regrew nearly all hair within 5 months.
Read the study ↗Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022
Tested: tofacitinib vs TNF inhibitors
Result: Raised concern about cardiovascular events and cancer, which led to class-wide JAK inhibitor warnings.
Read the study ↗Related
- BaricitinibA once-daily pill that was the first drug approved for severe alopecia areata, regrowing hair in about a third of patients while they keep taking it.
- RitlecitinibA once-daily pill approved for severe alopecia areata from age 12, which regrows hair in about 1 in 4 people by 6 months and keeps improving for years.
- RuxolitinibThe JAK1/2 blocker whose first use in three alopecia areata patients in 2014 launched the JAK era for hair; the pill regrows hair in small studies while the cream failed.
- JAK inhibitors and hairJanus kinase (JAK) inhibitors are pills that regrow hair in severe alopecia areata, but they are not treatments for ordinary pattern thinning.
- Alopecia areataAn autoimmune condition where the immune system attacks growing hair follicles, causing round patches or total hair loss; three oral JAK inhibitors are approved for severe cases but hair usually goes again when treatment stops.