Upadacitinib is a medication widely used for the treatment of rheumatoid arthritis that works by inhibiting Janus kinase (JAK) enzymes, which are involved in signaling pathways that regulate immune responses. Now, scientists have found another application for this immune system-modulating drug. Two recent Phase III international trials involving 1,399 people found that upadacitinib helped with alopecia areata, which causes people to lose hair, resulting in small, round bald patches on the scalp and elsewhere on the body.
The researchers set out to see how many people grew back enough hair to cover at least 80% of their scalp at the end of the trial. Nearly half of the people taking the 15 mg dose of upadacitinib reached the 80% coverage mark within 24 weeks. With the 30 mg dose, that figure rose to more than 54%. Among people given a placebo, only about 2% saw that degree of regrowth.
The regrowth wasn’t limited to the scalp. People taking upadacitinib also saw improvements in their eyebrows and eyelashes and reported feeling better emotionally and socially.
The findings are published in JAMA Dermatology.
Blocking proteins to boost regrowth
Alopecia areata (AA) is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue. It affects an estimated 1 in 50 people globally, or more than 160 million people worldwide. While hair loss may look like a cosmetic issue to others, for people living with alopecia areata, its impact can run much deeper. The shame and loss of self-confidence that can come with hair loss can cause significant emotional distress, contribute to mental health struggles and affect quality of life.
Current treatments for alopecia rarely help patients with severe cases. Even among the small number of approved drugs, many patients in past trials didn’t regrow enough hair to make a real difference. For adolescents, the problem is worse because there have been almost no approved treatment options.
How the trials were run
Since AA is linked to the immune system, scientists looked into whether upadacitinib, a drug belonging to a class called JAK inhibitors, could help. These drugs work by blocking specific proteins, called Janus kinases, that play a key role in triggering the inflammation and immune attack behind hair loss.
Scientists believed this precise targeting would allow the drug to work quickly and produce deep, lasting hair regrowth, and previous trials of other JAK inhibitors did restore hair for a portion of patients.
To find out, researchers put upadacitinib through two Phase III trials. UP-AA1 spanned 112 clinical centers across 25 countries, while UP-AA2 reached even further, covering 125 centers in 28 countries across Asia, Europe, North America and South or Central America. Together, the trials brought in adolescents ages 12 to 17 and adults up to age 64. Only those with a Severity of Alopecia Tool (SALT) score of 50 or higher, meaning they had already lost at least 50% of the hair on their scalp, were eligible for the trial.
Using a computer program, the team randomly divided patients in both the UP-AA1 and UP-AA2 studies into three treatment groups: 15 mg upadacitinib daily (40% of patients), 30 mg upadacitinib daily (40% of patients) and placebo (20% of patients).
The first 24 weeks tracked hair growth progression, with assessments at weeks 4, 8, 12 and 24, while safety was monitored throughout. Patients then entered a 28-week extension period, continuing the medication under blinded conditions to assess longer-term performance.
Strong regrowth and limited risks
People with severe alopecia areata who took upadacitinib saw substantially more hair regrowth than those given the placebo, with the results holding steady across both trials. More than 35% of patients on the 15 mg dose and about 46% on the 30 mg dose achieved deep hair regrowth (90% or more coverage), compared with roughly 1% in the placebo group.
Roughly 13% to 23% of participants on the low and high doses, respectively, achieved complete scalp hair regrowth, versus almost none in the placebo group. More than half of the 30 mg group had significant eyelash and eyebrow regrowth.
Early gains for severe cases
These improvements started showing as early as eight weeks into the trial for patients taking either dose of upadacitinib. The most commonly reported side effects included acne, colds, throat irritation and upper respiratory tract infections. Serious side effects, however, were quite rare.
Taken together, these results present upadacitinib as a promising treatment option for adults and adolescents living with severe alopecia areata, opening up the possibility of meaningful hair regrowth for millions of people living with the condition.