Design: Two replicate phase 3, double-blind, placebo-controlled randomised trials (UP-AA1 and UP-AA2)
Population: 1,399 adults and adolescents aged 12–64 with severe alopecia areata (SALT 50 or more)
Primary outcome: SALT score of 20 or less at week 24
Effect: 15 mg 45.2% and 44.6%; 30 mg 55.0% and 54.3%; placebo 1.5% and 3.4%

Two replicate, double-blind phase 3 trials randomised 1,399 people aged 12 to 64 with severe alopecia areata (SALT score 50 or more, mean about 84) to upadacitinib 15 mg, 30 mg or placebo once daily for 24 weeks, followed by a blinded extension.

At 24 weeks a SALT score of 20 or less, meaning at least 80% scalp coverage, was reached by about 45% on 15 mg and 55% on 30 mg, against 1.5% and 3.4% on placebo in the two trials. Safety looked like upadacitinib's profile in its licensed uses: upper respiratory infections, acne and raised creatine kinase were the commonest events, and serious adverse events were 1.6% and 2.3% on the two doses against 0.4% on placebo.

The result is large and replicated, and it adds a third oral JAK inhibitor option for severe disease, including adolescents. The usual JAK cautions apply: screening for tuberculosis and hepatitis, attention to cardiovascular and thrombotic risk in older adults, and monitoring of blood counts and lipids.

Regulatory status for this indication should be checked locally; this edition does not know of a CDSCO decision. Relapse after stopping is expected, so treatment is likely to be long-term.

Consider an oral JAK inhibitor for severe alopecia areata with SALT 50 or more, where licensed.
Screen for tuberculosis and hepatitis B and C before starting.
Check blood counts, lipids, liver tests and creatine kinase during treatment.
Discuss acne and infection risk, the commonest side effects in these trials.
Plan for long-term treatment; relapse after stopping is expected.

Why it matters

It broadens the effective options for a disease where most treatments, until recently, failed in severe cases.

The statistics, in plain English

45–55% against 1.5–3.4% is a very large difference, consistent across two separate trials, which makes chance an unlikely explanation. The 24-week results do not tell us about durability or rare harms that emerge only over years.