King 2022 — Baricitinib BRAVE-AA1 / BRAVE-AA2 (SALT as FDA / EMA primary endpoint)
Citation
King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022 May 5;386(18):1687–1699. DOI: 10.1056/NEJMoa2110343.
Study design and population
Two phase-3 RCTs (BRAVE-AA1 and BRAVE-AA2). n = 1,200 adults with severe alopecia areata (baseline SALT ≥ 50; ≥ 50 % scalp hair loss). Multicentre international.
Reported metrics
- Week-36 SALT ≤ 20 (primary): BRAVE-AA1 — 38.8 % (4 mg), 22.8 % (2 mg), 6.2 % (placebo); 4 mg vs. placebo difference 32.6 pp (95 % CI 25.6–39.5)
- BRAVE-AA2 — 35.9 % (4 mg), 19.4 % (2 mg), 3.3 % (placebo); 4 mg difference 32.6 pp (95 % CI 25.6–39.6)
- Concordant eyebrow and eyelash regrowth (ClinRO) and QoL gains
Surrogate-to-outcome linkage
Pivotal-trial evidence that SALT (Severity of Alopecia Tool) responds to effective therapy, with SALT ≤ 20 accompanied by patient-relevant outcomes (hair regrowth, self-reported appearance, QoL). Enabled the first FDA and EMA systemic approval for severe alopecia areata. Closes the severity-score → patient-outcome loop for the AA strand of the argument.
CRIT1–7 appraisal
| Criterion | Score | Justification |
|---|---|---|
| CRIT1 Relevance | 3 | Direct — SALT is the AA regulatory surrogate endpoint. |
| CRIT2 Methodology | 3 | Two identical phase-3 placebo-controlled RCTs; regulator-aligned design. |
| CRIT3 Reporting | 3 | Response rates with 95 % CIs; concordant PRO and ClinRO data. |
| CRIT4 Applicability | 3 | Severe AA adults — exact population for SALT surrogate claim. |
| CRIT5 Evidence weight | 2 | Pivotal phase-3 RCTs. |
| CRIT6 Risk of bias | 2 | Industry-funded (Eli Lilly); 36-week primary endpoint. |
| CRIT7 Contribution | 3 | Core anchor — FDA / EMA approval precedent for SALT. |
Aggregate: very strong.
Limitations and notes
Industry-funded; short primary endpoint horizon. Complementary ritlecitinib ALLEGRO and deuruxolitinib data available for triangulation if needed.
Strength as anchor
Very strong for the AA strand. Pairs with Olsen 2004 (SALT definition) and the subsequent ritlecitinib / deuruxolitinib approvals to anchor SALT as the regulator-accepted AA severity surrogate.