Simpson 2016 — Dupilumab SOLO 1 and SOLO 2 (EASI / IGA as regulatory primary endpoints)
Citation
Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al.; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016 Dec 15;375(24):2335–2348. DOI: 10.1056/NEJMoa1610020. PMID 27690741.
Study design and population
Two identical multinational phase-3 double-blind placebo-controlled RCTs (SOLO 1 n = 671; SOLO 2 n = 708) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topicals.
Reported metrics
- Week-16 IGA 0/1 with ≥ 2-point reduction (co-primary): SOLO 1 38 % dupilumab q2w vs. 10 % placebo; SOLO 2 36 % vs. 8 % (p < 0.001)
- Week-16 EASI-75 (key secondary): SOLO 1 51 %–52 % vs. 15 %; SOLO 2 44 %–48 % vs. 12 %
- Mean EASI % reduction 72 % ± 3 (dupilumab) vs. 38 % ± 3 (placebo) — SOLO 1
- Concordant improvements in POEM, pruritus NRS, DLQI, SCORAD
Surrogate-to-outcome linkage
Landmark regulatory-grade linkage: improvement in EASI / IGA surrogates tracks with improvement in patient-reported outcomes (POEM, peak-pruritus NRS, DLQI, sleep). This is the pivotal-trial evidence that closes the severity-score → patient-outcome loop for atopic dermatitis, underpinning FDA / EMA dupilumab approval.
CRIT1–7 appraisal
| Criterion | Score | Justification |
|---|---|---|
| CRIT1 Relevance | 3 | Direct — EASI / IGA as regulatory endpoints with concordant PRO change. |
| CRIT2 Methodology | 3 | Two identical phase-3 placebo-controlled RCTs; robust design and replication. |
| CRIT3 Reporting | 3 | All endpoints with point estimates and p-values; 95 % CIs in supplement. |
| CRIT4 Applicability | 3 | International multicentre; adult moderate-to-severe AD — exact population for the EASI / IGA surrogate claim. |
| CRIT5 Evidence weight | 2 | Pivotal phase-3 RCTs. |
| CRIT6 Risk of bias | 2 | Industry-funded (Sanofi / Regeneron); 16-week primary endpoint. |
| CRIT7 Contribution | 3 | Core anchor — demonstrates that regulatory-surrogate improvement produces concordant PRO improvement. |
Aggregate: very strong.
Limitations and notes
Industry-funded; short primary endpoint horizon (16 weeks); severe biologic-naïve population may not generalise to milder disease.
Strength as anchor
Very strong. Canonical EASI / IGA → PRO regulator-recognised linkage. Complements EMA CHMP/EWP/2454/02 (document evidence) and Mattei 2014 (meta-analytic PASI-DLQI linkage in psoriasis) to span both chronic-inflammatory-disease families.