Secukinumab in the Treatment of Moderate-to-Severe Hidradenitis Suppurativa: Pooled Pharmacokinetics and Safety Results From the SUNSHINE and SUNRISE Phase 3 Studies.

BACKGROUND

Secukinumab, a fully human, monoclonal antibody targeting interleukin-17A, is approved for moderate-to-severe HS in adults. This study evaluated pharmacokinetics (PK), high-sensitivity C-reactive protein (hsCRP) changes, and safety of secukinumab over 52 weeks in SUNSHINE and SUNRISE Phase 3 trials.

METHODS

An exploratory analysis of pooled Phase-3 trials evaluated serum PK and safety of secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W). A population PK model assessed the effects of body weight, disease severity, and baseline hsCRP on secukinumab serum concentration. Exposure-response analysis assessed the relationship between predicted PK and HS clinical response [HiSCR]. No confirmatory statistical testing was performed.

RESULTS

Mean serum trough concentration at Weeks 16, 24, and 52 was ~2-fold higher with SECQ2W vs. SECQ4W. At Week 16, exposure overlap was high, with an estimated numerical increase in HiSCR of ~3% for SECQ2W over SECQ4W. At Week 52, HiSCR levels plateaued. At Week 16, hsCRP decreased from 18.6 ± 26.3 mg/L to 12.8 ± 18.0 mg/L (SECQ2W), 15.9 ± 27.6 mg/L to 11.5 ± 18.4 mg/L (SECQ4W), and remained unchanged with placebo (14.4 ± 22.5 mg/L to 14.7 ± 23.8 mg/L); reductions were sustained through Week 52. Higher body weight, disease severity, and baseline hsCRP were associated with lower secukinumab serum concentrations. Secukinumab immunogenicity was low (< 1%), with no new safety signals.

CONCLUSION

Secukinumab serum concentrations in patients with HS varied with body weight, disease severity, and baseline hsCRP. SECQ2W may benefit certain patients. Secukinumab reduced hsCRP through Week 52. The safety profile of secukinumab was consistent with other approved indications, with no apparent dose-response relationship observed.

TRIAL REGISTRATION: NCT03713619 (Novartis study code CAIN457M2301). NCT03713632 (Novartis study code CAIN457M2302).