Summary Background Secukinumab is a fully human monoclonal antibody that selectively binds to and neutralizes interleukin‐17A. Objectives To assess the efficacy and safety of different maintenance dosing regimens of secukinumab 300 mg based on Psoriasis Area and Severity Index (PASI) response at week 24 in patients with moderate‐to‐severe plaque psoriasis. Methods OPTIMISE was a randomized, open‐label, rater‐blinded phase IIIb study. Patients (n = 1647) received secukinumab 300 mg at baseline; weeks 1, 2, 3 and 4; and every 4 weeks (q4w) to week 24. At week 24, PASI 90 responders (≥ 90% improvement in PASI; n = 1306) were randomized to secukinumab 300 mg q4w (n = 644) or q6w (n = 662) to week 52, and PASI ≥ 75 to < 90 responders (n = 206) were randomized to secukinumab 300 mg q4w (n = 114) or q2w (n = 92) to week 52. Results PASI 90 response was maintained at week 52 by 85·7% of patients with q4w dosing vs. 74·9% with q6w dosing (odds ratio 1·91, 95% confidence interval 1·44–2·55). The primary end point, noninferiority of q6w vs. q4w dosing, was not met. In PASI ≥ 75 to < 90 responders, the proportion of patients with PASI 90 response at week 52 was numerically higher in the q2w vs. the q4w group (57% vs. 46·5%, respectively, P = 0·10). Heavier patients (≥ 90 kg) demonstrated numerically higher PASI 90 response with the q2w (57·1%) vs. the q4w regimen (40%, P = 0·11). Conclusions Standard q4w dosing of secukinumab 300 mg is the optimal dosing regimen to achieve and maintain clear or almost clear skin. Patients with body weight ≥ 90 kg not achieving PASI 90 at week 24 may benefit from the q2w dosing regimen. What's already known about this topic? Individual responses to biologics in patients with psoriasis vary considerably and there may be a need to individualize treatment. Dose optimization strategies of currently available biologic drugs have been investigated mainly in rheumatic disorders. Secukinumab has shown long‐term PASI 90/100 responses (percentage improvement in Psoriasis Area and Severity Index) to year 5 in patients with moderate‐to‐severe plaque psoriasis when used at the dose of 300 mg every 4 weeks. What does this study add? Standard every 4 week (q4w) dosing of secukinumab 300 mg is the optimal regimen to achieve and maintain clear or almost clear skin at week 52; the majority of the patients (85·7%) maintain PASI 90 at week 52. Superiority of intensified (q2w) dosing over the q4w regimen could not be claimed. However, patients with a higher body weight (≥ 90 kg) not achieving PASI 90 response at week 24 may benefit from q2w dosing. Linked Comment: Morita and Ikumi. Br J Dermatol 2020; 182:264–266.