Secukinumab dosing optimization in patients with moderate-to-severe plaque psoriasis: results from the randomized, open-label OPTIMISE study


Por: Reich, K, Puig, L, Szepietowski, JC, Paul, C, Lacour, JP, Tsianakas, A, Sieder, C, Rissler, M, Pournara, E, Orsenigo, R

Publicada: 1 feb 2020
Resumen:
BackgroundSecukinumab is a fully human monoclonal antibody that selectively binds to and neutralizes interleukin-17A. ObjectivesTo 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. MethodsOPTIMISE 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. ResultsPASI 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). ConclusionsStandard 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.

Filiaciones:
Reich, K:
 Univ Med Ctr Hamburg Eppendorf, Skinflammat Ctr, Inst Hlth Serv Res Dermatol & Nursing, Hamburg, Germany

 Demiatologikum Berlin, Berlin, Germany

Puig, L:
 Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Demiatol, Barcelona, Spain

Szepietowski, JC:
 Wroclaw Med Univ, Dept Dermatol Venereol & Allergol, Wroclaw, Poland

Paul, C:
 Toulouse Univ, Dept Dermatol, Toulouse, France

 Larrey Hosp, Toulouse, France

Lacour, JP:
 CHU Nice, Hop Archet, Nice, France

Tsianakas, A:
 Univ Munster, Munster, Germany

Sieder, C:
 Novartis Pharma GmbH, Nurnberg, Germany

Rissler, M:
 Novartis Pharma AG, Basel, Switzerland

Pournara, E:
 Novartis Pharma AG, Basel, Switzerland

Orsenigo, R:
 Novartis Farma SpA, Origgio, Italy
ISSN: 00070963





BRITISH JOURNAL OF DERMATOLOGY
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Reino Unido
Tipo de documento: Article
Volumen: 182 Número: 2
Páginas: 304-315
WOS Id: 000511207000011
ID de PubMed: 31102257

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