Artikel
Comparison of Secukinumab and Adalimumab Monotherapy as First-line Biologic Therapy in Patients with Active Psoriatic Arthritis: Proposed Design of a Randomized, Double-blind, Active Control, Multicenter Study
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Autoren
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Shephard Mpofu
- Novartis Pharma AG, Basel, Switzerland
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Iain McInnes
- University of Glasgow, Glasgow, England
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Kevin Ding
- Novartis Pharmaceutical Corporation, East Hanover, NJ, USA
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Emanuele Noseda
- Novartis Pharma AG, Basel, Schweiz
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Luminita Pricop
- Novartis Pharmaceuticals Corporation, New Jersey, USA
| Veröffentlicht: | 29. August 2016 |
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Gliederung
Text
Background: Latest guidelines highlight the importance of biologics in the management of PsA, with TNF-inhibitors being the most widely used [1]. Secukinumab is an interleukin-17A inhibitor approved forthe treatment of PsA. Head-to-head trials are required to compare the biologics available for PsA-treatment.
Objectives: This Phase 3b study will compare the efficacy and safety of secukinumab 150 and 300 mg sc and adalimumab 40 mg sc as first-line biologic monotherapy through 1 year in pts with PsA.
Methods: Biologic-naïve adults with active PsA, defined as ≥3 tender and swollen joints for ≥6 months despite previous treatment with conventional disease-modifying antirheumatic drugs will be enrolled and randomized (1:1:1) to secukinumab 300 mg , secukinumab 150 mg, or adalimumab 40 mg. Secukinumab will be administered at BL,Wks 1, 2, and 3, and then every 4 wks (Wk 4-Wk 48). Adalimumab will be administered every 2 wks (BL-Wk 50). All groups will receive placebo sc injections to ensure a consistent number of injections at each dosing visit. The primary efficacy endpoint will be ACR50 at Wk 52 with secukinumab 300 mg. Secondary endpoints at Wk 52 will include: ACR20, PASI75 and PASI 90; resolution of enthesitis; improvement in HAQ-DI score; and ACR50 at Week 52 in non-inferiority test for secukinumab 150 mg. 284 pts per group (852 in total) will yield approximately 95% power to detect a treatment difference of 15% (secukinumab 300 mg vs. Adalimumab). This expected treatment difference is based on an overall adalimumab response rate of 38%, (Wk 48 data from monotherapy biologic-naïve pts in the ADEPT study) [2],and a secukinumab 300 mg response rate of 53%, (Wk 52 data from monotherapy biologic-naïve pts in the secukinumab PsA clinical trial program) [3], [4].Safety and tolerability will be assessed through Wk 60.
Conclusion: This will be the first large head-to-head clinical trial that is powered to compare the efficacy and safety of a novel targeted biologic, secukinumab, versus an established biologic, adalimumab, in pts with active PsA. On completion, this trial will help improve evidence-based decision making in the treatment of PsA pts requiring biologic therapy.
Figure 1 [Fig. 1]
Note: EUDRACT number 2015-004477-32
References
- 1.
- Gossec L, Smolen JS, Ramiro S, de Wit M, Cutolo M, Dougados M, Emery P, Landewé R, Oliver S, Aletaha D, Betteridge N, Braun J, Burmester G, Cañete JD, Damjanov N, FitzGerald O, Haglund E, Helliwell P, Kvien TK, Lories R, Luger T, Maccarone M, Marzo-Ortega H, McGonagle D, McInnes IB, Olivieri I, Pavelka K, Schett G, Sieper J, van den Bosch F, Veale DJ, Wollenhaupt J, Zink A, van der Heijde D. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016 Mar;75(3):499-510. DOI: 10.1136/annrheumdis-2015-208337
- 2.
- Gladman DD, Mease PJ, Ritchlin CT, Choy EH, Sharp JT, Ory PA, Perdok RJ, Sasso EH. Adalimumab for long-term treatment of psoriatic arthritis: forty-eight week data from the adalimumab effectiveness in psoriatic arthritis trial. Arthritis Rheum. 2007 Feb;56(2):476-88.
- 3.
- McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewé R, Conaghan PG, Gottlieb AB, Richards H, Pricop L, Ligozio G, Patekar M, Mpofu S; FUTURE 2 Study Group. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 Sep 19;386(9999):1137-46. DOI: 10.1016/S0140-6736(15)61134-5
- 4.
- Novartis Data on File 2016
