Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS)

ObjectiveTo evaluate efficacy and safety of guselkumab, an anti-interleukin-23p19-subunit antibody, in patients with psoriatic arthritis (PsA) with prior inadequate response (IR) to tumour necrosis factor inhibitors (TNFi).MethodsAdults with active PsA (≥3 swollen and ≥3 tender joints) who discontinued ≤2 TNFi due to IR (lack of efficacy or intolerance) were randomised (2:1) to subcutaneous guselkumab 100 mg or placebo at week 0, week 4, then every 8 weeks (Q8W) through week 44. Patients receiving placebo crossed over to guselkumab at week 24. The primary (ACR20) and key secondary (change in HAQ-DI, ACR50, change in SF-36 PCS and PASI100) endpoints, at week 24, underwent fixed-sequence testing (two-sided α=0.05). Adverse events (AEs) were assessed through week 56.ResultsAmong 285 participants (female (52%), one (88%) or two (12%) prior TNFi), 88% of 189 guselkumab and 86% of 96 placebo→guselkumab patients completed study agent through week 44. A statistically significantly higher proportion of patients receiving guselkumab (44.4%) than placebo (19.8%) achieved ACR20 (%difference (95% CI): 24.6 (14.1 to 35.2); multiplicity-adjusted p<0.001) at week 24. Guselkumab was superior to placebo for each key secondary endpoint (multiplicity-adjusted p<0.01). ACR20 response (non-responder imputation) in the guselkumab group was 58% at week 48; >80% of week 24 responders maintained response at week 48. Through week 24, serious AEs/serious infections occurred in 3.7%/0.5% of 189 guselkumab-randomised and 3.1%/0% of 96 placebo-randomised patients; the guselkumab safety profile was similar through week 56, with no deaths or opportunistic infections.ConclusionGuselkumab significantly improved joint and skin manifestations and physical function in patients with TNFi-IR PsA. A favourable benefit–risk profile was demonstrated through 1 year.Trial registration numberNCT03796858.

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OP0201 A phase 3 study of the efficacy and safety of ixekizumab in patients with active psoriatic arthritis and inadequate response to tumour necrosis factor inhibitor(s)

10.1136/annrheumdis-2017-eular.1576 ◽

2017 ◽

Cited By ~ 1

Author(s):

P Nash ◽

B Kirkham ◽

M Okada ◽

P Rahman ◽

B Combe ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Tumour Necrosis Factor Inhibitor ◽

Inadequate Response ◽

Efficacy And Safety ◽

Phase 3 ◽

Factor Inhibitor ◽

Necrosis Factor

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Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial

The Lancet ◽

10.1016/s0140-6736(17)31429-0 ◽

2017 ◽

Vol 389 (10086) ◽

pp. 2317-2327 ◽

Cited By ~ 162

Author(s):

Peter Nash ◽

Bruce Kirkham ◽

Masato Okada ◽

Proton Rahman ◽

Benard Combe ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Inadequate Response ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo ◽

Tumour Necrosis Factor Inhibitors ◽

Necrosis Factor

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Ixekizumab is efficacious when used alone or when added to conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor inhibitors

RMD Open ◽

10.1136/rmdopen-2018-000692 ◽

2018 ◽

Vol 4 (2) ◽

pp. e000692 ◽

Cited By ~ 4

Author(s):

Peter Nash ◽

Frank Behrens ◽

Ana-Maria Orbai ◽

Suchitrita S Rathmann ◽

David H Adams ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Disease Activity ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Short Form ◽

Joint Disease ◽

Inadequate Response ◽

Efficacy And Safety ◽

Disease Modifying ◽

Necrosis Factor

ObjectiveTo conduct subset analyses of SPIRIT-P2 (NCT02349295) to investigate the efficacy and safety of ixekizumab versus placebo in three subgroups of patients with active psoriatic arthritis (PsA) according to the concomitant conventional synthetic disease-modifying antirheumatic drug (cDMARD) received: any background cDMARDs (including methotrexate), background methotrexate only, or none.MethodsPatients were randomised to receive placebo, ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W). Efficacy and safety were assessed when patients were subdivided according to cDMARD use at baseline. Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50), achievement of minimal disease activity (MDA) state, Disease Activity Index for PsA (DAPSA), 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index and the 36-item Short-Form health survey physical functioning domain.ResultsRegardless of background cDMARD status, ACR20, ACR50 and MDA response rates were significantly higher than placebo with IXEQ4W or IXEQ2W treatment. Similarly, significant improvements were observed relative to placebo for DAS28-CRP and DAPSA across subgroups. Physical function also significantly improved relative to placebo with IXEQ4W treatment regardless of background cDMARD status and with IXEQ2W alone. Percentages of reported treatment-emergent adverse events (AEs), serious AEs (including serious infections) and discontinuations due to AEs in each subgroup were comparable to the overall SPIRIT-P2 population.ConclusionIxekizumab was efficacious in patients with active PsA and previous tumour necrosis factor inhibitor (TNFi) inadequate response or TNFi intolerance treated with ixekizumab alone or when added to cDMARDs with subgroup safety profiles that were consistent with that observed in the overall SPIRIT-P2 population.

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