Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial

McInnes, Iain B.; Behrens, Frank; Mease, Philip J.; Kavanaugh, Arthur; Ritchlin, Christopher T.; Nash, Peter; Masmitjá, Jordi Gratacós; Goupille, Philippe; Коротаева, Т. В.; Gottlieb, Alice B.; Martin, Ruvie; Ding, Kevin; Pellet, Pascale; Mpofu, S.; Pricop, Luminita

doi:10.1016/s0140-6736(20)30564-x

Cited by 204 publications

(240 citation statements)

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“…The results of EXCEED 1 were only presented in an abstract form thus far. 15 Due to disease heterogeneity in PsA, the requirement of assessing multiple PsA domains to identify appropriate treatments for individual patients is important. Therefore, we used simultaneous achievement of a relatively rigorous end point for articular disease (ACR50) and a very stringent end point for the skin disease (PASI100) at Wk24 as the primary end point for this study.…”

Section: Discussionmentioning

confidence: 99%

Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52

et al. 2020

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ObjectivesSPIRIT head-to-head (H2H) is a 52-week (Wk) trial comparing ixekizumab (IXE) with adalimumab (ADA) for simultaneous American College of Rheumatology (ACR)50 and Psoriasis Area and Severity Index (PASI)100 responses in 566 patients (distributed evenly across both groups) with psoriatic arthritis (PsA). IXE was superior to ADA for this primary end point at Wk24. We aimed to determine the final efficacy and safety results through Wk52 including a prespecified subgroup analysis of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) use.MethodsSPIRIT-H2H is a Wk52 multicentre, open-label, blinded-assessor study comparing IXE and ADA in bionaïve patients with PsA. Patients were randomised 1:1 to IXE or ADA with stratification by concomitant csDMARD use and presence of moderate-to-severe plaque psoriasis. Prespecified end points at Wk24 and Wk52 included musculoskeletal, psoriasis, quality-of life outcomes, subgroup analyses and safety.ResultsA significantly higher proportion of patients treated with IXE versus ADA simultaneously achieved ACR50 and PASI100 (39% vs 26%, p<0.001), PASI100 (64% vs 41%, p<0.001) at Wk52. Efficacy of IXE and ADA was similar at Wk52 for ACR50 (49.8% vs 49.8%, p=0.924), treat-to-target outcomes, enthesitis and dactylitis resolution. Responses to IXE were consistent irrespective of concomitant csDMARD use. Significantly more patients on IXE monotherapy versus ADA monotherapy had simultaneous ACR50 and PASI100 (38% vs 19%, p=0.007), and PASI100 responses (66% vs 35%, p<0.001) at Wk52. There were no new safety findings for IXE or ADA.ConclusionsIXE provided significantly greater simultaneous joint and skin improvement than ADA through Wk52 in bionaïve patients with PsA. IXE showed better efficacy on psoriasis and performed at least as well as ADA on musculoskeletal manifestations. IXE efficacy was consistent irrespective of concomitant csDMARD use.Trial registration numberNCT03151551.

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Section: Discussionmentioning

confidence: 99%

Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52

et al. 2020

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“…In this subanalysis of the SPIRIT-H2H trial comparing the effects of IXE to ADA in patients with PsA who were bDMARD-naïve, we demonstrated that response to IXE without MTX was higher than the response to ADA without MTX for multiple joint and skin endpoints. The EXCEED study comparing secuk- inumab safety and efficacy versus ADA without concomitant csDMARD use in patients with active PsA who were naïve to biologic therapy and intolerant or with inadequate response to csDMARD [28] failed to show the superiority of secukinumab versus ADA on ACR20 (primary endpoint). However, EXCEED reported a significantly higher response with secukinumab versus ADA in some joint and skin endpoints.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study

et al. 2020

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Introduction In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. Methods In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher’s exact test. Missing data were imputed using non-responder imputation. Results By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 ( p = 0.002) endpoint, minimal disease activity ( p = 0.016), and very low disease activity ( p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. Conclusion In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance. Electronic supplementary material The online version of this article (10.1007/s40744-020-00250-3) contains supplementary material, which is available to authorized users.

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“…A number of matching-adjusted indirect comparisons have been published demonstrating con icting though higher responses for secukinumab over in iximab (27), adalimumab (28) and etanercept (29). Notably, secukinumab only narrowly missed statistical signi cance for superiority over adalimumab in the primary endpoint of the head-to-head EXCEED trial, showing only numerically higher results versus adalimumab (30). Thus, our data might suggest that switching to secukinumab would be a better medication choice after TNFα blocker failure.…”

Section: Discussionmentioning

confidence: 65%

Treatment Persistence of Biologics among patients with Psoriatic Arthritis

Haddad

Gazitt

Feldhamer

et al. 2020

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Background Persistence of biologic therapy in psoriatic arthritis (PsA) patients is an important factor in individualized patient treatment planning and healthcare policy and guideline development. . Objective To estimate the persistence of biologic agents prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients. Methods Patients with PsA from a large health care provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1st, 2002 until December 31st, 2018 were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a permissible lag time of 6 months from the time of prescription issuance until medication filling date was exceeded. Treatment changes were based on physician decisions and patient preferences. Demographic data including age, sex, body mass index (BMI), ethnicity, smoking history and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence.Results 2301 PsA patients with 2958 treatment periods were identified and included in the analyses. Mean age of the study population was 50.9±14 years, 54% females, 70.4% with BMI>25, 40% current smokers, and 76% with a Charlson comorbidity index>1. The most commonly prescribed drug was etanercept (33%), followed by adalimumab (29%), golimumab (12%), secukinumab (10%), ustekinumab (8%) and infliximab (8%). While approximately 40% of patients persisted on therapy following 20 months of treatment, only about 20% of patients remained on any particular biologic agent after 5 years. Analyzing the data for all treatment periods while taking into account all lines of therapy, revealed that secukinumab had a higher persistency than adalimumab, infliximab and ustekinumab, with a Log Rank of 0.022, 0.047 and 0.001, respectively. Female sex and smoking were associated with lower drug persistence (HR=1.25, 95%CI=1.13-1.38 and HR=1.109, 95%CI=1.01-1.21, respectively). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-Tumor Necrosis Factor-alpha (anti-TNFα) agent was observed. While, secukinumab was found to be superior as second line therapy to adalimumab, etanercept, infliximab and ustekinumab but not to golimumab with a Log-Rank P-value of 0.001, 0.004, 0.025 and 0.002, respectively. Conclusions In this large observational cohort studied in the era of biologic therapy, a relatively low drug persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents was found to be more persistent than others as first line therapy, while secukinumab was found to be superior to other biologics when indicated as second line of therapy.

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Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial

Cited by 204 publications

References 23 publications

Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52

Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52

Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study

Treatment Persistence of Biologics among patients with Psoriatic Arthritis

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