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Ixekizumab improves patient-reported outcomes up to 52 weeks in bDMARD-naive patients with active psoriatic arthritis (SPIRIT-P1).

ABSTRACT: Objective:To report patient-reported outcomes of patients with PsA treated with ixekizumab up to 52 weeks. Methods:In SPIRIT-P1, biologic-naïve patients with active PsA were randomized to ixekizumab 80 mg every 4 weeks (IXEQ4W; N = 107) or every 2 weeks (IXEQ2W; N = 103) following a 160 mg starting dose, adalimumab 40 mg every 2 weeks (ADA; N = 101) or placebo (PBO; N = 106) during the initial 24-week double-blind treatment period. At week 24 (week 16 for inadequate responders), ADA (8-week washout before starting ixekizumab) and PBO patients were re-randomized to IXEQ2W or IXEQ4W. Patients receiving ixekizumab at week 24 received the same dose during the extension period (EP) to week 52. Patients completed measures including the Dermatology Life Quality Index (DLQI), Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2, European Quality of Life 5 Dimensions Visual Analogue Scale and Work Productivity and Activity Impairment Questionnaire-Specific Health Problem. Results:The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in DLQI at week 24; 22% (PBO), 53% (IXEQ4W), 63% (IXEQ2W) and 54% (ADA) of patients reported DLQI scores of 0/1. The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2 physical component summary and some domain scores, and European Quality of Life 5 Dimensions Visual Analogue Scale at weeks 12 and 24; and in three of four Work Productivity and Activity Impairment Questionnaire-Specific Health Problem domains at week 24. Results are also presented through week 52 for the EP. Conclusion:In biologic-naïve patients with active PsA, ixekizumab significantly improved skin symptoms, health-related quality of life and work productivity. Trial Registration:ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239; EU Clinical Trials Register, https://www.clinicaltrialsregister.eu, EudraCT2011-002326-49.

SUBMITTER: Gottlieb AB

PROVIDER: S-EPMC6152421 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Ixekizumab improves patient-reported outcomes up to 52 weeks in bDMARD-naïve patients with active psoriatic arthritis (SPIRIT-P1).

Gottlieb Alice B AB Strand Vibeke V Kishimoto Mitsumasa M Mease Philip P Thaçi Diamant D Birt Julie J Lee Chin H CH Shuler Catherine L CL Lin Chen-Yen CY Gladman Dafna D DD

Rheumatology (Oxford, England) 20181001 10

<h4>Objective</h4>To report patient-reported outcomes of patients with PsA treated with ixekizumab up to 52 weeks.<h4>Methods</h4>In SPIRIT-P1, biologic-naïve patients with active PsA were randomized to ixekizumab 80 mg every 4 weeks (IXEQ4W; N = 107) or every 2 weeks (IXEQ2W; N = 103) following a 160 mg starting dose, adalimumab 40 mg every 2 weeks (ADA; N = 101) or placebo (PBO; N = 106) during the initial 24-week double-blind treatment period. At week 24 (week 16 for inadequate responders), A ...[more]

PMID: 29945203

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Project description:IntroductionIn 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.MethodsIn 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.ResultsBy 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.ConclusionIn 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.

Project description:IntroductionImprovements in both musculoskeletal and non-musculoskeletal manifestations are important treatment goals in psoriatic arthritis (PsA).ObjectiveThese post hoc analyses determined whether additional benefits related to various PsA domains are observed in patients simultaneously achieving 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100), the primary endpoint of the SPIRIT-H2H study.MethodsPatients with active PsA and psoriasis in SPIRIT-H2H (N = 566) were categorised into two sets of four response groups irrespective of treatment allocation (approved dosages of ixekizumab or adalimumab): patients who simultaneously achieved ACR50 and PASI100 response, achieved ACR50 response only, achieved PASI100 response only, or did not achieve ACR50 or PASI100 response after 24 and 52 weeks of treatment. Patients achieving simultaneous ACR50 and PASI100 response were compared with the other patient response groups at the corresponding time point for efficacy and health-related quality of life (HRQoL) outcomes.ResultsPatients simultaneously achieving ACR50 and PASI100 responses at week 24 or 52 showed higher rates of ACR70 response, minimal disease activity, Disease Activity in Psoriatic Arthritis ≤ 4, resolution of enthesitis and dactylitis, and HRQoL improvement at weeks 24 and 52, respectively, than the other corresponding response groups at both time points.ConclusionHigh levels of disease control, such as those obtained with simultaneous achievement of ACR50 and PASI100 response, were linked to better outcomes across a wide range of endpoints that are important for patients with PsA. Patients meeting this combined endpoint showed more comprehensive and thus greater control of disease activity. Trial registration NCT03151551 Key Points • Treatment goals for patients with psoriatic arthritis emphasise the importance of improving both musculoskeletal and non-musculoskeletal manifestations of the disease. • A combined endpoint considering both these manifestations, achievement of at least 50% improvement in American College of Rheumatology criteria and 100% improvement in Psoriasis Area Severity Index, was linked with achievement of a number of other endpoints relevant to psoriatic arthritis, including health-related quality of life that are important to patients with psoriatic arthritis. • Patients meeting the combined endpoint were more likely to achieve a disease state of remission, which is the stated aim of treatment for psoriasis.

Project description:Introduction/objectivesTo evaluate the three-year efficacy and safety of ixekizumab with and without concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use in patients with active psoriatic arthritis (PsA).MethodPatients with PsA who were biologic-naïve (SPIRIT-P1, NCT01695239) or had prior inadequate response to tumor necrosis factor inhibitors (SPIRIT-P2, NCT02349295) were randomized to receive 80-mg ixekizumab every four weeks after receiving 160-mg ixekizumab at baseline. Efficacy, safety, and immunogenicity were evaluated in this post-hoc analysis in three subgroups: (1) ixekizumab monotherapy, (2) ixekizumab and methotrexate (MTX), (3) ixekizumab and any csDMARD (including MTX). Missing data were imputed using multiple imputation for continuous variables and modified non-responder imputation for categorical variables.ResultsEfficacy was similar across the three subgroups with 59.1%, 67.0%, and 66.1% of ixekizumab-treated patients achieving 20% improvement in the American College of Rheumatology scale score at week 156. Radiographic progression of structural joint damage (SPIRIT-P1 only) was similarly inhibited across the three subgroups with several outliers. No new safety signals were reported, and 91.0%, 84.1%, and 83.2% in the three subgroups reported ≥ 1 treatment-emergent adverse event. At week 156, 15.9%, 13.1%, and 11.0% in the three subgroups had antidrug antibodies; most had low titer status.ConclusionsIxekizumab showed sustained efficacy in treating patients with PsA for up to three years in monotherapy or in combination with MTX or any csDMARD. The three subgroups had similar safety and immunogenicity profiles, which supports that the use of concomitant MTX or csDMARDs does not seem to impact the benefit/risk profile of ixekizumab. Key Points • Ixekizumab treatment led to improved clinical responses over time when used as monotherapy or in combination with concomitant MTX or any concomitant csDMARD (including MTX) in patients with active PsA. • Ixekizumab monotherapy has similar radiographic efficacy as ixekizumab with MTX or ixekizumab with other csDMARDs (including MTX); similar inhibition of radiographic progression was observed between the subgroups of patients receiving ixekizumab monotherapy or ixekizumab with MTX or other csDMARDs. • The long-term safety profile of ixekizumab used as monotherapy or in combination with MTX or any other csDMARDs is consistent with what has been previously reported. The addition of MTX or any csDMARD to ixekizumab treatment did not negatively impact the favorable long-term safety profile of ixekizumab.

Project description:PurposeIxekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A. The objective of this study was to assess the long-term efficacy and safety (to week 156) of ixekizumab in patients with active psoriatic arthritis and inadequate response or intolerance to one or two tumor necrosis factor inhibitors.MethodsIn the SPIRIT-P2 study (ClinicalTrials.gov ID: NCT02349295), patients were randomized to placebo or ixekizumab 80 mg every 4 weeks (IXE Q4W) or every 2 weeks (IXE Q2W) following a 160-mg starting dose. During the extension period (weeks 24-156), patients maintained their original ixekizumab dose, and placebo patients received IXE Q4W or IXE Q2W (1:1). Exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) are presented.ResultsOf 363 patients enrolled in the study, 310 entered the extension period. In all patients treated with IXE Q4W and IXE Q2W at week 0, responses persisted to week 156. At week 156, clinical responses (observed) in patients treated with IXE Q4W and IXE Q2W were assessed [American College of Rheumatology (ACR) response criteria and minimal disease activity (MDA) criteria]: 84 and 85% showed 20% improvement (ACR20); 60 and 58% showed 50% improvement (ACR50); 35 and 47% showed 70% improvement (ACR70), respectively; and 48 and 54% showed MDA. Placebo patients re-randomized to ixekizumab also demonstrated sustained efficacy, as measured by ACR and MDA responses. In the All Ixekizumab Exposure Safety Population (n = 337), with 644 PY of ixekizumab exposure, treatment-emergent adverse events (TEAEs) were reported by 286 patients (44.4 IR). The most common TEAEs were upper respiratory tract infection (9.80 IR), nasopharyngitis (8.2 IR), sinusitis (6.2 IR), and bronchitis (4.5 IR). Serious adverse events were reported by 42 (6.5 IR) patients (included 3 deaths and 10 infections).ConclusionIn this 156-week study of ixekizumab, improvements in signs and symptoms of psoriatic arthritis and the safety profile remained consistent with those in previous reports.Trial registrationClinicalTrials.gov identifier: NCT02349295.

Dataset Information

Ixekizumab improves patient-reported outcomes up to 52 weeks in bDMARD-naive patients with active psoriatic arthritis (SPIRIT-P1).

Publications

Ixekizumab improves patient-reported outcomes up to 52 weeks in bDMARD-naïve patients with active psoriatic arthritis (SPIRIT-P1).

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