Dataset Information

Ixekizumab Improves Patient-Reported Outcomes in Non-Radiographic Axial Spondyloarthritis: Results from the Coast-X Trial.

ABSTRACT:

Introduction

Ixekizumab, an interleukin-17A antibody, has shown efficacy in non-radiographic axial spondyloarthritis (nr-axSpA). The objectives of this analysis were (a) to measure improvement in ixekizumab-treated patients in Assessment of Spondyloarthritis International Society (ASAS) response domains and other patient-reported outcomes (PROs) and (b) to determine how ASAS responses were associated with changes in patient global disease activity (PtGA), spinal pain, function, stiffness, fatigue, and spinal pain at night.

Methods

COAST-X was a phase 3, 52-week multicenter, randomized, controlled trial investigating the efficacy and safety of 80-mg ixekizumab every 2 weeks (Q2W) and every 4 weeks (Q4W) in patients with active nr-axSpA. Changes from baseline in PROs were analyzed via mixed-effects models for repeated measures. Association analyses for ASAS responses used analysis of covariance with Scheffé's method.

Results

Patients treated with ixekizumab Q2W and Q4W reported significantly greater improvements in PtGA, spinal pain, function, and stiffness at week 1, when these measures were first assessed, compared with placebo (p < 0.05). ASAS40 responders, in comparison to ASAS20 non-responders, had the highest correlations with improvements in all response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night (p < 0.001). ASAS40 responses were associated with 3.5- to 48.0-fold greater improvements in these PROs, with the highest values for PtGA and function, compared to ASAS20 non-achievement.

Conclusions

As early as week 1, patients with nr-axSpA treated with ixekizumab reported significant improvements in PtGA, spinal pain, function, and stiffness compared with those taking placebo. ASAS40 responders reported significantly greater improvements in all ASAS response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night than ASAS20 non-responders. Improvements in PtGA and function appear to be major drivers in achieving ASAS40 response in patients with nr-axSpA.

Trial registration

NCT02757352.

SUBMITTER: Deodhar A

PROVIDER: S-EPMC7991024 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThis analysis assessed improvements in patients with radiographic axial spondyloarthritis (r-axSpA) treated with ixekizumab in the Assessment of Spondyloarthritis International Society (ASAS) treatment response domains and additional patient-reported outcomes at 1 year of treatment.MethodsCOAST-V and COAST-W were 52-week, phase 3, randomized controlled trials evaluating the efficacy and safety of ixekizumab in biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with radiographic spondyloarthritis, respectively. Patients were treated with 80-mg ixekizumab either every 2 weeks or every 4 weeks. Patient-reported outcomes included Patient Global Disease Activity, Spinal Pain, stiffness as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6, function as measured by the Bath Ankylosing Spondylitis Functional Index, fatigue as measured by the Fatigue Numeric Rating Scale and BASDAI question 1, Spinal Pain at Night, and sleep quality as measured by the Jenkins Sleep Evaluation Questionnaire. Mixed-effects models for repeated measures were used to analyze changes from baseline in patient-reported outcomes from weeks 1 to 16, and descriptive statistics were reported from weeks 20 to 52. Analysis of covariance with Scheffé's method was used for the ASAS response association analyses.ResultsThis study assessed 341 bDMARD-naïve and 316 TNFi-experienced patients in the placebo-controlled blinded treatment dosing period (weeks 1-16) as well as 329 bDMARD-naïve and 281 TNFi-experienced patients in the dose double-blind extended treatment period (weeks 20-52). bDMARD-naïve or TNFi-experienced patients treated with ixekizumab every 2 weeks and every 4 weeks reported improvements in patient global disease activity, spinal pain, function, stiffness, fatigue, spinal pain at night, and sleep quality through week 52. Greater correlations with improvements in all response domains were seen when comparing ASAS40 responders to ASAS20 non-responders (p < 0.001), with up to 10.5-fold greater improvements observed in ASAS40 responses compared with ASAS20 non-responders. Function and fatigue demonstrated the highest values.ConclusionsIxekizumab-treated bDMARD-naïve and TNFi-experienced patients with radiographic axial spondyloarthritis achieving ASAS40 reported sustained and consistent improvement in all ASAS response domains and other patient-reported outcomes though week 52, with spinal pain, function, and stiffness as major drivers of the response.Trial registrationNCT02696785 and NCT02696798 , March 2, 2016.

Project description:BackgroundPatients with non-radiographic axial spondyloarthritis experience negative impacts on sleep, work productivity, and activity impairment. Ixekizumab, a monoclonal antibody selectively targeting interleukin-17A, has shown efficacy in treating the signs and symptoms of non-radiographic axial spondyloarthritis. This analysis evaluated the effect of ixekizumab treatment on sleep, work productivity, and activity impairment in patients with non-radiographic axial spondyloarthritis.MethodsCOAST-X ( NCT02757352 ) was a 52-week, phase 3, multicenter, randomised placebo-controlled trial evaluating 80-mg ixekizumab every 2 weeks and every 4 weeks in patients with active non-radiographic axial spondyloarthritis. Sleep disturbance was measured with the Jenkins Sleep Evaluation Questionnaire (JSEQ) and analysed using mixed-effects models for repeated measures. Work productivity and activity impairment were measured using the Work Productivity and Activity Impairment Questionnaire for Spondyloarthritis and analysed using analysis of covariance. Absenteeism, presenteeism, and overall work impairment were assessed for patients reporting paid work; activity impairment was assessed regardless of work status.ResultsOverall, patients treated with both dosing regimens of ixekizumab reported numerically greater improvements in sleep than placebo through Week 52. At Weeks 16 and 52, patients treated with ixekizumab every 4 weeks had significantly greater improvements in presenteeism (p = 0.007 and p = 0.003, respectively) and overall work impairment (p = 0.014 and p = 0.005, respectively) and numeric improvements in absenteeism than placebo. Patients treated with ixekizumab every 2 weeks had numerically greater improvements in absenteeism, presenteeism, and overall work impairment than placebo. Both dosing regimens of ixekizumab were associated with significantly greater improvements in activity impairment than placebo (ixekizumab every 4 weeks: p = 0.003 at Week 16 and p = 0.004 at Week 52; ixekizumab every 2 weeks: p = 0.007 at Week 16 and p = 0.006 at Week 52).ConclusionsTreatment with ixekizumab improved sleep, work productivity, and activity impairment in patients with nr-axSpA. Improvements in presenteeism and overall work impairment were sustained and consistent in the patients treated with ixekizumab every 4 weeks from Week 16 to Week 52. Improvements in activity impairment were sustained and consistent in both ixekizumab-treated groups from Week 16 to Week 52.Trial registrationNCT02757352 , May 2, 2016.

Project description:Patient-reported outcomes (PROs) provide an opportunity to collect important information relating to patient well-being, which is often difficult for physicians to measure (e.g., quality of life, pain, fatigue, and sleep). Here we evaluate the effects of certolizumab pegol (CZP) on PROs during the 24-week, double-blind phase of the RAPID axial spondyloarthritis (SpA) trial, a phase 3 trial of axial SpA patients, including both ankylosing spondylitis (AS) and nonradiographic axial SpA patients.A total of 325 patients with active axial SpA were randomized 1:1:1 to placebo, CZP 200 mg every 2 weeks, or CZP 400 mg every 4 weeks. The primary end point was the Assessment of SpondyloArthritis International Society criteria for 20% improvement in disease activity response at week 12, and has been reported previously. PROs included total back pain, nocturnal back pain, a daily pain diary, the Sleep Problems Index II (SPI) domain of the Medical Outcomes Study (MOS) Sleep Scale, fatigue, the Ankylosing Spondylitis Quality of Life (ASQOL) measure, and the Short Form 36-item (SF-36) health survey physical component summary (PCS), mental component summary (MCS), and domains.Patients treated with CZP reported significant improvements from week 1 for nocturnal back pain (placebo -0.6, CZP 200 mg every 2 weeks -1.9, and CZP 400 mg every 4 weeks -1.6; P < 0.001) and ASQOL (placebo -1.0, CZP 200 mg every 2 weeks -2.3, and CZP 400 mg every 4 weeks -1.9; P < 0.05) compared with placebo, while significant improvements in total back pain were seen from day 2. Patients treated with both CZP dosing regimens also had significantly greater improvements in fatigue, MOS-SPI, SF-36 PCS, MCS, and domains compared with placebo. Improvements were similar in both AS and nonradiographic axial SpA patients.Both CZP dosing schedules rapidly improved patient well-being, as measured by PROs, including pain, fatigue, sleep, SF-36, and ASQOL in both AS and nonradiographic axial SpA patients.

Project description:BACKGROUND:We assessed the external validity of composite indices Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Assessment in SpondyloArthritis international Society (ASAS) 40 response (ASAS40) by evaluating the correlations between the changes in some patient reported outcomes (PROs) for patients with non-radiographic axial spondyloarthritis (nr-axSpA) and the changes in the scores of the composite indices. METHODS:This was a post-hoc analysis of data from the EMBARK study in patients with nr-axSpA treated with etanercept. PROs were grouped according to ASDAS status (inactive [< 1.3], low [≥ 1.3 to < 2.1], high [≥ 2.1 to ≤3.5], and very high [> 3.5]), patient achievement of > 50% improvement in BASDAI (BASDAI50 responders), and > 40% improvement in ASAS (ASAS40 responders) at 104 weeks. Analyses were conducted on observed cases available at Week 104. Changes in PROs from Baseline to Week 104 were assessed using analysis of covariance with adjustment for baseline with linear contrast. RESULTS:Higher ASDAS disease activity at 104 weeks was associated with lower long-term improvement from baseline in PROs (e.g., total back pain [visual analog scale, cm (95% confidence interval): - 4.58 (- 4.95, - 4.21), - 3.86 (- 4.28, - 3.43), - 2.15 (- 2.68, - 1.61), and 1.30 (- 0.51, 3.12) for inactive, low, high, and very high ASDAS disease activity, respectively; Multidimensional Fatigue Inventory (MFI) general fatigue: - 4.77 (- 5.70, - 3.84), - 2.96 (- 4.04, - 1.87), - 1.00 (- 2.32, 0.31), and 2.14 (- 2.10, 6.38); all p < 0.001)]. BASDAI50 non-responders had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: - 1.61 (- 2.05, - 1.18) vs. -4.43 (- 4.69, - 4.18); MFI general fatigue: - 0.01 (- 1.12, 1.09) vs. -4.30 (- 4.98, - 3.62); all p < 0.001). ASAS40 non-responders also had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: - 1.91 (- 2.30, - 1.52) vs. -4.75 (- 5.05, - 4.46); MFI general fatigue: - 0.63 (- 1.56, 0.30) vs. -4.64 (- 5.37, - 3.91); all p < 0.001). CONCLUSION:Composite indices are valid for monitoring treatment response and adequately reflect treatment-related changes experienced by patients with nr-axSpA. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01258738. Registered 9 December 2010.