Dataset Information

Improvements in workplace and household productivity with certolizumab pegol treatment in axial spondyloarthritis: results to week 96 of a phase III study.

ABSTRACT: To evaluate the effect of certolizumab pegol (CZP) on work and household productivity, and on participation in family, social and leisure activities in patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic (nr-) axSpA.RAPID-axSpA (NCT01087762) was a phase III, double-blind, placebo-controlled trial to week (Wk) 24, dose-blind to Wk48 and open-label to Wk204. A total of 325 patients were randomised 1:1:1 to placebo, CZP 200?mg Q2W or CZP 400?mg Q4W. The validated arthritis-specific Work Productivity Survey assessed the impact of axSpA on work and household productivity and participation in social activities during the preceding month. Data are shown to Wk96, with responses compared between treatment arms (placebo vs CZP 200?mg and 400?mg dose groups combined) and subpopulations using a non-parametric bootstrap-t method.At baseline, 63.2% of placebo and 72.0% of CZP patients were employed. By Wk24, CZP patients reported on average 1.0 fewer days of absenteeism and 2.6 fewer days of presenteeism per month, compared with 0.4 and 0.9 fewer days for placebo. At home, by Wk24, CZP patients reported on average 3.0 household work days gained per month versus 1.3 for placebo. CZP patients reported fewer days with reduced household productivity or days lost for social participation. Similar improvements were observed in AS and nr-axSpA subpopulations and improvements with CZP were maintained to Wk96.Compared with placebo, treatment with CZP significantly improved work and household productivity and resulted in greater social participation for patients with axSpA, which could lead to considerable indirect cost gains.NCT01087762.

SUBMITTER: van der Heijde D

PROVIDER: S-EPMC5903272 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Improvements in workplace and household productivity with certolizumab pegol treatment in axial spondyloarthritis: results to week 96 of a phase III study.

van der Heijde Désirée D Braun Jürgen J Rudwaleit Martin M Purcaru Oana O Kavanaugh Arthur F AF

RMD open 20180409 1

<h4>Objectives</h4>To evaluate the effect of certolizumab pegol (CZP) on work and household productivity, and on participation in family, social and leisure activities in patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic (nr-) axSpA.<h4>Methods</h4>RAPID-axSpA (NCT01087762) was a phase III, double-blind, placebo-controlled trial to week (Wk) 24, dose-blind to Wk48 and open-label to Wk204. A total of 325 patients were randomised 1:1:1 to pla ...[more]

PMID: 29670761

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Project description:ObjectiveThe natural history of nonradiographic axial spondyloarthritis (SpA) is incompletely characterized, and there are concerns that nonsteroidal antiinflammatory drugs provide inadequate disease control in patients with active disease. This study was undertaken to investigate the effects of certolizumab pegol (CZP), an anti-tumor necrosis factor treatment, in patients with nonradiographic axial SpA with objective signs of inflammation.MethodsIn this ongoing parallel-group double-blind study, adults with active disease were recruited from 80 centers in Australia, Europe, North America, and Taiwan, and were randomized 1:1 to receive placebo or CZP (400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks) in addition to nonbiologic background medication (NBBM). Switching to open-label CZP (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged. The primary end point was the proportion of patients achieving major improvement (MI) (i.e., a ≥2.0-point decrease in the score from baseline or achievement of the lowest possible score [0.6]) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52.ResultsA total of 317 patients were randomized to receive placebo plus NBBM (n = 158) or CZP plus NBBM (n = 159). ASDAS-MI at week 52 was achieved in 47.2% (75 of 159) of CZP plus NBBM patients, which was significantly greater (P < 0.0001) than the 7.0% (11 of 158) of placebo plus NBBM patients in whom ASDAS-MI was achieved. Of the placebo plus NBBM patients, 60.8% (96 of 158) switched to open-label treatment before week 52 compared to 12.6% (20 of 159) of the CZP plus NBBM patients.ConclusionAdding CZP to background medication is superior to adding placebo in patients with active nonradiographic axial SpA. These results indicate that remission in nonradiographic axial SpA treated without biologics occurs infrequently, demonstrating the need for treatment beyond nonbiologic therapy.

Project description:IntroductionAchievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP.MethodsC-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, < 5 years' symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at week 32 and < 2.1 at week 36 [or vice versa], and < 1.3 at week 48).ResultsIn total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious.ConclusionsOver 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified.Trial registrationNCT02505542.

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:ObjectiveAxial spondyloarthritis (axial SpA) is characterized by inflammation of the spine and sacroiliac joints and can also affect extraarticular sites, with the most common manifestation being uveitis. Here we report the incidence of uveitis flares in axial SpA patients from the RAPID-axSpA trial, including ankylosing spondylitis (AS) and nonradiographic (nr) axial SpA.MethodsThe RAPID-axSpA (NCT01087762) trial is double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 204. Patients were randomized to certolizumab pegol (CZP) or placebo. Placebo patients entering the dose-blind phase were re-randomized to CZP. Uveitis events were recorded on extraarticular manifestation or adverse event forms. Events were analyzed in patients with/without history of uveitis, and rates reported per 100 patient-years.ResultsAt baseline, 38 of 218 CZP-randomized patients (17.4%) and 31 of 107 placebo-randomized patients (29.0%) had past uveitis history. During the 24-week double-blind phase, the rate of uveitis flares was lower in CZP (3.0 [95% confidence interval (95% CI) 0.6-8.8] per 100 patient-years) than in placebo (10.3 [95% CI 2.8-26.3] per 100 patient-years). All cases observed during the 24-week double-blind phase were in patients with a history of uveitis; in these patients, rates were similarly lower for CZP (17.1 [95% CI 3.5-50.1] per 100 patient-years) than placebo (38.5 [95% CI 10.5-98.5] per 100 patient-years). Rates of uveitis flares remained low up to week 96 (4.9 [95% CI 3.2-7.4] per 100 patient-years) and were similar between AS (4.4 [95% CI 2.3-7.7] per 100 patient-years) and nr-axial SpA (5.6 [95% CI 2.9-9.8] per 100 patient-years).ConclusionThe rate of uveitis flares was lower for axial SpA patients treated with CZP than placebo during the randomized controlled phase. Incidence of uveitis flares remained low to week 96 and was comparable to rates reported for AS patients receiving other anti-tumor necrosis factor antibodies.

Project description:BackgroundIdentification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP).MethodsC-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value <0.05 was required for forward selection into the model and p ≥0.1 for backward elimination. Missing data or values collected after switching to open-label treatment were accounted for using non-responder imputation. Sensitivity analyses accounted for patients with changes in non-biologic background medication.ResultsOf 317 enrolled patients, 159 and 158 were randomised to CZP and placebo, respectively. Younger age and male sex were identified as predictors of Week 12 response across all assessed efficacy outcomes in CZP-treated patients. Consistent predictors of Week 52 response, measured by ASDAS-MI, ASAS40 and BASDAI50, included human leukocyte antigen (HLA)-B27 positivity and sacroiliitis on MRI at baseline. MRI positivity was also predictive of achieving ASDAS-ID at Week 52. Sensitivity analyses were generally consistent with the primary analysis. In placebo-treated patients, no meaningful predictors of Week 52 response were identified.ConclusionsIn this 52-Week, placebo-controlled study in nr-axSpA patients with elevated CRP and/or active sacroiliitis on MRI at baseline, MRI sacroiliitis and HLA-B27 positivity, but not elevated CRP or responses at Week 12, were predictive of long-term clinical response to CZP. Findings may support rheumatologists to identify patients suitable for TNFi treatment.Trial registrationClinicalTrials.gov, NCT02552212 . Registered on 15 September 2015.

Project description:BackgroundPatients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment.ObjectivesThe objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA.DesignRAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA.MethodsThe impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity.ResultsOf 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism.ConclusionsOver 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients' daily lives.

Project description:IntroductionThe arthritis-specific Work Productivity Survey (WPS) was developed to evaluate productivity limitations associated with arthritis within and outside the home. There is an unmet need for an instrument assessing similar productivity limitations in axial spondyloarthritis (axSpA), including nonradiographic axSpA and ankylosing spondylitis. Following its validation in rheumatoid and psoriatic arthritis, we aimed to assess psychometric properties of WPS in adult-onset active axSpA in this analysis.MethodsPsychometric properties were assessed using data from the RAPID-axSpA trial (NCT01087762) in which researchers investigated certolizumab pegol efficacy and safety in axSpA. WPS was completed at baseline and every 4 weeks until week 24. Validity was evaluated at study baseline via known-groups defined by the first and third quartile cutoffs of patient scores to Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain, Bath Ankylosing Spondylitis Functional Index (BASFI), Short Form 36 health survey (SF-36) and Ankylosing Spondylitis Quality of Life Scale (ASQoL). Responsiveness and reliability were assessed by comparing WPS mean changes in ASAS 20% improvement criteria (ASAS20), BASDAI50, ASDAS clinically important improvement/major improvement (CII/MI) and BASFI minimum clinically important difference (MCID) responders versus nonresponders at week 12. All comparisons were conducted on observed cases in the randomized set using a nonparametric bootstrap-t method.ResultsThe results confirmed the psychometric properties of WPS. AxSpA patients with a worse health state had significantly more days of household work lost, household work with reduced productivity, social activities missed and outside help hired, as well as a higher interference rate of arthritis, than patients with a better health state. Similarly, employed patients with a worse health state had significantly more work days lost or with productivity reduced, and a higher interference of arthritis on work productivity. Similar findings were also observed in the nonradiographic (nr) axSpA and AS subpopulations. The WPS was responsive to clinical changes, with responders reporting larger improvements at week 12 in WPS scores versus nonresponders. Effect sizes in responders were generally moderate to large (standardized response mean >0.5).ConclusionsThese analyses demonstrate that WPS is a valid, responsive and reliable instrument for the measurement of productivity within and outside the home in adult-onset axSpA, as well as the in subpopulations of AS and nr-axSpA.

Dataset Information

Improvements in workplace and household productivity with certolizumab pegol treatment in axial spondyloarthritis: results to week 96 of a phase III study.

Publications

Improvements in workplace and household productivity with certolizumab pegol treatment in axial spondyloarthritis: results to week 96 of a phase III study.

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