Impact of Ixekizumab on Work Productivity in Patients with Ankylosing Spondylitis: Results from the COAST-V and COAST-W Trials at 52 Weeks (original) (raw)
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BMC Rheumatology
Background Patients 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. Methods COAST-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 Sp...
Rheumatology and Therapy, 2019
Introduction: Ixekizumab, a humanized interleukin-17A antibody, has shown efficacy in ankylosing spondylitis (AS), with a greater proportion of ixekizumab-treated patients achieving an ASAS40 (Assessment of Spondyloarthritis International Society 40) endpoint compared to placebo. An ASAS40 response is a high standard that is not routinely used in clinical practice. The goals of this study were (a) to measure improvement in ixekizumab-treated patients in the four ASAS treatment response domains and in other patient-reported outcomes, and (b) to determine how the ASAS response was associated with changes in spinal pain at night, fatigue, sleep, and the Short Form 36-Item Physical Component Summary (SF-36 PCS). Methods: The COAST-V and COAST-W trials were randomized, double-blind, controlled trials examining ixekizumab efficacy in patients with AS who were biologic disease-modifying
The Lancet
Background: Biologic disease modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis (r-axSpA), otherwise known as ankylosing spondylitis, when conventional therapies fail. We report efficacy and safety results of a Phase 3 study of ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, in bDMARDnaïve patients with r-axSpA. Methods: In this randomized, double-blind, Phase 3 study, adult patients with inadequate response/intolerance to NSAIDs, an established diagnosis of r-axSpA, and with radiographic sacroiliitis centrally defined by modified New York criteria and ≥1 spondyloarthritis feature according to Assessment of Spondyloarthritis International Society (ASAS) criteria were recruited from 84 sites (12 countries) in Europe, Asia, and North America. Patients were randomized 1:1:1:1 using a computer-generated random sequence to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference arm), or placebo. The primary endpoint was the proportion of patients achieving an ASAS40 response at Week 16. Findings: Between June 20, 2016 and August 22, 2017, 341 patients were randomized to placebo (N=87), adalimumab (N=90), ixekizumab Q2W (N=83), or ixekizumab Q4W (N=81). At Week 16, significantly more patients achieved ASAS40 with ixekizumab Q2W (n=43, 51•8%, p<0•0001), ixekizumab Q4W (n=39, 48•1%, p<0•0001), and adalimumab (n=32, 35•6%; p=0•0053) versus placebo (n=16, 18•4%). One serious infection occurred in each of the ixekizumab Q2W (1•2%), ixekizumab Q4W (1•2%), and adalimumab (1•1%) arms; none were reported with placebo. One (1•1%) Candida infection occurred in the adalimumab arm and one (1•2%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No opportunistic infections, malignancies, or deaths occurred. Interpretation: Each dosing regimen of ixekizumab was superior to placebo for improving r-axSpA signs and symptoms in bDMARD-naïve patients; the safety profile was consistent with previous studies of ixekizumab. The adalimumab control arm performed as expected. Funding: Eli Lilly and Company Research in context Evidence before this study Pubmed was searched using the terms "ankylosing spondylitis", "axial spondyloarthritis", and "disease-modifying anti-rheumatic drugs", including articles through May 30, 2018. Axial spondyloarthritis (axSpA) is a chronic immune-mediated disease characterized by inflammation of the spine and sacroiliac joint (SIJ), peripheral joint involvement, extra articular manifestations, and a strong genetic association with human leukocyte antigen (HLA)-B27. Radiographic axSpA (r-axSpA) was previously classified as ankylosing spondylitis (AS) in 1984 and updated to r-axSpA as part of the ASAS criteria. Both criteria sets require the same radiographically confirmed structural damage to the sacroiliac joint as well as at least one accompanying clinical element. Recommendations for the management of r-axSpA generally include exercise and physiotherapy in combination with non-steroidal anti-inflammatory drugs, sometimes accompanied by conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) to treat peripheral arthritis symptoms. Biologic DMARDs (bDMARDs) such as tumor necrosis factor inhibitors (TNFi) or anti-Interleukin (IL)-17 therapies are recommended for patients with persistent disease activity despite conventional therapy. In comparison to other chronic inflammatory conditions, the number of treatment options, other than those targeting TNF, are limited. Ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, is approved for the treatment of patients with moderate-to-severe psoriasis as well as patients with active psoriatic arthritis. However, prior to this study, the efficacy and safety of ixekizumab in patients with r-axSpA have not been evaluated.
Arthritis & rheumatology (Hoboken, N.J.), 2016
To evaluate the effect of secukinumab (interleukin-17A inhibitor) on patient-reported outcomes (PROs) in patients with active ankylosing spondylitis (AS). In this phase 3 study, 371 patients received (1:1:1) intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 150 mg (IV→150 mg) or 75 mg (IV→75 mg) every 4 weeks or placebo. PROs included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI 50, short form-36 (SF-36) Physical (PCS) and Mental Component Scores (MCS), AS quality of life (ASQoL), Bath Ankylosing Spondylitis Functional Index (BASFI), EuroQoL-5-dimension health status questionnaire (EQ-5D), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Work Productivity and Activity Impairment-General Health questionnaire (WPAI-GH). At week 16, secukinumab IV→150 mg or IV→75 mg was associated with statistically and clinically significant improvements from baseline versus placebo in BASDAI (-2.3 for both reg...
Clinical and experimental rheumatology, 2019
OBJECTIVES Netakimab (NTK) is a humanised monoclonal antibody targeting interleukin-17A, previously investigated in a phase 1 trial in healthy volunteers. Here, we report the results of a phase 2 trial, conducted to assess safety and pharmacokinetics (PK), to establish a therapeutic dose of NTK in a target population of patients with active ankylosing spondylitis (AS). METHODS 89 patients with active AS, despite non-steroidal anti-inflammatory (NSAID) drug treatment, were randomised to receive 40, 80 or 120 mg of subcutaneous NTK or placebo at weeks 0, 1, 2 and q2wk thereafter until week 12. The primary endpoint was to achieve a proportion of patients with ≥20% improvement in Assessment of Spondyloarthritis. RESULTS Rates of ASAS20 response at week 16 for NTK with 95%CI for difference in ASAS20 rates NTK vs. placebo were 72.73% [1.69%;58.05%], 81.82% [12.36%;65.56%], 90.91% [23.71%;72.39%] at doses of 40, 80 and 120 mg. The response rate in the placebo arm was 42.86%. The pre-specif...
RMD Open, 2022
Van den Bosch F, et al. Effect of tofacitinib on pain, fatigue, health-related quality of life and work productivity in patients with active ankylosing spondylitis: results from a phase III, randomised, double-blind, placebocontrolled trial.
Clinical and experimental rheumatology, 2008
OBJECTIVE The aim of this study was to prospectively investigate the therapeutic efficacy and safety of infliximab therapy in NSAID-refractory AS patients, with special emphasis on impact on quality of life in daily practice. PATIENTS AND METHODS 101 AS patients with active disease (mean Bath ankylosing spondylitis activity index (BASDAI) 6.3, range 4.0-9.8) were enrolled in an open label study. Infliximab 5 mg/kg body weight was administered intravenously at week 0, 2, 6, 12, 18 and 24 followed by a final assessment at week 28. Clinical assessments included quality of life (SF-36, primary endpoint), disease activity (BASDAI), function (BASFI), metrology (BASMI), patients' and physicians' global, pain, work productivity (WPAI) and CRP. RESULTS Using an intention to treat (ITT) analysis, the mean SF-36 physical health component improved from 27.6 at baseline to 40.9 at study end (p<0.001), the mean SF-36 mental health component improved from 44.4 at study entry to 53.0 at ...
The Lancet, 2013
Background Ankylosing spondylitis is a chronic immune-mediated infl ammatory disease characterised by spinal infl ammation, progressive spinal rigidity, and peripheral arthritis. Interleukin 17 (IL-17) is thought to be a key infl ammatory cytokine in the development of ankylosing spondylitis, the prototypical form of spondyloarthritis. We assessed the effi cacy and safety of the anti-IL-17A monoclonal antibody secukinumab in treating patients with active ankylosing spondylitis. Methods We did a randomised double-blind proof-of-concept study at eight centres in Europe (four in Germany, two in the Netherlands, and two in the UK). Patients aged 18-65 years were randomly assigned (in a 4:1 ratio) to either intravenous secukinumab (2 × 10 mg/kg) or placebo, given 3 weeks apart. Randomisation was done with a computergenerated block randomisation list without a stratifi cation process. The primary effi cacy endpoint was the percentage of patients with a 20% response according to the Assessment of SpondyloArthritis international Society criteria for improvement (ASAS20) at week 6 (Bayesian analysis). Safety was assessed up to week 28. This study is registered with ClinicalTrials.gov, number NCT00809159. Findings 37 patients with moderate-to-severe ankylosing spondylitis were screened, and 30 were randomly assigned to receive either intravenous secukinumab (n=24) or placebo (n=6). The fi nal effi cacy analysis included 23 patients receiving secukinumab and six patients receiving placebo, and the safety analysis included all 30 patients. At week 6, ASAS20 response estimates were 59% on secukinumab versus 24% on placebo (99•8% probability that secukinumab is superior to placebo). One serious adverse event (subcutaneous abscess caused by Staphylococcus aureus) occurred in the secukinumab-treated group. Interpretation Secukinumab rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated. It is the fi rst targeted therapy that we know of that is an alternative to tumour necrosis factor inhibition to reach its primary endpoint in a phase 2 trial. Funding Novartis.
Rheumatology, 2017
Objectives. To assess if a change in disease activity is associated with a change in work productivity loss (WPL) over 1 year in early axial SpA (axSpA) patients. Methods. Baseline and 1 year data of axSpA patients in the SPondyloArthritis Caught Early cohort were analysed. Linear regression models were built explaining the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS) over time by the change in absenteeism, presenteeism, WPL and activity impairment over time. Effect modification and confounding were tested for age, gender, arm of Assessment of SpondyloArthritis international Society classification criteria, HLA-B27, duration of chronic back pain, profession and medication. Results. At baseline, in 105 axSpA patients (48% female, mean age 30.8 years, mean symptom duration 13.6 months, 92% HLA-B27 positive, 24% radiographic sacroiliitis), the mean ASDAS was 2.4 (S.D. 1.0), absenteeism 9% (S.D. 23), presenteeism 33% (S.D. 28), WPL 36% (S.D. 30) and activity impairment 37% (S.D. 25). After 1 year, the mean ASDAS decreased to 2.0 (S.D. 0.8) and absenteeism, presenteeism, WPL and activity impairment improved to 6% (S.D. 22), 26% (S.D. 26), 27% (S.D. 29) and 27% (S.D. 26), respectively. Models showed that if ASDAS decreased 1 unit, absenteeism, presenteeism, WPL and activity impairment improved by 5, 17, 16 and 18%, respectively. The impact of disease activity on work productivity was higher in patients with shorter symptom duration and the impact on absenteeism was higher in patients starting pharmacological treatment. Conclusions. In early axSpA patients, work productivity and daily activities are seriously impacted at baseline and 1 year. However, decreasing disease activity is associated with marked improvements in work productivity and daily activities.
Arthritis care & research, 2017
Secukinumab improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks in the phase III MEASURE 2 study. Here, we report longer-term (104 weeks) efficacy and safety results. Patients with active AS were randomized to subcutaneous secukinumab 150 mg, 75 mg, or placebo at baseline; weeks 1, 2, and 3; and every 4 weeks from week 4. The primary end point was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16. Other end points included ASAS40, high-sensitivity C-reactive protein, ASAS5/6, Bath Ankylosing Spondylitis Disease Activity Index, Short Form 36 health survey physical component summary, ASAS partial remission, EuroQol 5-domain measure, and Functional Assessment of Chronic Illness Therapy fatigue subscale. End points were assessed through week 104, with multiple imputation for binary variables and a mixed-effects model repeated measures for continuous variables. Of 219 randomized patients, 60 o...