Dataset Information

Effect of Upadacitinib on Quality of Life and Work Productivity in Active Non-radiographic Axial Spondyloarthritis: Results From Randomized Phase 3 Trial SELECT-AXIS 2.

ABSTRACT:

Introduction

To evaluate the effect of upadacitinib vs. placebo on health-related quality of life (HRQoL) and work productivity in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) enrolled in the SELECT-AXIS 2 phase 3 randomized controlled trial.

Methods

Adult patients with active nr-axSpA and an inadequate response to non-steroidal anti-inflammatory drugs were randomized 1:1 to receive upadacitinib 15 mg once daily or placebo. Mean changes from baseline in measures of HRQoL (Ankylosing Spondylitis QoL [ASQoL], Assessment of SpondyloArthritis international Society Health Index [ASAS HI], Short-Form 36 Physical Component Summary [SF-36 PCS] score) and Work Productivity and Activity Impairment (WPAI) were assessed through 14 weeks based on mixed-effects repeated measures or analysis of covariance models. The proportions of patients with improvements ≥ minimum clinically important differences (MCID) were assessed in HRQoL measures at week 14 using non-responder imputation with multiple imputation.

Results

At week 14, upadacitinib- vs. placebo-treated patients reported greater improvements from baseline in ASQoL and ASAS HI (ranked, P < 0.001) and in SF-36 PCS and WPAI overall work impairment (nominal P < 0.05). Improvements were observed as early as week 2 in ASAS HI. Greater proportions of upadacitinib vs. placebo-treated patients reported improvements ≥ MCID in ASQoL (62.6 vs. 40.9%), ASAS HI (44.8 vs. 28.8%), and SF-36 PCS (69.3 vs. 52.0%), with numbers needed to treat < 10 for all (nominal P ≤ 0.01). Improvements ≥ MCID were consistently observed irrespectively of prior exposure to tumor necrosis factor inhibitors.

Conclusions

Upadacitinib provides clinically meaningful improvements in HRQoL and work productivity in patients with active nr-axSpA.

Clinical registration number

NCT04169373, SELECT-AXIS 2.

SUBMITTER: Kiltz U

PROVIDER: S-EPMC10186301 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Effect of Upadacitinib on Quality of Life and Work Productivity in Active Non-radiographic Axial Spondyloarthritis: Results From Randomized Phase 3 Trial SELECT-AXIS 2.

Kiltz Uta U Kishimoto Mitsumasa M Walsh Jessica A JA Sampaio-Barros Percival P Mittal Manish M Saffore Christopher D CD Wung Peter P Ganz Fabiana F Biljan Ana A Poddubnyy Denis D

Rheumatology and therapy 20230516 4

<h4>Introduction</h4>To evaluate the effect of upadacitinib vs. placebo on health-related quality of life (HRQoL) and work productivity in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) enrolled in the SELECT-AXIS 2 phase 3 randomized controlled trial.<h4>Methods</h4>Adult patients with active nr-axSpA and an inadequate response to non-steroidal anti-inflammatory drugs were randomized 1:1 to receive upadacitinib 15 mg once daily or placebo. Mean changes from baseline in ...[more]

PMID: 37191738

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Project description:BackgroundIn SELECT-AXIS 2, upadacitinib improved the signs and symptoms of active non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks versus placebo and was well tolerated. Here, we evaluated the efficacy and safety of upadacitinib through 2 years.MethodsThe study enrolled eligible adult patients with a clinical diagnosis of nr-axSpA who met the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective signs of active inflammation on magnetic resonance imaging (MRI) of sacroiliac joints and/or high-sensitivity C-reactive protein. Patients were randomized 1:1 to receive double-blinded treatment with upadacitinib 15 mg once daily (QD) or placebo for 52 weeks, after which all patients received open-label treatment with upadacitinib 15 mg QD. Efficacy results over 104 weeks were reported as observed (AO) and either AO with non-responder imputation (AO-NRI; binary endpoints) or AO with mixed-effect model for repeated measures (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized through week 104.ResultsOf 313 patients randomized and treated, 224 (continuous upadacitinib n = 117; placebo/upadacitinib n = 107) completed 104 weeks of treatment. In patients who received continuous upadacitinib, sustained improvement was observed through 2 years of treatment across efficacy endpoints including disease activity, pain, function, enthesitis, quality of life, and MRI measures of inflammation. At week 104, 57.1%, 59.0%, and 31.4% of patients achieved ASAS40 response, and low disease activity and inactive disease (as defined by Axial Spondyloarthritis Disease Activity Score), respectively (AO-NRI); week 104 outcomes were generally similar in patients who initially received placebo and were switched to upadacitinib at week 52. In total, 286 patients were exposed to ≥ 1 dose of upadacitinib, comprising 378.3 patient-years (PY) of exposure. Upadacitinib was generally well tolerated, with exposure-adjusted event rates (EAERs) for TEAEs, serious adverse events (AEs), and AEs leading to study drug discontinuation of 207.5, 8.7, and 5.3 events/100 PY, respectively. EAERs of TEAEs of special interest were broadly consistent with those reported through week 52.ConclusionsTreatment with upadacitinib demonstrated consistent improvement and maintenance of treatment effect across efficacy endpoints through 2 years; no new safety signals were identified with additional exposure.Trial registrationNCT04169373.

Project description:Although the pathogenesis of spondyloarthritis (SpA) has still not been elucidated our options to treat SpA have definitely improved in the last decades. There are two main types of SpA: (i) axial spondyloarthritis (axSpA), also covering the classical ankylosing spondylitis (AS) which is largely equivalent to radiographic (r)-axSpA but different from non-radiographic (nr)-axSpA, and (ii) peripheral SpA (pSpA) also covering psoriatic arthritis (PsA) as the main subtype. The subtype nr-axSpA has historically developed because the approval of drugs for AS did not cover forms without structural changes in the sacroiliac joints which is mandatory in the 1984 New York criteria. The definitions for axSpA are based on the 2009 Assessments in AxSpA International Society (ASAS) classification criteria. Several biologic disease modifying anti-rheumatic drugs (bDMARDs) such as the tumor necrosis factor alpha inhibitors (TNFi) and the interleukin-17-inhibitors (IL-17i) are approved mostly for the whole spectrum of SpA including axSpA and PsA but L-17i does not work in inflammatory bowel disease (IBD). Targeted synthetic (ts) DMARDs cover mainly the janus kinase (JAK)-inhibitors which have recently been developed to inhibit inflammation in several rheumatic and other immune mediated diseases such as IBD. Indeed, the physiologic mechanism of JAK-mediated signal transduction has been recognized as an important target because the inhibition of its actions was shown to successfully work as a therapeutic mechanism. There are now 4 small molecule JAK inhibitors (JAKi) that currently play a role in rheumatology with variable selectivity for the four different JAK isoforms: tofacitinib, baricitinib, upadacitinib and filgotinib. In this review, we summarize current clinical trial data and evaluate the use of the JAK1 selective inhibitor upadacitinib in the treatment of axSpA, including nr-axSpA and r-axSpA. Even though the efficacy and safety of upadacitinib over shorter periods of time has been convincing to date, long-term trials are needed to fully establish its performance and also evaluate the safety at higher doses, and its use in PsA.

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:IntroductionThis article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators.MethodsThis integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years).ResultsMedian treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs.ConclusionRates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA.Trial registrationClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

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

Effect of Upadacitinib on Quality of Life and Work Productivity in Active Non-radiographic Axial Spondyloarthritis: Results From Randomized Phase 3 Trial SELECT-AXIS 2.

Introduction

Methods

Results

Conclusions

Clinical registration number

Publications

Effect of Upadacitinib on Quality of Life and Work Productivity in Active Non-radiographic Axial Spondyloarthritis: Results From Randomized Phase 3 Trial SELECT-AXIS 2.

Similar Datasets

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