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Effect of filgotinib on health-related quality of life in active psoriatic arthritis: a randomized phase 2 trial (EQUATOR).

ABSTRACT: OBJECTIVE:To examine the effects of filgotinib, an oral, selective Janus kinase 1 inhibitor, on health-related quality of life (HRQoL) using the Psoriatic Arthritis Impact of Disease (PsAID)9 questionnaire in active PsA. METHODS:Patients were randomized 1 : 1 to filgotinib 200 mg or placebo once daily for 16 weeks in EQUATOR, a multicentre, double-blind, phase 2 randomized controlled trial. HRQoL was assessed with PsAID9 at Weeks 4 and 16. Change from baseline in total and individual domain scores, plus the proportions of patients achieving minimal clinically important improvement (MCII; ?3 points) and patient-accepted symptom status (PASS; score <4), were evaluated. Correlation with the 36-item short-form health survey (SF-36) was investigated. RESULTS:One hundred and thirty-one patients were randomized to filgotinib or placebo. Filgotinib effects on PsAID9 were observed from Week 4. At Week 16, mean (s.d.) change from baseline in PsAID9 was -2.3 (1.8) and -0.8 (2.2) for filgotinib and placebo, respectively (least-squares mean of group difference -1.48 [95% CI -2.12, -0.84], P < 0.0001), with significant improvements in all domains vs placebo. Significantly more patients on filgotinib achieved MCII (group difference 25.4% [95% CI 8.92, 39.99], P = 0.0022) and PASS (group difference 29.6% [95% CI 10.65, 45.60], P = 0.0018) at Week 16 vs placebo. Similar improvements in SF-36 were observed, with moderate to strong negative correlation between PsAID9 and SF-36. CONCLUSION:Filgotinib significantly improved HRQoL vs placebo in patients with active PsA, as measured by PsAID9. To our knowledge, EQUATOR is the first randomized controlled trial to evaluate PsAID9. TRIAL REGISTRATION:ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show, NCT03101670.

SUBMITTER: Orbai AM

PROVIDER: S-EPMC7310097 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Effect of filgotinib on health-related quality of life in active psoriatic arthritis: a randomized phase 2 trial (EQUATOR).

Orbai Ana-Maria AM Ogdie Alexis A Gossec Laure L Tillett William W Leung Ying Ying YY Gao Jingjing J Trivedi Mona M Tasset Chantal C Meuleners Luc L Besuyen Robin R Hendrikx Thijs T Coates Laura C LC

Rheumatology (Oxford, England) 20200701 7

<h4>Objective</h4>To examine the effects of filgotinib, an oral, selective Janus kinase 1 inhibitor, on health-related quality of life (HRQoL) using the Psoriatic Arthritis Impact of Disease (PsAID)9 questionnaire in active PsA.<h4>Methods</h4>Patients were randomized 1 : 1 to filgotinib 200 mg or placebo once daily for 16 weeks in EQUATOR, a multicentre, double-blind, phase 2 randomized controlled trial. HRQoL was assessed with PsAID9 at Weeks 4 and 16. Change from baseline in total and individ ...[more]

PMID: 31624837

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Project description:Introduction/objectivesTo evaluate changes in health-related quality of life (HRQoL) and productivity following treatment with intravenous (IV) golimumab in patients with psoriatic arthritis (PsA).MethodsPatients were randomized to IV golimumab 2 mg/kg (n=241) at Weeks 0, 4, then every 8 weeks (q8w) through Week 52 or placebo (n=239) at Weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at Weeks 24, 28, then q8w through Week 52. Change from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, and the Work Limitations Questionnaire (WLQ) was assessed. Relationships between these outcomes and disease activity and patient functional capability were evaluated post hoc.ResultsAt Week 8, change from baseline in EQ-5D-5L index (0.14 vs 0.04), EQ-VAS (17.16 vs 3.69), daily productivity VAS (-2.91 vs -0.71), and WLQ productivity loss score (-2.92 vs -0.78) was greater in the golimumab group versus the placebo group, respectively. At Week 52, change from baseline was similar in the golimumab and placebo-crossover groups (EQ-5D-5L index: 0.17 and 0.15; EQ-VAS: 21.61 and 20.84; daily productivity VAS: -2.89 and -3.31; WLQ productivity loss: -4.49 and -3.28, respectively). HRQoL and productivity were generally associated with disease activity and functional capability, with continued association from Week 8 through Week 52.ConclusionIV golimumab resulted in early and sustained improvements in HRQoL and productivity from Week 8 through 1 year in patients with PsA. HRQoL and productivity improvements were associated with improvements in disease activity and patient functional capability. Key Points • In patients with active psoriatic arthritis (PsA), intravenous (IV) golimumab improved health-related quality of life (HRQoL) and productivity as early as 8 weeks and maintained improvement through 1 year • Improvements in HRQoL and productivity outcomes in patients with PsA treated with IV golimumab were associated with improvements in disease activity and patient functional capability outcomes • IV golimumab is an effective treatment option for PsA that can mitigate the negative effects of the disease on HRQoL and productivity.

Project description:BackgroundPsoriatic arthritis (PsA) is a chronic, systemic immune-mediated inflammatory musculoskeletal disease. The onset of dermatologic symptoms often precedes rheumatic manifestations. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA that has been shown to improve dermatologic symptoms in patients with PsA.ObjectivesTo investigate the efficacy of tofacitinib in improving dermatologic endpoints in adult patients with active PsA.MethodsThis analysis included data from two placebo-controlled, double-blind, phase 3 studies in patients with active PsA and an inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) who were tumor necrosis factor inhibitor (TNFi)-naïve (OPAL Broaden; NCT01877668) or an IR to ≥1 TNFi (OPAL Beyond; NCT01882439). Patients had active plaque psoriasis at screening and received a stable dose of one csDMARD during the study. Patients were randomized to tofacitinib 5 mg twice daily (BID), 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only) or placebo (to Month 3). Dermatologic endpoints: Psoriasis Area and Severity Index (PASI) total score; PASI90 overall; PASI75 and PASI90 by baseline PASI severity; Physician's Global Assessment of Psoriasis; Nail Psoriasis Severity Index; Dermatology Life Quality Index total and sub-dimension scores; Itch Severity Item; and Patient's Global Joint and Skin Assessment-Visual Analog Scale-Psoriasis question.ResultsIn patients with active PsA, including those stratified by mild or moderate/severe dermatologic symptoms, greater improvements from baseline and percentage of responders were observed in tofacitinib-treated patients vs. placebo for the majority of analyzed dermatologic endpoints at Months 1 and 3, and improvements were maintained to Month 12 in OPAL Broaden and Month 6 in OPAL Beyond. Similar effects were observed in adalimumab-treated patients vs. placebo in OPAL Broaden across dermatologic endpoints.ConclusionsTofacitinib provides a treatment option for patients with active PsA, including the burdensome dermatologic symptoms of PsA.

Project description:BackgroundThe effects of filgotinib on patient-reported outcomes (PROs) from 3 trials in patients with active rheumatoid arthritis were investigated.MethodsMethotrexate (MTX)-naïve patients received filgotinib 200 or 100 mg plus MTX (FIL200+MTX, FIL100+MTX), filgotinib 200 mg monotherapy (FIL200), or MTX monotherapy through 52 weeks (NCT02886728). Patients with inadequate response (IR) to MTX (MTX-IR) received FIL200+MTX, FIL100+MTX, adalimumab 40 mg +MTX (ADA+MTX), or placebo (PBO)+MTX (rerandomized to FIL200+MTX or FIL100+MTX at week 24) through 52 weeks (NCT02889796). Patients with IR to biologic disease-modifying antirheumatic drugs (bDMARD-IR) received FIL200 or FIL100 or PBO with background stable conventional synthetic (cs) DMARDs for up to 24 weeks (NCT02873936). PROs included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) physical/mental component summary (PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and Patient Global Assessment of Disease Activity (PtGA). Data are reported as least-squares mean changes from baseline with standard error to the timepoint representing each study's primary endpoint. All statistical comparisons are of filgotinib groups vs their respective control groups.ResultsAt week 24, among MTX-naïve patients, change from baseline (standard deviation) in HAQ-DI was - 1.00 (0.03; P < 0.001) with FIL200+MTX, - 0.94 (0.04; P < 0.01) with FIL100+MTX, and - 0.91 (0.04; P < 0.05) with FIL200 alone compared with - 0.81 (0.03) with MTX alone. At week 12, among MTX-IR patients, change from baseline in HAQ-DI was - 0.69 (0.04; P < 0.001 vs PBO+MTX, P < 0.05 vs ADA) with FIL200+MTX, - 0.57 (0.04; P < 0.001 vs placebo) with FIL100+MTX, and - 0.60 (0.04) with ADA vs - 0.40 (0.04) with PBO+MTX. At week 12, among bDMARD-IR patients, change from baseline in HAQ-DI was - 0.50 (0.06; P < 0.001) with FIL200+csDMARD and - 0.46 (0.05; P < 0.001) with FIL100+csDMARD vs - 0.19 (0.06) with placebo+csDMARD. Changes in SF-36 PCS and MCS, FACIT-Fatigue, WPAI, and PtGA tended to favor filgotinib over PBO, MTX, and ADA. Greater proportions of patients experienced clinically meaningful differences with either dosage of FIL in combination with csDMARDs (including MTX) and with FIL200 monotherapy vs comparators.ConclusionsFilgotinib provided improvements in PROs across patient populations. These findings suggest filgotinib can be an effective treatment option for patients with insufficient response to MTX or bDMARDs and patients who are MTX-naïve.Trial registrationClinicalTrials.gov , FINCH 1, NCT02889796 , first posted September 7, 2016; FINCH 2, NCT02873936 , first posted August 22, 2016, retrospectively registered; FINCH 3, NCT02886728 , first posted September 1, 2016, retrospectively registered.

Project description:BackgroundGuselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression.MethodsPatients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively.DiscussionDISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression.Trial registrationThis trial was registered at ClinicalTrials.gov, NCT04882098 . Registered on 11 May 2021.

Project description:IntroductionPsoriatic arthritis (PsA) is considered a multifaceted disease, with patients reporting low health-related quality of life (HRQoL). Data on disease burden are substantial and there exists a need for properly designed studies to learn more about the evolution of HRQoL in this condition. This study aims to identify factors associated to HRQoL evolution in PsA patients followed-up in a real-world setting in Spain.MethodsWe conducted a retrospective longitudinal observational study including incident patients from the rheumatology outpatient clinic of Hospital Clínico San Carlos (Madrid, Spain), diagnosed for the first time of PsA, defined as having received any ICD9/ICD10 diagnosis code of PsA, from 2007 to 2016, and followed-up until loss of follow-up, death, or November 2017. The influence of demographic and clinical variables in baseline HRQoL [assessed with the Rosser Classification Index (RCI)] was analyzed using bivariable and multivariable generalized linear models. The influence of those variables and of treatment-related factors in repeated measures of HRQoL was analyzed using bivariable and multivariable generalized estimating equations (GEE) models nested by patient.ResultsTwo hundred and thirty patients were included in the analysis, with 3384 registered visits. At baseline, older age, a previous diagnosis of obesity, and the presence of enthesitis were significantly associated with worse HRQoL. During follow-up, using an exchangeable working correlation structure, the presence of enthesitis was also associated with worse HRQoL, coefficient (95% CI) - 0.006 (- 0.01 to - 0.002), p = 1.00E-03; conversely, treatment with methotrexate or antimalarials was associated with better HRQoL with 0.007 (0.001-0.014), p = 0.020 and 0.003 (0.001-0.005), p = 3.00E-03, respectively.ConclusionsMusculoskeletal manifestations and comorbidities exert a deleterious effect in HRQoL of PsA patients. Therefore, the optimal management of this condition needs to also address these manifestations in order to try to restore the QoL of these patients.

Dataset Information

Effect of filgotinib on health-related quality of life in active psoriatic arthritis: a randomized phase 2 trial (EQUATOR).

Publications

Effect of filgotinib on health-related quality of life in active psoriatic arthritis: a randomized phase 2 trial (EQUATOR).

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