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

Ana-Maria Orbai, Alexis Ogdie, Laure Gossec, William Tillett, Ying Ying Leung, Jingjing Gao, Mona Trivedi, Chantal Tasset, Luc Meuleners, Robin Besuyen, Thijs Hendrikx, Laura C Coates, Ana-Maria Orbai, Alexis Ogdie, Laure Gossec, William Tillett, Ying Ying Leung, Jingjing Gao, Mona Trivedi, Chantal Tasset, Luc Meuleners, Robin Besuyen, Thijs Hendrikx, Laura C Coates

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://ichgcp.net/clinical-trials-registry/NCT03101670" title="See in ClinicalTrials.gov">NCT03101670.

Keywords: DMARDs; clinical trials and methods; outcome measures; psoriatic arthritis; quality of life.

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
Change from baseline in (A) PsAID9 total, (B) SF-36 PCS and (C) SF-36 MCS scores (LOCF; FAS) Data shown are mean (s.d.). **P < 0.01, ***P < 0.001 (between-group differences, calculated from an ANCOVA model). ANCOVA: analysis of covariance; FAS: full analysis set; LOCF: last observation carried forward; MCS: Mental Component Summary; PCS: Physical Component Summary; PsAID: Psoriatic Arthritis Impact of Disease; SF-36: 36-item short-form health survey.
Fig . 2
Fig. 2
Mean absolute scores in individual domains of PsAID9a (A and B) and SF-36b (C and D) (LOCF; FAS) aHigher PsAID9 scores are worse and correspond to poorer PsA-specific HRQoL. bHigher SF-36 scores correspond to better HRQoL. *P < 0.05, ** P < 0.01, *** P < 0.001 (between-group differences in change from baseline scores at Week 16, calculated from an ANCOVA model). ANCOVA: analysis of covariance; FAS: full analysis set; HRQoL: health-related quality of life; LOCF: last observation carried forward; PsAID: Psoriatic Arthritis Impact of Disease; SF-36: 36-item short-form health survey.
Fig . 3
Fig. 3
Proportions of patients achieving (A) MCIIa in PsAID9 score at Week 4, (B) MCIIa in PsAID9 score at Week 16 and (C) PASSb in PsAID9 score at Week 4 and 16 (NRI; FAS) aMCII defined as a change ≥1.25, ≥3 or ≥3.6 points. bPASS defined as total score <4. *P < 0.05, **P < 0.01, ***P < 0.001 (between-group differences in MCII or PASS, calculated from Cochran-Mantel-Haenszel test). FAS: full analysis set; MCII: minimal clinically important improvement; NRI: non-responder imputation; PASS: patient-acceptable symptom state; PsAID: Psoriatic Arthritis Impact of Disease.
Fig . 4
Fig. 4
Correlation between change from baseline in PsAID9 and SF-36 at Weeks 4 (A and B) and 16 (C and D) (FAS) MCS: Mental Component Summary; PCS: Physical Component Summary; PsAID: Psoriatic Arthritis Impact of Disease; r: correlation coefficient; SF-36: 36-item short-form health survey.

References

    1. Ritchlin CT, Colbert RA, Gladman DD.. Psoriatic arthritis. N Engl J Med 2017;376:957–70.
    1. Gudu T, Gossec L.. Quality of life in psoriatic arthritis. Expert Rev Clin Immunol 2018;14:405–17.
    1. Orbai A-M, Ogdie A.. Patient-reported outcomes in psoriatic arthritis. Rheum Dis Clin North Am 2016;42:265–83.
    1. Leung Y-Y, Zhu TY, Tam LS, Kun E-L, Li E-M.. Minimal important difference and responsiveness to change of the SF-36 in patients with psoriatic arthritis receiving tumor necrosis factor-α blockers. J Rheumatol 2011;38:2077–9.
    1. Ware JE Jr, Sherbourne CD.. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473–83.
    1. Gossec L, de Wit M, Kiltz U. et al. A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative. Ann Rheum Dis 2014;73:1012–9.
    1. Di Carlo M, Becciolini A, Lato V. et al. The 12-item Psoriatic Arthritis Impact of Disease questionnaire: construct validity, reliability, and interpretability in a clinical setting. J Rheumatol 2017;44:279–85.
    1. Holland R, Tillett W, Ogdie A. et al. Content and face validity and feasibility of 5 candidate instruments for psoriatic arthritis randomized controlled trials: the PsA OMERACT core set workshop at the GRAPPA 2017 annual meeting. J Rheumatol Suppl 2018;94:17–25.
    1. Orbai A-M, Holland R, Leung YY. et al. PsAID12 provisionally endorsed at OMERACT 2018 as core outcome measure to assess psoriatic arthritis-specific health-related quality of life in clinical trials. J Rheumatol 2019;46:990–5.
    1. Robin-Jagerschmidt C, Lavazais S, Marsais F. et al. OP0161 The JAK1 selective inhibitor filgotinib regulates both enthesis and colon inflammation in a mouse model of psoriatic arthritis. Ann Rheum Dis 2017;76(Suppl 2):118–9.
    1. Van Rompaey L, Galien R, van der Aar EM. et al. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol 2013;191:3568–77.
    1. Mease P, Coates LC, Helliwell PS. et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet 2018;392:2367–77.
    1. Kavanaugh A, Kremer J, Ponce L. et al. Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2). Ann Rheum Dis 2017;76:1009–19.
    1. Westhovens R, Taylor PC, Alten R. et al. Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). Ann Rheum Dis 2017;76:998–1008.
    1. Taft C, Karlsson J, Sullivan M.. Do SF-36 summary component scores accurately summarize subscale scores? Qual Life Res 2001;10:395–404.
    1. Evans JD. Straightforward statistics for the behavioral sciences Pacific Grove: Brooks/Cole Pub. Co, 1996.
    1. Holland R, Tillett W, Korendowych E. et al. Validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire and its potential as a single-item outcome measure in clinical practice. Ann Rheum Dis 2018;77:343–7.
    1. Talli S, Etcheto A, Fautrel B. et al. Patient global assessment in psoriatic arthritis - what does it mean? An analysis of 223 patients from the Psoriatic Arthritis Impact of Disease (PsAID) study. Joint Bone Spine 2016;83:335–40.
    1. Salaffi F, Di Carlo M, Carotti M, Farah S, Gutierrez M.. The psoriatic arthritis impact of disease 12-item questionnaire: equivalence, reliability, validity, and feasibility of the touch-screen administration versus the paper-and-pencil version. Ther Clin Risk Manag 2016;12:631–42.
    1. de Wit MPT, Kvien TK, Gossec L.. Patient participation as an integral part of patient-reported outcomes development ensures the representation of the patient voice: a case study from the field of rheumatology. RMD Open 2015;1:e000129.
    1. Al-Tannir M, AlGahtani F, Abu-Shaheen A, Al-Tannir S, AlFayyad I.. Patient experiences of engagement with care plans and healthcare professionals' perceptions of that engagement. BMC Health Serv Res 2017;17:853.
    1. Doyle C, Lennox L, Bell D.. A systematic review of evidence on the links between patient experience and clinical safety and effectiveness. BMJ Open 2013;3:e001570.
    1. Fautrel B, Alten R, Kirkham B. et al. Call for action: how to improve use of patient-reported outcomes to guide clinical decision making in rheumatoid arthritis. Rheumatol Int 2018;38:935–47.
    1. Orbai A-M, de Wit M, Mease PJ. et al. Updating the psoriatic arthritis (PsA) core domain set: a report from the PsA workshop at OMERACT 2016. J Rheumatol 2017;44:1522–8.
    1. Orbai AM, de Wit M, Mease P. et al. International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials. Ann Rheum Dis 2017;76:673–80.
    1. Sunkureddi P, Doogan S, Heid J. et al. Evaluation of self-reported patient experiences: insights from digital patient communities in psoriatic arthritis. J Rheumatol 2018;45:638–47.
    1. Dures E, Hewlett S, Lord J. et al. Important treatment outcomes for patients with psoriatic arthritis: a multisite qualitative study. Patient 2017;10:455–62.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅