Radiographic Progression of Patients With Psoriatic Arthritis Who Achieve Minimal Disease Activity in Response to Golimumab Therapy: Results Through 5 Years of a Randomized, Placebo-Controlled Study

Arthur Kavanaugh, Désirée van der Heijde, Anna Beutler, Dafna Gladman, Philip Mease, Gerald G Krueger, Iain B McInnes, Philip Helliwell, Laura C Coates, Stephen Xu, Arthur Kavanaugh, Désirée van der Heijde, Anna Beutler, Dafna Gladman, Philip Mease, Gerald G Krueger, Iain B McInnes, Philip Helliwell, Laura C Coates, Stephen Xu

Abstract

Objective: To evaluate long-term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in the GO-REVEAL trial.

Methods: The GO-REVEAL trial was a phase III, randomized, double-blind trial with placebo-control through week 24 followed by an open-label extension of golimumab 50/100 mg treatment up to 5 years. In these post-hoc analyses, MDA was defined by the presence of ≥5 of 7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity score ≤20 [range 0-100], Health Assessment Questionnaire disability index [HAQ DI] ≤0.5, and ≤1 tender enthesis point).

Results: Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at week 14 (23.5% versus 1.0%; P < 0.0001), week 24 (28.1% versus 7.7%; P < 0.0001), and week 52 (42.4% versus 30.2%; P = 0.037). MDA was achieved at least once by ∼50% of golimumab-treated patients overall. Irrespective of treatment randomization, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ DI) and overall disease activity (patient global assessment of disease activity) at week 256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1-unit higher baseline HAQ DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio 0.514 [95% confidence interval 0.321-0.824]; P = 0.006) and ≥4 (odds ratio 0.480 [95% confidence interval 0.290-0.795]; P = 0.004) consecutive visits.

Conclusion: Among golimumab-treated PsA patients, better long-term functional improvement, patient global assessment, and radiographic outcomes were observed when patients achieved persistent MDA.

Trial registration: ClinicalTrials.gov NCT00265096.

© 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Figures

Figure 1
Figure 1
Proportions of patients who achieved minimal disease activity by randomized treatment and visit over 5 years. The placebo→golimumab 50 mg/100 mg group includes patients randomized to placebo who early escaped/crossed over at week 16/24 to receive golimumab 50 mg, with the possibility to increase golimumab from 50 to 100 mg after the week‐52 database lock. All patients could decrease the golimumab dose from 100 to 50 mg after the week‐52 database lock. The golimumab 50 mg/100 mg group includes patients randomized to receive golimumab 50 mg who early escaped at week 16 or dose escalated after the week‐52 database lock to receive golimumab 100 mg and also includes patients randomized to receive golimumab 100 mg. All patients could decrease the golimumab dose from 100 to 50 mg after the week‐52 database lock. EE = early escape; † = P < 0.0001 vs. placebo; ‡ = P < 0.05 vs. placebo.
Figure 2
Figure 2
Mean change in psoriatic arthritis–modified Sharp/van der Heijde score (SHS) from baseline to week 256 by randomized treatment (A, B) and by baseline methotrexate (MTX) use (C, D). Decreases from baseline in SHS represent improvement. (See Supplementary Table 1 available on the Arthritis Care & Research web site at http://onlinelibrary.wiley.com/doi/10.1002/acr.22576/abstract for baseline SHS values). The placebo→golimumab 50 mg/100 mg group includes patients randomized to placebo who early escaped/crossed over at week 16/24 to receive golimumab 50 mg, with the possibility to increase golimumab from 50 to 100 mg after the week‐52 database lock. All patients could decrease the golimumab dose from 100 to 50 mg after the week‐52 database lock. The golimumab 50 mg/100 mg group includes patients randomized to receive golimumab 50 mg who early escaped at week 16 or dose escalated after the week‐52 database lock to receive golimumab 100 mg and also includes patients randomized to receive golimumab 100 mg. All patients could decrease the golimumab dose from 100 to 50 mg after the week‐52 database lock. MDA = minimal disease activity; ∗ = P < 0.005 vs. never achieved MDA; ‡ = P < 0.05 vs. never achieved MDA; ∗∗ = P < 0.01 vs. never achieved MDA; † = P < 0.0001 vs. never achieved MDA.
Figure 3
Figure 3
Mean change in Health Assessment Questionnaire disability index (HAQ DI) (A, B) and patient global assessment of disease activity (PtGA) (C, D) from baseline to week 256 by randomized treatment. Decreases from baseline in HAQ DI represent improvement and increases in PtGA indicate worsening disease activity (See Supplementary Table 1 available on the Arthritis Care & Research web site at http://onlinelibrary.wiley.com/doi/10.1002/acr.22576/abstract for baseline HAQ DI and PtGA values). The placebo→golimumab 50 mg/100 mg group includes patients randomized to placebo who early escaped/crossed over at week 16/24 to receive golimumab 50 mg, with the possibility to increase golimumab from 50 to 100 mg after the week‐52 database lock. All patients could decrease the golimumab dose from 100 to 50 mg after the week‐52 database lock. The golimumab 50 mg/100 mg group includes patients randomized to receive golimumab 50 mg who early escaped at week 16 or dose escalated after the week‐52 database lock to receive golimumab 100 mg and also includes patients randomized to receive golimumab 100 mg. All patients could decrease the golimumab dose from 100 to 50 mg after the week‐52 database lock. MDA = minimal disease activity; ∗ = P < 0.005 vs. never achieved MDA; † = P < 0.0001 vs. never achieved MDA.
Figure 4
Figure 4
Mean change in Psoriasis Area and Severity Index (PASI) score from baseline to week 256 by randomized treatment (A, B) and by baseline methotrexate (MTX) use (C, D). Decreases from baseline indicate improved activity (See Supplementary Table 1 available on the Arthritis Care & Research web site at http://onlinelibrary.wiley.com/doi/10.1002/acr.22576/abstract for baseline PASI values). The placebo→golimumab 50 mg/100 mg group includes patients randomized to placebo who early escaped/crossed over at week 16/24 to receive golimumab 50 mg, with the possibility to increase golimumab from 50 to 100 mg after the week‐52 database lock. All patients could decrease the golimumab dose from 100 to 50 mg after the week‐52 database lock. The golimumab 50 mg/100 mg group includes patients randomized to receive golimumab 50 mg who early escaped at week 16 or dose escalated after the week‐52 database lock to receive golimumab 100 mg and also includes patients randomized to receive golimumab 100 mg. All patients could decrease the golimumab dose from 100 to 50 mg after the week‐52 database lock. MDA = minimal disease activity; ‡ = P < 0.05 vs. without MTX at baseline; ∗∗ = P < 0.01 vs. without MTX at baseline.

References

    1. Olivieri I, D'Angelo S, Palazzi C, Padula A. Advances in the management of psoriatic arthritis. Nat Rev Rheumatol 2014;10:531–42.
    1. Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis 2010;69:48–53.
    1. Smolen JS, Braun J, Dougados M, Emery P, Fitzgerald O, Helliwell P, et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis 2014;73:6–16.
    1. Wells GA, Boers M, Shea B, Brooks PM, Simon LS, Strand CV, et al. Minimal disease activity for rheumatoid arthritis: a preliminary definition. J Rheumatol 2005;32:2016–24.
    1. Coates LC, Helliwell PS. Validation of minimal disease activity criteria for psoriatic arthritis using interventional trial data. Arthritis Care Res (Hoboken) 2010;62:965–9.
    1. Coates LC, Cook R, Lee KA, Chandran V, Gladman DD. Frequency, predictors, and prognosis of sustained minimal disease activity in an observational psoriatic arthritis cohort. Arthritis Care Res (Hoboken) 2010;62:970–6.
    1. Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez‐Reino J, et al. Golimumab, a new human tumor necrosis factor α antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty‐four–week efficacy and safety results of a randomized, placebo‐controlled study. Arthritis Rheum 2009;60:976–86.
    1. Kavanaugh A, van der Heijde D, McInnes IB, Mease P, Krueger GG, Gladman DD, et al. Golimumab in psoriatic arthritis: one‐year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo‐controlled trial. Arthritis Rheum 2012;64:2504–17.
    1. Kavanaugh A, McInnes IB, Mease PJ, Krueger GG, Gladman DD, van der Heijde D, et al. Clinical efficacy, radiographic and safety findings through 2 years of golimumab treatment in patients with active psoriatic arthritis: results from a long‐term extension of the randomised, placebo‐controlled GO‐REVEAL study. Ann Rheum Dis 2013;72:1777–85.
    1. Kavanaugh A, McInnes IB, Mease P, Krueger GG, Gladman D, van der Heijde D, et al. Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long‐term extension of a randomised, placebo‐controlled trial (the GO‐REVEAL study). Ann Rheum Dis 2014;73:1689–94.
    1. Fredriksson T, Pettersson U. Severe psoriasis: oral therapy with a new retinoid. Dermatologica 1978;157:238–44.
    1. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum 1980;23:137–45.
    1. Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol 1982;9:789–93.
    1. Van der Heijde DM, van Leeuwen MA, van Riel PL, Koster AM, van 't Hof MA, van Rijswijk MH, et al. Biannual radiographic assessments of hands and feet in a three‐year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum 1992;35:26–34.
    1. Van der Heijde D, Sharp J, Wassenberg S, Gladman DD. Psoriatic arthritis imaging: a review of scoring methods [review]. Ann Rheum Dis 2005;64(Suppl II):ii61–4.
    1. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty‐eight‐joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–8.
    1. Wells G, Becker JC, Teng J, Dougados M, Schiff M, Smolen J, et al. Validation of the 28‐joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C‐reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis 2009;68:954–60.
    1. Iervolino S, Di Minno MN, Peluso R, Lofrano M, Russolillo A, Di Minno G, et al. Predictors of early minimal disease activity in patients with psoriatic arthritis treated with tumor necrosis factor‐α blockers. J Rheumatol 2012;39:568–73.

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