Composite Measures of Disease Activity in Psoriatic Arthritis: Comparative Instrument Performance Based on the Efficacy of Guselkumab in an Interventional Phase II Trial

Abstract

Objective: To assess performance of psoriatic arthritis (PsA) composite indices and evaluate guselkumab's effect on achieving low disease activity or remission.

Methods: In this phase II trial, patients with active PsA (≥3 tender and ≥3 swollen joints, C-reactive protein level ≥0.3 mg/dl, ≥3% body surface-area with psoriasis involvement) were randomized 2:1 to subcutaneous guselkumab 100 mg (n = 100) or placebo (n = 49) at week 0, week 4, and every 8 weeks through week 44. At week 16, patients with <5% improvement in swollen and tender joints could early escape to open-label ustekinumab. Patients continuing placebo crossed over to receive guselkumab 100 mg at weeks 24, 28, 36, and 44 (placebo to guselkumab). PsA composite indices (Psoriatic Arthritis Disease Activity Score [PASDAS], Group for Research and Assessment of Psoriasis and Psoriatic Arthritis composite score [GRACE], modified Composite Psoriatic Disease Activity Index [mCPDAI], and Disease Activity in Psoriatic Arthritis [DAPSA]) were analyzed as secondary outcomes (last observation carried forward for missing/post-early escape data through week 24; observed data post-week 24). Instrument performance was assessed.

Results: Baseline PASDAS, GRACE, mCPDAI, and DAPSA scores indicated moderate-to-high disease activity. At week 24, mean changes in each of these composite indices showed significant improvement with guselkumab (-2.50, -2.73, -3.8, and -23.08, respectively) versus placebo (-0.49, 0.35, -0.8, and -4.98, respectively; P < 0.001 for all). Significantly more guselkumab-treated patients achieved low/very low/remitted disease activity states according to PASDAS (very low + low 35% versus 4%; P < 0.001), GRACE (30% versus 2%; P < 0.001), mCPDAI (46% versus 10%; P < 0.001), and DAPSA (remission + low 40% versus 12%; P < 0.001). A total of 12% of guselkumab-treated versus no placebo-treated patients achieved DAPSA remission (P < 0.01). The PASDAS and GRACE instruments were more sensitive than the mCPDAI and DAPSA tools in detecting treatment effect. Residual skin disease and enthesitis were marginally more prominent in patients achieving DAPSA low disease activity versus other indices.

Conclusion: Guselkumab demonstrated efficacy in achieving low disease activity/remission based on all PsA composite indices assessed. Composite index use in PsA trials and the clinic requires careful consideration to optimize feasibility and instrument performance.

Trial registration: ClinicalTrials.gov NCT02319759.

© 2019, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Figures

Figure 1

Proportions of patients achieving disease activity states for psoriatic arthritis–specific composite end points at week 16 and week 24 (full analysis set; last observation carried forward for missing data). A, Psoriatic Arthritis Disease Activity Score; B, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis composite score (GRACE); C, modified Composite Psoriatic Disease Activity Index (mCPDAI); and D, Disease Activity in Psoriatic Arthritis. P values were calculated post hoc. * = P ≤ 0.001; † = P ≤ 0.01.

Figure 2

Mean (SD, shown as error bars) changes from baseline at week 24 in the 36‐item Short Form health survey (SF‐36) physical component summary (PCS) score by disease activity state according to psoriatic arthritis–specific composite end points (guselkumab‐treated patients in the full analysis set; last observation carried forward for missing data). A, Psoriatic Arthritis Disease Activity Score; B, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis composite score; C, modified Composite Psoriatic Disease Activity Index; and D, Disease Activity in Psoriatic Arthritis.

Figure 3

Proportions of patients (%) achieving minimal disease activity (MDA) and very low disease activity (VLDA). A, At week 16 (MDA, left) and week 24 (VLDA, right) (full analysis set; nonresponder imputation). B, At week 24 (MDA, left) and week 44 (VLDA, right) (post–week 24 efficacy analysis set, observed data; week‐24 observed data in the same population included as a reference; P values were calculated post hoc). * = P ≤ 0.001.

Figure 4

Proportions of patients achieving disease activity states post–week 24 for the psoriatic arthritis–specific composite end points. A, Psoriatic Arthritis Disease Activity Score; B, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis composite score; C, modified Composite Psoriatic Disease Activity Index; and D, Disease Activity in Psoriatic Arthritis. Week‐44 data derived from the post–week 24 efficacy analysis set–based observed data (week‐24 observed data in the same population included for reference).

Figure 5

Comparative statistics evaluating guselkumab treatment effects detected at week 24 according to the Psoriatic Arthritis Disease Activity Score (PASDAS), Group for Research and Assessment of Psoriasis and Psoriatic Arthritis composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), and Disease Activity in Psoriatic Arthritis (DAPSA) psoriatic arthritis–specific composite end points. A, standardized mean difference; B, effect size; and C, standardized response mean (full analysis set; last observation carried forward for missing data).