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/postearly 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. ClinicalTrials.gov identifier: NCT02319759.

Measuring Outcomes in Psoriatic Arthritis

“…It also has good responsiveness in LOS (121). The effect size is smaller than that for the PASDAS (101,119,120) in clinical trial post hoc analysis. The CPDAI is sensitive to change in skin disease and is well confirmed in post hoc analysis of the PRESTA data set (122).…”

“…It shows good correlation with other joint measures (114,117) but not with other domains (116,118). Remission is associated with low residual articular disease, but other domains can remain active (104–106,119).…”

“…DAPSA has good responsiveness to change in trials and is able to differentiate between drug and placebo (101,108,115,119), but the effect size is lower than that of the PASDAS in most trial post hoc analyses (101,119,120). DAPSA has lower responsiveness than other composite disease measures in LOS (121).…”

“…The CPDAI has good responsiveness to change and differentiates between drug plus placebo (101,108,119) and active comparators (122,127). It also has good responsiveness in LOS (121).…”

“…The PASDAS has good responsiveness to change in clinical trial data sets differentiating between drug plus placebo (101,108,119) and active comparators (111,112,127). The effect size is usually highest of the newer composite measures (compared with DAPSA, CPDAI, and GRAPPA Composite Exercise [GRACE]) (101,119). The PASDAS has good responsiveness in LOS (121).…”