Risk factors for radiographic progression in psoriatic arthritis: subanalysis of the randomized controlled trial ADEPT

Abstract

Introduction: To identify independent predictors of radiographic progression in psoriatic arthritis (PsA) for patients treated with adalimumab or placebo in the Adalimumab Effectiveness in PsA Trial (ADEPT).

Methods: Univariate analyses and multivariate linear regression analyses assessed risk for radiographic progression (change in modified total Sharp score, DeltamTSS>0.5) from baseline to week 24 for C-reactive protein (CRP) and other baseline variables, and for 24-week time-averaged CRP (univariate analysis only). Subanalyses determined mean DeltamTSS for CRP subgroups. Analyses were post hoc, with observed data.

Results: One hundred and forty-four adalimumab-treated patients and 152 placebo-treated patients were assessed. Mean CRP was 64% lower by week 2 with adalimumab and essentially unchanged with placebo. Univariate analyses indicated that elevated CRP at baseline and time-averaged CRP were strongly associated with radiographic progression for placebo-treated patients but not for adalimumab-treated patients. Multivariate analysis confirmed that elevated baseline CRP was the only strong independent risk factor for radiographic progression (for CRP>or=1.0 mg/dl: odds ratio=3.28, 95% confidence interval=1.66 to 6.51, P<0.001). Adalimumab treatment reduced risk of progression approximately fivefold. The difference between mean DeltamTSS for adalimumab versus placebo was greatest for patients with baseline CRP>or=2.0 mg/dl (-0.5 vs. 2.6).

Conclusions: Systemic inflammation in PsA, as indicated by elevated baseline CRP, was the only strong independent predictor of radiographic progression. This association was observed predominantly for placebo-treated patients. Adalimumab treatment substantially reduced the overall risk of radiographic progression, and provided greatest radiographic benefit for patients with the greatest CRP concentrations at baseline.

Trial registration: Trial registration: NCT00195689.

Figure 1

Mean C-reactive protein concentrations over time. Serum concentrations of C-reactive protein (CRP) were determined from baseline to week 24 for patients treated with placebo or adalimumab in ADEPT. Data are presented as mean values at each time point. Data are observed; n values at baseline/week 24 were 152/146 for placebo and 143/138 for adalimumab. P < 0.001 for the comparison of mean changes from baseline for adalimumab versus placebo at all time points after week 0.

Figure 2

Mean change in modified total Sharp score for C-reactive protein subgroups. Changes in modified total Sharp score (ΔmTSS) from baseline to week 24 with standard error were determined for patients grouped post hoc by (a) baseline C-reactive protein (CRP) categorized as < 1 mg/dl and ≥1 mg/dl, (b) baseline C-reactive protein (CRP) categorized as ≤0.287 mg/dl, > 0.287 to < 1 mg/dl, ≥1.0 to < 2.0 mg/dl, and ≥2 mg/dl, and (c) 24-week time-averaged CRP categorized as ≤0.287 mg/dl, > 0.287 to < 1 mg/dl, ≥1.0 to < 2.0 mg/dl, and ≥2 mg/dl. (d) Mean CRP values at baseline and week 24, with standard error, were determined for patients grouped according to whether they had radiographic progression (ΔmTSS > 0.5) between baseline and week 24. Data are observed; except for CRP values in (c), which used the last observation carried forward for missing values. *P < 0.05, **P < 0.01, ***P ≤0.001, †P = 0.052 vs. placebo.

Figure 3

Cumulative probability plots of mean change in modified total Sharp score. Cumulative probability plots displaying the changes in modified total Sharp score (ΔmTSS) from baseline to week 24 were generated for (a) patients with baseline C-reactive protein (CRP) < 1.0 mg/dl and (b) patients with baseline CRP ≥1.0 mg/dl. For each CRP category, the placebo curve is above the adalimumab curve, indicating greater radiographic progression.