BASELINE CRP CONCENTRATIONS PREDICT RADIOGRAPHIC PROGRESSION IN MTX-NAÏVE PATIENTS WITH EARLY RA: SUBANALYSIS OF THE PREMIER STUDY

Background: Rheumatoid arthritis (RA) has a variable course with a wide range of potential outcomes, making it difficult to predict disease progression and magnitude of therapeutic response.Objectives: This analysis examined baseline characteristics that might predict radiographic progression in methotrexate-naïve patients with recent-onset RA in the PREMIER study.Methods: PREMIER was a 2-year, double-blind, Phase III study of adult patients with active, early RA (<3 years) who were naïve to methotrexate (MTX). Treatment arms included adalimumab 40 mg every other week (eow) + MTX; adalimumab 40 mg eow alone, or MTX alone. Radiographic progression was assessed by mean change from baseline in Total Sharp Score and stratified into those with (ΔTSS>0.5) and without (Δ≤TSS 0.5). A logistic regression model was developed to examine predictors of progression, using characteristics identified at baseline, including age, disease duration, RF status, TJC, SJC, erosions, and C-reactive protein concentration (CRP).Results: Of the 799 patients who enrolled in the study, CRP concentrations and X-rays were available for 585 patients at baseline and 1 year. The percentages of patients with no worsening in TSS (ΔTSS≤0.5) at 1 year were significantly higher in patients receiving combination therapy (64%) compared with patients who received either adalimumab alone (51%, p<0.01) or MTX alone (38%, p<0.01). Using logistic regression, we looked for baseline predictors of radiographic progression at Year 1. Only baseline CRP (normal/abnormal) had any significant effect on radiographic progression. Patients with elevated CRP at baseline were 3.5 times more likely to have progressed by 1 year than patients who had normal concentrations at baseline. In further analyses, we examined the effect of treatment on CRP at 1 year to assess correlation with CRP normalization and radiographic progression. Patients who had normal CRP at baseline and at 1 year were least likely to progress (84% had no progression overall).Patients who had abnormal CRP at baseline but normal concentrations at 1 year were less likely to progress than those who had elevated concentrations at both time points (55% vs 35%). Patients with an abnormal CRP at baseline were more likely to normalize their CRP at 1 year if they received combination therapy (84%) than if they received either adalimumab alone (52%) or MTX alone (53%). Further, patients with abnormal CRP at baseline who normalized their CRP at 1 year were less likely to progress if they received combination therapy (68%) than if they received either adalimumab alone (53%) or MTX alone (33%). Patients who had elevated CRP at both baseline and 1 year were still less likely to progress if they received combination therapy (54%) than if they received either adalimumab alone (32%) or MTX alone (31%). Patients with No Radiographic Progression at 1 Year CRP Concentration (BL and Year 1) Always Normal Abnormal to Normal Never Normal Adalimumab + MTX (n=211) 75% 68% 54% Adalimumab alone (n=187) 91% 53%* 32% MTX alone (n=187) 86% 33% 31% Overall (n=585) 84% 55% 35% £p<0.05 ada+MTX vs MTX alone, §p<0.05 ada+MTX vs ada alone, *p<0.05 ada vs MTX alone. £p<0.05 ada+MTX vs MTX alone, §p<0.05 ada+MTX vs ada alone, *p<0.05 ada vs MTX alone.Conclusion: Normalization of CRP correlated well with less radiographic progression, and combination therapy with adalimumab plus MTX was the most effective therapy to normalize CRP and inhibit radiographic progression. Approximately two-thirds of patients receiving MTX alone who had elevated baseline CRP developed radiographic progression whether or not their CRP normalized. In recent-onset RA, CRP at baseline and during follow-up could be used to trace those patients who may benefit most from combination therapy.Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 436Session: Rheumatoid Arthritis – Treatment