• J S Smolen, C Han, M Bala, R N Maini, J R Kalden, D van der Heijde, F C Breedveld, D E Furst, P E Lipsky, and ATTRACT Study Group.
• Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna and Lainz Hospital, Vienna, Austria. josef.smolen@wienkav.at
• Arthritis Rheum. 2005 Apr 1; 52 (4): 1020-30.

ObjectiveTo assess the relationship between inflammation and joint destruction in rheumatoid arthritis (RA) patients who have not responded clinically to treatment.MethodsChanges from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab (3 mg/kg or 10 mg/kg every 4 or 8 weeks) plus methotrexate (MTX) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy trial.ResultsAt week 54, patients who did not show 20% improvement by American College of Rheumatology criteria (ACR20 nonresponders) while receiving infliximab plus MTX exhibited mild but statistically significant improvement in clinical variables, including the 28-joint Disease Activity Score (DAS28) (P < 0.001), tender joint count (P = 0.014), swollen joint count (P < 0.001), and C-reactive protein (CRP) level (P < 0.001). Whereas the clinical and CRP changes among ACR20 nonresponders to infliximab plus MTX were small and much lower than among ACR20 responders to this treatment, radiographic progression among ACR20 nonresponders to infliximab plus MTX was significantly inhibited (P < 0.001) compared with ACR20 nonresponders to MTX plus placebo. Radiographic progression was much greater in patients receiving MTX plus placebo than in patients receiving infliximab plus MTX, irrespective of ACR response status (mean change in modified Sharp/van der Heijde score 6.0 in ACR20 responders and 7.2 in ACR20 nonresponders in the MTX plus placebo-treated group, versus 0.1 in ACR20 responders and 1.2 in ACR20 nonresponders in the infliximab plus MTX-treated group). Furthermore, among patients who were ACR20 nonresponders through week 54, patients who were DAS nonresponders at weeks 30 and 54, and patients without any improvement in individual clinical variables, those receiving infliximab plus MTX still demonstrated inhibition of structural damage that was statistically significant compared with inhibition in patients who received MTX plus placebo (P < 0.05 to P < 0.001).ConclusionEven in patients without clinical improvement, treatment with infliximab plus MTX provided significant benefit with regard to the destructive process, suggesting that in such patients these 2 measures of disease are dissociated.

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