Four-year follow-up of infliximab therapy in rheumatoid arthritis patients with long-standing refractory disease: attrition and long-term evolution of disease activity

Abstract

Although there is strong evidence supporting the short-term efficacy and safety of anti-tumour necrosis factor-alpha agents, few studies have examined the long-term effects. We evaluated 511 patients with long-standing refractory rheumatoid arthritis treated with intravenous infusions of infliximab 3 mg/kg at weeks 0, 2, 6, and 14 and every 8 weeks thereafter for 4 years. Among the initial 511 patients included in the study, 479 could be evaluated; of these, 295 (61.6%) were still receiving infliximab treatment at year 4 of follow-up. The most common reasons for treatment discontinuation were lack of efficacy (65 patients, 13.6%), safety (81 patients, 16.9%), and elective change (38 patients, 7.9%). Analysis of disease activity scores (DAS28 [disease activity score based on the 28-joint count]) over time showed that, after the initial rapid improvement during the first 6 to 22 weeks of therapy, a further decrease in disease activity of 0.2 units in the DAS28 score per year was observed. DAS28 scores, measured at week 14 or 22, were found to predict subsequent discontinuation due to lack of efficacy. In conclusion, long-term maintenance therapy with infliximab 3 mg/kg is effective in producing further reductions in disease activity. Disease activity measured by the DAS28 at week 14 or 22 of infliximab therapy was the best predictor of long-term attrition.

Figure 1

Flow chart of the patient population. ITT= intention to treat.

Figure 2

Kaplan-Meier plot and cumulative discontinuation due to the different stop reasons.

Figure 3

Evolution of the DAS28 (disease activity score based on the 28-joint count) scores and its components over time. DAS28 scores at the last clinical evaluation (evaluation at discontinuation of infliximab (IFX) treatment; median 119 weeks, interquartile range = 74 weeks) and the year 4 evaluation (median 205 weeks, interquartile range = 22 weeks). SE, standard error.

Figure 4

Receiver operating characteristic (ROC) analysis of DAS28 (disease activity score based on the 28-joint count) to predict withdrawal from treatment due to inefficacy.