74-week follow-up of safety of infliximab in patients with refractory rheumatoid arthritis

Abstract

Introduction: The objective was to describe the prevalence, types, and predictors of adverse events (AEs) in rheumatoid arthritis (RA) patients treated with infliximab and methotrexate in a daily clinical setting.

Methods: This was a prospective, multi-center, open-label, 74-week observational study in patients with active RA despite treatment with methotrexate and at least one other disease-modifying anti-rheumatic drug. Patients were treated with 3 mg/kg infliximab at weeks 0, 2, and 6 and then every 8 weeks. At weeks 0, 6, 26, 50, and 74, patients answered a health assessment questionnaire, a swollen joint count was made, and adverse events (AEs) occurring during the previous period were registered.

Results: Five hundred and seventy-five patients were treated with infliximab, of which 346 were still on infliximab at the study end, 158 discontinued treatment, and 71 were lost to follow-up. Reasons for discontinuation included safety (n=74), elective reasons (n=43), and inefficacy (n=41). Infusion reactions (n=33) and infections (n=20) were the most common AEs causing discontinuation and the most common AEs overall. There were four cases of tuberculosis, all of which occurred in patients negative at screening. Total AEs, serious AEs, and infusion reactions as well as discontinuations for AEs were most frequent during the first 26 weeks. Higher age was a predictor of serious adverse events (SAEs), infection, and discontinuation due to an SAE, but odds ratios were close to one.

Conclusions: AEs and discontinuations due to AEs occur most frequently during the first half year of infliximab treatment in refractory RA patients. The main reasons for discontinuing treatment are infections and infusion reactions. Tuberculosis and other infections remain an important concern in these patients.

Figure 1

Patient disposition. (a) Flow chart of patient disposition. A total of 596 patients were screened for this study, of which 575 started infliximab. Of these, 71 were lost to follow-up, so that 504 were evaluated. There were 158 patients that discontinued treatment before week 74, and the remaining 346 completed the study according to protocol and were still on infliximab at study end. 'Other' under treatment discontinuations included three patients that wished to become pregnant and one that withdrew prior to an elective surgery. (b) Patients remaining on infliximab at each visit. (c) Fraction of evaluable patients completing the study or discontinuing for safety reasons, inefficacy, or elective reasons.

Figure 2

Incidence of (a) AEs, (b) infections, and (c) IRs during the study. The incidence of (a) all adverse events (AEs), (b) infections, and (c) infusion reactions (IRs) are shown for weeks 0 to 26, 27 to 50, and 51 to 74. The week 0 to 26 values were calculated by summing the number events for weeks 0 to 6 and weeks 7 to 26. For each time period, the presence or absence of IRs was recorded only a single time. However, this did not affect the calculation of the week 0 to 26 value from the week 0 to 6 and week 7 to 26 values.

Figure 3

Treatment discontinuations over time.