Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blind study failed to confirm its efficacy

Abstract

Objective: To evaluate the effect of infliximab dose escalation in incomplete responders in a randomised controlled trial. Methods: 141 rheumatoid arthritis (RA) patients treated with infliximab for 12 months (3 mg/kg; intervals 0, 2, 6 and then 8 weeks) who responded to the drug (disease activity score in 28 joints (DAS28) decrease .1.2) but who were not in remission (DAS28 .2.6) were enrolled into the study. Patients were randomly assigned into arm A, 3 mg/kg, and arm B, 5 mg/kg infliximab every 8 weeks. Outcome measures included the DAS28, its components and C-reactive protein (CRP). Results: There were no significant differences in changes in the DAS28, its components, or CRP in patients in arms A and B during the 12 months of treatment. All patients showed a DAS28 decrease greater than 0.6 after 28 weeks. Eleven patients interrupted therapy in arm A and 14 in arm B. Infusion reactions and non-serious adverse events were observed in 4.2% and 28.2% of arm A patients and in 7.2% and 47.8% of arm B patients. The frequency of serious adverse events was comparable between arms A and B (16.9% and 15.9%, respectively), and the frequency of serious infections was not significantly greater in the higher dose group (5.8%) than in the lower dose group (5.6%). Conclusions: In this setting, increasing the infliximab dose from 3 mg/kg to 5 mg/kg in RA patients with residual disease activity did not improve efficacy but moderately increased toxicity. These data indicate that a switch to another biological treatment would be a more appropriate strategy in incomplete responders.

When to initiate and discontinue biologic treatments for rheumatoid arthritis?

“…) after initial failure of the lower dosage to lead to remission [31]. Moreover, the higher dosage had a poorer safety profile.…”

Cost and Effectiveness of Biologics for Rheumatoid Arthritis in a Commercially Insured Population

“…Dose escalation of anti-TNF agents has shown only limited effectiveness in the long-term control of RA (mainly for infliximab and less so for other biologics). 34,40,41 Similarly, approximately 15% of patients failed the criterion for increased corticosteroid doses, but in clinical practice, this may enable patients to achieve clinical endpoints without changing the dose of the biologic. Conversely, the low adherence criterion caused a substantial proportion of both SC and IV biologics to be classified as "not effective"; some patients may reduce the frequency of dosing or stop the medication when their symptoms improve (i.e., the medication is highly effective), yet the algorithm would categorize the biologic as "not effective."…”

Prediction of Clinical Response After 1 Year of Infliximab Therapy in Rheumatoid Arthritis Based on Disease Activity at 3 Months: Posthoc Analysis of the RISING Study

“…Although higher-dose or dose-escalating treatment did not show statistically better efficacy than standard-dose treatment in several clinical trials 2,4,5,21 , nonresponders at standard-dose treatment have been reported to respond to early dose-escalating treatment 13,22 .…”