Updated systematic review and meta-analysis of randomized controlled trials comparing low- versus high-dose rituximab for rheumatoid arthritis

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Updated systematic review and meta-analysis of randomized controlled trials comparing low- versus high-dose rituximab for rheumatoid arthritis
Key Take-Away: 

There were no significant differences in the primary outcomes and change in Health Assessment Questionnaire (HAQ), although the mean change in modified Total Sharp Score (mTSS) was 0.25 units (95 % CI, 0.01 to 0.49; P=0.04) higher in low-dose group at week 52. The author observed no significant difference in the median reduction in IgG levels between the study group.

We have previously published a systematic review and meta-analysis (SRMA) comparing low- versus high-dose rituximab (RTX) for the treatment of rheumatoid arthritis (RA), which showed no significant differences in primary efficacy outcomes between the two RTX schemes.

ABSTRACT: 
Background: 

We have previously published a systematic review and meta-analysis (SRMA) comparing low- versus high-dose rituximab (RTX) for the treatment of rheumatoid arthritis (RA), which showed no significant differences in primary efficacy outcomes between the two RTX schemes.

We suggested that low-dose should be the preferred RTX regimen based on lower costs, but this conclusion has lead to substantial debate in the literature. In addition, the effects of the different RTX schemes in anti-TNF experienced patients were not clearly reported, so we were not able to evaluate the impact on immunoglobulin levels or perform a meta-analysis on radiographic outcomes. Considering that, and the emergence of novel evidence on efficacy and safety outcomes our purpose in the present study was to briefly update the SRMA of randomized controlled trials (RCTs) comparing the two regimens of RTX.

  • Rationale behind research
  1. The previously published systematic review and meta-analysis (SRMA) comparing low- versus high-dose rituximab (RTX) for the treatment of RA, showed no significant differences in primary efficacy outcomes.
  • Objective

To evaluate the efficacy and safety outcomes & briefly update the SRMA of randomized controlled trials (RCTs) comparing the two regimens of RTX

Methods: 

 

 

  • Study outcomes
    • Primary outcome: The primary efficacy outcomes were the American College of Rheumatolog (ACR) criteria for 20% improvement in disease activity (ACR20), ACR50, and ACR70 responses and the Disease Activity Score in 28 joints (DAS28) at 24 and 48/52 weeks.
    • Secondary outcome:  Health Assessment Questionnaire (HAQ) score, change in the radiographic modified Total Sharp Score (mTSS), levels of immunoglobulin G (IgG), and adverse events. 
Results: 

 

 

  • Primary Outcome
    • There were no significant differences between low and high dose RTX in the primary efficacy outcomes
  • Secondary Outcome
  • There were no significant differences in HAQ, although the mean change in mTSS was 0.25 units (95 % CI, 0.01 to 0.49; P=0.04) higher in low dose group at week 52.
  • Two RCTs did not demonstrate difference between RTX regimens for maintaining clinical response (obtained initially using high-dose RTX) in anti-TNF experienced patients. IgG levels were significantly higher (P≤0.02), and first infusion reactions were less frequent in low-dose group (P=0.02). 
Conclusion: 

Results support the similar efficacy of both RTX regimens in different subsets of RA patients, demonstrating a better clinical and laboratory safety profile of low-dose scheme.

In the present report, we were able to identify better results on IgG levels in the low-dose RTX arm. These results derived from a meta-analysis as well as the extraction and reanalysis of data of the SMART trial. Considering that lower immunoglobulin levels may discourage the use of repeat courses of RTX and may be associated with a higher incidence of infections, these results may imply in better long-term effectiveness of low-dose RTX.

Clin Rheumatol. 2015 Oct;34(10):1801-5

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