Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration

Primary tabs

SCIENCE
Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration
Key Take-Away: 

The results from the present study showed that initial treatment with RTX at 500 mg x 2 and 1000 mg x 2 led to comparable clinical outcomes after 6 months.

Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for rheumatoid arthritis (RA) treatment in combination with methotrexate in patients showing no response to at least one tumor necrosis factor (TNF) inhibitor.

ABSTRACT: 
Background: 

Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for rheumatoid arthritis (RA) treatment in combination with methotrexate in patients showing no response to at least one tumor necrosis factor (TNF) inhibitor.

The effectiveness of RTX have been established in RCTs and in large observational cohorts. The 1000 mg × 2 (with a 2-week interval) per treatment course is an approved dose of RTX. However, evidence suggest that lower dose of RTX, 500 mg × 2, is also effective but not approved. In SERENE trial, both 500 mg × 2 and 1000 mg × 2 doses of RTX considerably enhanced clinical outcomes as compared to placebo in a biologic-agent-naïve population of patients with RA. Similar findings were observed with the MIRROR, DANCER and IMAGE trials.

  • Rationale behind research

  • In all clinical trials, no significance difference was detected between 1000 mg x 2 and 500 mg x 2 in almost all clinical outcomes.

  • Therefore, this study was conducted to compare the effectiveness of regular and low doses given as first treatment course.

  • Objective

  • To assess and compare the effectiveness at 6 months of the higher (1000 mg x 2) and lower (500 mg x 2) dose of RTX given as the first treatment course in a merged dataset from observational cohorts.

     

Methods: 

NOTE: Twelve participating European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis European registries (CERERRA) submitted fully anonymized datasets with baseline demographic and disease characteristics, including age, gender, disease duration, number of previous synthetic and biological DMARDs, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) status of all patients with an established diagnosis of RA who started treatment with RTX.

  • Study outcomes

  • Effectiveness of RTX: Effectiveness of RTX in the higher (1000 mg × 2) and the lower dose (500 mg × 2) was assessed by DAS28 (Disease activity score in 28 joints) and HAQ (Health assessment questionnaire) status at 3 and 6 months, by the improvement of DAS28 and HAQ at 3 and 6 months, by disease activity at 3 and 6 months based on DAS28 status and by EULAR (European league against rheumatism responses) at 6 months.

  • Time points

  • Efficacy: Baseline, 3 months and 6 months

Results: 

  • Baseline characteristics: No significant differences between the two population at the baseline were observed.

  • Outcomes

  • The mean DAS28 improvement at 3 months was greater for patients treated with the higher dose than for those treated with the lower dose (1.9 ± 1.4 vs. 1.3 ± 1.3) and it remained significant in the ANCOVA (p = 0.004). The difference in mean DAS28 improvement was also significant at 6 months (2.0 ± 1.3 vs. 1.7 ± 1.4) in the unadjusted analysis. Inclusion of country as a random variable in the ANCOVA did not change the results. Improvements in function as assessed by the HAQ were also similar between the groups both at 3 and 6 months. The proportion of patients with high, moderate and low disease activity and remission based on the DAS28 was similar in the two groups at baseline, 3 and 6 months, as was the proportion of EULAR good responders, moderate responders and non-responders at 6 months.

Figure 1: Effectiveness of treatment across the two treatment groups as assessed by DAS28

Figure 2: Effectiveness of treatment across the two treatment groups as assessed by HAQ

  • Multivariate regression analysis showed that RTX dose (lower dose vs. higher dose) was not a statistically significant predictor of achieving a good EULAR response (odds ratio (OR) 1.08, 95 % CI 0.40, 2.94, p = 0.88) or good/moderate response EULAR (OR 1.22, 95 % CI 0.37, 4.09, p = 0.74). Similar results were observed when country was introduced into the model.

Conclusion: 

In this study, based on data from the CERERRA collaboration RTX provided significant clinical improvement at 3 and 6 months in patients with active RA. On comparison of the higher (1000 mg × 2) and lower dose (500 mg x 2) of RTX, there was a significant difference in DAS28 improvement at 3 months, but not in clinical effectiveness, as assessed by change in DAS28 and HAQ score at 6 months.

The results of our study were found to be consistent with those from the SERENE, IMAGE and MIRROR trials. In MIRROR trial, the percentage of patients with good/moderate EULAR responses was borderline significantly higher in the 1000 mg × 2 (89%) compared to the 500 mg × 2 group (73%). The overall conclusion of MIRROR trial was that the two RTX doses could not be clearly differentiated, although some clinical outcomes were in favor of the higher dose. A recent systematic review and meta-analysis also made a similar conclusion. The similar effectiveness of lower dose RTX in patients with RA in clinical practice might have important pharmacoeconomic implications for health systems globally.

Arthritis Research & Therapy 2016; 18:50
Log in or register to post comments