A systematic review of the literature was conducted with the objective of assessing whether RTX alone or with methotrexate (MTX) is a safe, effective RA treatment.
Published and grey literature were identified by contacting the manufacturer and searching electronic databases, conference abstracts, and the Internet, including websites of regulatory and health technology assessment agencies. One reviewer established study criteria, data extraction and quality assessment forms a priori. Efficacy and safety data were extracted and dichotomous RCT data were pooled as meta-analyses, where possible. A draft report was sent to the requestor for initial review prior to provision of the final report and formal evaluation form.
Of 296 citations, three industry-sponsored RCTs were identified, reported as two full publications and ten abstracts. Jadad quality scores ranged from 3-4; all withdrawals and dropouts were reported. American College of Rheumatology (ACR) response rates were significantly improved in RTX+MTX users compared to MTX monotherapy with no difference in severe adverse events (SAEs). At 24 weeks, 54%, 31% and 15% of RTX+MTX users achieved 20%, 50% and 70% improvement in ACR responses versus 25%, 10%, and 3% in MTX users. The RR of achieving an ACR 20, 50, or 70 response was 2.23 (95% CI: 1.77, 2.81), 3.34 (95% CI: 2.24, 4.99), and 5.53 (95% CI: 2.64, 10.94), with NNT of 3, 5, and 8, respectively. SAEs were experienced by 7% of RTX+MTX versus 8% of MTX users, RR=0.93 (95% CI: 0.57, 1.50).
While RTX+MTX is safe and effective treatment for RA based on a single reviewer review, current industry-supported RCT evidence is limited. The optimal dose, duration of treatment, re-treatment, long-term efficacy and safety, and placement in therapy need further investigation. Policy makers must consider limitations in the evidence and potential discrepancies between meeting abstracts and full publication when making coverage decisions for new indications. While formal evaluation comments are pending use of the report within the Ministry's decision making process, initial requestor feedback was helpful in ensuring the final report met policy maker needs.