PMS12 TOCILIZUMAB IN MODERATE-TO-SEVERE RHEUMATOID ARTHRITIS: SYSTEMATIC REVIEW OF EFFICACY AND SAFETY

Abstract

The objective of this systematic review was to assess efficacy and safety of tocilizumab versus placebo in patients with moderate-to-severe active rheumatoid arthritis (RA) and with inadequate response to disease-modifying antirheumatic drugs (DMARDs). The subpopulation of special interest was patients with moderate RA. Medline, Embase and CENTRAL databases were searched through October 2018, following a review protocol prepared a priori. Search criteria covered keywords for rheumatoid arthritis and tocilizumab. Published (in English and Polish) and unpublished randomized controlled trials (RCTs) for tocilizumab versus placebo in RA were included. The risk of bias was assessed according to Cochrane Handbook. Seven included RCTs (Baek 2018, CHARISMA, LITHE, MEASURE, OPTION, ROSE and TOWARD study) assessed the efficacy and safety of tocilizumab+DMARDs versus placebo+DMARDs. Meta-analysis for the proportion of ACR20, ACR50 and ACR70 responders showed significantly higher rate in the tocilizumab group than in the placebo group at week 24 (OR (95%CI)= 3.75 (2.87, 4.89), 3.91 (2.57, 5.96) and 7.70 (5.35, 11.08) respectively). The mean DAS28 change was also significantly higher in the tocilizumab group. For the moderate RA subpopulation there was data on-file available from TOWARD study. Results prove, that in this group of patients tocilizumab is also more effective than placebo (statistically significant difference in ACR20, ACR50 and ACR70 rate at week 24, OR (95%CI)=4.86 (2.31, 10.22), 5.07 (1.95, 13.16) and 6.59 (1.45, 29.88) respectively). Safety profile of tocilizumab in moderate-to-severe RA patients is acceptable (no difference versus placebo in deaths, serious adverse events related to the drug or serious adverse events rate). In the moderate RA subgroup, safety profile is similar. Tocilizumab in combination with DMARDs reduced disease activity over 24 weeks more significantly and rapidly when compared to placebo+DMARDs. This high efficacy is proven both in moderate-to-severe RA and moderate RA subgroup.