Background Tocilizumab, an intravenous agent, is approved for rheumatoid arthritis (RA) treatment in Canada since April 30th, 2010. It was the sixth approved agent after adalimumab, etanercept, abatacept, infliximab and rituximab. It has been demonstrated effective in the treatment of RA either in mono or combo therapy after non-biologic or biologic DMARDS.
Objectives The goal of this analysis is to describe the six-year effectiveness of tocilizumab used in patients with RA failing a first anti-TNF agent and to compare it with adalimumab and etanercept used in the same clinical situation.
Methods All patients with RA having failed a first anti-TNF agent and subsequently exposed to tocilizumab after the 1st of January 2008 were extracted from the Rhumadata® database. Three cohorts were created according to the time tocilizumab or the subsequent anti-TNF agents were introduced: One cohort of patients starting tocilizumab and two other cohorts starting either adalimumab or etanercept. Demographics and baseline characteristics including age, gender, disease duration, rheumatoid factor and anti-CCP antibodies, CRP and ESR, the number of previously failed treatments, DAS-28(ESR) and CDAI, HAQ-DI were included for each cohort. Kaplan-Meier model and were used to compare retention rates and Cox proportional hazard models were used to generate adjusted hazard ratios.
Results The data from 128 patients prescribed either tocilizumab (44=34%), adalimumab (38=30%) or etanercept (46=36%) as a second biologic agent was extracted from the Rhumadata® registry and clinical database. Most subjects were female (77.3%), and the average age of cohort subjects was 54.4 (SD=13.2). 69.3% and 62.2% of patients were respectively RF+ or anti-CCP+. Mean CRP and ESR were respectively 14.8 (SD=21.5) mg/L and 28.6 (SD=24.2) mm/hr. No clinically significant differences at baseline were observed between groups. The six-year retention rates of tocilizumab, adalimumab, and etanercept as second-line biologic agents were respectively 54.6% (95% CI=35.9–70.0), 22.8% (9.7–39.1), 21.9% (8.9 -38.6) respectively. Kaplan-Meier survival analysis revealed significant differences in drug retention rates (log rank p=0.0007). Multivariate analysis adjusting for patient characteristics yielded hazard ratios of 2.66 (1.10–6.44), 5.33 (2.30–12.38) when respectively comparing adalimumab and etanercept to tocilizumab. Of the censored patients taking tocilizumab, 35% and 12% were in remission and had low disease activity (LDA) respectively, according to the DAS-28(CRP) criteria. In patients treated with anti-TNF agents, 50% and 17% were in remission and LDA.
Conclusions In RA patient having failed their first anti-TNF agent, tocilizumab, an Il-6 inhibitor, is a more valuable alternative than cycling to a second anti-TNF agent. Similarly to previously presented analysis, in a patient having failed a first anti-TNF agent, it seems that using an agent with a different mode of action such as abatacept, rituximab or tocilizumab as opposed to a second anti-TNF agent delivers better long-term retention.
Disclosure of Interest None declared