Background The treatment of rheumatoid arthritis (RA) has changed significantly, and biological agents now occupy an extremely prominent position in treatment strategies. The 2010 EULAR recommendations list TNF inhibitors as the first-line treatment, and alternative TNF inhibitors, abatacept, rituximab, and tocilizumab (TCZ) as second-line and subsequent treatments. However, there are few reports of studies of direct comparisons of biological agents over the same time period, and particularly of direct comparisons conducted in the clinical setting that include TNF inhibitors and TCZ.
Objectives We directly compared the therapeutic efficacy and continuation rates of TCZ and three TNF inhibitors, infliximab (IFX), etanercept (ETN), and adalimumab (ADA), in bio-naïve RA patients started on treatment at the same time under actual clinical conditions.
Methods The subjects were 147 bio-naïve RA patients who started receiving treatment in or after July 2008 (36 patients received IFX, 36 ETN, 37 ADA, and 38 TCZ). The ESR, CRP, MMP-3, swollen joint count, tender joint count, DAS28-ESR, and EULAR improvement scores were assessed after six and twelve months. The continuation rates for each agent were also investigated.
Results No significant differences were found among the groups at baseline. After both six and twelve months, the ESR, CRP, MMP-3, swollen joint count, tender joint count, and DAS28-ESR scores were significantly lower than at baseline for all four agents. Direct comparison of the agents revealed that the DAS28-ESR scores were significantly lower in patients receiving TCZ than in patients receiving any of the other three agents. After six months, the proportion of patients with decreased MMP-3 scores was higher in the TCZ group than in the IFX group. After both six and twelve months, a majority of patients in the TCZ group exhibited “good response” according to the EULAR criteria. After 12 months, the continuation rate was 86% in the IFX group, 78% in the ETN group, 73% in the ADA group, and 91% in the TCZ group. No significant differences were found among the groups in the incidence of adverse events.
Conclusions We used the DAS28-ESR as an endpoint in this study. It has been reported that, particularly with TCZ, which directly inhibits the inflammatory response, comparatively high values may be obtained both for efficacy and the remission rate. However, there are also reports of relationships having been found between the DAS28-ESR and the CDAI and SDAI, indicating that DAS28 assessments are sufficiently useful. In our study, the decrease in MMP-3 was greater with TCZ than with IFX, and the continuation rate was higher as well. These results suggest that it may be possible to use TCZ, which affords therapeutic efficacy at least equivalent to that afforded by TNF inhibitors, and which is equally safe, as the first-line biological treatment in bio-naïve RA patients.
Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69:964-75.
Smolen JS, Aletaha D. Interleukin-6 Receptor Inhibition with Tocilizumab and Attainment of Disease Remission in Rheumatoid Arthritis. Arthritis Rheum 2011;63:43-52.
Disclosure of Interest None Declared