Efficacy of methotrexate in comparison to biologics in rheumatoid arthritis
Rau R.
Clin Exp Rheumatol 2010; 28 (5 Suppl. 61):S58–S64.
This article reviews clinical trials comparing the efficacy of methotrexate (MTX) with that of biologics in the treatment of rheumatoid arthritis. The review included trials of nine biologics clinically evaluated vs. MTX. Two types of randomised, double-blind, controlled multicentre trials were included:
- Parallel design, head-to-head comparisons of biologic monotherapy vs. MTX monotherapy, including ERA, TEMPO, PREMIER, GO-BEFORE, and AMBITION
- Step-up studies comparing MTX + placebo vs. MTX + biologic therapy, including COMET, ATTRACT, RAPID1, REFLEX and AIM
Overall, MTX showed similar clinical and radiographic efficacy to biologics in head-to-head trials. In the AMBITION trial, the results with tocilizumab compare favourably with those from trials of anti-TNFs using similar MTX dose titration.
While the results of different trials cannot be compared directly, the relative efficacy vs. MTX appeared to differ between biologics:
- MTX performed slightly better than adalimumab
- MTX showed similar efficacy to etanercept and golimumab
- MTX was significantly inferior to tocilizumab
In general, biologics had a more rapid onset of efficacy vs. MTX; however, clinical remission occurred with MTX at a similar frequency to that with biologics. Retardation of radiographic progression was stronger with anti-TNFs when compared with MTX. However, due to limited radiographic progression in these trials, the differences between biologics and MTX may not be clinically significant.
In step-up trials the combination of MTX + biologics always performed better than biologic monotherapies, indicating that the efficacy of biologics is potentiated by combining them with MTX. Negative radiographic progression (i.e. repair) occurred more frequently with combination therapy than with MTX monotherapy.
In summary, comparative trials with biologics and MTX have confirmed MTX as a very effective DMARD.