Inhibition of structural joint damage by rituximab in patients with with RA and a previous inadequate response to TNF inhibitors was first described over a 1-year period.10
Here we have demonstrated that the initial effects of rituximab are maintained over an extended interval of 2 years, with all measures of joint damage significantly improved compared with placebo plus MTX.
Treatment with rituximab was associated with a significantly higher proportion of patients with no progression of joint damage over the 2 years compared with placebo plus MTX. The proportion of patients with no progression (57%) achieved with rituximab treatment compares well with that seen with other treatments with biological agents, albeit in less treatment-refractory patient populations.6 13 14
Importantly, of those rituximab patients with no progression in the first year, 87% maintained a non-progressive status during the second year.
Although patients were initially randomised to either rituximab or placebo, 82% of placebo patients had switched to rituximab by 2 years. The impact of this switch on the progression of joint damage in this placebo–rituximab group is evident by the reduced changes in scores between time periods and the gradual slowing in their APR. The consequence of this switch to active treatment is that the degree of progression observed in the ‘placebo’ group is less than would have been observed had those patients been maintained solely on MTX, thereby underestimating the relative treatment effect. The extent of this discrepancy can be estimated using the method devised by Strand and Sharp15
for estimating APRs. By dividing the baseline mean mTSS (32.5) by the mean disease duration (11.7), the predicted progression for the placebo group over 2 years was 5.55. However, the observed progression was much lower (2.81), suggesting that the switch to rituximab had a large influence on the progression of joint damage in this control group. Consequently, the relative treatment effect size cannot be accurately measured. Nevertheless, using the predicted and observed progression in the placebo group a reduction in joint damage of 59–79% for rituximab plus MTX compared with placebo plus MTX could be estimated. Given the estimated nature of this effect, together with the lack of available radiographic data in similar patient populations, comparisons of this effect size with other biological agents used for RA would not be appropriate.
In conclusion, this 2-year analysis demonstrates that rituximab plus MTX has significant and sustained effects on the inhibition of joint damage in a population of patients with active RA who had previously experienced an inadequate response to TNF inhibitors.