Abatacept (CTLA4Ig) treatment increases the remission rate in rheumatoid arthritis patients refractory to methotrexate treatment

Background

Effective amelioration of symptoms and induction of remission are goals in treatment of rheumatoid arthritis (RA).

Objectives

Data from a Phase II study for RA treatment with abatacept, a selective co-stimulation modulator, showing induction of remission (DAS-28 score < 2.6) are presented.

Methods

Patients on background methotrexate (MTX) who met ACR criteria for active RA with ≥ 10 swollen joints (66 joint count) and ≥ 12 tender joints (68 joint count) were randomly assigned to receive 10 mg/kg abatacept (n = 115) or placebo (n = 119) treatment for 1 year. DAS-28 scores and serum cytokine levels were assessed at days 1, 90, 180 and 360.

Results

Abatacept-treated patients showed a progressive increase in remission rates up to 1 year (analysis not prespecified) compared with placebo (P < 0.001; Fig. 1). Abatacept treatment also decreased serum levels of proinflammatory cytokines. In particular, levels of serum IL-6, a multifunctional cytokine that contributes both to acute phase response and to pathological B cell activation, were reduced by 67% at 180 days and by 73% at 360 days (P < 0.05). Placebo-treated patients showed no reduction. Abatacept was generally safe and well tolerated.

Figure 1

Abatacept increases the remission rate in RA patients refractory to MTX treatment. Means and 95% confidence intervals are shown.

Conclusions

In patients with active RA who were receiving MTX, abatacept treatment significantly improved RA symptoms and produced a progressive increase in remission rates for over one-third of the treatment group, which was sustained at 1 year. In addition, abatacept decreased serum IL-6 levels. The results of this phase II study suggest that abatacept may have potential as therapy for patients with active RA despite MTX treatment.