Background/Purpose:

Early, intensive treatment of rheumatoid arthritis (RA) with combination therapy (COBRA therapy) considerably lowers disease activity and suppresses radiological progression. Although proven to be very effective, uptake of COBRA therapy among rheumatologists has been suboptimal, for reasons including fear of possible side-effects. A modified schedule of the COBRA therapy with a lower dose of prednisone (‘COBRA-light’), might be equally effective and lessen concerns about side-effects. The purpose of this study was to investigate whether COBRA-light therapy is non-inferior to COBRA-therapy in patients with early, active RA. Trial duration: one year.

Methods:

164 patients with early, active RA were randomised to either COBRA therapy (MTX 7.5 mg/week, SSZ 2 g/day and prednisone 60 mg/d, tapered to 7.5 mg/day) (n=81) or COBRA-light therapy (MTX 25 mg/week and 30 mg prednisone, tapered to 7.5 mg/day) (n=83). Primary treatment goal was minimal disease activity, defined as DAS44 < 1.6. After 3 months treatment, MTX dose could be increased up to 25mg/week, when DAS44 remained above 1.6. A difference in change of DAS44 > 0.5 between the groups after 6 months was considered clinically relevant, and set as the boundary of non-inferiority. Patients, physicians and assessors were aware of treatment allocation as this trial is an open label trial.

Results:

At baseline, patients had moderately active disease: COBRA, mean (SD) DAS44 4.13 (0.81); COBRA-light, 3.95 (0.90). Two patients (COBRA-light arm) did not initiate treatment and two patients dropped-out of the study due to adverse events (myocardial infarction in COBRA-arm and manic episode in COBRA-light arm). At 6 months DAS44 had significantly decreased in both groups: COBRA, –2.50 (1.21); COBRA-light, –2.18 (1.10) (Table). The difference between the groups in DAS44 change was 0.32 (95% CI: –0.03;0.68; p=0.08), i.e. within the noninferiority boundary. Minimal disease activity (DAS₄₄<1.6) was reached in almost half of patients in both groups (49% and 41% in COBRA and COBRA-light respectively). There were no significant differences between the treatment groups with respect to other measurements of disease activity including the EULAR and ACR response criteria and the HAQ-score.

Conclusion:

Results at 6 months suggest that COBRA-light therapy is non-inferior to standard COBRA therapy: both strategies effectively lower disease activity in early, active RA patients. The clinical and radiological effects at one year are pending.

Table 1 Outcome week 26

* D: delta, difference between 0 and 26 weeks

Data are presented as mean (±SD) or median (interquartile range). Differences between groups were tested with independent T-test, Mann-Whitney U test or Chi square test. A p<0.05 was considered statistically significant.