Comparison of long-term clinical outcome with etanercept and adalimumab treatment of rheumatoid arthritis with respect to immunogenicity

Objective To compare rates of sustained low and minimal disease activity and remission according to the American College of Rheumatology/European League Against Rheumatism criteria during 3-year follow-up in rheumatoid arthritis (RA) patients treated with etanercept and adalimumab in routine care. Methods Four hundred seven RA patients previously unexposed to tumor necrosis factor antagonists were treated with etanercept (n=203) or adalimumab (n=204) and assessed at 3and later 6-month intervals. Treatment allocation was at the discretion of the treating rheumatologist. Clinical parameters were measured at each time point, as were antiadalimumab antibodies in adalimumab-treated patients. Achievement of clinical outcome was defined as the occurrence of sustained (at least 12 consecutive months) low disease activity (28-joint Disease Activity Score [DAS28] <3.2), minimal disease activity (DAS28 <2.6) or ACR/EULAR remission based on the Simplified Disease Activity Index (SDAI). Nonoverlapping response rates were calculated. Results Among the adalimumab group, 13% reached sustained low disease activity but not sustained minimal disease activity, 15% reached sustained minimal disease activity but not sustained remission according to the SDAI and 16% reached sustained ACR/EULAR remission. In the etanercept group corresponding rates were 16%, 11% and 12%, respectively (p=0.42, overall test for linear trend). Adalimumab-treated patients without antiadalimumab antibodies (n=150, [74%]) had the best outcomes and adalimumab-treated patients with anti-adalimumab antibodies the worst, with outcomes in etanercept-treated patients in between (p<0.0001). Differences were most apparent in the SDAI remission and sustained minimal disease activity categories. For example, 40% of anti-adalimumab antibody-negative patients, 23% of etanercept-treated patients and 4% of anti-adalimumab antibody-positive patients achieved at least sustained minimal disease activity. Conclusion Overall, etanercept and adalimumab treatment appear similar in inducing a good long-term clinical outcome. However, in the case of adalimumab this is strongly dependent on the presence or absence of anti-adalimumab antibodies.