Objectives: To evaluate different methods of reporting response to treatment or disease status for their ability to discriminate between active therapy and placebo, or to reflect structural progression or patient satisfaction with treatment using an exploratory analysis of the AIM (Abatacept in Inadequate responders to Methotrexate) trial.
Methods: A total of 424 active- (abatacept ~10 mg/kg) and 214 placebo-treated patients with RA were evaluated. Methods of reporting included: 1) response (American College of Rheumatology [ACR] criteria) versus state (Disease Activity Score 28 (DAS28) criteria); 2) stringency (ACR20 vs 50 vs 70; Moderate Disease Activity State [MDAS; DAS<5.1] vs Low Disease Activity State [LDAS; DAS28≤3.2] vs DAS28-defined remission [DAS28<2.6]); 3) time to onset (time to first ACR50/LDAS); and 4) sustainability of ACR50/LDAS for consecutive visits). Methods were assessed according to: 1) discriminatory capacity (number of patients needed to study [NNS]); 2) structural progression (Genant-modified Sharp score); and 3) patient satisfaction with treatment. Positive likelihood ratios (LR+) evaluated the ability of the above methods to reflect structural damage and patient satisfaction.
Results: MDAS and ACR20 had the highest discriminatory capacity (NNS=49 and 69). Sustained LDAS best reflected no radiographic progression (LR+ ≥2). More stringent criteria (at least ACR50/LDAS), faster onset (≤3 months) and sustainability (>3 visits) of ACR50/LDAS best reflected patient satisfaction (LR+ >10).
Conclusions: The optimal method for reporting a measure of disease activity may differ depending on the outcome of interest. Time to onset and sustainability can be important factors when evaluating treatment response and disease status in patients with RA.