ADALIMUMAB PLUS METHOTREXATE RESULTS IN LESS FREQUENT AND LESS SEVERE RADIOGRAPHIC PROGRESSION THAN METHOTREXATE ALONE AT ALL LEVELS OF CLINICAL RESPONSE IN EARLY RHEUMATOID ARTHRITIS

Background: In the PREMIER trial, MTX-naive patients with early, aggressive rheumatoid arthritis (RA) had better clinical responses and developed less radiographic progression over 2 years when treated with adalimumab + MTX than with MTX alone. Moreover, radiographic efficacy of treatment in RA does not correlate well with clinical efficacy.Objectives: To determine, in a subanalysis of PREMIER, if adalimumab + MTX controlled structural damage in early, aggressive RA with greater effectiveness than MTX alone at all levels of clinical response.Methods: PREMIER was a 2-year, Phase III study of MTX-naive, adult patients with active, early RA (<3 years) who received either adalimumab 40 mg every other week (eow)+ MTX, adalimumab 40 mg eow, or MTX (with placebo injections). In the present subanalysis, patients for whom clinical and radiographic data were available at 6 months and 2 years were classified by clinical response (non-responder, ACR20, ACR50, ACR70, TJC=0, SJC=0, DAS28<2.6, ACR100) and by either having radiographic progression (change Δ in Total Sharp Score [TSS] >0.5) or not (DeltaTSS<0.5). Mean DeltaTSS was calculated for each of the subgroups resulting from these classifications at 6 months and 2 years. All data were observed (no imputation).Results: Of the 525 patients who enrolled in the adalimumab + MTX arm or the MTX monotherapy arm, clinical and radiographic outcomes data were available for 453 and 365 patients at 6 months and 2 years, respectively. Baseline mean TSS values in the 6-month and 2-year cohorts were 18.2 and 18.1 (combination therapy) and 21.8 and 22.7 (MTX alone). The observed ACR20/50/70 response rates at 6 months and 2 years, respectively, were 82/69/49 and 92/78/62 for patients who had received combination therapy, and 79/52/29 and 86/66/43 for patients who had received MTX alone. At each level of clinical response at 6 months, the percentage of patients with radiographic progression and the mean DeltaTSS among progressors were smaller with combination therapy vs. MTX alone (table). At 2 years, 57% of ACR70 responders on MTX had progression vs. 28% of those on combination therapy (p<0.001). The mean DeltaTSS of these ACR70, Year-2 progressors were 7.5 for MTX therapy and 3.9 for combination therapy (p<0.01). At 2 years, progression was also less frequent, and among progressors, less severe, in patients with TJC=0 or DAS28<2.6 (and to a lesser degree, SJC=0 or ACR100), if they had received combination therapy rather than MTX alone. Frequency & Severity of Rad. Progression Among Pts With Specified Responses at 6 Mos N Radiographic Non-respndr % ACR20 % ACR50 % ACR70 % Progression (TSS change‡) (TSS change‡) (TSS change‡) (TSS change‡) Combination 240 no 63 (–0.4*) 76 (–0.4†) 77 (–0.4†) 77 (–0.3†) yes 37 (3.2†) 24† (3.3*) 23† (3.2) 23† (2.8) MTX alone 213 no 41 (–0.4) 45 (–0.3) 49 (–0.2) 51 (–0.1) yes 59 (10.8) 55 (4.8) 51 (3.8) 49 (3.4) *p<0.05 vs. MTX; † p<0.001 vs. MTX; ‡ mean change; non-responder means <ACR20.Conclusion: In early, aggressive RA, patients who achieved any given level of clinical response on MTX alone had more frequent and more severe radiographic progression than patients achieving the same level of response on adalimumab plus MTX. This benefit was seen by 6 months, increased during 2 years of therapy, and occurred even in patients acheiving remission-like responses such as TJC=0 or DAS28<2.6. Thus, patients with early RA who achieve excellent clinical responses with MTX alone are not necessarily as well-protected from disease progression as patients who achieve the same response with adalimumab plus MTX.Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 88Session: RA prognosis, predictors and treatment