Background/Purpose: Although available data has suggested successful withdrawal of a monoclonal antibody TNF blocker after achieving low disease activity (LDA) or remission over the short-term for a large proportion of patients with early rheumatoid arthritis (RA), longer term follow-up data are needed to predict maintenance of biologic-free disease control. The purpose of this study was to identify the factors associated with maintenance of disease control for 2 years of adalimumab (ADA) discontinuation after treatment with ADA plus methotrexate (MTX) in patients with early RA.

Methods: In the HOPEFUL-1 study, patients with early RA were randomized to receive ADA 40 mg every other week (EOW) plus weekly MTX 6-8 mg , or only MTX 6-8 mg every week for 26 weeks. Thereafter, all patients received open-label ADA 40 mg EOW plus weekly MTX for 26 weeks. At week 52, patients could enroll in HOPEFUL-2, an observational follow-up study, where they received ADA plus MTX (ADA-continued group) or MTX alone (ADA-withdrawn group) for 52 weeks based on investigator and/or patient decision. At week 104, patients could enroll in HOPEFUL-3, a 104-week follow-up extension. Data at week 156 were used in this interim analysis. Using multivariate analysis, factors associated with remaining in ADA-withdrawn group as well as sustaining LDA in the ADA-withdrawn group at week 156, were analyzed. The 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire Disability Index (HAQ-DI), and modified total Sharp score (mTSS) were also examined.

Results: Among the 220 HOPEFUL-2 patients, 172 were enrolled in the HOPEFUL-3 study, 79 from ADA-continued and 93 from ADA-withdrawn. Patient characteristics at the baseline of HOPEFUL-2 were similar in the ADA-continued and -withdrawn groups, except for SJC, which was significantly higher in the former group. At week 156, 73 patients out of 93 (78%) remained in the ADA-withdrawn group, with the remainder of patients either discontinuing from the study or continuing/restarting treatment with ADA. At week 156, there were no differences in clinical, functional, and structural outcomes between the patients in ADA-withdrawn group and the remainder of patients. (table). The predictive factors for remaining in the ADA-withdrawn group at week 156 were level of CRP at week 0, as well as SJC, CRP, and titer of rheumatoid factor at week 52 (cut-offs =week 0 CRP, 2.04; week 52 CRP, 0.21; week 52 SJC, 0). Moreover, DAS28-ESR 2.6 at week 52 distinguished 44 patients, those who were able to sustain LDA without using ADA at week 156.

Conclusion: The attainment of low disease activity based on serological markers at the onset and at the time of ADA withdrawal was the key determinant for maintenance of biologic-free disease control for up to 2 years in early RA patients.