Low disease activity for up to 3 years after adalimumab discontinuation in patients with early rheumatoid arthritis: 2-year results of the HOPEFUL-3 Study

Abstract

Background: This study was conducted to evaluate the feasibility of long-term adalimumab (ADA) discontinuation after achievement of low disease activity (LDA) in Japanese patients with early rheumatoid arthritis (RA) and to identify predictors of LDA maintenance.

Methods: In the HOPEFUL-1 study, patients received initial therapy with either ADA plus methotrexate (MTX; intensive therapy) or MTX alone (standard therapy) for 26 weeks, followed by ADA + MTX for 26 weeks. In the HOPEFUL-2 study, patients received ADA + MTX (ADA continuation) or MTX alone (ADA discontinuation) for 52 weeks. HOPEFUL-3 was an observational study that enrolled patients who had completed HOPEFUL-2; these patients were followed for an additional 104 weeks.

Results: Of the 172 patients enrolled in the HOPEFUL-3 study, 135 (ADA continuation, n = 61; ADA discontinuation, n = 74) with 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) values at both week 52 (start of HOPEFUL-2) and week 208 (end of HOPEFUL-3) were included in the effectiveness analysis. At week 208, 58 (95.1%) of 61 patients and 59 (79.7%) of 74 patients who continued or discontinued ADA, respectively, had LDA (DAS28-CRP <3.2). Initial intensive therapy was associated with a better outcome than standard therapy in terms of change in modified total Sharp score from week 0 to week 208, which was ≤0.5 (64% vs. 30%). The incidence of adverse events was significantly lower in the ADA discontinuation group than in the ADA continuation group (9.7% vs. 32.9%; p < 0.001).

Conclusions: Approximately 80% of patients who discontinued ADA for 3 years after achieving LDA with ADA + MTX were still in LDA, with a lower incidence of adverse events than patients who continued ADA.

Trial registration: ClinicalTrials.gov identifier: NCT01346501. Registered 29 April 2011.

Keywords: Adalimumab; Biological agent; Observational study; Remission induction; Rheumatoid arthritis.

Figures

Fig. 1

Study design for the HOPEFUL-1, HOPEFUL-2, and HOPEFUL-3 studies. ADA Adalimumab, MTX Methotrexate

Fig. 2

Changes in DAS28-CRP (mean ± SD) over time in patients whose data were used in the analysis of effectiveness (n = 135) (a). Proportion of patients with LDA during the study period (b). Comparison of proportion of patients with LDA at the end of the HOPEFUL-3 study period (week 208) according to the initial therapy in the ADA continuation group (c) and in the ADA discontinuation group (d). ADA Adalimumab, DAS28-CRP 28-joint Disease Activity Score based on C-reactive protein, LDA Low disease activity, MTX Methotrexate

Fig. 3

Proportion of patients who achieved a clinical remission, defined as DAS28-CRP <2.6, b functional remission, defined as HAQ-DI ≤0.5, at weeks 52, 104, 156, and 208, and c structural remission, defined as ΔmTSS ≤0.5 per year, within specified 52-week periods. ADA Adalimumab, DAS28-CRP 28-joint Disease Activity Score based on C-reactive protein, HAQ-DI Health Assessment Questionnaire Disability Index, mTSS Modified total Sharp score, ΔmTSS Change in modified total Sharp score

Fig. 4

Cumulative probability plots showing ΔmTSS. Comparison of the ADA continuation group and the ADA discontinuation group over 4 years (weeks 0–208) (a) and over 3 years (weeks 52–208) (b); comparison of the initial intensive therapy group and the standard therapy group over 4 years (weeks 0–208) (c) and over 3 years (weeks 52–208) (d); and comparison of the initial intensive therapy group and the standard therapy group over 4 years (weeks 0–208) in the ADA continuation group (e) and in the ADA discontinuation group (f). ADA Adalimumab, ΔmTSS Change in modified total Sharp score