Background/Purpose:   Although available data have suggested successful withdrawal of anti-TNF monoclonal antibodies after achieving low disease activity (LDA) or remission in patients with rheumatoid arthritis (RA), longer term follow-up data are needed to confirm these findings. The purpose of this study was to evaluate the feasibility of long-term adalimumab (ADA) discontinuation after achievement of LDA in Japanese patients with early RA.

Methods:  In HOPEFUL-1, patients received initial therapy with either ADA 40 mg eow plus methotrexate (MTX weekly 6-8 mg) (intensive therapy) or MTX alone (MTX 6-8mg weekly, standard therapy) for 26 weeks, together followed by OL ADA+MTX for 26 weeks. In HOPEFUL-2, patients, who have continued ADA at the end of HOPEFUL-1, received OL ADA+MTX (ADA continuation) or OL MTX alone (ADA discontinuation) based on patient and physician decision for 52 weeks. HOPEFUL-3 was an observational study which included patients who had completed HOPEFUL-2 and continued for up to an additional 104 weeks. To assess efficacy, the primary endpoints were changes in 28-joint disease activity scores using C-reactive protein (DAS28-CRP) and the proportion of patients who achieved sustained LDA (DAS28–CRP <3.2) at week 208. Other endpoints, including modified total Sharp score (mTSS), were also evaluated. We compared the efficacy results between patients who received initial intensive therapy and standard therapy in HOPEFUL-1, and between patients who continued and discontinued ADA in HOPEFUL-2, using Fisher’s exact test or the chi-square test for categorical variables, and the Wilcoxon rank sum test for continuous variables. To assess safety, all adverse events during HOPEFUL-3 were recorded. Fisher’s exact test was used to compare the total number of adverse events between the ADA continuation and discontinuation groups.

Results:  

Of 172 patients enrolled, 135 (ADA continuation, n=61; ADA discontinuation, n=74) with DAS28–CRP at both week 52 (start of HOPEFUL-2) and week 208 (end of HOPEFUL-3) were included in the effectiveness analysis. . Initial intensive therapy was associated with better outcome in terms of structural remission at week 208 compared with standard therapy (64% vs. 30%). At week 208, 59/74 (79.7%) and 58/61(95.1%) patients who discontinued and continued ADA, respectively, were in sustained LDA (p=0.01). The incidence of adverse events was significantly lower in the ADA discontinuation group than in the ADA continuation group (9.7% vs. 34.2%, p<0.001).

Conclusion:  Approximately eighty percent of patients who discontinued ADA for 3 years after achieving LDA with ADA+MTX had sustained LDA with a lower incidence of adverse events than patients who continued ADA. Initial intensive therapy with ADA+ MTX demonstrated greater structural remission at 4 years compared to initial standard therapy with MTX alone despite 3 years of ADA discontinuation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/initial-intensive-therapy-of-adalimumab-and-methotrexate-is-associated-with-long-term-structural-remission-and-low-disease-activity-after-adalimumab-discontinuation-is-maintained-up-to-3-years-in-japa/