Approximately 80% of patients with early rheumatoid arthritis (RA) who discontinued adalimumab use for 3 years after achieving low disease activity (LDA) with adalimumab plus methotrexate maintained LDA, with a lower incidence of adverse events than patients who continued adalimumab, according to a clinical trial conducted by Yoshiya Tanaka, MD, PhD, Professor and Chair, The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, and colleagues (Tanaka Y, et al. Arthritis Res Ther. 2017;19:56).
The HOPEFUL-3 study was a follow-up to the HOPEFUL-1 and -2 studies. HOPEFUL-1 compared the effectiveness of the combination of adalimumab plus methotrexate with methotrexate alone for 26 weeks. HOPEFUL-2 was a 52-week observational study that evaluated the effects of adalimumab discontinuation on RA disease activity. Most patients maintained LDA in the adalimumab-continuation (combination) and discontinuation (methotrexate-only) groups. HOPEFUL-3 was an observational study of 172 patients previously enrolled in HOPEFUL-2 who were followed for an additional 104 weeks to determine the feasibility of discontinuing adalimumab for an extended period of time.
“In the present HOPEFUL-3 study, we observed patients with RA who had completed HOPEFUL-2 to assess the long-term effects of ADA [adalimumab] discontinuation in terms of the proportion of patients without disease flare…as well as other measures of RA disease activity and safety,” said Dr Tanaka and colleagues.
Other recent studies investigated the possibility of discontinuing adalimumab in patients who had reached LDA, which is defined as a 28-joint Disease Activity Score based on C-reactive protein <3.2. In the OPTIMA trial, patients with early RA (duration <1 year) who were treated with an adalimumab plus methotrexate combination, with adalimumab discontinued at week 26, had LDA outcomes at week 78 similar to those who continued to receive adalimumab. The HONOR study examined the feasibility of discontinuing adalimumab for 1 year in patients receiving the adalimumab plus methotrexate regimen for established RA. Of patients with deep remission, 79% discontinued adalimumab without disease flare, which was comparable to the percentage of patients who continued to receive adalimumab.
“These results suggest that the achievement of disease control with initial intensive therapy may be necessary for the prevention of disease flare after discontinuation of ADA. This finding is useful in clinical practice; however, the effects of ADA discontinuation over a longer time period (ie, >1 year) remain unknown,” explained Dr Tanaka and colleagues.
To determine whether adalimumab discontinuation yields results similar to continuation of adalimumab over a longer period, Dr Tanaka and colleagues conducted the HOPEFUL-3 study. Of the 172 patients enrolled in the study, 79 continued receiving adalimumab, and 93 remained in the discontinuation group. Data from 61 and 74 patients in both cohorts, respectively, were included in the effectiveness analysis set.
One primary end point of the study was the proportion of patients who achieved LDA at week 208. At the end of HOPEFUL-3, 59 (79.7%) patients in the adalimumab-discontinuation group had LDA, although this was significantly lower than the corresponding value in the adalimumab-continuation group (58 [95.1%]; P = .010).
During the course of HOPEFUL-3, there were no deaths or cases of tuberculosis. Overall, the number of adverse events was higher in the adalimumab-continuation group, with 32.9% of patients experiencing an adverse event compared with 9.7% in the discontinuation group. Four serious adverse events (ie, bronchiolitis, urinary tract stone, ascites fluid, and hepatic cirrhosis) occurred in the adalimumab-continuation group, whereas just 1 patient had a serious adverse event (interstitial lung disease) in the discontinuation group.
The proportion of patients who achieved clinical remission—defined as a 28-joint Disease Activity Score based on C-reactive protein <2.6—at week 208 was significantly higher in the adalimumab-continuation group than in the discontinuation group (89% vs 65%, respectively; P = .001). There was no significant difference between the 2 groups in terms of the proportion of patients who achieved structural remission, which was assessed on the basis of changes in the modified total Sharp score. Similarly, the proportion of patients who achieved functional remission, defined as a Health Assessment Questionnaire Disability Index ≤0.5, at week 208 was approximately 90% in both groups.
“The results of this study were not conclusive, but they suggested that long-term discontinuation of ADA treatment might be a feasible and beneficial therapeutic option for patients with early rheumatoid arthritis who achieved LDA,” Dr Tanaka and colleagues summarized.