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Treatment Tapering and Withdrawal in People with Rheumatoid Arthritis in Stable Remission

INCREASING remission rates means that the management of people with rheumatoid arthritis in stable remission is an area of growing interest. For this reason, the Rheumatoid Arthritis in Ongoing Remission (RETRO) study aimed to determine outcomes following tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in this patient population. Such research is important to elucidate whether remission can be retained without the need to take DMARD therapy despite an absence of symptoms.  

This multicentre, prospective, randomised, controlled, open-label Phase III trial included adults (at least 18 years old) with rheumatoid arthritis with 12 months sustained remission, which was defined according to Disease Activity Score using 28 joints with erythrocyte sedimentation rate (DAS28-ESR) score of <2.6 units. Eligible patients, who were recruited consecutively from 14 German hospitals or rheumatology practices, were randomly assigned in a 1:1:1 ratio to continue 100% dose DMARD, taper to 50% dose DMARD, or 50% dose DMARD for 6 months before stopping DMARDs. The primary endpoint was the proportion of patients in sustained DAS28-ESR remission without relapse at 12 months. 

In total, remission was maintained at 12 months by 81.2% of patients in the continue group, 58.6% in the taper group, and 43.3% in the stop group. In comparison with the continue group, tapering DMARD dose was associated with a three-fold increased risk for disease relapse (p=0.0003) and treatment withdrawal was associated with a greater than four-fold increased risk for relapse (p<0.0001). The majority of individuals who relapsed were found to regain remission after reintroduction of 100% dose DMARDs. 

During the study period, 38 serious adverse events were reported across 29 patients: 11 in the continue group, 7 in the taper group, and 13 in the stop group. None of these events were related to the study or led to withdrawal. 

The authors highlighted the relevance of their research: “Reducing antirheumatic drugs in patients with rheumatoid arthritis in stable remission is feasible, with maintenance of remission occurring in about half of the patients. Because relapse rates were significantly higher in patients who tapered or stopped antirheumatic drugs than in patients who continued with a 100% dose, such approached will require tight monitoring of disease activity.” In conclusion, the authors believe that these results might ultimately “help to prevent overtreatment in a substantial number of patients with rheumatoid arthritis.”