Discontinuation of Disease-modifying Anti-rheumatic Drugs (DMARDs) in Rheumatoid Arthritis Patients Also Using TNF Inhibitors

Rationale Rheumatoid arthritis (RA) is a long‐term inflammatory disease that causes jointpain, swelling, and stiffness. Many patients are treated with a combination ofmedications to control inflammation. These usually include a biological medicine called aTNF inhibitor (TNFi) and another medicine, methotrexate (MTX) or leflunomide (LEF).Although this combination treatment is effective, patients often experience side effects(such as gastro‐intestinal complaints and fatigue), require frequent blood tests, and mayexperience treatment fatigue from taking multiple medications. Patients would thereforeprefer to reduce their medication. The safe reduction of TNFi treatment has been studiedbefore. It is still unclear whether patients can safely discontinue MTX or LEF when theirdisease is well controlled. This study investigates whether attempting to discontinue MTXor LEF while using a TNF inhibitor is no worse than continuing combination treatment interms of disease activity, with the hope of reducing side effects, the need formonitoring, and healthcare costs.Objective The objective is to investigate whether a strategy of attempting to discontinueof MTX or LEF (and restart when necessary) in RA patients treated with an optimal dose(allowed dose or lower, tapered to the maximum, or according to patient preference) TNFiis not worser to a continuation of combination therapy. The study will also examine thedisease‐related effects of treatment that attempts to discontinue MTX or LEF, howpatients experience it, its safety, and its impact on medication usage and healthcarecosts.Main trial endpoints The main endpoint is the difference between treatments in averagedisease activity over 24 months. The study will compare whether disease activity remainssimilar between patients who attempt to discontinue MTX or LEF and those who continuecombination therapy.Secondary trial endpoints Other study outcomes include the proportion of patients in thediscontinuation strategy group using MTX/LEF and/or a TNFi after 24 months, anddifferences between treatments in patient‐reported outcomes, joint damage measured byX‐ray, blood levels of TNF inhibitors, safety and cost‐effectiveness.Trial design This study is being conducted in multiple hospitals. A total of 202 patientswith RA will be randomly assigned to stopping MTX/LEF or continuation of combinationtherapy and followed for 24 months. Two‐thirds of the patients will attempt todiscontinue MTX or LEF (discontinuation group), and one‐third will continue using thecombination treatment (continuation group).Trial population Adult patients aged 18 years and older with RA are eligible toparticipate if their disease has low disease activity for at least six months duringtreatment with a TNFi in combination with MTX or LEF.Interventions In this study, we examine the difference between two groups: thediscontinuation group and the continuation group. In the discontinuation group, patientsimmediately stop taking MTX or LEF and use only the TNFi at a stable dose. When diseaseactivity increases, MTX or LEF can be restarted at the previous dose. If necessary,temporary treatment, such as glucocorticoids, can be administered. In the continuationgroup, patients continue using combination therapy with MTX or LEF and a TNFi at stabledoses. In both groups, the goal is to maintain a stable dose of the TNFi throughout thestudy. Dosage adjustments or switching to a different biologic drug are permitted ifdisease activity increases or if side effects occur. These decisions are made by thetreating rheumatologist in consultation with the patient.During the 24‐month study, patients continue to receive regular care, includingsix‐monthly check‐ups and laboratory tests. An additional study visit takes place after 3months to detect changes in disease activity at an early stage. In addition, remotevisits (by telephone) will take place at 9, 15 and 21 months. Additional visits can bescheduled if a disease flare is suspected.