I CEA. Induction of Cure in Early Arthritis
A single blind randomized clinical trial

A newly diagnosed arthritis, where the cause is not yet clear (so-called undifferentiated arthritis, UA), can go into spontaneous remission, or become chronic and potentially progress to rheumatoid arthritis. At presentation it is not yet clear how things will develop, and therefore it is difficult to decide who to treat it. Suppression of symptoms with NSAIDs and a local corticosteroid injection may be sufficient, or it is necessary to start an antirheumatic treatment as rapidly as possible, to prevent progression and maybe induce cure. If the latter is true, we need to start with the most effective treatment, but which that is, is also not clear. Therefore we propose to invite patients with previously untreated undifferentiated arthritis to participate in this trial, where they will be randomized to either symptomatic treatment with NSAIDs and a local injection (arm 1), or to (as well) methotrexate, a slow-acting antirheumatic drug (arm 2), or baricitinib, a fast-acting antirheumatic drug (arm 3). Clinical evaluation by an independent joint assessor every three months will determine if remission is achieved or not. If not, medication will be changed: patients in arm 1 will be randomized to either arm 2 or arm 3, patients in arm 2 will switch to treatment according to arm 3, and vice versa. If remission is achieved on NSAIDs, they can be stopped. If remission is achieved on MTX, this can be stopped after an additional 6 months (for fear of relapse after stop), and if remission is achieved on baricitinib, patients will again be randomized, to either stop immediately, or continue for an additional 6 months. Total follow-up time per patient will be 18 months. There are 2 primary endpoints: percentage in remission at 3 months, and percentage in sustained (at least 6 previous months) drug free remission at 18 months.

initial treatment with baricitinib results in more rapid remission and more sustained drug free remission compared to initial treatment with NSAIDs or methotrexate

February 2020 MEC approved, April 2020 first patient included, expected inclusion period 3 years, follow-up time per patients 18 months

All arms: one intraarticular or intramuscular injection with corticosteroids (40 mg methylprednisolone or equivalent). Arm 1: start with NSAID (naproxen 2 dd 500 mg or equivalent). If no remission after 3 months: randomize to treatment according to arm 2 or arm 3. Arm 2: start with methotrexate 15 mg/week increased to 25 mg/week by week 4 or highest tolerated dose (oral or subcutaneous). NSAID or analgetic allowed. If no remission after 3 months: switch to baricitinib according to protocol of arm 3. In case remission is achieved on MTX: continue for 6 months then taper in 4 weeks to nil. In case of disease flare during or after tapering: switch to baricitinib. Arm 3: start with baricitinib 4 mg/day. NSAID or analgetic allowed. If no remission after 3 months: switch to methotrexate according to protocol of arm 2. In case remission is achieved on baricitinib: randomize to either immediate discontinuation or continuation for 6 more months. In case of disease flare after remission: switch to methotrexate.