Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Abstract

Background: Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.

Methods: A multicenter stratified randomized single-blind controlled trial is currently being performed in patients 18 years or older with recent-onset arthritis. Eight hundred ten patients are being stratified according to the likelihood of their developing persistent arthritis. In patients with a high probability of persistent arthritis, we will study combination Disease Modifying Antirheumatic Drug therapy compared to monotherapy methotrexate. In patients with an intermediate probability of persistent arthritis, we will study Disease Modifying Antirheumatic Drug of various intensities. In patients with a low probability, we will study non-steroidal anti-inflammatory drugs, hydroxychloroquine and a single dose of corticosteroids. If disease activity is not sufficiently reduced, treatment will be adjusted according to a step-up protocol. If remission is achieved for at least six months, medication will be tapered off. Patients will be followed up every three months over two years.

Discussion: This is the first rheumatological study to base treatment in early arthritis on a prediction rule. Treatment will be stratified according to the probability of persistent arthritis, and different combinations of treatment per stratum will be evaluated. Treatment will be started early, and patients will not need to meet the ACR-criteria for rheumatoid arthritis.

Trial registration: This trial has been registered in Current Controlled Trials with the ISRCTN26791028.

Figure 1

Medication strategies in the high-probability group. Dosages: MTX: 25 mg/week oral or subcutaneously. SSZ: 2 grams/day. HCQ: 200 mg twice a day. Single-dose corticosteroids intramuscularly: kenacort 80 mg once intramuscularly, or depomedrol 120 mg once intramuscularly. Prednisone scheme: Week 1–4 15 mg a day. Week 5–6: 10 mg a day. Week 7–8: 5 mg a day. Week: 9–10: 2.5 mg a day. Etanercept: 50 mg once a week subcutaneously. Adalumimab: 40 mg once every two weeks subcutaneously. Rituximab: 1 gram intravenously, repeated after two weeks. Leflunomide: 20 mg once daily.

Figure 2

Medication strategies in the intermediate probability group. Dosages: see figure 1 legend.

Figure 3

Medication strategies in the low-probability group. Dosages: see figure 1 legend. NSAID: Naproxen 1000 mg/day.