A randomized double-blind placebo-controlled study on addition of 6-month induction therapy with infliximab to triple DMARD plus prednisolone therapy in patients with early active rheumatoid arthritis: High remission rates and no joint destruction during first 2 years. The neo-raco study

Background: We have previously reported a 37% remission rate in patients with early rheumatoid arthritis (RA) treated with a combination therapy with 3 DMARDs and prednisolone (the FIN-RACo treatment strategy). Here we set out to study the contribution of infliximab (INFL) added as an induction therapy during the first 6 months in patients with early RA treated with FIN-RACo strategy by using full doses of methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ) and prednisolone (PRED) (= COMBI) compared with COMBI+ placebo (PLA). Here we report the 2- year clinical and radiological outcome. Methods: In this multicenter (15 centres), randomized, double-blind, parallel-group trial, we enrolled 100 patients aged <65 y with early RA (symptoms ≤ 12 mo), active (≥ 6 swollen and ≥ 6 tender joints, early morning stiffness ≥ 45 min and/or ESR ≥ 30 mm/h and/or CRP520 mg/l). COMBI was started in all patients targeted to remission. The patients were randomized in a double-blind way to receive INFL (3 mg/kg) or PLA at weeks 4 6, 10, 18 and 26. Doses of MTX (max 25 mg) and SSZ (max 2 g) were individually tailored to reach remission. Doses of HCQ (35 mg/ kg/week) and PRED (7.5 mg/day) were constant. Remission was assessed by the strict ACR criteria (no swollen or tender joints), and by DAS28. In cases of inefficacy/intolerability, the DMARDs were substituted, but it was obligatory to use 3 DMARDs and PRED. Local glucocorticoid injections were allowed. Primary outcomes were proportion of patients in remission and radiology. Results: At entry, the mean age (SD) of the patients was 46 y (10), median duration (IQR) of symptoms 4 mo (2, 6), 68% were RF+, and 67% female. Mean number (SD) of swollen joints was 15 (6), tender joints 20 (10), ESR 33 (22) mm/h and HAQ 1.0 (0.7). At 24 months, 62% of the patients were in ACR remission (COMBI+PLA 53%, COMBI+INFL 70%). Remission rate over time was higher in the COMBI+INFL group [OR=1.97 (95% CI.: 1.03 to 3.74), p=0.04]. By DAS28 criteria, 85% of the patients were in remission (COMBI+PLA 82%, COMBI+INFL 88%, n.s., over 3-24 months more often in COMBI+INFL (p=0.047). The median total Sharp score (TSS) was 0 in both groups at baseline. At 24 months, 41% of patients in COMBI+PLA and 54% in COMBI+INFL had 0 score. A mean (95% CI) change of TSS from baseline to 24 months was 1.4 (0.8 to 2.2) in COMBI+PLA and -0.2 (-1.1 to 0.4) in COMBI+INFL (p=0.005). Conclusions: Intensified use of the FIN-RACo combination strategy in patients with early active RA induced strict remission by ACR criteria in 62% and by DAS28criteria in 82% of the patients. Radiological changes were rare during the study. Adding INFL during the first 6 months reflected in higher frequency of remissions and prevention of radiological progression during 2 years.