Objectives To evaluate the 2 year clinical outcomes of remission steered therapy in early arthritis patients in the IMPROVED study.
Methods 610 patients with early rheumatoid or undifferentiated arthritis (RA or UA) started with methotrexate (MTX) 25mg/wk and prednisone 60mg/day tapered to 7.5mg/day in 7 weeks. Patients who achieved a Disease Activity Score (DAS) <1.6 after 4 months (early remission) tapered prednisone to 0 and when still in remission at 8 months, tapered MTX to 0. Patients not in early remission were randomized to either MTX 25mg/wk plus hydroxychloroquine 400mg/day, sulphasalazine 2000mg/day and prednisone 7.5mg/day (arm 1) or to adalimumab 40mg/2weeks and MTX 25mg/wk (arm 2). During follow-up medication was increased or switched in case of no remission and tapered or stopped in case of remission. Proportions of (drug free) remission (DFR) after 2 years were analyzed for the different treatment strategies, patients with RA or UA and patients positive or negative for anti-citrullinated protein antibodies (ACPA).
Results 387 patients achieved early remission and 221 patients did not; 83 patients were randomized to arm 1 and 78 to arm 2, and 50 did not follow the protocol. After 2 years, 49% (301/610) were in remission and 21% (131/610) in drug free remission (DFR). Of the early remission patients, 62% (241/387) were in remission after 2 years, compared to 27% (22/83) in arm 1 and 31% (24/78) in arm 2, and 28% (110/387) were in DFR after 2 years compared to 8% (7/83) in arm 1 and 9% (7/78) in arm 2. After 2 years, patients in arms 1 and 2 had a higher tender joint count (median (IQR) arm 1: 3 (1-7) and arm 2: 3 (1-6)) than patients in the early remission group (0 (0-2)). CRP (median (IQR) arm 1: 4 (3-9), arm 2: 4 (3-6), early remission: 3 (3-6)), BSE (median (IQR) arm 1: 11 (6-20), arm 2: 9 (6-17), early remission: 8 (4-16)), and swollen joint count (median (IQR) arm 1: 1 (0-2), arm 2: 0 (0-2), early remission: 0 (0-1)) were comparable. Patients treated outside the protocol had similar results as patients in arm 1 and 2. There were no significant differences in remission rates between patients with RA and UA or between ACPA positive and ACPA negative patients, but for achieving DFR at 2 years absence of ACPA was an independent predictor (Odds Ratio (OR) 1.64 95%CI 1.0-2.6) (OR for UA 1.56 95%CI (0.9-2.7)).
Conclusions After 2 years of remission steered treatment, 49% of the patients with early RA and UA were in remission. Patients who were in remission after 4 months most often achieved (drug free) remission at 2 years. For those who did not achieve early remission, 2 treatment strategies perform similar probably due to remission steered treatment adjustments and result in less but similar (drug free) remission rates. These results suggest that there is a window of opportunity to aim at remission with antirheumatic therapy. In addition, it appears that achieving DFR is linked to absence of ACPA and not achieving remission largely depends on joint pain.
Disclosure of Interest None Declared