Objectives To evaluate the 1 year clinical outcomes of remission steered therapy in early arthritis, initially with methotrexate (MTX) and a tapered high dose of prednisone, in case of remission followed by tapering medication to zero, in case of no remission followed by randomization to two combination therapy strategies.
Methods IMPROVED is a multicenter clinical trial in 479 patients with early (symptoms <2 years) rheumatoid arthritis (RA 2010 criteria) and 131 patients with undifferentiated arthritis (UA) with a baseline Disease Activity Score (DAS) ≥1.6. All patients started with MTX 25mg/wk and prednisone 60mg/day tapered in 7 weeks to 7.5 mg/day. Patients in early remission (DAS <1.6 at t=4 months) tapered prednisone to zero and when still in remission at t=8 months, also tapered MTX to zero. Patients not in early remission were randomized either to a combination of MTX 25 mg/wk, hydroxychloroquine (HCQ) 400mg/day, sulphasalazine 2000mg/day (SSZ) and prednisone 7.5 mg/day (arm 1) or to adalimumab (ADA) 40mg/2weeks with MTX 25mg/wk (arm 2). If not in remission at t=8 months, patients in arm 1 switched to ADA+MTX and patients in arm 2 increased ADA to 40mg/week. Proportions of remission after one year follow up were compared between the different treatment strategies and between RA and UA patients.
Results After 4 months 375/610 (61%) patients achieved early remission (mean DAS (SD) 0.94 (0.36)) and 221/610 (36%) did not (mean DAS (SD) 2.45 (0.65), p<0.001). 161/610 patients (26%) were randomized, 83 to arm 1 and 78 to arm 2. In 66/610 (11%) patients the appropriate treatment step was not taken for various reasons. 12 patients were lost to follow up at t=4 months and 34 at t=1 year.
At t=4 months, 361/375 (96%) patients in early remission started tapering prednisone. At t=8 months 257/375 (68%) were still in remission on MTX monotherapy and 200/375 (53%) tapered MTX to zero. At t=1 year, 255/375 (68%) were in remission, 135/375 (36%) were in drug free remission.
At t=8 months 50/83 (60%) patients in arm 1 did not achieve remission and 31/83 (37%) switched to ADA+MTX. 47/78 (60%) patients in arm 2 did not achieve remission and 27/78 (35%) increased ADA. At t=1 year 21/83 (25%) patients in arm 1 and 32/78 (41%) in arm 2 were in remission (p<0.001). At t=1 year, 326/610 (53%) of the total study population were in remission: 252/479 (53%) RA patients and 70/131 (53%) UA patients.
Conclusions In patients with early RA or UA, early remission was achieved in 61% after initial treatment with MTX and a tapered high dose of prednisone. After one year of tapering treatment, 68% of those were still in remission and 36% in drug free remission. For those not in early remission, treatment with adalimumab resulted in more remission than a combination of DMARDs with low dose prednisone. Of the total study population 53% were in remission after one year, without a significant difference between early RA and UA patients.
Disclosure of Interest L. Heimans: None Declared, K. Wevers-de Boer Grant/Research support from: Abbott, K. Visser: None Declared, H. Ronday: None Declared, M. Oosterhout: None Declared, J. Harbers: None Declared, A. Peeters: None Declared, M. Westedt: None Declared, P. de Buck: None Declared, P. de Sonnaville: None Declared, B. Grillet: None Declared, T. Huizinga: None Declared, C. Allaart: None Declared
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