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Abstract
Background The window of opportunity hypothesis suggests that early initiation of treatment targeted at remission in early arthritis patients may avoid chronicity of inflammation and may result in early drug-free remission (DFR).
Objectives To assess clinical outcomes of induction therapy followed by 5 years DAS-remission targeted therapy including rapid drug tapering strategies in early arthritis patients.
Methods The IMPROVED study included 610 early rheumatoid arthritis (RA, 2010 criteria) or undifferentiated arthritis (UA) patients starting with methotrexate (MTX) and tapered high dose of prednisone. Patients in early DAS-remission (ER) (disease activity score (DAS)<1.6 after 4 months) stopped prednisone and if remission persisted at t=8 months also MTX. Patients not in ER (DAS≥1.6) were randomized to MTX+sulfasalazine+hydroxychloroquine+low dose prednisone (arm 1) or MTX+adalimumab (arm 2), 50 patients were not randomized and were treated “outside of protocol” (OP). Four monthly treatment adjustments aimed at DAS<1.6; if DAS<1.6 taper/stop medication and if DAS≥1.6 restart/intensify medication. Percentages of patients in (drug free) DAS-remission after 5 years were compared between RA and UA patients and the different treatment strategies. Logistic regression analysis was used to identify predictive factors of DAS-remission and DFR after 5 years.
Results After 5 years mean±SD DAS decreased and functional ability improved in all treatment groups without differences between arm 1 and 2. 295/610 (48%) patients were in DAS-remission: 220/387 (57%) in the ER group, 31/83 (37%) in arm 1, 29/78 (37%) in arm 2 (p=0.768 arm 1 vs arm 2) and 15/50 (30%) in OP. 134/610 (22%) patients were in DFR: 105/387 (27%) in the ER group, 9/83 (11%) in arm 1, 12/78 (15%) in arm 2 (p=0.374 arm 1 vs arm 2) and 8/50 (16%) in OP. DAS-remission was achieved in similar percentages in RA and UA patients and autoantibody positive (+) vs negative (−) patients. More UA than RA patients were in DFR at year 5 (33% vs 19%, p<0.001), and the same was true for anti-citrullinated protein antibodies (ACPA)− vs ACPA+ patients (31% vs 15%, p<0.001) and rheumatoid factor (RF)− vs RF+ positive patients (28% vs 17%, p<0.001). Between anti-carbamylated antibodies (anti-CarP)+ and − patients there was no difference in DFR rates.
Predictors of DAS-remission were age (OR 0.97 (95% CI 0.96–0.99)), symptom duration (0.99 (0.98–0.99)), baseline tender joint count (0.95 (0.90–1.00)) and achieving ER (1.95 (1.23–3.10)) (figure). Predictors of DFR were symptom duration (0.99 (0.97–1.00) and ER (2.67 (1.48–4.84)). ACPA+ was mostly associated with less DFR.
Conclusions After 5 years of DAS-remission steered treatment, 48% of early RA and UA patients were in DAS-remission and 22% in DFR. Remission results were better for patients who achieved ER and who had a shorter symptom duration. Remission results were similar for RA and UA patients, randomization arms and autoantibody status, but more UA than RA patients and more autoantibody? than + patients were in DFR.
Disclosure of Interest G. Akdemir: None declared, L. Heimans: None declared, R. J. Goekoop: None declared, M. van Oosterhout: None declared, J. B. Harbers: None declared, C. Bijkerk: None declared, G. M. Steup-Beekman: None declared, L. Lard: None declared, P. B. J. de Sonnaville: None declared, B. A. M. Grillet: None declared, T. W. J. Huizinga: None declared, C. F. Allaart Grant/research support from: Year 1 of the IMPROVED study was sponsored by Abbott.