Background Long term studies with treat-to-target therapy are essential to guide treatment strategies.
Objectives To compare clinical and radiographic outcomes of 4 treatment strategies in early rheumatoid arthritis (RA) patients after 10 years.
Methods The BeSt study enrolled 508 patients with early RA. Patients were randomized to: 1 sequential monotherapy, 2 step-up therapy, 3 initial combination with prednisone, 4 initial combination with infliximab. Treatment adjustments were based on 3-monthly disease activity score (DAS) measurements (DAS>2.4: next step; DAS≤2.4 for ≥6 months: taper to maintenance dose, next if DAS<1.6 for ≥6 months: stop last drug). Functional ability (Health Assessment Questionnaire, HAQ) over time was analyzed with a linear mixed model (LMM). Annual X-rays were scored ine one session by 2 blinded readers with the Sharp van der Heijde Score (SHS). SHS progression was categorized per year into “no” (<0.5), “little” (≥0.5 - ≤5) and “much” (>5) and analyzed over time with a generalized LMM.
Results 10 year follow-up was completed by 313 patients (62%). Drop-out rates were lowest in arm 4. Mean age of completers was 61 years and 67% were female. Mean (SD) DAS was 1.6 (0.8) and mean (SD) HAQ was 0.6 (0.6). 82% had a DAS≤2.4, 53% had a DAS<1.6, 15% were in drug-free remission (DFR) with a mean (median) duration of 52 (58) months. After 10 years, 38% were still on the initial treatment step, others had changed medication at least once. Toxicity was similar in all arms. Table 1 shows outcomes per treatment arm. The initial functional improvement achieved during year 1 was maintained during 10 years. Over time HAQ was significantly lower in arm 4 than in arm 2 (0.52 vs 0.70, p=0.03, other differences non-significant). Ten year progression rates were low in all arms. Over time, patients in arm 3 less often developed progression compared to arm 1 (p=0.03, other comparisons non-significant). If progression was present, estimates were 8, 11, 8 and 5 SHS progression in 10 years in arm 1 to 4, respectively.
Conclusions 10 year follow-up in the BeSt study shows the benefit of continued treat-to-target therapy, steering at low disease activity. After initial improvement functional ability remained stable. Of the completers, 53% and 15% were in DAS- and drug-free remission, respectively. Development of radiographic progression was comparable between groups, although more severe in initial monotherapy arms.
Disclosure of Interest : I. Markusse: None declared, L. Dirven: None declared, M. vd Broek: None declared, G. Akdemir: None declared, Y. Goekoop-Ruiterman: None declared, H. Han: None declared, P. Kerstens: None declared, W. Lems: None declared, T. Huizinga: None declared, C. Allaart Grant/research support: The study was designed by the investigators and supported by a government grant from the Dutch Insurance Companies, with additional funding from Schering-Plough B.V. and Janssen B.V. Data collection, trial management, data analysis and preparation of the manuscript were performed by the authors.