Clinical and radiological outcomes of four disease activity driven treatment strategies: 8-year results of the best study

Objectives To compare clinical and radiological outcomes of 8 years targeted treatment with four treatment strategies in recent onset rheumatoid arthritis (RA) patients. Methods Patients (n=508) with recent onset RA were randomized to 4 treatment strategies: 1. sequential monotherapy, 2. step-up combination therapy, 3. initial combination with prednisone, 4. initial combination with infliximab. Treatment was DAS≤2.4 steered, with measurements every three months: DAS >2.4: next treatment step; DAS ≤2.4 during ≥6 months: taper to maintenance dose, next if DAS <1.6 during ≥6 months: stop anti-rheumatic treatment. Functional ability, measured with the Health Assessment Questionnaire (HAQ), was analyzed with a linear mixed model with time, treatment and time∗treatment as independent variables. Radiographs of baseline and years 1-8 were scored with the Sharp/vd Heijde Score (SHS), blinded for patient identity and in random order, to asses radiological damage progression. Results After 8 years, 347 patients were still in follow-up. A DAS ≤2.4 was achieved in 79% of these and 52% were in remission (DAS <1.6), without differences between the treatment groups (table). 18, 19, 17 and 15% of the patients in groups 1-4 were in drug-free remission with a median (mean) duration of 45 (39) months. Six patients lost and 12 patients achieved drug-free remission in year 8, while 8 patients with prolonged drug-free remission dropped out. After initial differences in years 1 and 2 between the 4 groups, yearly radiological damage progression rates were low and similar between all groups, reflecting the efficacy of DAS-steered therapy. Median (mean) total damage progression after 8 years was 3 (11) points SHS (n.s. between groups). Patients in sustained drug-free remission had a mean SHS progression of 0.1 (median (IQR) 0 (0-0.03)) per personyear drug-free. The initial improvement of function, which occurred earlier in groups 3 and 4 than in groups 1 and 2, was maintained without deterioration over 8 years in all groups. No differences were found for functional ability over time, with the exception of better functional ability in group 4, compared to group 2: mean

HAQ:

0.57 and 0.71. Toxicity was comparable between the groups. Conclusions After 8 years DAS≤2.4 targeted treatment, radiological damage is still very low and following initial improvement (earlier with initial combination therapy than with initial monotherapy), functional ability was maintained in all groups without deterioration over time. A stabilization of the percentages of patients in clinical remission and in drug-free remission was observed. (Table Presented).