SAT0067 Further treatment intensifications in undifferentiated and rheumatoid arthritis patients already in low disease activity have limited benefit towards physical functioning
Authors: SA Bergstra, O Olivas, G Akdemir, N Riyazi, G Collee, JH Van Groenendael, RB Landewé, CF Allaart
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> It is recommended to optimize treatment as long as a predefined treatment target is not met, but should we aim at remission if patients are in low disease activity (LDA)? <h3>Objectives</h3> To assess if RA or undifferentiated arthritis (UA) patients who achieved LDA benefit with better functional ability from treatment intensification aimed at DAS remission. <h3>Methods</h3> In the IMPROVED study 610 patients with early RA (ACR 2010) or UA were "treated to target" aimed at DAS remission, assessed 4-monthly. Initial treatment was methotrexate (MTX) + tapered high dose prednisone. Patients with DAS≤1.6 tapered treatment. Patients with DAS&gt;1.6 were randomized to MTX + hydroxychloroquine + sulphasalazine + prednisone or to MTX + adalimumab. Over 5 years, patients with DAS&gt;1.6 were required to increase, change or restart medication. HAQ was measured 4-monthly. A linear mixed model analysis with random intercept was performed to test the relationship between changes in therapy and HAQ over time. Patients in LDA with DAS&gt;1.6 with and without (i.e. protocol violation) treatment change were compared. ΔHAQ and ΔDAS at each visit compared to the previous visit were calculated. We tested the interaction effect between change in treatment and follow-up time adjusted for possible confounders. <h3>Results</h3> Overall, over 5 years DAS (baseline mean (SD) 3.2 (1.7)) and HAQ (1.2 (0.7)) showed a statistically significant and clinically relevant decrease (ΔHAQ -0.59, 95% CI -0.61, -0.57; ΔDAS -1.77, 95% CI -1.79; -1.75). The number of patients in LDA per visit ranged from 88 to 146, of which 26% to 73% (increasing over time) had no treatment change due to protocol violations. We found a statistically significant but not clinically relevant effect of treatment change on ΔHAQ, corrected for baseline HAQ, age, gender and treatment arm (model 1, β -0.085, 95% CI -0.13, -0.044). When ΔDAS was added (model 2), the effect of treatment change was partly explained by ΔDAS and no longer statistically significant (β -0.022, 95% CI -0.060; 0.015). The effect of treatment intensification on HAQ improvement became less over time, as demonstrated by a statistically significant interaction between change in HAQ and time in follow-up in model 3 (β 0.0098, 95% CI 0.0010; 0.019) (table 1). <h3>Conclusions</h3> Treatment intensification in early RA or UA patients who have already achieved low disease activity is associated with a statistically significant decrease in HAQ, but not with a clinically meaningful improvement in functional ability. The effect on ΔHAQ decreased with increasing follow-up time. Therefore not remission or low disease activity, but good functional ability may be the optimal treatment target at which to steer treatment adjustments. These results suggest that, whereas remission may be the optimal goal, when patients in low disease activity have acceptably low HAQ, further treatment intensification may only have downsides such as side effects and costs. <h3>Disclosure of Interest</h3> None declared