P88 Intensive management in moderate established rheumatoid arthritis: the titrate trial
Authors: Nikiphorou Elena , behalf of the on , Investigators TITRATE Programme 
Published: April 2020

Abstract

Background
Intensive management (IM) using treat-to-target principles has been shown to be effective in many trials of early rheumatoid arthritis (RA) in patients with high disease activity levels. There is no trial evidence that this approach benefits patients with moderately active RA - a dominant group in clinics. We tested the hypothesis that IM increases remission rates in established moderate RA patients (DAS28-ESR 3.2-5.1) receiving stable conventional synthetic disease modifying drugs (csDMARDs) compared to standard care (SC). IM comprised of: (a)monthly clinical assessments; (b)treat-to-target titrated medication including biologics; (c)psycho-social support delivered by trained nurses and other practitioners in motivational interviewing techniques.

Methods
A multicentre individually randomised trial compared IM (using combination DMARDs, depot steroid, biologics in non-responders, alongside supportive care using motivational interviewing techniques from trained nurses) to standard care (SC) patients receiving their usual clinical care. The primary outcome was 12-months remission by DAS28-ESR. Secondary outcomes: alternative remission assessments, disability via the health assessment questionnaire (HAQ), pain, fatigue, erosive progression and harm. Multivariable logistic and linear regression compared treatment approaches under intention-to-treat with multiple imputation for missing data. Cost, quality-adjusted life years (QALYs) from the EQ-5D-5L instrument mapped to EQ5D-3L, and incremental cost-effectiveness ratios (ICERs) were calculated, for within trial period.

Results
459 patients were screened and 335 randomised (168 IM; 167 SC); 303(90%) gave 12-month outcome measures. 139(83%) IM patients attended sessions. At 12 months IM significantly increased DAS28-ESR remissions compared to SC (32% vs 18%, p = 0.004) and other remission assessments. IM increased DAS28-ESR low disease activity (48% vs 32%, p = 0.005). Clinically important reductions in HAQ were seen in patients who achieved remission following IM (mean change at 12-months -0.40; 95% confidence intervals -0.57,-0.22), as well as improvements in both fatigue and pain. There was a minimal increase in erosive damage over 12 months in both groups. Serious adverse events (IM = 15 vs SC = 11) and other adverse events (114 IM,151 SC) were similar between groups. The base case ICER was £43,972 (€51,474) with a probability of being cost effective at £30,000/€35,000 of 0.17. The ICER fell to £29,363 (€24,384) after including patients’ personal costs and lost working time with a probability IM is cost-effective of 0.5 at UK willing to pay thresholds. This estimate was based on the historic prices of biologics and the probability is higher when current drug acquisition costs are applied.

Conclusion
IM by trained nurses in motivational interviewing techniques is clinically effective in moderate established RA, achieving more remission without increasing harm. It also gave clinically important improvement in pain and fatigue. There is a strong case to adopt this approach in routine practice as increasing remission rates may improve long-term outcomes, reduce future biologic prescribing and thereby improve long term cost-effectiveness.

Disclosures
E. Nikiphorou None.