The TITRATE study is designed to investigate whether intensive management of RA leads to a greater number of remissions at 12 months, in addition to examining levels of disability, quality of life and acceptability, and cost-effectiveness.
In the United Kingdom, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis (RA) who have intermediate disease activity. In order to address the lack of treatment consensus, a new study, TITRATE, is being conducted in over 40 hospitals in the United Kingdom. TITRATE is designed to investigate whether intensive management of RA leads to a greater number of remissions at 12 months, in addition to examining levels of disability, quality of life and acceptability, and cost-effectiveness.
The study comprises 398 patients with established RA. Researchers enrolled patients with intermediate disease activity, defined as a disease activity score for 28 joints (DAS28) assessed using erythrocyte sedimentation rate (ESR) of 3.2 to 5.1 with at least 3 active joints, and the use of 1 or more disease-modifying anti-rheumatic drugs (dMARD).
TITRATE will be a 12-month, pragmatic, randomized, open-label, 2-arm, parallel-group, multicenter trial. Participants in the study are randomly selected to receive either intensive management or the current standard of care.
Intensive management will involve monthly clinical reviews with a specialist health practitioner, and drug treatment will be individualized and optimized based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue, and adherence.
Standard care will follow the standard local pathways in the United Kingdom in line with current guidelines from the National Institute for Health and Clinical Excellence (NICE). The patients will be assessed during enrollment and at 6 and 12 months through questionnaires and clinical evaluation.
The primary outcome measure of the study is the number of patients in each treatment arm who achieve remission as measured by DAS28-ESR. In addition, running concurrently with the trial is a cost-utility analysis to estimate the incremental cost per quality-adjusted life year (QALY) of intense management compared to that of standard care. This analysis is being conducted in line with the NICE Guide to the Methods of Technology Appraisal.
In preparing for the start of the trial, researchers noted 3 potential problems within the patient population selected for study: the potential heterogeneity of this group of patients (including the potential presence of fibromyalgic RA that may not respond greatly to dMARDs), whether complete remission is the optimal target of the study (versus low disease activity), and the variability of experience among RA nurses in the United Kingdom due to the absence of accredited national training programs.
Researchers anticipate that, when the results of TITRATE are available, they will be able to inform the National Health Service of the United Kingdom on how best to manage this group of patients as well as the benefits of delivering a more intensive management approach.
Martin N, Ibrahim F, Tom B, et al. Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomized controlled trial. Trials. 2017;18:591. doi.org/10.1186/s13063-017-2330-8.