Intensive therapy and remissions in rheumatoid arthritis: a systematic review.

BACKGROUND: We systematically reviewed the effectiveness of intensive treatment strategies in achieving remission in patients with both early and established Rheumatoid Arthritis (RA). METHODS: A systematic literature review and meta-analysis evaluated trials and comparative studies reporting remission in RA patients treated intensively with disease modifying anti-rheumatic drugs (DMARDs), biologics and Janus Kinase (JAK) inhibitors. Analysis used RevMan 5.3 to report relative risks (RR) in random effects models with 95% confidence intervals (CI). RESULTS: We identified 928 publications: 53 studies were included (48 superiority studies; 6 head-to-head trials). In the superiority studies 3013/11259 patients achieved remission with intensive treatment compared with 1211/8493 of controls. Analysis of the 53 comparisons showed a significant benefit for intensive treatment (RR 2.23; 95% CI 1.90, 2.61). Intensive treatment increased remissions in both early RA (23 comparisons; RR 1.56; 1.38, 1.76) and established RA (29 comparisons RR 4.21, 2.92, 6.07). All intensive strategies (combination DMARDs, biologics, JAK inhibitors) increased remissions. In the 6 head-to-head trials 317/787 patients achieved remission with biologics compared with 229/671 of patients receiving combination DMARD therapies and there was no difference between treatment strategies (RR 1.06; 0.93. 1.21). There were differences in the frequency of remissions between early and established RA. In early RA the frequency of remissions with active treatment was 49% compared with 34% in controls. In established RA the frequency of remissions with active treatment was 19% compared with 6% in controls. CONCLUSIONS: Intensive treatment with combination DMARDs, biologics or JAK inhibitors increases the frequency of remission compared to control non-intensive strategies. The benefits are seen in both early and established RA.CH is a South Thames Rheumatology Specialist Registrar working in Kings College Hospital. FI is supported by the Academic department of Rheumatology. DLS is supported by TITRATE study programme. The TITRATE study is funded by the National Institute for Health Research (NIHR) as one of its Programme Grants For Applied Research (Grant Reference Number: RP-PG-0610-10066; Programme Title: Treatment Intensities and Targets in Rheumatoid Arthritis Therapy: Integrating Patients’ And Clinicians’ Views – The TITRATE Programme

Intensive management for moderate rheumatoid arthritis: a qualitative study of patients' and practitioners' views

Background: The TITRATE trial seeks to test whether intensive management is valuable in achieving disease remission in moderately active rheumatoid arthritis. Intensive management is a complex intervention consisting of: 1) 12 x monthly appointments, 2) tailored 'treatment support' based on motivational interviewing techniques, 3) optimised medication (including the opportunity for biologics), 4) provision of a Patient Handbook, and 5) shared treatment planning. This study aims to understand: a) patients' and practitioners' views on the feasibility and acceptability of intensive management, and b) patients' and practitioners' experience of receiving/providing intensive management. Methods: A qualitative study, nested within a randomised controlled trial. Participants were patients (n = 15) in the intensive management arm of the trial and rheumatology practitioners (n = 16) providing the intensive management intervention, from 18/42 clinics across England. Data were collected via semi-structured interviews and analysed using thematic analysis and iterative categorization. Results: Monthly appointments were largely acceptable to both groups who cited several treatment benefits (e.g. regular review of medication, practitioners built close relationships with patients). Practitioners were 'fairly confident' using the motivational interviewing techniques. Learning to pace was the most commonly reported self-management technique that patients and healthcare professionals worked on together, followed by gaining control over pain and fatigue. Practitioners liked having the option to offer biologics to patients with moderate RA. Most patients found the optimised medication (following monthly joint assessment) helpful and side-effects experienced were resolved. Variation existed in the extent to which patients engaged with the Patient Handbook and shared treatment planning, with those who did engage doing so in the early stages. Conclusions: Feedback from patient participants about the intensive management intervention was positive. They found increased medication helpful. Continuity of care with the same healthcare professional at regular intensive management sessions, and the treatment support provided, were highly rated. Feedback from practitioners indicated that intensive management training is feasible. Evidence from the interviews showed that some practitioners applied motivational interviewing techniques during standard care appointments and they would like the opportunity to address lifestyle issues with patients

Intensive therapy and remissions in rheumatoid arthritis: a systematic review

Abstract Background We systematically reviewed the effectiveness of intensive treatment strategies in achieving remission in patients with both early and established Rheumatoid Arthritis (RA). Methods A systematic literature review and meta-analysis evaluated trials and comparative studies reporting remission in RA patients treated intensively with disease modifying anti-rheumatic drugs (DMARDs), biologics and Janus Kinase (JAK) inhibitors. Analysis used RevMan 5.3 to report relative risks (RR) in random effects models with 95% confidence intervals (CI). Results We identified 928 publications: 53 studies were included (48 superiority studies; 6 head-to-head trials). In the superiority studies 3013/11259 patients achieved remission with intensive treatment compared with 1211/8493 of controls. Analysis of the 53 comparisons showed a significant benefit for intensive treatment (RR 2.23; 95% CI 1.90, 2.61). Intensive treatment increased remissions in both early RA (23 comparisons; RR 1.56; 1.38, 1.76) and established RA (29 comparisons RR 4.21, 2.92, 6.07). All intensive strategies (combination DMARDs, biologics, JAK inhibitors) increased remissions. In the 6 head-to-head trials 317/787 patients achieved remission with biologics compared with 229/671 of patients receiving combination DMARD therapies and there was no difference between treatment strategies (RR 1.06; 0.93. 1.21). There were differences in the frequency of remissions between early and established RA. In early RA the frequency of remissions with active treatment was 49% compared with 34% in controls. In established RA the frequency of remissions with active treatment was 19% compared with 6% in controls. Conclusions Intensive treatment with combination DMARDs, biologics or JAK inhibitors increases the frequency of remission compared to control non-intensive strategies. The benefits are seen in both early and established RA

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.MRC Funding: MC_UP_1302/3 NIHR Funding: RP-PG-0610-1006

Real world long-term impact of intensive treatment on disease activity, disability and health-related quality of life in rheumatoid arthritis.

Abstract Background The emphasis on treating rheumatoid arthritis (RA) intensively reduces disease activity but its impact in routine care is uncertain. We evaluated temporal changes in disease activities and outcomes in a 10-year prospective observational cohort study of patients in routine care at one unit. Methods The Guy’s and St Thomas’ RA cohort was established in 2005. It involved most RA patients managed in this hospital. Clinical diagnoses of RA were made by rheumatologists. Patients were seen regularly in routine care. Each visit included measurement of disease activity scores for 28 joints (DAS28), health assessment questionnaire scores (HAQ) and EuroQol scores. Patients received intensive treatments targeting DAS28 remission. Results In 1693 RA patients mean DAS28 scores fell from 2005 to 15 by 11% from 4.08 (95% CI: 3.91, 4.25) in 2005 to 3.64 (3.34, 3.78); these falls were highly significant (p  5.1) decreased (25% in 2005; 16% in 2015). In 752 patients seen at least annually for 3 years, persisting remission (68 patients) and intermittent remission (376 patients) were associated with less disability and better health related quality of life. Over time biologic use increased, but they were used infrequently in patients in persistent remission. Conclusions Over 10 years an intensive management strategy in a routine practice setting increased combination DMARD and biologic use: disease activity levels declined; this association is in keeping with a causal relationship. Patients who achieved remission, even transiently, had better functional outcomes than patients never achieving remission