M.E.J.L. Hulscher

Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome

OBJECTIVES Tight control studies including regular assessments of disease activity have shown that this approach has beneficial effects on disease activity, disability and joint damage in treating RA patients. Some of these studies included tight control with protocolized treatment, while others applied tight control without protocolized treatment. The aim of this study was to compare the effects of tight control with usual care and to compare the effects of tight control studies with and without protocolized treatment adjustments. METHODS A systematic literature search was performed to identify clinical trials in RA that evaluated tight control strategies in comparison with usual care. Two types of study were compared: (i) those using disease activity monitoring with protocolized treatment adjustments, and (ii) those using disease activity monitoring without protocolized treatment adjustments. The databases PubMed and Cochrane were searched from 1995 up to 2009. Primary outcome measure was the mean change in the 28-joint DAS (DAS-28), which was used in a random-effects meta-analysis. RESULTS Six controlled trials regarding tight control in RA patients were included in the meta-analysis. In all trials, patients treated in the tight control arms had significantly higher DAS-28 responses than patients treated according to usual care [weighted mean difference (WMD) = 0.59, P < 0.001]. Moreover, tight control was significantly more effective (P < 0.001) by means of protocolized treatment adjustments (WMD = 0.97) compared with non-protocolized monitoring of disease activity (WMD = 0.25). CONCLUSION Tight control in RA resulted in significantly better clinical outcomes than usual care. It is suggested but not proved that tight control with protocolized treatment adjustments is more beneficial than if no such protocol is used.

Development of quality indicators for monitoring of the disease course in rheumatoid arthritis

Objectives: To suppress rheumatoid arthritis (RA) patients’ disease activity, it should be periodically measured and patients should be treated on the basis of the disease activity outcomes. Insight into the actual care, by using quality indicators, is the first step in achieving optimal care. The objective of this study was to develop a set of quality indicators to evaluate RA disease course monitoring of rheumatologists in daily clinical practice. Methods: A RAND-modified Delphi method in a five-step procedure was applied: a literature search for quality indicators and recommendations about disease course monitoring; a first questionnaire round; a consensus meeting; a second questionnaire round and drawing up the final set. Results: The systematic procedure resulted in the development of 18 quality indicators: 10 process, five structure and three outcome indicators that describe seven domains of disease course monitoring: schedule follow-up visits; measure disease activity; functional impairment; structural damage; change medication; preconditions for measuring disease activity and outcome measures in terms of disease activity. Conclusions: This quality indicator set can be used to assess the quality of disease course monitoring of rheumatologists in daily clinical practice, and to determine for which aspects of disease course monitoring rheumatologists perform well, or where there is room for improvement. This information can be used to improve the quality of disease course monitoring.

Factors influencing the prescription of intensive combination treatment strategies for early rheumatoid arthritis

Objectives: Despite the availability and demonstrated effectiveness of intensive combination treatment strategies (ICTS) for early rheumatoid arthritis (RA), a discrepancy seems to exist between theoretical evidence and actual prescription in daily practice. The purpose of this study was to explore and identify the factors influencing the prescription of ICTS. Method: This study involved rheumatologists and nurses participating in the Care for Rheumatoid Arthritis (CareRA) trial, a multicentre randomized controlled trial (RCT) comparing different ICTS for early RA with conventional disease-modifying anti-rheumatic drugs (DMARDs) plus step-down glucocorticoids (GCs). A qualitative study was carried out using individual semi-structured interviews. Each interview was recorded, transcribed literally, and analysed thematically. In addition, observations at outpatient clinics were used to clarify the interpretation of the results. Results: We interviewed 26 rheumatologists and six nurses and observed five outpatient visits. Identified facilitators included available scientific evidence, personal faith in treatment strategy, staff support, and low treatment costs. Rheumatologists had no doubts about the value of methotrexate (MTX) but some questioned the value of combination strategy, others the effectiveness and/or the dosage of individual compounds. Additional barriers for prescribing ICTS included need for patient education, fear for patients’ preconceptions, concerns about applicability to the individual patient, difficulties with breaking routine, interference with organizational structures and processes, time constraints, and lack of financial support. Conclusions: A heterogeneous set of factors highlights the complexity of prescribing ICTS for early RA in daily clinical practice. Future improvement strategies should stimulate the facilitators while at the same time addressing the barriers. The generalizability of these findings to other health care systems needs further examination.

THU0207 Finding the optimal treatment strategy for disease activity-guided dose reduction of adalimumab and etanercept in rheumatoid arthritis: a modelling study

Background Several studies have shown that disease activity-guided dose reduction without deterioration of disease activity is possible, while saving costs in patients with stable and low disease activity.(1 Despite these positive results, questions remain on the optimal tapering strategy. Different strategies are conceivable, with varying results regarding the balance between number of flares, utilities and costs. Objectives The objective of this study was to investigate the most cost-effective TNFi dose reduction strategy for RA patients using a modelling design. Methods In a cost-utility analysis using Markov modelling based on data from the DRESS study, STRASS study, and the RA Nijmegen cohort, the following strategies were tested against continuation: 1. Four-step DRESS tapering (figure 1: 100%–67%–50%–0%); 2. Tapering with an extra dosage step of 33%; 3. Tapering without withdrawal; 4. Use of a stricter flare criterion (DAS >2.6); and 5. Use of a predictor (biomarker: 80% specific, 80% sensitive, €100 per test) for successful tapering. Scenario analyses with 30% and 50% drug price discount and no discounting were executed. Also, it was examined how well a biomarker should be able to predict to become cost-effective compared to the other strategies. Results All examined tapering strategies were found to be cost saving but yielded more short-lived flares compared to continuation (table 1). The change in utilities was minimal and not clinically relevant. Strategy 1 was cost-effective compared to all other strategies (highest incremental Net Monetary Benefit (iNMB)). However, there was a large overlap in credible intervals, especially between strategy 1 and 2. Scenario analyses showed that 50% reduction of drug prices would result in the highest iNMB for strategy 2. A biomarker only becomes cost-effective when it has a sensitivity and specificity of at least 86%. Data is mean values per patient over 1.5 years (95% credible intervals). *Stricter flare criterion (DAS28 >2.6). ** NMB=QALYs * WTP/WTA – costs; iNMBs are given at a WTP/WTA of €80 000. Conclusions All dose reduction strategies dominated the continuation strategy regarding cost-effectiveness. Because our study showed a comparable iNMB for tapering in four or five steps, we recommend a choice between these strategies, based on shared decision making. Reference [1] Nam JL, et al. Ann Rheum Dis2017Jun;76(6):1113–1136. Disclosure of Interest L. Verhoef: None declared, D. Bos: None declared, C. van den Ende: None declared, F. van den Hoogen Consultant for: Biogen, Celltrion and Mundipharma, B. Fautrel: None declared, M. Hulscher: None declared, W. Kievit: None declared, A. den Broeder: None declaredAbstract THU0207 – Table 1 Main outcomes of each strategy Outcome measure 0. Continuation (comparator) 1. DRESS strategy (four-step tapering) 2. Five-step tapering 3. No withdrawal 4. Stricter flare criterion 5. Predictor Costs (€) 21 071(20,563–21,383 13 198(12,469–13,988 13 794(13,150–14,496 14 266(13,685–14,856 15 943(15,115–16,793 14 327(13,281–15,359 QALYs 1.182(1.165–1.199) 1.177(1.160–1.193) 1.181(1.165–1.197) 1.182(1.166–1.198) 1.189(1.173–1.205) 1.185(1.168–1.200) Mean number of short-lived flares 0.53(0.35–0.73) 0.97(0.83–1.12) 0.74(0.58–0.93) 0.69(0.52–0.87) 2.08*(1.80–2.41) 0.55(0.53–0.56) iNMB** - 7434(6,514–8,302 7176(6,307–8,000 6798(5,977–7,539 5650(3,598–7,625 6938(5,863–8,040

FRI0586 The Effects of An Educational Meeting and Subsequent Computer Reminders on The Ordering of Laboratory Tests by Rheumatologists: An Interrupted Time Series Analysis

Background Excessive use of diagnostic laboratory does not only constitute a waste of resources, it may also result in an increased rate of false positives which may lead to further unnecessary testing, unnecessary treatment, and increased anxiety in both patients and physicians. Still, many clinicians order irrelevant laboratory tests despite the available information about unnecessary test utilization. Objectives To examine the effects of an educational meeting and subsequent computer reminders on the number of ordered laboratory tests. Methods Using interrupted time series analysis we assessed whether trends in the number of laboratory tests ordered by rheumatologists between September 2012 and September 2015 at the Sint Maartenskliniek (the Netherlands) changed following an educational meeting (September 2013) and introduction of computer reminders into the Computerized Physician Order Entry System (July 2014). The reminders functioned as follows: whenever a clinician tried to order one of the intervention tests a pop-up message appeared explaining in which specific rheumatology-related situation the test was indicated or not, and asked for a reason for ordering the test. The analyses were done for the set of tests on which both interventions had focussed (intervention tests; complement, cryoglobulins, immunoglobins, M protein) and for a set of tests unrelated to the interventions, included as a control (alanine transferase, anti-cyclic citrullinated peptide, C-reactive protein, creatine, haemoglobin, leukocytes, mean corpuscular volume, rheumatoid factor and thrombocytes). Secondary outcomes were the percentage of abnormal intervention test results and the percentage of valid reasons provided with the intervention test orders, as judged by two experts. Results At study start 101 intervention tests and 7660 control tests were ordered per month by the rheumatologists. After the educational meeting both the level and trend of ordered intervention and control tests did not change significantly. After implementation of the reminders, the level of ordered intervention tests decreased with 85 tests (95%>CI -133 to -37, p<0.01), though the trend did not change significantly (1.06, 95%>CI -6.2 to 8.3, p=0.77). The level and trend of control tests did not change following the introduction of reminders. Of the reasons given for ordering the intervention tests after the introduction of reminders, only 34% was deemed valid by two experts. Interestingly, the percentage of abnormal results in the intervention tests did not change significantly after the introduction of the reminders (17.4% before introduction of reminders compared 18.4% after introduction (p=0.73)), nor was it different in those cases were the reason for ordering the test was judged as valid (18.8%). Conclusions The educational meeting alone was not effective in decreasing the number of ordered intervention tests, but subsequent introduction of computer reminders did result in a large decrease of those tests. Therefore, we recommend using computer reminders additionally to education if reduction of inappropriate test use is aimed for. Disclosure of Interest None declared

AB0849-HPR Patients’ perceptions and experiences related to intensive combination treatment strategies for early rheumatoid arthritis: a qualitative study

Background In the current recommendations for early rheumatoid arthritis (RA) management, the focus is set to achieve clinical remission as soon as possible with an early and intensive treatment. Our previous research indicated that rheumatologists’ perception of patients’ concerns at initation influenced their prescription behaviour of intensive combination treatment strategies (ICTS). Understanding patients’ perspectives on ICTS is necessary to identify opportunities to improve early RA care. Objectives To explore early RA patients’ perceptions of and experiences with ICTS at an early stage in their care process. Methods A qualitative study was carried out using individual semi-structured interviews with early RA patients who agreed to ICTS within the CareRA trial four months earlier. The CareRA trial is a multicentre RCT across Flanders comparing different ICTS for early RA with conventional DMARDs plus step-down glucocorticoids. Data saturation was reached after 26 interviews. Each interview was recorded, transcribed literally and thematically coded using the constant comparative method. Results Patients indicated that when ICTS was advised they were afraid of the side-effects in the short term and of the health consequences of the treatment in the long-term. At the same time, many patients reported that it was confronting to hear what the treatment entailed just after being burdened with the diagnosis of RA. Motivations for the decision to agree with intensive treatment initiation were faith in the treatment and healthcare team and knowing the medication would be phased out eventually. Patients who initiated ICTS reported that their negative feelings disappeared and that ICTS was easily incorporated into their daily life. Conclusions Despite their concerns when ICTS was advised, most patients had positive experiences with ICTS once initiated. The study findings may be helpful for healthcare professionals to understand patients’ concerns and to support them in their decision-making process to initiate ICTS. References Meyfroidt S, van Hulst L, De Cock D, Van der Elst K, Joly J, Westhovens R, Hulscher M, and Verschueren P. (2012) Intensive combination treatment strategies for early rheumatoid arthritis: a qualitative study of rheumatologists’ and nurses’ experiences and views. Manuscript submitted for publication. Acknowledgements The authors thank the healthcare professionals and their patients for their participation in this study. Disclosure of Interest None Declared