Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background. Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis. Methods. A multicenter stratified randomized single-blind controlled trial is currently being performed in patients 18 years or older with recent-onset arthritis. Eight hundred ten patients are being stratified according to the likelihood of their developing persistent arthritis. In patients with a high probability of persistent arthritis, we will study combination Disease Modifying Antirheumatic Drug therapy compared to monotherapy methotrexate. In patients with an intermediate probability of persistent arthritis, we will study Disease Modifying Antirheumatic Drug of various intensities. In patients with a low probability, we will study non-steroidal anti-inflammatory drugs, hydroxychloroquine and a single dose of corticosteroids. If disease activity is not sufficiently reduced, treatment will be adjusted according to a step-up protocol. If remission is achieved for at least six months, medication will be tapered off. Patients will be followed up every three months over two years. Discussion. This is the first rheumatological study to base treatment in early arthritis on a prediction rule. Treatment will be stratified according to the probability of persistent arthritis, and different combinations of treatment per stratum will be evaluated. Treatment will be started early, and patients will not need to meet the ACR-criteria for rheumatoid arthritis. Trial registration. This trial has been registered in Current Controlled Trials with the ISRCTN26791028

Cost-utility analysis of tapering strategies of biologicals in rheumatoid arthritis patients in the Netherlands

OBJECTIVES: Current guidelines recommend tapering biological disease-modifying antirheumatoid drugs (bDMARDs) in rheumatoid arthritis (RA) if the disease is under control. However, guidelines on tapering are lacking. Assessing cost-effectiveness of different tapering strategies might provide broader input for creating guidelines on how to taper bDMARDs in patients with RA. The aim of this study is to evaluate the long-term cost-effectiveness from a societal perspective of bDMARD tapering strategies in Dutch patients with RA, namely 50% dose reduction (tapering), discontinuation and a 50% dose reduction followed by discontinuation (de-escalation).METHODS: Using a societal perspective, a Markov model with a life-time horizon of 30 years was used to simulate 3-monthly transitions between Disease Activity 28 (DAS28)-defined health states of remission (&lt;2.6), low disease activity (2.6&lt;DAS28 &lt;3.2) and medium-high disease activity (DAS28&gt;3.2). Transition probabilities were estimated through literature search and random effects pooling. Incremental costs, incremental quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits for each tapering strategy were compared with continuation. Deterministic, probabilistic sensitivity analyses and multiple scenario analyses were performed. RESULTS: After 30 years, the ICERs were €115 157/QALY lost, €74 226/QALY lost and €67 137/QALY lost for tapering, de-escalation and discontinuation, respectively; mainly driven by bDMARD cost savings and a 72.8% probability of a loss in quality of life. This corresponds to a 76.1%, 64.3% and 60.1% probability of tapering, de-escalation and discontinuation being cost-effective, provided a willingness-to-accept threshold of €50 000/QALY lost.CONCLUSIONS: Based on these analyses, the 50% tapering approach saved the highest cost per QALY lost.</p

No clear association between ultrasound remission and health status in rheumatoid arthritis patients in clinical remission

\u3cp\u3eObjectives: Although RA patients achieve clinical remission, risk of flare still exists. Given the association between US synovitis and increased risk of flare, it is of clinical interest whether these patients report a different health status. Therefore, our aim was to evaluate the frequency of US remission in RA patients in clinical remission and to compare the health status of RA patients in clinical remission with those who were also in US remission.\u3c/p\u3e\u3cp\u3eMethods: In a prospective study, we included 89 RA patients (aged &gt;17 years) treated with a synthetic DMARD and a TNF inhibitor who were in remission (DAS in 44 joints ⩽2.4 and swollen joint count ⩽1). Demographic characteristics, swollen and tender joints, laboratory variables, US (MCP2-5, PIP2-5, wrists and MTP2-5) and patient-reported outcomes (general health, functional ability, fatigue, depression and anxiety, pain and morning stiffness) were recorded at two consecutive visits (3 months apart). US remission was defined as grey scale grade ⩽1 and power Doppler = 0.\u3c/p\u3e\u3cp\u3eResults: At visit 1, 39% of patients were in US remission. At visit 2, 32% of patients were in US remission. At visit 1, functional ability (HAQ) was scored lower by patients in US remission (P = 0.029). At visit 2, HAQ scores were similar (P = 0.928). At visit 2, Hospital Anxiety and Depression Scale anxiety score and visual analog scale pain were significantly higher in patients in US remission. Similar levels were found for the other patient-reported outcomes.\u3c/p\u3e\u3cp\u3eConclusion: One-third of RA patients in clinical remission were in US remission. In our study population, we could not find a clear association between health status of RA patients and being in US remission.\u3c/p\u3

Performance of screening tools for psoriatic arthritis:a cross-sectional study in primary care

\u3cp\u3eObjective. To compare the screening performance of the Psoriasis Epidemiology Screening Tool (PEST), Psoriatic Arthritis Screening and Evaluation (PASE) and Early Arthritis for Psoriatic Patients (EARP) questionnaires for detecting PsA among psoriasis patients in a primary care setting. Methods. In a cross-sectional study, 473 primary care psoriasis patients at risk for PsA completed the PEST, PASE and EARP questionnaires and were clinically evaluated by a trained research nurse. A PsA case was defined by a rheumatologist according to the CASPAR criteria. Sensitivity and specificity were determined for the PEST and EARP cut-offs (53) and the PASE cut-offs (544 and547). Results. PsA was diagnosed in 53 patients. The PEST had a sensitivity of 0.68 and a specificity of 0.71. The PASE was validated for two different cut-offs. The cut-offof 47 led to a sensitivity of 0.59 and a specificity of 0.66, whereas the lower cut-offof 44 led to a sensitivity of 0.66 and a specificity of 0.57. For the EARP we found a sensitivity of 0.87 with a specificity of 0.34. Conclusion. The PEST questionnaire has the most favourable trade-offbetween sensitivity and specificity to screen for PsA. However, as the prevalence of psoriasis and PsA is fairly low in primary care, screening only psoriasis patients with musculoskeletal complaints may be a better allocation of resources.\u3c/p\u3