Urinary methotrexate dosage in rheumatoid arthritis, in patients treated for at least 6 months: a potential marker of adherence.

OBJECTIVES: Non-adherence to rheumatoid arthritis (RA) treatments must be identified. A methotrexate (MTX) urinary dosage (METU) was recently developed. The aim of our study was to assess adherence to MTX in RA using METU in real-life conditions and to compare it with indirect adherence measurement technics. METHODS: We performed a cross-sectional study at Reims University Hospital. We included over 18-year-old patients with RA treated by MTX for more than 6 months. Patients were invited to complete demographic, clinical and psychological questionnaires and adherence measurement technics (Compliance Questionnaire of Rheumatology (CQR) and Medication Possession Ratio (MPR)). A urinary sample was collected to measure MTX and information about tolerance was evaluated through Methotrexate Intolerance Severity Score. RESULTS: 84 patients were included, 26 using oral MTX, 58 subcutaneous (SC) MTX. Among them, 73% were female, mean age was 61.5 years, MTX mean dose was 15 mg/week and 61.9% were treated by biological DMARDs (Disease Modifying Antirheumatic Drugs). 77 patients (91.7%) were adherent to treatment according to METU, whereas MPR and CQR reported less adherence (69.5% and 61.9%, respectively). MPR and METU were not significantly different in SC MTX users (p=0.059). Non-adherent patients had a higher number of tender joints and C reactive protein value (p<0.05). CONCLUSION: This is the first largest study evaluating MTX adherence in patients with RA using a urinary dosage. We identified that indirect adherence measurements did not reflect real-life adherence. It would be appreciable to realise METU, in a new study, in patients with RA with unexplained response to treatment, to consider it before escalating therapeutic strategy.

"The least significant change on bone mineral density scan increased in patients with higher degrees of obesity".

BACKGROUND: The least significant change (LSC) threshold of 0.03 g/cm² is used to interpret bone mineral density (BMD) scans in the general population. Our working hypothesis was that the current LSC threshold would not be applicable in obese populations. AIMS: The aim of this study was to calculate the LSC in an obese population. METHODS: We performed an interventional study among 120 obesity patients, in whom two measurements of BMD were performed at 3 sites. Pairs of measures were used to calculate the LSC, using the Bland and Altman method. RESULTS: We calculated that the LSC was 0.046 g/cm² at the lumbar spine, 0.069 g/cm² at the femoral neck, and 0.06 g/cm² at the total hip. We also calculated the LSC for each class of obesity and observed an increase in LSC with increasing body mass index (BMI). We calculated a LSC of 0.05 g/cm² in patients with class 2 or class 3 obesity, whereas the LSC in patients with class 1 obesity is similar to the threshold used in the general population. DISCUSSION: In obese population, like BMD, LSC is higher than the threshold value of the general population, and increases with increasing BMI. CONCLUSION: LSC of 0.05 g/cm² could be used in clinical practice in patients with class 2 or 3 obesity. These findings should help to improve the interpretation of BMD scans in these patients and optimize their management. TRIAL REGISTRATION NUMBER: Comité de Protection des Personnes Ile-de France VII, France.

A new pharmacokinetic model of urinary methotrexate to assess adherence in rheumatoid arthritis.

BACKGROUND AND OBJECTIVES: Methotrexate (MTX) is the first-line therapy for rheumatoid arthritis (RA). While therapeutic adherence is essential to successful management, no objective MTX assay is currently available. Using population pharmacokinetic modelling (PopPK), our objective was to describe the urinary MTX (MTXu) kinetics in treated patients and to evaluate its abilities to assess the MTX-adherence. METHODS: The association between urinary methotrexate level and methotrexate administration was assessed using a generalized linear model. Then, a population pharmacokinetic model was developed based on data from 59 patients using with Monolix 2021. R2. Simulations were run to establish a reference kinetic profile and evaluate the proportion of samples predicted as true positives. RESULTS: Compared to the control group, multivariate analysis showed that MTXu was independently associated with methotrexate administration (p < 0.0001) with a sensitivity and specificity greater than 99%. The final PopPK model selected was a two-compartment model with first-order absorption and elimination. Internal and external validation of the model met all predefined criteria. When using an analytical assay with a LOQ equal to 1 nM, the proportion of samples predicted as true positives is over 90%, as a function of MTX dose (7.5-25 mg/week) and post-administration sampling days (1-7 days). CONCLUSION: We developed a pharmacokinetic model able to describe expected patterns of urinary methotrexate. This allowed us to propose a new objective test of MTX adherence, which could help in routine practice to differentiate patients who are truly unresponsive to methotrexate from those who are unresponsive because of non-adherence.

Prognostic Factors Related to Clinical Response in 210 Knees Treated by Platelet-Rich Plasma for Osteoarthritis.

Many studies have shown the effectiveness of platelet-rich plasma (PRP) in the treatment of knee osteoarthritis. We aimed to determine the factors associated with good or poor response to PRP injections in knee osteoarthritis. This was a prospective observational study. Patients with knee osteoarthritis were recruited from a university hospital. PRP was injected twice at a one-month interval. Pain was assessed on a visual analog scale (VAS) and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Radiographic stage was collected and defined according to the Kellgren-Lawrence classification. Patients were classified as responders if they met the OMERACT-OARSI criteria at 7 months. We included 210 knees. At 7 months, 43.8% were classified as responders. Total WOMAC and VAS were significantly improved between M0 and M7. Physical therapy and a heel-buttock distance >35 cm were the two criteria associated with poor response at M7 by multivariate analysis. Pain VAS at M7 appeared to be lower in patients with osteoarthritis for less than 24 months. No adverse effects were reported. PRP treatment in knee osteoarthritis appears to be well-tolerated and effective, even in patients who reacted poorly to hyaluronic acid. Response was not associated with radiographic stage.

Impact of Bariatric Surgery on Bone Mineral Density: Observational Study of 110 Patients Followed up in a Specialized Center for the Treatment of Obesity in France.

INTRODUCTION: Bariatric surgery is used to treat severe obesity. We aimed to investigate the incidence of clinically significant bone mineral density (BMD) loss at 6 and 12 months after bariatric surgery. METHODS: Observational study performed in a specialized center for the treatment of obesity at the University Hospital of Reims, France. Surface BMD was measured by dual x-ray absorptiometry (DEXA). A reduction of > 0.03 g/cm2 was considered clinically significant. RESULTS: A total of 110 patients were included. A clinically significant reduction in BMD was observed in 62.1% of patients at 6 months, and in 71.6% at 12 months after surgery. No case of osteoporosis was observed. There were four cases of osteopenia and one fracture post-surgery. BMD loss was related by univariate analysis to the reduction in body mass index (BMI) (p < 0.01), weight loss (p < 0.01), fat mass (p < 0.01), and lean mass (p < 0.01). Multivariable analysis found a significant association between the reduction in BMD and the excess weight loss percentage (odds ratio 1.11, 95% confidence interval (1.05-1.18), p < 0.001). CONCLUSION: There was a clinically significant reduction in BMD at 6 months after surgery in over 60% of patients undergoing bariatric surgery. BMD loss is persistent over time and predominantly situated at the femoral level, and strongly associated with weight loss. Systematic vitamin and calcium supplementation, as well as follow-up by DEXA scan seems appropriate. Systematic DEXA scan pre- and post-surgery, and annually thereafter until weight has stabilized seems appropriate.

Diagnostic contribution of a second percutaneous needle biopsy in patients with spontaneous diskitis and negative blood cultures and first biopsy.

OBJECTIVES: The primary objective was to assess the diagnostic contribution of a second percutaneous needle biopsy in patients with spontaneous diskitis and negative findings from blood cultures and the first biopsy. We also assessed the sensitivity of the first biopsy and the diagnostic contribution of post-biopsy blood cultures. METHODS: Multicenter retrospective study of patients managed between 2004 and 2014. We excluded patients with postoperative diskitis. RESULTS: We identified 63 patients with spontaneous diskitis, negative blood cultures, and at least one percutaneous needle biopsy during the study period. The first biopsy established the diagnosis in 33 (52%) patients. Of the 30 remaining patients, 10 (33%) had a second biopsy, which was positive in 6 (60%), and 20 (67%) received probabilistic antibiotic therapy. There were 8 positive blood cultures after the first biopsy but, among them, 7 occurred in biopsy-positive patients. Biopsy yield varied with the guidance method (needle guidance software or imaging by computed tomography and/or fluoroscopy) and operators. Antibiotic therapy within the 6months preceding the first biopsy was significantly associated with having a negative first biopsy (15/30 versus 7/33; odds ratio, 3.13; 95% confidence interval, 1.07-9.13; P<0.05). CONCLUSION: In our study, a second needle biopsy was useful, providing the bacteriological diagnosis in 60% of cases of spontaneous diskitis with negative findings from blood cultures and the first biopsy.