Safety of rituximab in rheumatoid arthritis: A long-term prospective single-center study of gammaglobulin concentrations and infections

ObjectiveRituximab seems well tolerated in patients with rheumatoid arthritis (RA). However, variations in the gammaglobulin profile that might increase the infection risk have been reported. Here, our objective was to evaluate gammaglobulin concentrations and the infection risk in patients receiving rituximab therapy for RA in everyday practice.MethodsProspective single-center observational study of 65 patients with refractory RA (median age, 59 years; range, 26–83) treated with rituximab 1 g twice 15 days apart, with or without a further 1-g dose at least 6 months later depending on the clinical response. Gammaglobulins were assayed before each rituximab dose.ResultsThe median cumulative rituximab dose was 4 g (1–16) and the median time to retreatment was 8 months (6–16). Rituximab therapy significantly improved the DAS-28 score. The gammaglobulin concentration decreased significantly between the first and last rituximab dose (from 11.6 g/L [5–26] to 8.2 g/L [3–20], a ?2.6 g/L difference; P < 0.05). The decrease was larger in the 24 patients with cumulative rituximab doses greater than 5 g than in the 41 other patients (difference of ?4 vs ?2.7 g/L; P < 0.05). Three patients experienced severe infections, two in the high-dose group and one in the other group (P = 0.5).ConclusionThese data obtained in everyday practice constitute further evidence that rituximab is well-tolerated in patients with RA. Rituximab therapy was associated with a decrease in gammaglobulin concentrations that was greater in patients receiving higher cumulative doses.     

Bidirectional association between physical activity and symptoms of anxiety and depression: the Whitehall II study

Although it has been hypothesized that the association of physical activity with depressive and anxiety symptoms is bidirectional, few studies have examined this issue in a prospective setting. We studied this bidirectional association using data on physical activity and symptoms of anxiety and depression at three points in time over 8?years. A total of 9,309 participants of the British Whitehall II prospective cohort study provided data on physical activity, anxiety and depression symptoms and 10 covariates at baseline in 1985. We analysed the associations of physical activity with anxiety and/or depression symptoms using multinomial logistic regression (with anxiety and depression symptoms as dependent variables) and binary logistic regression (with physical activity as the dependent variable). There was a cross-sectional inverse association between physical activity and anxiety and/or depressive symptoms at baseline (ORs between 0.63 and 0.72). In cumulative analyses, regular physical activity across all three data waves, but not irregular physical activity, was associated with reduced likelihood of depressive symptoms at follow-up (OR?=?0.71, 95?% CI 0.54, 0.99). In a converse analysis, participants with anxiety and depression symptoms at baseline had higher odds of not meeting the recommended levels of physical activity at follow-up (OR?=?1.79, 95?% CI 1.17, 2.74). This was also the case in individuals with anxiety and/or depression symptoms at both baseline and follow-up (OR?=?1.70, 95?% CI 1.10, 2.63). The association between physical activity and symptoms of anxiety and/or depression appears to be bidirectional.     

Synovial fluid analysis with leukocyte esterase reagent strip test

To determine whether leukocyte esterase reagent strip test (LERST) analysis could help distinguish inflammatory arthritis from mechanical joint effusion. We analyzed synovial fluid (SF) from consecutive patients with a non-traumatic joint effusion during a 6-month period. Inflammatory SF was defined by white blood cell (WBC) count ≥ 2000/mm³. The LERST was performed with both semi-quantitative visual analysis (VA) and automated colorimetric reader (ACR) analysis. Leukocytes ≥ 1+ was considered a positive LERST result and WBC count was the reference. We obtained 100 SF samples (87 knees, 7 ankles, 5 hips, and 1 elbow) from 100 patients (mean ± SD age 61 ± 17 years, 59% men). The laboratory analyzed 88 SF samples (37 mechanical and 51 inflammatory). The remaining 12 SF samples were 10 hemarthrosis not allowing LERST analysis and 2 samples with coagulum not allowing WBC count. As compared with the laboratory analysis, the LERST had sensitivity and specificity 55% and 89% with VA and 47% and 92% with ACR analysis. The positive and negative predictive values were 87.5% and 59% with VA and 89% and 55% with ACR analysis. We found almost perfect agreement between VA and ACR results (kappa 0.70 [95% CI 0.50–0.90]). The WBC count increased with number of + observed after VA. Our results confirm that the LERST is able to detect inflammation in SF of native joints, thereby representing a useful and cheap tool in primary care. Its low sensitivity limits its use for ruling out inflammatory disorders.