Bisphosphonates for treatment of Complex Regional Pain Syndrome type 1: A systematic literature review and meta-analysis of randomized controlled trials versus placebo.

OBJECTIVES: Complex Regional Pain Syndrome Type 1 is a severely disabling pain syndrome with no definite established treatment. We have performed a systematic literature review and meta-analysis of all randomized controlled trials to assess the benefit of bisphosphonates on pain and function in patients with Complex Regional Pain Syndrome Type 1. METHODS: A systematic literature search was performed in the Medline, Embase and Cochrane databases. Two authors selected independently blinded randomized trials comparing bisphosphonates to placebo on short-term (J30 to J40) and medium term pain (M2-M3), safety and function in patients with CRPS 1. The methodological quality of the studies was analyzed. Data were aggregated using the method of the inverse of the variance. RESULTS: 258 articles were identified. Four trials of moderate to good quality comprising 181 patients (90 in the bisphosphonate group and 91 in the placebo group) were included in this meta-analysis. Short-term pain Visual Analog Scale was significantly lower in the bisphosphonate group versus the placebo group (SMD=-2.6, 95%CI [-1.8, -3.4], P<0.001), as well as the medium term Visual Analog Scale pain (SMD=-2.5, 95%CI [-1.4, -3.6], P<0.001). There were more adverse events in the bisphosphonate group (35.5%) than in the placebo group (16.4%) with a relative risk of 2.1 (95%CI [1.3, 3.5], P=0.004) and a number needed to harm of 4.6, (95%CI [2.4, 168.0]) but no serious side effects. CONCLUSIONS: Our results suggest that bisphosphonates reduce pain in patients with Complex Regional Pain Syndrome type 1. Other studies are needed to determine their effectiveness.

Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies.

Growth arrest and DNA damage-inducible gene 34 (GADD34) is an inducible cofactor of protein phosphatase 1, which has an important role in the unfolded protein response. GADD34 has been shown to be necessary for type I interferon and proinflammatory cytokine production in response to viral infection in murine models. We investigate the expression of GADD34 in rheumatoid arthritis (RA), in which proinflammatory cytokines have an important pathogenic role. The objective of this study was to evaluate the potential of GADD34 expression as a biomarker in RA patients. We report a case-control study on GADD34 gene expression in peripheral blood mononuclear cells of patients (n = 75) with RA and age- and sex-matched healthy controls (n = 25). The study was approved by the relevant local ethics committees. GADD34 gene expression level in peripheral blood mononuclear cells was measured by quantitative PCR and analyzed with Mann-Whitney test. The relation between GADD34 gene overexpression and clinical or biological characteristics was analyzed with univariate and multivariate analysis. GADD34 gene expression was significantly higher in RA patients compared with healthy controls (p ≤ 0.001). Interestingly, GADD34 overexpression in PBMC of patients was related to the presence of circulating anti-citrullinated protein antibodies (p = 0.030). Data of this study strengthen the evidence of an unfolded protein response during the course of RA and provide an insight of the potential interest in GADD34 as a relevant marker for RA.

Application of the European Society of Cardiology, Adult Treatment Panel III and American College of Cardiology/American Heart Association guidelines for cardiovascular risk management in a French cohort of rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) have greater rates of cardiovascular mortality and RA is an independent cardiovascular risk factor. For the management of cholesterol, the American College of Cardiology/American Heart Association (ACC/AHA) developed new guidelines for the general population. None of the European or American guidelines are specific to RA. The European League Against Rheumatism (EULAR) recommends applying a coefficient to cardiovascular risk equations based on the characteristics of RA. Our objective was to compare the three different sets of guidelines for the eligibility of statin therapy in RA-specific population with very high risk of cardiovascular disease. METHODS AND RESULTS: We calculated the proportion of patients eligible for statins according to the guidelines of the European Society of Cardiology (ESC), the Adult Treatment Panel III (ATP-III) and the ACC/AHA in a French cohort of statin-naïve RA patients at least 40 years age. Of the 547 women and 130 men analyzed, statins would be recommended for 9.1% of the women and 26.4% of the men, 15.6% of the women and 53.1% of the men, 38.8% of the women and 78.5% of the men, according to the ESC, ATP-III and ACC/AHA guidelines respectively. CONCLUSIONS: In RA patients, as has been observed in the general population, discordance in risk assessment and cholesterol treatment was observed between the three sets of guidelines. The use of the new ACC/AHA guidelines would expand the eligibility for statins and may be applied to RA population a condition at very high risk of cardiovascular disease.