JAK inhibitors and risk of major cardiovascular events or venous thromboembolism: a self-controlled case series study

PURPOSE: JAK-inhibitors (JAK-i) might be associated with venous (VTE) and arterial thromboembolic events (ATE). To evaluate the association between JAK-i and the risk of VTE and ATE. METHODS: A self-controlled case series was performed using data from the nationwide French healthcare insurance system database SNDS. We included all patients treated with JAK-i (baricitinib or tofacitinib), and having presented at least one VTE or ATE between November 1, 2017 and June 30, 2019. Associations were estimated using the incident rate ratio (IRR). Two post-exposure periods (until day 30 and until day 60) were individualized. RESULTS: Among 5870 patients with JAK-i dispensing, 92 had an incident VTE or ATE within the study period. Their median age at JAK-i initiation was 65.7 years [IQR: 56.1-75.8] and 65.2% were female (n = 60). Before event incidence, 65.2% (n = 60) received baricitinib, 32.6% (n = 30) tofacitinib and 2.2% (n = 2) had both medications. Moreover, 41.3% (n = 38) presented a VTE and 58.7% (n = 54) an ATE. The median time-to-onset after JAK-i initiation was 4.6 months [IQR: 2.5-9.2] for VTE and 6.1 months [IQR: 3.0-8.5] for ATE. An IRR of 8.27 (95% CI 3.41-20.04) for VTE was detected during JAK-i treatment and remained increased over the 30-day period of post-exposure (6.52 [2.02-21.11]). An IRR of 9.27 (3.68-23.34) was also found for ATE, which remained increased over the 30-day period of post-exposure (10.12 [3.27-31.37]). No increased risk was detected during long-term post-exposure for either VTE or ATE. CONCLUSIONS: This study shows evidence of an increased risk of VTE and ATE associated with the use of baricitinib and tofacitinib

Clinical and Sociodemographic Characteristics Associated With Thick Melanomas: A Population-Based, Case-Case Study in France.

International audienceOBJECTIVE To identify clinical and sociodemographic factors associated with very thick melanoma (VTM) (Breslow thickness, ≥3 mm) in France. DESIGN Retrospective, population-based, case-case study using a survey of cancer registries and questionnaires to practitioners. SETTING Five regions covering 19.2% of the French territory and 8.2 million inhabitants. CASES Cases included all incident melanomas with a Breslow thickness of 3 mm or greater (ie, VTM), diagnosed between January 1 and December 31, 2008, in residents of the study area (Alsace, Bourgogne, Champagne-Ardenne, Franche-Comté, and Lorraine, France), and a randomly selected sample of melanomas thinner than 3 mm. MAIN OUTCOME MEASURES Circumstances of diagnosis, clinical and pathological characteristics of melanomas, and sociodemographic characteristics of patients (age, sex, residence, home and family life conditions, educational level, and smoking habits). RESULTS Among 898 melanomas, 149 (16.6%) were VTMs. Very thick melanomas were more often diagnosed in a general-practice setting than thinner melanomas. The rate of immediate clinical recognition by dermatologists was lower for VTMs than for thinner melanomas. In a multivariate logistic regression analysis, factors associated with VTM were the nodular and acrolentiginous types; the head and neck and lower limb locations; older age; male sex; and being single, separated, divorced, or widowed. When only factors related to patients were taken into account, older age, male sex, and living alone were independent risk factors for VTM. The most significant risk was observed for patients living alone. CONCLUSIONS Intrinsic factors related to the tumor and sociodemographic characteristics of patients contribute to the occurrence of VTM. These factors should be better targeted in future secondary prevention programs

Efficacy and safety of febuxostat in 73 gouty patients with stage 4/5 chronic kidney disease: A retrospective study of 10 centers

International audienceObjectives - The allopurinol dose is limited in chronic kidney disease, particularly stage 4/5 chronic kidney disease. Febuxostat has a hepatic metabolism and has been approved without dose adaptation in gouty patients with stage 1-3 chronic kidney disease. We aimed to study the safety and efficacy of febuxostat for stage 4/5 chronic kidney disease. Methods - In this retrospective study, we included patients with (1) a diagnosis of gout, (2) febuxostat treatment, (3) estimated glomerular filtration rate≤30mL/min/1.73m (Modification of Diet in Renal Disease formula) at febuxostat initiation and (4) follow-up for at least 3 months after febuxostat initiation. Efficacy, safety and variation in estimated glomerular filtration rate were analyzed. Results - We included 73 patients (mean age 70.2±11.8, 61 men, 31 with vascular chronic kidney disease and 18 renal transplantation) with gout (baseline serum uric acid level=9.86±2.85mg/dL, mean gout duration 6.2±7.0 years) from 10 academic centers. Comorbidities included cardiac failure (17.8%), hypertension (98.6%), diabetes mellitus (30.1%), dyslipidemia (64.8%) and history of cardiovascular events (38.4%). At the last visit (mean follow-up 68.5±64.8 weeks), the daily dose of febuxostat was 40mg for 7 patients (10.5%), 80mg for 50 (74.6%) and 120mg for 10 (14.9%). Serum uric acid level was<6mg/dL for 49 patients (67%). Renal function improved for 18 patients, was unchanged for 24 and worsened for 31; 19 patients experienced flares and 1 patient, limb edema. Conclusion - Febuxostat seemed efficient in gouty patients with stage 4/5 chronic kidney disease. However, safety data were not clear regarding renal function. Larger studies are needed to assess safety

Efficacité et tolérance du fébuxostat chez 73 patients goutteux avec une insuffisance rénale chronique stade 4/5 : étude rétrospective de 10 centres

International audienc

Efficacy and Safety of Febuxostat in 55 Gouty Patients with Stage 4/5 Chronic Kidney Disease: Results from a Retrospective Multicenter Study

International audience2015 ACR/ARHP Annual Meeting, 201

Correlation of nailfold capillaroscopy findings with history of digital ulcer on same finger: Results of SCLEROCAP study

International audienceSystemic sclerosis may be complicated by digital ulcers. Nailfold capillaroscopy on one finger might reflect an increased risk of digital ulcer (DU). In the present study we studied the correlations between a history of ulcer and capillary findings on the finger.Method: This study is part of Sclerocap, a multicenter study aiming at validating prospectively the prognostic value of Maricq's and Cutolo's capillaroscopic classifications during a three-year longitudinal follow-up. A history of past or present digital ulcer was recorded at inclusion and nailfold capillaroscopy was performed. Elementary findings as well as Cutolo and Maricq's classifications were assessed.Results: 387 patients were included in Sclerocap (327 females, 60 males) and 3096 fingers were examined by capillaroscopy at inclusion: 316 fingers (10%) belonging to 113 patients had a history of DU. Late Cutolo's stage was statistically correlated with a history of DU, both by univariate: OR 2.08 [1.09-3.96] and multivariate analysis: OR 1.97 [1.06-3.63]. Among the elemental abnormalities, only edema and decreased capillary density were correlated with a history of DU by multivariate analysis: respectively OR 1.92 [1.17-3.16] and 0.65 [0.49-0.85].Conclusion: This cross-sectional study in a large cohort of patients with systemic sclerosis shows a correlation between a history of digital ulcer and edema, a decrease in capillary density and the late stage in Cutolo's classification. The extent of capillary abnormalities on one finger is associated with a history of local digital ulcer. Capillaroscopy might be used to predict the risk of DU but these results need first to be confirmed by prospective studies