Oral Janus kinase inhibitors and venous thromboembolic events in atopic dermatitis: protocols for a case-time control study and a nested case-control study based on the French national health insurance (SNDS) cohort.

INTRODUCTION: Atopic dermatitis (AD) is a highly prevalent, chronic, inflammatory skin disease. Several orally administered Janus kinase inhibitors (JAKis, including baricitinib, upadacitinib and abrocitinib) have received a marketing authorisation for AD.Clinical trials in rheumatoid arthritis (RA) have flagged up a potential risk of JAKi-induced venous thromboembolic events (VTEs). Accordingly, the summary of product characteristics for a JAKi must mention VTEs as potential adverse drug reactions. In contrast to RA, AD per se is not associated with an elevated risk of VTEs. Assessing this potential risk among patients with AD would shed further light on the putative underlying relationship between JAKis and VTEs.Our research question is to investigate whether JAKi administration increases the risk of VTEs in adults with AD. Our primary objective is to assess the risk of VTEs in adults with AD exposed to JAKis compared to AD adults not exposed to JAKis, and our secondary objective is to evaluate whether JAKi initiation acts as a trigger of VTEs in adults with AD within 3 months. METHODS AND ANALYSIS: Hence, we have designed (1) a nested case-control study and (2) a case-time control study in a cohort of adults with AD with data from the French national health insurance system (2017-2025).Here, we describe the study protocol, our methodological choices and certain novel aspects, including the combined value of the two assumptions and the use of an exhaustive national health insurance database with potentially greater statistical power for studying rare events in the population of patients with AD at a low risk of VTEs (thus limiting the influence of confounding factors). ETHICS AND DISSEMINATION: The protocol has been approved by an independent ethics committee and registered with the French National Data Protection Commission. The study's findings will be published in peer-reviewed scientific journals and presented at international conferences.

[Drug interactions with colchicine, are the contraindications well respected? A descriptive study of prescriptions in Brittany based on data from the French National Health Data System]. / Interactions médicamenteuses avec la colchicine, les contre-indications sont-elles bien respectées ? Étude descriptive des prescriptions en Bretagne à partir des données de l'Assurance maladie.

Although the French Health Authority "ANSM" widely informed healthcare professionals about the risk factors for colchicine overdose, its impact and suitable dosages, cases of potentially fatal preventable overdose continue to be reported in France. Using the French National Health Insurance of the Brittany area, we quantified the proportion of prescriptions presenting an absolute drug contraindication (CI) to colchicine (according to the ANSM Drug Interactions "Thesaurus") and its impact in terms of hospitalisation. Between 2013 and 2016, nearly 77,000 patients (mean age, 66±15 years) were reimbursed for at least one colchicine-based drug (Colchimax®, Colchicine Opocalcium®), representing nearly 205,000 prescriptions. General practitioners were the main prescribers (93%). Among the prescriptions, 0.5% had absolute IC with colchicine: in 51% of cases with pristinamycin, followed by azithromycin (15.6%), clarithromycin (15.2%) and roxithromycin (11.9%). In the 15 days following the simultaneous prescription of colchicine and a contraindicated drug, 53 hospital stays were recorded. However, using only the primary diagnosis of hospitalization was not sufficiently relevant to conclude that there was no potential overdose of colchicine. Over the study period, the Thesaurus contained inconsistencies that confused clinicians: mention of absolute IC with colchicine in the "macrolide" and "pristinamycin" sections but not in the sections of 'potent CYP inhibitors' or macrolide class molecules. Overall, very few prescriptions included absolute IC with colchicine. Regular training and information of healthcare professionals remains essential to limit the risk of colchicine overdose and to remind them of the potentially fatal consequences.

Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high grade prostate cancer: a French population-based study.

OBJECTIVE: To assess the association between 5α-reductase inhibitor (5-ARI) use and high grade (Gleason score 8-10) prostate cancer. PATIENTS AND METHODS: We conducted a population-based nested matched case-control study using the French national health insurance database linked to data from all pathology laboratories in Brittany, France. Among 74 596 patients with ≥1 drug reimbursement for symptomatic benign prostate hypertrophy (BPH) between 1 January 2010 and 31 December 2011, 767 incident prostate cancer cases between 1 January 2012 and 31 December 2013 were matched according to age and delay between the first observed delivery of drug for BPH (5-ARIs, α-blockers or phytotherapy) and diagnostic date of the case to five control patients, using an incidence density sampling design. RESULTS: A total of 963 patients (153 cases, 810 controls) had been exposed to 5-ARIs. A significant heterogeneity (P = 0.005) was detected across cancer grades when estimating the association between prostate cancer and long-term (≥2 years) 5-ARI use vs no 5-ARI exposure: adjusted conditional odds ratio 1.76 (95% confidence interval [CI] 0.97-3.21) for Gleason score ≥8 and 0.64 (95% CI 0.44-0.93) for Gleason score < 8. CONCLUSION: Our results indicate an increased risk of high grade and a decreased risk of low grade prostate cancer associated with 5-ARI use. Patients treated for >2 years with 5-ARIs should be informed about the increased risk of development of high grade disease.

Rationale and design of the CANARI study: a case-control study investigating the association between prostate cancer and 5-alpha-reductase inhibitors for symptomatic benign prostate hypertrophy by linking SNIIRAM and pathology laboratories in a specific region in France.

Benign prostate hypertrophy (BPH) could be associated with low urinary symptoms requiring medical treatment: 5-alpha-reductase inhibitors (5-ARI) or ɑ-blockers. Two clinical trials investigating 5-ARI use in prostate cancer (PCa) primary prevention highlighted a potential safety signal with an increased risk of high-grade PCa. Later observational studies failed to show similar results but have some limits. This paper focuses on describing the protocol of the CANARI study and its feasibility, as regards the matching process of two pseudo-anonymous databases. The study concerned patients living in the Brittany region (France) between 2010 and 2013. We designed a case-control study nested within a cohort of men treated by medical drugs licensed for symptomatic BPH between 2010 and 2011. Cases were patients with incident PCa diagnosed between 2012 and 2013 identified through French Health database (SNIIRAM). Gleason score was searched through Brittany pathology laboratories. Controls were patients without PCa diagnosis. Local pathology laboratories database was constituted in Brittany, gathering Gleason scores. No unique identification number is available in France; linkage of SNIIRAM and Brittany pathology laboratories database was made by deterministic matching. We matched 859 cases to Gleason grading (119 had Gleason score ≥8 and 740 had Gleason <8); around 22% of cases received 5-ARI and 78% α-blockers or phytotherapy. The CANARI study investigated in a population of men treated for BPH the risk of PCa with 5-ARI, according to Gleason grade thanks to SNIIRAM database enriched by local pathological results.