Do dimethyl fumarate and nicotinic acid elicit common, potentially HCA 2 ‐mediated adverse reactions? A combined epidemiological‐experimental approach
| Autor: | Stefan Offermanns, B. Sachs, Nina Himmerkus, Joanna Kosinska, Matthias Schmid, Diana Dubrall, Markus Schwaninger, Markus Bleich, René Pflock |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Gastrointestinal tract Dimethyl fumarate business.industry MedDRA Odds ratio medicine.disease 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Nicotinic agonist chemistry Vomiting Medicine Pharmacology (medical) 030212 general & internal medicine Liver function medicine.symptom business Adverse drug reaction |
| Zdroj: | British Journal of Clinical Pharmacology. 87:3813-3824 |
| ISSN: | 1365-2125 0306-5251 |
| Popis: | AIM Dimethyl fumarate and nicotinic acid activate the hydroxy-carboxylic acid receptor 2 (HCA2 ) and induce flushing. It is not known whether HCA2 mediates other adverse drug reactions (ADRs) to these two substances. This study aims to compare ADRs associated with dimethyl fumarate and nicotinic acid, and to discuss whether they are HCA2 -mediated. METHODS We identified spontaneous reports of suspected ADRs to dimethyl fumarate and nicotinic acid in the European Adverse Drug Reaction Database (EudraVigilance). These reports were analysed at different hierarchical levels of the Medical Dictionary for Regulatory Activities (MedDRA). In addition, we screened murine organs for HCA2 expression. RESULTS Similarities in the ADR profile of dimethyl fumarate and nicotinic acid included "gastrointestinal signs and symptoms" (odds ratio [OR] 0.8 [0.6-1.1]), "hepatobiliary investigations" (OR 1.3 [0.7-2.5]) and "anxiety disorders and symptoms" (OR 0.9 [0.3-2.2]) in High Level Group Terms; "diarrhoea (excluding infective)" (OR 1.2 [0.7-1.8]) and "liver function analyses" (OR 1.3 [0.7-2.6]) in High Level Terms; and "diarrhoea" (OR 1.2 [0.7-2.0]) and "vomiting" (OR 0.9 [0.4-1.7]) in Preferred Terms. In analogy, HCA2 was expressed in the gastrointestinal tract, liver and central nervous system (CNS) of murine organs. A discrepant ADR profile was seen for "lymphopenia" (n = 777) at the preferred term level (only reported for dimethyl fumarate) and "blood glucose increased" (more often reported for nicotinic acid; OR 0.1 [0.0-0.5]). CONCLUSION The gastrointestinal ADRs common to both substances may be mediated by HCA2 . Other ADRs not common to both substances are compound or indication-specific reactions and likely do not involve HCA2 . |
| Databáze: | OpenAIRE |
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