Potentially inappropriate drug use in myasthenia gravis: a real-world population-based cohort study in Italy

Giada Crescioli; Marco Finocchietti; Olga Paoletti; Paola Brunori; Francesco Sciancalepore; Marco Tuccori; Antonio Addis; Alfredo Vannacci; Niccolò Lombardi; Ursula Kirchmayer; CAESAR study group

doi:10.3389/fneur.2023.1293626

Potentially inappropriate drug use in myasthenia gravis: a real-world population-based cohort study in Italy

Front Neurol. 2023 Dec 21:14:1293626. doi: 10.3389/fneur.2023.1293626. eCollection 2023.

Authors

Giada Crescioli^#^{1

2}, Marco Finocchietti^#³, Olga Paoletti⁴, Paola Brunori⁵, Francesco Sciancalepore⁶, Marco Tuccori^{2

7}, Antonio Addis³, Alfredo Vannacci^{1

2}, Niccolò Lombardi^#^{1

2}, Ursula Kirchmayer^#³; CAESAR study group

Affiliations

¹ Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.
² Tuscan Regional Center of Pharmacovigilance, Florence, Italy.
³ Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
⁴ Pharmacoepidemiology Unit, Regional Health Agency of Tuscany, Florence, Italy.
⁵ Unit of Neurophysiopathology, Perugia Hospital, Perugia, Italy.
⁶ National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy.
⁷ Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, Pisa, Italy.

^# Contributed equally.

Abstract

Introduction: To evaluate the use of pyridostigmine in presence of contraindications, and the use of concomitant potentially contraindicated drugs in a cohort of patients affected by Myasthenia Gravis (MG) in the Italian Regions of Lazio, Tuscany, and Umbria.

Methods: This is a retrospective cohort study. A multivariate logistic regression model was used to evaluate the determinants of pyridostigmine and of potentially contraindicated drugs use in MG patients.

Results: Among 591 incident pyridostigmine users affected by MG, 91 (15.4%) had at least one of the contraindications considered at the first prescription of pyridostigmine. Patients prescribed with pyridostigmine in presence of contraindications were more frequently affected by diabetes, obesity, and renal diseases. Age 75+ years (odds ratio, OR 4.94, 95% confidence interval, CI 1.60-15.22 for Latium; OR 3.78, 95%CI: 1.26-11.34 for Tuscany; OR 5.83, 95%CI 1.19-28.52 for Umbria), the presence of at least one specific comorbidity (OR 3.93; 95%CI 1.68-9.17 for Latium), and polytherapy (6+ drugs, OR 4.90, 95%CI: 1.35-17.85 for Tuscany) were found to be significantly associated with pyridostigmine use in presence of contraindications. Among patients affected by MG, 1,483 (62.6%) were treated with potentially contraindicated drugs in the first year of follow-up (67.06.9% in Latium; 59% in Tuscany; 57.6% in Umbria). Patients aged 75+ years, those with at least one specific complication or comorbidity, and those exposed to polytherapy were more likely to be treated with a potential contraindicated drug.

Conclusion: Among incident users of pyridostigmine, more than 15% of patients have at least one of the contraindications considered, and among patients diagnosed with MG, in the first year of follow-up >60% of subjects were treated with potentially contraindicated drugs.

Keywords: cohort study; contraindication; drug use; drug–drug interaction; myasthenia gravis; pharmacoepidemiology.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study is co-funded by a research grant from the Italian Medicines Agency (AIFA) in the multiregional pharmacovigilance call 2012-13-14. The funder of the study had no role in the collection, analysis, and interpretation of data, nor in the writing of the report, nor in the decision to submit the article for publication.