Real-life prognosis of neurological complications of botulinum toxin: a nationwide pharmacovigilance study of adverse drug reactions reported in France between 1994 and 2020 - 20/12/24

Doi : 10.1016/j.rehab.2024.101924

Vincent T. CARPENTIER ^1,^⁎ , Nicolas WEISS ² , Joe-Elie SALEM ^3,⁴ , Charles JOUSSAIN ⁵ , Jonathan LEVY ⁵ , Louise-Laure MARIANI ⁶ , François MONTASTRUC ⁷ , Julien MAHÉ ⁸ , Bénédicte LEBRUN-VIGNES ^9,¹⁰ , Djamel BENSMAIL ⁵ , Pierre DENYS ⁵ , François GENÊT ^1,^{^{#
Equal contribution as co-last author}} , Kévin BIHAN ^9,^{^{#
Equal contribution as co-last author}}
¹ AP-HP. Paris Saclay University, Raymond Poincaré Hospital, Department of Physical Medicine and Rehabilitation, Neuro-Orthopaedics Unit (UPOH), Parasports Unit, ISPC Synergies, Garches Neuro-Orthopaedics Research Group (GRENOG), U1179 END-ICAP, INSERM, Versailles Saint-Quentin-en-Yvelines University (UVSQ), Paris Saclay University, 104 boulevard Raymond Poincaré, 92380 Garches, France
² AP-HP. Sorbonne University, La Pitié-Salpêtrière Hospital, Department of Neurology, Neurological Intensive Care Unit, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, UMR-S938 Centre de recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition (ICAN), INSERM, Sorbonne University, Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE), 47-83 boulevard de l'Hôpital, 75013 Paris, France
³ AP-HP. Sorbonne University, La Pitié-Salpêtrière Hospital, Department of Pharmacology, Regional Pharmacovigilance Center, Clinical Investigation Centre - Paris Est, INSERM Sorbonne University, 47-83 boulevard de l'Hôpital, 75013 Paris, France
⁴ Vanderbilt University Medical Center, Department of Medicine and Pharmacology, 1211 Medical Center Drive, Nashville, TN 37232, USA
⁵ AP-HP. Paris Saclay University, Raymond Poincaré Hospital, Department of Physical Medicine and Rehabilitation, U1179 END-ICAP, INSERM, Versailles Saint-Quentin-en-Yvelines University (UVSQ), Paris Saclay University, 104 boulevard Raymond Poincaré, 92380 Garches, France
⁶ AP-HP. Sorbonne University, La Pitié-Salpêtrière Hospital, Departments of Neurology and Pharmacology, Clinical Investigation Centre for Neurosciences, Institut du Cerveau - Paris Brain Institute - ICM, INSERM, CNRS, Sorbonne University Paris, 47-83 boulevard de l'Hôpital, 75013 Paris, France
⁷ Toulouse University Hospital, Department of Medical and Clinical Pharmacology, Centre of Pharmacovigilance and Pharmacoepidemiology, UMR 1027 Pharmacoepidemiology, Assessment of Drug Utilization and Drug Safety, INSERM, Toulouse Paul Sabatier University, 2 rue Charles Viguerie, 31300 Toulouse, France
⁸ Nantes University Hospital, Department of Clinical Pharmacology, Regional Pharmacovigilance Center, 5 allée de l'Île-Gloriette. 44093 Nantes, France
⁹ AP-HP. Sorbonne University, La Pitié-Salpêtrière Hospital, Department of Pharmacology, Regional Pharmacovigilance Center, 47-83 boulevard de l'Hôpital, 75013 Paris, France
¹⁰ EA 7379 EpiDermE, University Paris-Est Créteil Val de Marne, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil Créteil, France

^⁎Corresponding author: Dr. Vincent T. Carpentier, Department of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, 104 Bd Raymond Poincaré, 92380, Garches, France, Phone: +33 1 47 10 70 68Department of Physical Medicine and RehabilitationRaymond Poincaré Hospital104 Bd Raymond PoincaréGarches92380France

Sous presse. Manuscrit accepté. Disponible en ligne depuis le Friday 20 December 2024

Highlights

•	Neurological adverse drug reactions (ADRs) may occur after botulinum toxin injection
•	59% of botulinum toxin-related neurologic ADRs were initially serious
•	87% of cases recovered spontaneously or were recovering
•	Neurological ADRs may be isolated symptoms or groups of symptoms
•	Neurological ADRs may be either local or distant from the injection site

Le texte complet de cet article est disponible en PDF.

ABSTRACT

Background

Botulinum toxin is commonly used in the treatment of neurological disorders. Although neurological complications predominate and can lead to respiratory failure or death, no observational studies have specifically described their clinical features or prognoses.

Objectives

To characterise real-life clinical features and prognoses of botulinum toxin-related neurological complications.

Methods

Observational, retrospective, nationwide pharmacovigilance study of all neurological adverse drug reactions (ADRs) related to the use of botulinum toxin in France for neurological indications between 1994 and 2020. The characteristics of neurological complications were collected.

Results

In total, 141 people with systemic neurologic complications (ie, distant from the injection site) and 50 with local complications were included. Median (IQR) age was 53 (36; 66) years, and 107 (56%) were women. The estimated incidence range (min – max) was 25 – 413 neurologic ADRs per 100 000 injection sessions for neurological indications. Except for 3 miscellaneous cases, all presented symptoms within the clinical spectrum of botulism, either as an isolated symptom (41%) or as multiple symptoms (59%), with a time to onset of 12 (7; 15) days after injection and a duration of 54 (28; 90) days. A total of 87% of cases recovered spontaneously or were recovering on the date of the notification. Drug types were not different between cases with systemic or local ADRs, although the doses were higher in cases with systemic ADRs (P <0.001). Serious cases were more frequent for systemic ADRs (67% versus 34%; P <0.001). Three complications resulted in death, all after treatment for cervical dystonia or sialorrhea.

Conclusion

In this pharmacovigilance study, the outcomes of botulism spectrum symptoms occurring after a botulinum toxin injection for a neurological indication were mostly favourable, although symptoms were often initially serious.

Le texte complet de cet article est disponible en PDF.

Keywords : Botulinum toxins, neurological manifestations, drug monitoring, pharmacovigilance

Abbreviations : ADRs, ANSM, ATC, ATIH, CNIL, EMA, FDA, MedDRA, PMSI, PT, SFEMG, SOC