Intra-articular botulinum toxin A injection for painful base-of-thumb osteoarthritis: a double-blind, randomised, controlled, phase 3 trial (RHIBOT).

Journal

The Lancet. Rheumatology
ISSN: 2665-9913
Titre abrégé: Lancet Rheumatol
Pays: England
ID NLM: 101765308

Informations de publication

Date de publication:
Jul 2022
Historique:
received: 11 02 2022
revised: 15 04 2022
accepted: 19 04 2022
medline: 1 7 2022
pubmed: 1 7 2022
entrez: 31 1 2024
Statut: ppublish

Résumé

Intra-articular botulinum toxin A injection might have analgesic effects in patients with joint diseases. We aimed to compare the effects of intra-articular botulinum toxin A injection with those of intra-articular saline injection for patients with painful base-of-thumb osteoarthritis. RHIBOT was a double-blind, randomised, controlled, phase 3 trial conducted at Cochin Hospital, Paris, France. We recruited adult patients with x-ray evidence of trapeziometacarpal osteoarthritis who fulfilled the 1990 American College of Rheumatology criteria for hand osteoarthritis and reported a pain intensity score of at least 30 on an 11-point numeric rating scale (0: no pain to 100: maximal pain). Participants were randomly assigned (1:1), using a computer-generated randomisation list with permuted blocks of variable size (4 or 6), to receive an ultrasound-guided injection of either botulinum toxin A (50 Allergan units) in 1 mL of saline (experimental group) or 1 mL of saline alone (control group) in the trapeziometacarpal joint, in addition to custom-made rigid splinting. The primary outcome was the mean change from baseline in base-of-thumb pain in the previous 48 h on a numeric rating scale at 3 months after injection, analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT03187626. Between Nov 2, 2018, and Nov 3, 2020, we assessed 370 individuals for eligibility and recruited 60 (16%) participants (mean age 64·9 years [SD 9·4], 47 [78%] women and 13 [22%] men), of whom 30 (50%) participants were randomly assigned to the experimental group and 30 (50%) to the control group. At baseline, base-of-thumb pain score was 60·0 of 100·0 (SD 15·9). At 3 months, the mean reduction in base-of-thumb pain was -25·7 (95% CI -35·5 to -15·8) in the experimental group and -9·7 (-17·1 to -2·2) in the control group (absolute difference -16·0 [-28·1 to -3·9]; p=0·043). Overall, 51 adverse events were reported in both groups: 27 (53%) in the experimental group and 24 (47%) in the control group. During follow-up, 14 (47%) participants in the experimental group and two (7%) participants in the control group reported mild transient motor deficit of the thenar muscle. No serious adverse events were reported. Botulinum toxin A could be considered as a fast-acting, intra-articular therapy targeting chronic pain in individuals with base-of-thumb osteoarthritis. Future studies are needed to investigate the potential mechanism of the effects observed in this trial, to replicate our findings, and to assess the effects of repeated injections over time and their clinical effectiveness, including an analysis of cost-effectiveness. Assistance Publique-Hôpitaux de Paris.

Sections du résumé

BACKGROUND BACKGROUND
Intra-articular botulinum toxin A injection might have analgesic effects in patients with joint diseases. We aimed to compare the effects of intra-articular botulinum toxin A injection with those of intra-articular saline injection for patients with painful base-of-thumb osteoarthritis.
METHODS METHODS
RHIBOT was a double-blind, randomised, controlled, phase 3 trial conducted at Cochin Hospital, Paris, France. We recruited adult patients with x-ray evidence of trapeziometacarpal osteoarthritis who fulfilled the 1990 American College of Rheumatology criteria for hand osteoarthritis and reported a pain intensity score of at least 30 on an 11-point numeric rating scale (0: no pain to 100: maximal pain). Participants were randomly assigned (1:1), using a computer-generated randomisation list with permuted blocks of variable size (4 or 6), to receive an ultrasound-guided injection of either botulinum toxin A (50 Allergan units) in 1 mL of saline (experimental group) or 1 mL of saline alone (control group) in the trapeziometacarpal joint, in addition to custom-made rigid splinting. The primary outcome was the mean change from baseline in base-of-thumb pain in the previous 48 h on a numeric rating scale at 3 months after injection, analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT03187626.
FINDINGS RESULTS
Between Nov 2, 2018, and Nov 3, 2020, we assessed 370 individuals for eligibility and recruited 60 (16%) participants (mean age 64·9 years [SD 9·4], 47 [78%] women and 13 [22%] men), of whom 30 (50%) participants were randomly assigned to the experimental group and 30 (50%) to the control group. At baseline, base-of-thumb pain score was 60·0 of 100·0 (SD 15·9). At 3 months, the mean reduction in base-of-thumb pain was -25·7 (95% CI -35·5 to -15·8) in the experimental group and -9·7 (-17·1 to -2·2) in the control group (absolute difference -16·0 [-28·1 to -3·9]; p=0·043). Overall, 51 adverse events were reported in both groups: 27 (53%) in the experimental group and 24 (47%) in the control group. During follow-up, 14 (47%) participants in the experimental group and two (7%) participants in the control group reported mild transient motor deficit of the thenar muscle. No serious adverse events were reported.
INTERPRETATION CONCLUSIONS
Botulinum toxin A could be considered as a fast-acting, intra-articular therapy targeting chronic pain in individuals with base-of-thumb osteoarthritis. Future studies are needed to investigate the potential mechanism of the effects observed in this trial, to replicate our findings, and to assess the effects of repeated injections over time and their clinical effectiveness, including an analysis of cost-effectiveness.
FUNDING BACKGROUND
Assistance Publique-Hôpitaux de Paris.

Identifiants

DOI: 10.1016/S2665-9913(22)00129-1 PMID: 38294016
pubmed: 38294016
pii: S2665-9913(22)00129-1
doi: 10.1016/S2665-9913(22)00129-1
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT03187626']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e480-e489

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests CN reports receiving consulting fees from Thuasne; speaker fees from Actelion Pharmaceuticals France, Ipsen, and Meda Pharmaceuticals; reimbursement of conference registration and accommodation by Grünenthal and Merz; and hospitality from Preciphar, Takeda France, UCB Pharma SA, and Sandoz, outside of the submitted work. CD reports receiving hospitality from Merz, outside of the submitted work. All other authors declare no competing interests.

Auteurs

Christelle Nguyen (C)

Faculté de Santé, UFR de Médecine, Université Paris Cité, Paris, France; Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France; INSERM UMR-S 1124, Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs, Paris, France. Electronic address: christelle.nguyen2@aphp.fr.

Hendy Abdoul (H)

Unité de Recherche Clinique-Centre d'Investigation Clinique Paris Descartes Necker-Cochin, Hôpital Tarnier, Paris, France.

Raphaël Campagna (R)

Service de Radiologie B, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Henri Guerini (H)

Service de Radiologie B, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Léa Jilet (L)

Unité de Recherche Clinique-Centre d'Investigation Clinique Paris Descartes Necker-Cochin, Hôpital Tarnier, Paris, France.

Catherine Bedin (C)

Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Franck Chagny (F)

Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Gaëlle Couraud (G)

Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Camille Daste (C)

Faculté de Santé, UFR de Médecine, Université Paris Cité, Paris, France; Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France; INSERM UMR-S 1153, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité, Paris, France.

Jean-Luc Drapé (JL)

Faculté de Santé, UFR de Médecine, Université Paris Cité, Paris, France; Service de Radiologie B, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France; INSERM UMR-S 1153, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité, Paris, France.

Rémy Fléchon (R)

Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Charlotte Gil (C)

Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Corinne Guérin (C)

Service de Pharmacie Clinique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Marie-Martine Lefèvre-Colau (MM)

Faculté de Santé, UFR de Médecine, Université Paris Cité, Paris, France; Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France; INSERM UMR-S 1153, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité, Paris, France; Fédération pour la Recherche sur le Handicap et l'Autonomie, Paris, France.

Serge Poiraudeau (S)

Faculté de Santé, UFR de Médecine, Université Paris Cité, Paris, France; Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France; INSERM UMR-S 1153, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité, Paris, France; Fédération pour la Recherche sur le Handicap et l'Autonomie, Paris, France.

Estelle Randriamampandry (E)

Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France.

Alexandra Roren (A)

Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France; Fédération pour la Recherche sur le Handicap et l'Autonomie, Paris, France.

Antoine Feydy (A)

Faculté de Santé, UFR de Médecine, Université Paris Cité, Paris, France; Service de Radiologie B, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France; INSERM UMR-S 1153, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité, Paris, France.

François Rannou (F)

Faculté de Santé, UFR de Médecine, Université Paris Cité, Paris, France; Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris, Paris, France; INSERM UMR-S 1124, Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs, Paris, France.

Classifications MeSH