Abstract
Background: Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain, but the quality of the evidence is low. We aimed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain. Methods: We did a randomised, double-blind, placebo-controlled trial at two outpatient clinics in France (Clinical Pain Centre, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, and Neurological Centre, Hôpital Dupuytren, Limoges) and one in Brazil (Neurological Department, Hospital das Clínicas da FMUSP, São Paulo). Patients aged 18-85 years with peripheral neuropathic pain were randomly assigned (1:1) by block randomisation, according to a centralised schedule, to receive two subcutaneous administrations of botulinum toxin A (up to 300 units) or placebo, 12 weeks apart. All patients and investigators were masked to treatment assignment. The primary outcome was the efficacy of botulinum toxin A versus placebo, measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration. The primary efficacy analysis was a mixed-model repeated-measures analysis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01251211. Findings: Between Oct 2, 2010, and Aug 2, 2013, 152 patients were enrolled, of whom 68 were randomly assigned (34 per group), and 66 (37 [56%] men) were included in the primary analysis (34 in the botulinum toxin A group and 32 in the placebo group). Botulinum toxin A reduced pain intensity over 24 weeks compared with placebo (adjusted effect estimate -0·77, 95% CI -0·95 to -0·59; p<0·0001). Pain on injection was the only adverse effect reported, and occurred in 19 (56%) participants in the botulinum toxin A group and 17 (53%) of those in the placebo group (p=1·0). Severe pain was experienced by ten (29%) participants in the botulinum toxin A group and 11 (34%) in the placebo group (p=0·8). Interpretation: Two administrations of botulinum toxin A, each of which comprised several injections, have a sustained analgesic effect against peripheral neuropathic pain. Several factors, such as the presence of allodynia and a limited thermal deficit, may be useful in predicting treatment response and should be investigated further. Funding: Institut National de la Santé et de la Recherche Médicale (INSERM) and Fondation CNP (France).
| Original language | English |
|---|---|
| Journal | The Lancet Neurology |
| Volume | 15 |
| Issue number | 6 |
| Pages (from-to) | 555-565 |
| Number of pages | 11 |
| ISSN | 1474-4422 |
| DOIs | |
| Publication status | Published - 1 May 2016 |
| Externally published | Yes |
Bibliographical note
Funding Information:NA has received honoraria from Pfizer, Eli Lilly, Johnson & Johnson, Astellas, Sanofi Pasteur MSD, Grünenthal, and Teva for advisory boards, speakers bureaus, or clinical trials. DCdA and MJT have served on advisory boards and as speakers for Pfizer, Grünenthal, Medtronic, Saint Jude Medical, and Mundipharma. DR has received honoraria from Allergan for advisory boards. NÜ has received honoraria from Astellas, Baxter, Genzyme, Shire, and Pfizer for speakers bureaus. CS has received personal fees from Pfizer, CSL Behring, Baxter, Genzyme, Allergan, and Astellas, and grants from Genzyme and Kedrion for advisory boards or speakers bureau. DB has received honoraria from Pfizer, Astellas, Grünenthal, and Indivior for advisory boards or speakers bureau. FA, RG, and IR declare no competing interests.
Publisher Copyright:
© 2016 Elsevier Ltd.