A multicentre randomised study of intrasphincteric botulinum toxin in patients with oesophageal achalasia

Abstract

Background-Intrasphincteric injection of botulinum toxin (Botx) has been proposed as treatment for oesophageal achalasia. However, the predictors of response and optimal dose remain unclear. Aims-To compare the eVect of diVerent doses of Botx and to identify predictors of response. Patients/methods-A total of 118 achalasic patients were randomised to receive one of three doses of Botx in a single injection: 50 U (n=40), 100 U (n=38), and 200 U (n=40). Of those who received 100 U, responsive patients were reinjected with an identical dose after 30 days. Clinical and manometric assessments were performed at baseline, 30 days after the initial injection of botulinum toxin, and at the end of follow up (mean 12 months; range 7-24 months). Results-Thirty days after the initial injection, 82% of patients were considered responders without a clear dose related eVect. At the end of follow up however, relapse of symptoms was evident in 19% of patients who received two injections of 100 U compared with 47% and 43% in the 50 U and 200 U groups, respectively. Using Kaplan-Meier analysis, patients in the 100×2 U group were more likely to remain in remission at any time (p<0.04), with 68% (95% CI 59-83) still in remission at 24 months. In a multiple adjusted model, response to Botx was independently predicted by the occurrence of vigorous achalasia (odds ratio 3.3) and the 100×2 U regimen (odds ratio 3.2). Conclusions-Two injections of 100 U of Botx 30 days apart appeared to be the most eVective therapeutic schedule. The presence of vigorous achalasia was the principal determinant of the response to Botx.

Advances in the management of oesophageal motility disorders in the era of high-resolution manometry: a focus on achalasia syndromes

“…A randomized controlled trial published in 2017 comparing POEM with pneumatic dilation found the POEM procedure to be more efficacious in terms of therapeutic success, but also more likely to result in post-procedure reflux oesophagitis 61 . The preceding discussion makes no mention of medical treatments for achalasia, specifically botulinum toxin [62][63][64][65] , calcium-channel blockers 66 , nitrates 66 and phosphodiesterase type 5 inhibitors 67 primarily because, although these agents provide some symptomatic benefit, they are not durable therapies and they do not halt the disease progression toward oesophageal decompensation characterized by dilatation and food retention. For example, in the case of botulinum toxin injected into the LES, about two-thirds of patients with achalasia report an improvement in dysphagia, but most relapse within a year and repeat treatments have diminished effectiveness, making it a poor firstline therapy [62][63][64][65] .…”

Achalasia: A review of Western and Iranian experiences

“…Achalasia and those who suffer from vigorous achalasia may benefit more from botulinum toxin [76] . A multicenter randomized study suggested that dose of botulinum toxin may be a predictor of outcome: the higher the dose, the better the response [77] . The use of botulinum toxin in achalasia was first introduced by Pasricha et al [78] .…”

Systematic review and meta‐analysis: Efficacy and safety of POEM for achalasia

“…[3][4][5][6][7] An innovative endoscopic method for dissection of the LES, using a needle-knife to cut the muscular fibers from the lumenal side, was first described by Ortega et al 8 in 1980. Two decades later, Pasricha et al 9 first described the feasibility of an endoscopic submucosal esophageal myotomy in a survival animal model.…”