Botulinum toxin for the treatment of hypercontractile esophagus: Results of a double‐blind randomized sham‐controlled study

Abstract

Introduction Botulinum toxin injection is known to be efficient to treat achalasia. We conducted a randomized trial in order to evaluate its efficacy to treat symptomatic hypercontractile esophageal disorders as characterized by esophageal high‐resolution manometry. Methods Patients with significant dysphagia and/or thoracic pain related to an hypercontractile esophageal motility disorder as defined by the Chicago Classification were randomized to receive an injection of botulinum toxin (100 U in 10 points in the distal part of the esophageal wall) or a sham procedure. Symptoms were assessed at 3 months with the Eckardt score. Patients could receive a first or second botulinum toxin injection 1 month later if symptoms persisted. Results Twenty‐three patients (13 women, mean age 60 years) were included: 13 received botulinum toxin injection, and 10 a sham procedure. The improvement of symptoms at 3 months was significant compared to baseline, but similar in the active treatment and sham procedure arms. However, there was no change in quality of life scores. Seventeen patients received a second injection at 4 months. There was a significant trend toward improvement of symptoms up to the end of follow‐up at 12 months, without a significant relationship with the administration of botulinum toxin. Discussion Botulinum toxin injection is not superior to a sham procedure to improve symptoms related to hypercontractile esophageal disorders, suggesting an important placebo effect in for this type of disease. This observation must be taken into account when evaluating more aggressive therapies such as endoscopic myotomy (clinicaltrials.gov: NCT01955174).

Jackhammer esophagus: Clinical presentation, manometric diagnosis, and therapeutic results—Results from a multicenter French cohort

“…However, a recent randomized study in patients with hypercontractile esophagus, including JE, demonstrated that symptom improvement after botulinum toxin was not superior to a sham procedure and that symptoms and manometric patterns may improve spontaneously over time 26 . Surprisingly, in this study, 3 out of 10 patients who did not receive any treatment had a favorable evolution of hypercontractile esophagus, including one with JE 26 ; this could be due to a placebo effect or to the spontaneous evolution of the disease. Regarding POEM, two recent multicenter retrospective studies demonstrated the efficacy of this technique in patients with a spastic motor disorder of the esophagus, including patients with JE, refractory to medical treatment, 13,15 and a recent meta‐analysis also confirmed these results 14 .…”

Endoscopic management of gastrointestinal motility disorders – part 1: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

“…Two RCTs compared endoscopic botulinum toxin injections in the esophagus with sham injections. The first study showed some effect of botulinum toxin on symptoms over and above that of the sham injection, but a second study showed no more effect for botulinum toxin than for the sham injection, with a benign natural history reported in both cohorts [70,71]. It thus seems questionable whether an invasive treatment such as POEM is justified in patients with spastic motility disorders, given this benign natural history and lack of evidence on efficacy and safety from methodologically sound studies.…”

The hypercontractile esophagus: Still a tough nut to crack

“…The importance of a sham-or placebo-controlled study design is underlined by the results of a randomized sham-controlled botulinum toxin injection trial carried out by Mion et al32 In this study that included 23 patients with HE, there was no difference in symptom improvement, as assessed by the Eckardt score at 3 months, between patients who received Botox and those who were in the sham-control group. Patients in both groups reported symptom improvement, suggesting a relevant placebo effect in both treatment groups 32.…”

“…The importance of a sham-or placebo-controlled study design is underlined by the results of a randomized sham-controlled botulinum toxin injection trial carried out by Mion et al32 In this study that included 23 patients with HE, there was no difference in symptom improvement, as assessed by the Eckardt score at 3 months, between patients who received Botox and those who were in the sham-control group. Patients in both groups reported symptom improvement, suggesting a relevant placebo effect in both treatment groups 32. A third paper published in this issue of the journal describes a patient in whom dysphagia and manometric signs of HE resolved immediately after radiofrequency ablation for atrial fibrillation33 The authors speculate that damage to extrinsic nervous fibers (vagus nerve branches?)…”