Effect of Peroral Endoscopic Myotomy vs Pneumatic Dilation on Symptom Severity and Treatment Outcomes Among Treatment-Naive Patients With Achalasia: A Randomized Clinical Trial

Abstract

Importance: Case series suggest favorable results of peroral endoscopic myotomy (POEM) for treatment of patients with achalasia. Data comparing POEM with pneumatic dilation, the standard treatment for patients with achalasia, are lacking.

Objective: To compare the effects of POEM vs pneumatic dilation as initial treatment of treatment-naive patients with achalasia.

Design, setting, and participants: This randomized multicenter clinical trial was conducted at 6 hospitals in the Netherlands, Germany, Italy, Hong Kong, and the United States. Adult patients with newly diagnosed achalasia and an Eckardt score greater than 3 who had not undergone previous treatment were included. The study was conducted between September 2012 and July 2015, the duration of follow-up was 2 years after the initial treatment, and the final date of follow-up was November 22, 2017.

Interventions: Randomization to receive POEM (n = 67) or pneumatic dilation with a 30-mm and a 35-mm balloon (n = 66), with stratification according to hospital.

Main outcomes and measures: The primary outcome was treatment success (defined as an Eckardt score ≤3 and the absence of severe complications or re-treatment) at the 2-year follow-up. A total of 14 secondary end points were examined among patients without treatment failure, including integrated relaxation pressure of the lower esophageal sphincter via high-resolution manometry, barium column height on timed barium esophagogram, and presence of reflux esophagitis.

Results: Of the 133 randomized patients, 130 (mean age, 48.6 years; 73 [56%] men) underwent treatment (64 in the POEM group and 66 in the pneumatic dilation group) and 126 (95%) completed the study. The primary outcome of treatment success occurred in 58 of 63 patients (92%) in the POEM group vs 34 of 63 (54%) in the pneumatic dilation group, a difference of 38% ([95% CI, 22%-52%]; P < .001). Of the 14 prespecified secondary end points, no significant difference between groups was demonstrated in 10 end points. There was no significant between-group difference in median integrated relaxation pressure (9.9 mm Hg in the POEM group vs 12.6 mm Hg in the pneumatic dilation group; difference, 2.7 mm Hg [95% CI, -2.1 to 7.5]; P = .07) or median barium column height (2.3 cm in the POEM group vs 0 cm in the pneumatic dilation group; difference, 2.3 cm [95% CI, 1.0-3.6]; P = .05). Reflux esophagitis occurred more often in the POEM group than in the pneumatic dilation group (22 of 54 [41%] vs 2 of 29 [7%]; difference, 34% [95% CI, 12%-49%]; P = .002). Two serious adverse events, including 1 perforation, occurred after pneumatic dilation, while no serious adverse events occurred after POEM.

Conclusions and relevance: Among treatment-naive patients with achalasia, treatment with POEM compared with pneumatic dilation resulted in a significantly higher treatment success rate at 2 years. These findings support consideration of POEM as an initial treatment option for patients with achalasia.

Trial registration: Netherlands Trial Register number: NTR3593.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Fockens reported receiving personal fees from Cook Endoscopy, Olympus, Ethicon Endosurgery, and Fujifilm, consulting for Medtronic, and receiving research support from Boston Scientific and Ovesco outside the submitted work. Dr Beyna reported receiving grants, personal fees, and nonfinancial support from Olympus, and Boston Scientific, personal fees and nonfinancial support from Medtronic, personal fees from Falk Foundation, and grants and nonfinancial support from Erbe USA outside the submitted work. Dr Wu reported receiving personal fees from AstraZeneca, Takeda, Reckitt Benckiser, and Menarini outside the submitted work. Dr Costamagna reported receiving personal fees and nonfinancial support from Olympus, grants from Boston Scientific, and grants and nonfinancial support from Cook Medical outside the submitted work. Dr Kahrilas reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Pandolfino reported receiving personal fees from Medtronic, Diversatek, Torax, Ironwood, and Takeda and a grant from Impleo outside the submitted work. Dr Bredenoord reported receiving grants and personal fees from Norgine, grants and personal fees from Laborie, personal fees from Medtronic, personal fees from Diversatek, grants from Nutricia, personal fees from Regeneron, personal fees from Celgene, grants and personal fees from Bayer, and personal fees from DrFalk outside the submitted work and grants from Fonds NutsOhra and ESGE Research during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Enrollment, Randomization, and Follow-up of Patients in a Study of the Effect of Peroral Endoscopic Myotomy (POEM) vs Pneumatic Dilation on Symptom Severity and Treatment Outcomes in Patients With Achalasia

aThese patients only underwent a pneumodilation with a 30-mm balloon because adequate symptom control (Eckardt score ≤3) was achieved after a single pneumatic dilation procedure, confirmed by an IRP less than 10 mm Hg during high-resolution manometry. Of the 16 patients, 6 patients refused to undergo the additional high-resolution manometry.

Figure 2.. Eckardt Score at Baseline and the 2-Year Follow-up of Patients With Achalasia After Peroral Endoscopic Myotomy (POEM) or Pneumatic Dilation

Each vertical line represents an individual patient. Patients who achieved an Eckardt score of ≤3 (vertical line ends at or below the dashed horizontal line) had adequate symptom control and were considered successfully treated. One patient had a severe complication (a perforation) during pneumatic dilation and was considered a direct treatment failure, but still had an Eckardt score of 0 after treatment.