Pradeep Mundre1, Christopher J Black2, Noor Mohammed3, Alexander C Ford4. 1. Bradford Teaching Hospitals, Bradford, UK. 2. Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK; Leeds Institute of Medical Research, St James's University Hospital, Leeds, UK. 3. Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK. 4. Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK; Leeds Institute of Medical Research, St James's University Hospital, Leeds, UK. Electronic address: alexf12399@yahoo.com.
Abstract
BACKGROUND: Treatment of achalasia has changed substantially over the past 20 years. Therapeutic options offered to patients vary, depending on access to both resources and expertise, and include pneumatic dilation (PD), laparoscopic Heller's myotomy (LHM), or per-oral endoscopic myotomy (POEM). Although there are head-to-head trials of these interventions, many of these are small and underpowered, so relative efficacy is unknown. We did a systematic review and network meta-analysis to try to resolve this uncertainty. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Embase Classic from database inception up to June 11, 2020, for randomised controlled trials (RCTs) assessing the efficacy of POEM, LHM, or PD, compared with each other in adults with idiopathic achalasia. We extracted all data as dichotomous outcomes (treatment success or failure) after completion of therapy. We also extracted country of origin, number of centres, duration of follow-up, and primary outcome measure used to define treatment success or failure. Data were extracted for intention-to-treat analyses, with all dropouts assumed to be treatment failures (ie, symptomatic at final point of follow-up), wherever trial reporting allowed this. We pooled data using a random effects model, and assessed heterogeneity between studies using the I2 statistic. Risk of bias was examined for all studies. The primary outcome was efficacy, in terms of a dichotomous measure of treatment success or failure, after a minimum of 1 year of follow-up. Secondary outcomes were occurrence of perforation, adverse events, serious adverse events (including death), need for reintervention, need for surgery as a result of complications, development of gastro-oesophageal reflux, or erosive oesophagitis. Efficacy was reported as a pooled relative risk (RR) of treatment failure, with a 95% CI, for each comparison tested, and ranked by therapy according to P-score. FINDINGS: Of 1044 studies initially assessed, nine were eligible RCTs, which comprised 911 participants in total. None of the nine studies were at low risk of bias. Of the 911 participants 372 (41%) participants were randomly assigned to LHM, 317 (35%) participants to PD, and 222 (24%) participants to POEM. Of the three strategies, POEM was ranked first (RR of failure of treatment 0·33, 95% CI 0·15-0·71; P-score 0·89), then LHM (RR 0·45, 0·26-0·78, P-score 0·61). There was moderate heterogeneity between studies (I2=61·5%). Both POEM and LHM were superior to PD on direct and indirect comparison, but neither was significantly more effective than the other. There were no significant differences in perforation rates, need for re-intervention or surgery, gastro-oesophageal reflux, erosive oesophagitis, or serious adverse events, but PD was less likely to lead to adverse events than POEM. INTERPRETATION: POEM and LHM should be the preferred treatments for idiopathic achalasia. PD performed worst in terms of treatment success, and therefore its role in the management of patients with achalasia is less certain. FUNDING: None.
BACKGROUND: Treatment of achalasia has changed substantially over the past 20 years. Therapeutic options offered to patients vary, depending on access to both resources and expertise, and include pneumatic dilation (PD), laparoscopic Heller's myotomy (LHM), or per-oral endoscopic myotomy (POEM). Although there are head-to-head trials of these interventions, many of these are small and underpowered, so relative efficacy is unknown. We did a systematic review and network meta-analysis to try to resolve this uncertainty. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Embase Classic from database inception up to June 11, 2020, for randomised controlled trials (RCTs) assessing the efficacy of POEM, LHM, or PD, compared with each other in adults with idiopathic achalasia. We extracted all data as dichotomous outcomes (treatment success or failure) after completion of therapy. We also extracted country of origin, number of centres, duration of follow-up, and primary outcome measure used to define treatment success or failure. Data were extracted for intention-to-treat analyses, with all dropouts assumed to be treatment failures (ie, symptomatic at final point of follow-up), wherever trial reporting allowed this. We pooled data using a random effects model, and assessed heterogeneity between studies using the I2 statistic. Risk of bias was examined for all studies. The primary outcome was efficacy, in terms of a dichotomous measure of treatment success or failure, after a minimum of 1 year of follow-up. Secondary outcomes were occurrence of perforation, adverse events, serious adverse events (including death), need for reintervention, need for surgery as a result of complications, development of gastro-oesophageal reflux, or erosive oesophagitis. Efficacy was reported as a pooled relative risk (RR) of treatment failure, with a 95% CI, for each comparison tested, and ranked by therapy according to P-score. FINDINGS: Of 1044 studies initially assessed, nine were eligible RCTs, which comprised 911 participants in total. None of the nine studies were at low risk of bias. Of the 911 participants 372 (41%) participants were randomly assigned to LHM, 317 (35%) participants to PD, and 222 (24%) participants to POEM. Of the three strategies, POEM was ranked first (RR of failure of treatment 0·33, 95% CI 0·15-0·71; P-score 0·89), then LHM (RR 0·45, 0·26-0·78, P-score 0·61). There was moderate heterogeneity between studies (I2=61·5%). Both POEM and LHM were superior to PD on direct and indirect comparison, but neither was significantly more effective than the other. There were no significant differences in perforation rates, need for re-intervention or surgery, gastro-oesophageal reflux, erosive oesophagitis, or serious adverse events, but PD was less likely to lead to adverse events than POEM. INTERPRETATION: POEM and LHM should be the preferred treatments for idiopathic achalasia. PD performed worst in terms of treatment success, and therefore its role in the management of patients with achalasia is less certain. FUNDING: None.