Highlights from the literature

Randomised trial of medical versus surgical treatment for refractory heartburn

A randomised placebo-controlled study published in the New England Journal of Medicine aimed to compare medical and surgical management of patients with dyspepsia refractory to treatment with proton-pump inhibitors (PPIs).¹ Patients presenting with dyspepsia were asked to complete a baseline Gastro-oesophageal Reflux Disease–Health-Related Quality of Life (GERD-HRQL) score and were given a 2-week course of omeprazole 20 mg once daily. Patients with <50% improvement in GERD-HQRL score and with no other identifiable cause of gastro-oesophageal reflux disease (GORD) were deemed to have refractory heartburn and were randomised to further medical or surgical treatment or placebo. Patients were excluded if they had other identifiable causes of heartburn, such as motility disorders, structural abnormalities or other forms of functional heartburn. A total of 366 patients were enrolled in the trial, with 78 patients meeting the inclusion criteria. The authors screened patients for functional disorders by ensuring all trial participants underwent endoscopy and biopsy, oesophageal manometry and oesophageal multichannel intraluminal impedance and pH monitoring.

Patients on medical treatment were given 20 mg of omeprazole with addition of baclofen or placebo. At 3 monthly assessment, desipramine or placebo was added if <50% improvement in GERD-HRQL score or patients could not tolerate side effects. Patients who did not improve by >50% after treatment with baclofen and desipramine (or were unable to take desipramine) at each quarterly visit were deemed to have failed treatment. The primary outcome was treatment success defined as an improvement of ≥50% in the GERD-HRQL at 12 months from baseline.

Patients randomised to the surgical group underwent laparoscopic Nissen fundoplication; treatment failure was defined as <50% improvement in GERD-HQRL score, at any quarterly visit or as a requirement for further medical treatment (eg, PPI, baclofen and desipramine) postoperatively.

The success rate for the surgical group (18/27 patients, 67%) was substantially higher when compared with the active medical group (7/25 patients, 28%; p=0.007) and the control medical group (3/26 patients, 12%; p<0.001). This small study suggests that surgical intervention may be associated with an increase in quality of life when compared with medical management of refractory heartburn; however, it is difficult to generalise this to clinical practice due to the strict exclusion criteria and small sample size.

Ustekinumab as induction and maintenance therapy for ulcerative colitis

A randomised controlled UNIFI trial published in the New England Journal of Medicine compares ustekinumab with placebo as an induction and maintenance therapy in patients with moderate-to-severe ulcerative colitis who had previously not responded to/tolerated conventional treatment, TNF antagonists or vedolizumab.² Nine hundred sixty-one patients were randomised to receive either ustekinumab (subdivided into two active treatment groups; 130 mg fixed induction dose (320 patients) or 6 mg/kg induction dose (322 patients), or placebo (319 patients)). The trial’s primary endpoint was clinical remission (ie, Mayo scale score of 2 or less, with no subscore greater than 1 in any of the Mayo score components). Patients who responded to the induction dose of ustekinumab were further randomised for maintenance treatment (90 mg injection every 12 weeks (172 patients) or 8 weeks (176 patients), or placebo (175 patients)).

The study found that patients in the active treatment groups were more likely to be in remission at 8 weeks following induction (15.6% for fixed dose and 15.5% for weight-based dose) when compared with placebo (5.3%, p<0.001).

Among patients who responded to active treatment at 8 weeks, those who received subsequent ustekinumab 90 mg every 8 weeks (43.8%) or 12 weeks (38.4%) were more likely to be in remission at 44 weeks than those given placebo (24.0%, p=0.002 and p<0.001). The number of patients reporting at least one adverse event after induction was comparable between fixed-dose (41.4%), weight-based dose (50.6%) and placebo (48.0%) groups. However, two patients in the treatment group unexpectedly died (one from oesophageal variceal bleed and one from acute respiratory distress syndrome); seven patients developed cancer (including three skin cancers), compared with one case of cancer and no deaths in the placebo group. The study concluded that ustekinumab was superior to placebo at inducing and maintaining remission in patients with ulcerative colitis.

Infliximab induction regimens in steroid‐refractory acute severe colitis: multicentre retrospective cohort study with propensity score analysis

A retrospective cohort study published in Alimentary Pharmacology and Therapeutics looked to evaluate the efficacy of rapid and standard infliximab induction regimens in the treatment of acute severe ulcerative colitis (ASCU) refractory to steroid treatment.³

One hundred thirty-one patients receiving infliximab for ACSU were included, with 29 undergoing accelerated induction. Patients were included if they were hospitalised and were already being treated with intravenous corticosteroids and met modified Truelove and Witt’s criteria for ASCU. The primary endpoint, colectomy at 30 days post-treatment, was not significantly different between patients undergoing accelerated (n=18, 17.6%) and normal (n=6, 20.7%; p=0.45) induction regimens. Fifty-two patients were evaluated using propensity score matching (account for variables including age, gender, disease extent and Mayo score). Overall colectomy rates at 1 year were no different between the two groups (57% vs 31%, p=0.09). However, the incidence of index admission colectomy was significantly lower in the accelerated group (23% vs 53%, p=0.045), as was 30-day colectomy rate (27% vs 57%, p=0.048).

The authors conclude that using an accelerated infliximab induction regimen is not associated with any significant difference in colectomy rates in patients with ACSU, although there seemed to be a reduction in early, in-hospital colectomies in patients matched using propensity score analysis.