Clinical trial: a controlled trial of baclofen add‐on therapy in PPI‐refractory gastro‐oesophageal reflux symptoms

Abstract

Summary Background Proton pump inhibitors (PPI) have no effect on non‐acid reflux events which can continue to provoke gastro‐oesophageal reflux disease (GERD) symptoms. Baclofen, a γ‐aminobutyric acid agonist, can decrease non‐acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied. Aims To assess the efficacy of baclofen 10 mg t.i.d. vs placebo as add‐on therapy in PPI‐refractory GERD symptoms, in a randomised, double‐blind, placebo‐controlled study. Methods Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomised to 4 weeks of baclofen 10 mg or placebo t.i.d. Before and after treatment, patients underwent 24 h impedance‐pH monitoring on‐PPI. Throughout the study, patients filled out ReQuest diaries. Data were analysed using mixed models. Results About 60 patients were included (age 47.5 years [range 19–73], 41f/19 m), 31 patients were randomised to baclofen. One patient withdrew consent and five in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen‐treated group compared to placebo (p = 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP+ (n = 25) group improved significantly with baclofen (pcorr = 0.02), and worsened with placebo (pcorr = 0.008). The total number of reflux events decreased over time (p = 0.01), mainly due to the baclofen condition (pcorr = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (pcorr = 0.009), but not placebo. Conclusion Baclofen decreases several reflux parameters in PPI refractory GERD symptoms, but pH‐impedance monitoring is necessary before treatment as only SAP+ patients experience clinical benefit after 4 weeks.

On‐therapy impedance‐pH monitoring can efficiently characterize PPI‐refractory GERD and support treatment escalation

“…Several patients fear of side effects and complications of laparoscopic fundoplication 28 or are unfit for surgery, however. As an alternative to surgical interventions, baclofen can represent an effective add‐on therapy to PPIs, acting by reduction of overall reflux burden, 29 but its use is limited by side effects 4,12,13 . New medical therapies overcoming PPI failure with negligible side effects are actively investigated, including potassium‐competitive acid blockers 30 .…”

Editorial: refractory reflux sensitivity—A place for baclofen? Authors' reply

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We thank Dr Katz for his editorial on our paper 1,2 and agree that it offers a ray of hope for the use of baclofen in a selected group of patients with refractory gastro-oesophageal reflux disease (GORD) symptoms despite PPI intake. Those patients are commonly seen in clinical practice and, based on multichannel intraluminal impedance-pH (MII-pH) monitoring, can be subdivided into true refractory GORD (true rGORD), reflux hypersensitivity (RH) and functional heartburn (FH).

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Editorial: refractory reflux sensitivity ‐ a place for baclofen?

“…For those looking for a place for baclofen as add‐on medical therapy to proton pump inhibitors (PPIs) for refractory GERD, the 4‐week randomised, placebo‐controlled trial by Pauwels et al, 1 comparing baclofen 10 mg t.i.d. versus placebo added to twice‐daily PPI in 60 patients with continued typical GERD symptoms (without grade C or D erosions) offers a ray of hope, however faint, for a place for baclofen.…”