Laparoscopic surgery in idiopathic pulmonary fibrosis (IPF) patients with acid reflux is safe and well-tolerated, but does not appear to significantly ease the decline in respiratory function that’s thought to be aggravated by reflux, according to a Phase 2 study.
The research, “Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial,” was published in the journal The Lancet Respiratory Medicine.
Patients with IPF often have abnormal acid gastro-esophageal reflux (GER), a condition in which acid from the stomach leaks into the esophagus. GER is thought to contribute to IPF worsening through aspiration of acid and non-acid components into the lungs.
Evidence linking such GER to its treatment on IPF progression is mixed. Two analyses of clinical trials came to opposite conclusions — while one showed a reduced rate of physiological decline and acute exacerbation with anti-acid treatments, the other reported no effect.
However, two other studies suggested that surgical treatment for GER, including laparoscopic anti-reflux procedure — a minimally-invasive procedure that creates an effective valve mechanism at the bottom of the esophagus — improved IPF patients’ survival, while showing excellent safety outcomes and stabilized respiratory function.
A review study in patients with interstitial pulmonary disease also suggested that anti-reflex laparoscopy may slow disease progression.
Aiming to determine if preventing abnormal acid GER with laparoscopy lowers the rate of disease progression — as assessed by changes in forced vital capacity (FVC), a test of pulmonary — and eases lung damage, acute flares, respiratory-related hospitalizations and death rates, researchers conducted the Phase 2 WRAP-IPF trial (NCT01982968).
The study was conducted at six U.S. academic sites, selected due to their expertise in IPF and experience with this type of surgery. Only IPF patients with evidence of unusual acid reflux and preserved FVC (above 50% predicted) were eligible. Treatment with IPF medications Ofev (nintedanib, by Boehringer Ingelheim) and Esbriet (pirfenidone, by Genentech) was allowed.
A total of 58 patients were randomly divided into surgery (29 patients; mean age, 70.6) or no surgery (29 patients; mean age, 69.2) groups.
All were assessed at baseline, or study start, and again at weeks 12, 24, 36, and 48. Spirometry, which measures the rate of air flow in and out of the lungs, the six-min walk test — an assessment of exercise capacity — and patient-related evaluations were done at each visit.
Safety assessments were done at weeks 4, 8, 16, 20, 28, 32, 40, 44, and 52. Patients also completed a questionnaire on reflux symptoms at baseline and at 48 weeks.
Twenty-seven of the 29 assigned surgery were available for analysis at week 48 (two underwent the procedure after week 24), as were 20 patients in the non-surgery group.
Findings revealed that patients who underwent surgery had better FVC at 48 weeks — the trial’s main goal — compared to those who did not. However, although surgery eased FVC decline at 48 weeks compared to baseline values (-0.05 L), the difference in FVC between the groups was not statistically significant.
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Acute flare-ups, respiratory-related hospitalization, lung transplant, and death were comparatively less common in patients who underwent surgery, but again improvements here were not statistically significant, meaning they did not carry scientific weight.
The data further revealed that time to death, or a 10% decline in FVC, or acute IPF exacerbation, was longer in the surgery group, but differences in parameters that included cough severity, shortness of breath, health-related quality of life, exercise capacity, or reflux severity were again not significant.
The most frequent adverse events after surgery were dysphagia (difficulty swallowing) in eight of 28 patients (29%) and abdominal distention, or swelling, in four (14%). One surgery patient had to be hospitalized due to dehydration and adrenal insufficiency.
Five people died, one in the surgery group. All deaths were preceded by acute flares, which “suggests that patients with IPF and abnormal acid GER might be at particularly high risk for developing an acute exacerbation,” the researchers wrote.
Overall, “laparoscopic anti-reflux surgery is safe and well tolerated but did not show that such surgery significantly slows the rate of FVC decline,” the team concluded.
The researchers emphasized that more patients would be needed to properly assess improvements, and that further studies are warranted to also determine the effect of anti-acid medications on IPF progression, as well as differences between acid and non-acid GER.
The study authors reported they have worked consultants, and received perceived fees, grants and/or non-financial support from several pharmaceutical companies, but such receipts are unrelated to this study.