Dec 072018

by Diana Swift, Contributing Writer, MedPage Today

Laparoscopic anti-reflux surgery deserves further investigation for prevention of idiopathic pulmonary fibrosis (IPF) progression in some patients with gastroesophageal reflux disorder (GERD), after favorable results were seen in a phase II study.

Known as the WRAP-IPF trial, the study found GERD surgery was safe and well tolerated, with fewer serious adverse events and deaths in those receiving surgery. "The potential therapeutic value of laparoscopic anti-reflux surgery in this disease subgroup should be confirmed in larger, more generalizable trials," Ganesh Raghu, MD, of the University of Washington in Seattle, and colleagues wrote in The Lancet Respiratory Medicine.

Commenting on his group's findings in a university news release, Raghu said, "It is clear that there is a strong association of abnormal acid reflux and IPF and the hypothesis that it may contribute to progression of disease is a longstanding one. But what is not clear is the evidence to date regarding the clinical impact of the acid gastroesophageal reflux and treatment as far as disease progression. We found that outcomes that are meaningful to patients with pulmonary fibrosis – acute exacerbation, hospitalization for respiratory problems, and deaths – were numerically fewer within the group who had surgery compared to the group that did not receive the surgery."

Stabilizing fibrosis is critical since the median survival following an IPF diagnosis is 3 to 5 years. MedPage Today previously reported that antacid therapies, including proton pump inhibitors, do not improve outcomes in IPF patients.

During 2014-2016, the WRAP investigators screened 72 patients from six centers for IPF with abnormal acid reflux, enrolling 58 randomized 1:1 to laparoscopic anti-reflux surgery or standard medical treatment with antacids. Eligible participants had abnormal acid reflux, with a DeMeester score of ≥14.7 measured by 24-hour pH monitoring and preserved forced vital capacity (FVC). The mean age in both arms was about 70 years, but males predominated in both groups at 97% in the surgery group and 66% in the standard care group. Caucasians made up 93% of both arms. DeMeester scores were high in both groups, and the majority were former smokers.

At 48 weeks, no significant difference in FVC was observed in the 27 surgery patients versus 20 no-surgery patients having an FVC measurement. Intention-to-treat analysis adjusted for baseline anti-fibrotic use revealed an adjusted rate of change in FVC over 48 weeks of –0.05 L (95% CI –0.15 to 0.05) in the surgery group and –0.13 L (95% CI –0.23 to –0.02) in the non-surgery group (P=0.28).

While fewer surgery patients experienced acute exacerbations (one versus four), respiratory-related hospitalizations (two versus six), and deaths (one versus four), the differences were not statistically significant. After surgery, the most common adverse events were dysphagia (eight of 28 patients) and abdominal distention (four of 28).

"These results suggest that patients with IPF and abnormal acid [reflux] might be an important subgroup of this disease and further research is needed to discover whether they could benefit from anti-reflux surgery to prevent microaspiration and further injury to the lung," Raghu and associates wrote. In an earlier retrospective study, the group had similarly documented the safety of the procedure as well as a trend to slowing disease progression in IPF patients who underwent fundoplication.

Asked to give her perspective on the findings, Kerri Johannson, MD, of the University of Calgary in Alberta, Canada, and not involved in the trial, said, "This well-conducted phase II study demonstrates that laparoscopic anti-reflux surgery [LARS] is safe in a subset of patients with IPF and abnormal reflux. There are encouraging trends favoring LARS in improving clinical outcomes, and these preliminary data justify further research to determine if this intervention should be offered to patients as a treatment for IPF."

Commenting in the university new release, James Kiley, PhD, of the National Heart, Lung and Blood Institute, which funded the trial, agreed: "These results are interesting and open new research questions about the morbidity associated with IPF and the mechanisms of disease exacerbation."

Addressing study limitations, the authors noted that the surgery was performed by highly experienced surgeons at established academic centers of excellence for IPF, with 17 (61%) of 28 surgeries done at one center, raising the question of generalizability to community populations. Other limitations included the small number of participants and missing information, both of which reduced the study's statistical power. In addition, the trial was not designed to stratify the use of proton-pump inhibitors or H2 receptor antagonists, so the potential effects of specific antacid treatments could not be determined. In addition, the no-surgery group included considerably more women than the surgery group (34% versus 3%).

The U.S. National Institutes of Health's National Heart, Lung and Blood Institute funded this work. Raghu is a consultant to Bellerophan, Boehringer-Ingelheim, BMS, Biogen, Fibrogen, Nitto, Patara, Promedior, Sanofi, and Veracyte for IPF-related studies, outside of the submitted work. Several other study authors disclosed financial ties to industry partners.

Primary Source: Lancet Respiratory Medicine

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