Endoscopic sinus surgery for chronic rhinosinusitis (CRS) provides significantly better disease-specific quality of life at 6 months than long-term, low-dose treatment with the macrolide antibiotic clarithromycin.

Therefore, if intranasal corticosteroids, saline nasal irrigations, and a short course of oral antibiotics do not achieve symptom control of this debilitating condition, surgery is recommended, according to investigators in the MACRO trial, led by Surgeon Carl M. Philpott, MB ChB, a professor of rhinology and olfactology at Norwich Medical School in the University of East Anglia, Norwich, England.

CRS had a pooled prevalence of approximately 9% among adults during 1980-2021. It entails nasal obstruction and discharge, facial pain, anosmia, and sleep disturbance and can have a major negative effect on quality of life.

Reported in The Lancet, the pragmatic, three-arm randomized, placebo-controlled study found 6-month scores on the 22-item Sino-Nasal Outcome Test were significantly lower in the surgery group than in the clarithromycin group, for an adjusted mean difference of 18.13 (98.33% CI, -24.26 to -11.99; P < .0001).

Ten serious adverse events occurred in nine participants: two events in two patients in the clarithromycin group, three events in three patients in the placebo group, and five events in four patients in the surgery group.

Offering a nonparticipant’s US perspective on the study, Chadi A. Makary, MD, MSc, associate professor and chief of rhinology at West Virginia University in Morgantown, West Virginia, told Medscape Medical News the recommendations “align with typical US pathways that escalate to endoscopic sinus surgery for refractory CRS and do not routinely rely on long-term macrolides except in selected CRS [cases] without nasal polyps.” 

He noted that this year the American Academy of Otolaryngology-Head and Neck Surgery issued a new evidence-based guideline on the surgical management of CRS. The guideline suggests that surgery is especially effective for those with fungal infections or nasal polyps, who often don’t respond well to medication alone.

Makary added that the MACRO group’s ongoing 5-year follow-up is crucial to quantify symptom durability, recurrence, and revision rates. “Head-to-head studies of endoscopic sinus surgery vs other medical treatments such as biologics in CRS with nasal polyps with cost-effectiveness analysis will better position surgery in contemporary care algorithms.”

In terms of generalizability, Makary said MACRO was conducted in predominantly White participants and UK care pathways. “US-based effectiveness and implementation studies in diverse populations and different insurance/authorization dynamics would strengthen generalizability.”

“Patients who have failed topical medication such as steroid sprays and saline rinses should be referred to ENT [ear, nose, and throat specialty] for consideration of sinus surgery,” Philpott said. Antibiotics should not be used in primary care and should not be used in secondary care for CRS with nasal polyps especially cases with type 2 inflammation, he said.

“And in the era of monoclonal antibodies, we will need to establish which patients need these medications. For now, it will be those who failed to improve after sinus surgery, as we saw with 13 patients in the surgical arm of our trial.”

In summary, Makary said MACRO provides high-quality evidence for offering endoscopic sinus surgery confidently and avoiding routine long-term macrolides in unselected patients. “Shared decision-making should still weigh patient phenotype, comorbid asthma, aspirin-exacerbated respiratory disease, prior surgery, access, and financial considerations.”

This study was funded by the UK’s National Institute for Health and Care Research (NIHR). Philpott reported receiving grants from the NIHR and the Engineering and Physical Sciences Research Council, as well as consultancy fees from GSK, Sanofi, Medtronic, and Stryker and royalties from Thieme. Several coauthors reported similar research support, as well as financial relationships with the private sector. Makary had no relevant conflicts of interest.