Another Ivermectin Flop; ‘Instant’ Lung Cancer Decision Tool; Triple COPD Tx & Death

Several studies caught our eye at the just-concluded European Respiratory Society’s virtual annual meeting. Among them: more negative findings for ivermectin as a COVID-19 treatment; clinical performance of a novel image-analysis system that determines in real time whether lung tissue biopsies collected during surgery contain malignant cells; and insights into just how triple therapy for chronic obstructive pulmonary disease (COPD) reduced mortality in the pivotal ETHOS trial.

Ivermectin Fails (Again)

If more proof were needed that ivermectin isn’t a helpful treatment for COVID-19, now come data from Pakistan that will be hard to dismiss as the pharmaco-industrial complex at work.

Clinicians at Aga Khan University Hospital in Karachi treated 65 inpatients with ivermectin at 12 mg three times daily plus standard care, which at the time (October 2020 to January 2021) consisted of steroids and vitamin C. Their outcomes were no better than in 67 similar patients receiving only standard treatment. All patients were considered to have mild to moderate COVID-19 that nevertheless needed hospital care.

Both median hospital stays (4.39 days with ivermectin vs 4.68 for controls) and the number needing assisted ventilation (five vs six) were similar in the two groups.

“No symptomatic improvement,” relative to standard care, was seen either, said study authors led by S.M. Zubair.

Confirming Lung Cancer in the OR

Wouldn’t it be good if surgeons collecting lung tissue biopsies could determine then and there whether they are malignant, without waiting for conventional pathology lab analysis?

Laura van Huizen, a doctoral student at Vrije University in Amsterdam, described a novel system based on so-called higher harmonic generation (HHG) microscopy, a self-contained unit that can be rolled right into the operating room.

She explained that it provides real-time three-dimensional imaging, based on 1070-nm laser light, at subcellular resolution with software that distinguishes malignant from benign cells. Results come in 5 to 10 minutes (mean 7 minutes).

To this point, 67 biopsy samples from 32 patients have been analyzed with the system and with “gold standard” pathology examination, to help refine the analytic software. The system is not yet commercially available, and van Huizen did not indicate when it might be. However, she said, its successful development could provide faster and better decision making in the OR, with fewer biopsies and potentially fewer repeat diagnostic procedures needed to establish treatment plans.

CV Events Drove Mortality Reduction in ETHOS

One of the enduring mysteries in COPD has been why patients don’t get a survival benefit from treatments that demonstrably reduce exacerbation rates. That nut appeared to have been cracked last year, when the ETHOS trial showed that triple therapy — combining an inhaled corticosteroid (ICS) with a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) — did indeed reduce all-cause mortality by 46% relative to either LABA/LAMA or ICS/LABA dual therapy.

That study was funded by AstraZeneca, whose budesonide/formoterol/glycopyrrolate combination, Breztri Aerosphere, is in hot competition with a similar product from GlaxoSmithKline. Both were approved as COPD maintenance therapy within months of each other last summer. AstraZeneca was keen to explore the details of this survival benefit. It funded a post-hoc analysis of ETHOS, and the results are now in.

As reported by Mona Bafadhel, MBChB, PhD, of the University of Oxford in England, it appears that reductions in fatal cardiovascular events drove the all-cause mortality findings. Cardiovascular death rates with triple therapy were less than half that seen with LABA/LAMA, though similar to the rate for ICS/LABA. A similar pattern was seen for all major cardiovascular events, including nonfatal MI and stroke, as well as fatal ones.

A key mediating factor was eosinophil counts, Bafadhel indicated. LABA/LAMA’s poor performance was seen primarily in patients with counts of 100 cells/mm³; in patients with counts above 300, cardiovascular death rates were massively lower with triple therapy compared with both dual therapies. Similarly, nonfatal MI also increased with LABA/LAMA relative to the other therapies, mainly for patients with higher eosinophil counts. This relationship with eosinophil counts was seen in the all-cause mortality data reported last year.

One oddity in the findings was that nonfatal stroke rates did not differ markedly between any of the therapies, irrespective of eosinophil counts. “I would presume this is a consequence of very low event numbers of nonfatal stroke in this study,” Bafadhel said.

One other takeaway from these data is the importance of including ICS as part of COPD maintenance therapy, she concluded.