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Demodex Blepharitis
New drug found effective for disease that may affect more than half of patients. Howard Larkin reports from ASCRS 2021 in Las Vegas, USA
Anew treatment for Demodex blepharitis has been shown safe and effective in a pivotal phase 2b/3 US FDA trial, Elizabeth Yeu MD said. It is the first of two FDA studies, she added.
According to epidemiological studies, somewhere between 9 million and 25 million people are affected by Demodex blepharitis in the USA alone. “And yet there is no FDA-approved prescription therapeutic for the management of this disease,” Dr Yeu said.
Caused by an infestation of Demodex mites, Demodex blepharitis is also likely involved with many cases of dry eye. In a recent study conducted at six busy eye centres across the United States, 57.7% of 1,032 patients had collarettes or about the same number as had dry eye diagnoses, Ehsan Sadri MD said. Among patients who were using cyclosporine or lifitegrast for dry eye, 60% had collarettes—a major sign of Demodex blepharitis.
A separate study reported demodicosis newly diagnosed in 53.3% of eye patients, with 61.8% and 63.3% having blepharitis and dry eye, respectively, Dr Sadri said (Teo et al. ARVO 2021). Extrapolating numbers from these two studies, about 25 million of 45 million eye patients seen annually in the USA may have Demodex blepharitis, though this is higher than the 9 million estimated in population studies. A prospective study is needed to better understand its prevalence, he added.
SUCCESSFUL TREATMENT The randomised, controlled double-masked FDA pivotal trial involved 421 patients at 15 clinics across the USA. A test of a 0.25% ophthalmic solution of lotilaner called TP-03 (Tarsus Pharmaceuticals) against the medication vehicle alone in patients with confirmed Demodex blepharitis. A total of 206 treated patients and 204 control patients completed the sixweek study, Dr Yeu reported. Zero patients in the treatment group and one patient in the control group dropped out due to a mild treatment-related adverse event, while five dropped out due to COVID-19.
Demodex waste and by-products create collarettes, which can easily be seen on patients’ upper eyelashes when they look down. Patients included in the study needed to have at least one eye with more than 10 upper lid eyelashes with collarettes, 1.5 or more Demodex mites per lash on the upper and lower lids, and mild or worse lid margin erythema. Patients using lid hygiene within 14 days of screening were excluded.
Lotilaner has previous FDA approval as an oral medication to control fleas and ticks in dogs and cats. “It is a very well-known and utilised anti-parasitic agent,” Dr Yeu said. In Demodex blepharitis, it works by paralysing and killing Demodex mites.
On day 43 of treatment, 44% of the treated group and 7% of the control group reached the study’s primary endpoint—a complete collarette cure, defined as grade 0, or no more than two lashes with collarettes (p<0.0001). A clinically meaningful collarette cure, defined as grade 0 to 1 or no more than 10 collarettes, was achieved by 81% of the treated group and 23% of the control group (p<0.0001), Dr Yeu reported. Greater numbers of treated patients also achieved complete and meaningful collarette cures after 11 and 22 days of treatment, results also statistically significant (p<0.001 at all time points). Mean collarette grade before treatment in both groups was 2.8, or between about 50 and 100 collarettes.
MITE ERADICATION At 43 days, 68% of treated patients achieved complete mite eradication compared with 18% of controls (p<0.0001), Dr Yeu said. Mean mite density dropped from about 3.2 mites per lash before treatment in both groups to 0.14 in the treated group and 1.34 in the control group (p<0.0001).
Overall, 13.9% of treated patients and 1.0% of controls achieved a complete composite cure, defined as collarette and erythema grades of 0, while 68% and 20% respectively reached a clinically meaningful cure, with collarettes and erythema at grades 0–1. Grade 0 erythema was achieved in 19% of treated patients while 45% saw one grade or more decline.
Adverse events were also very low, with less than 1% occurring at any time during the trial, and none were serious in either group, Dr Yeu said. At day 43, there was minimal change in corneal staining and IOP in both eyes in both groups. Among 21 patients at one centre with endothelial cell results, change from baseline was less than 1.2%.
“It’s very exciting to see TP-03 proven a potentially safe and effective treatment for Demodex blepharitis,” Dr Yeu said. In addition to reaching all primary and secondary endpoints, TP-03 was well-tolerated, had a good safety profile, and 92% of patients rated it neutral to very comfortable, she concluded.
Dr Elizabeth Yeu is the Medical Director of the Virginia Eye Consultants—CVP Mid-Atlantic Cornea, Cataract, External Disease, and Refractive Surgery. She is an Assistant Professor of Ophthalmology, Eastern Virginia Medical School, Norfolk, Virginia, USA. She is also the co-host of the popular Ophthalmology Quicksand Chronicles podcast. eyeulin@gmail.com
