Take-home: Dexamethasone insert, 0.4 mg (Dextenza, Ocular Therapeutix), a newly developed, sustained-release intracanalicular insert, is safe, effective, and well tolerated for treating ocular itching associated with allergic conjunctivitis.
A phase III study of dexamethasone insert, 0.4 mg (Dextenza, Ocular Therapeutix) found that the sustained-release intracanalicular insert is safe, effective, and well tolerated for treating ocular itching associated with allergic conjunctivitis.
Intracanalicular inserts may be the next step to relieving the signs and symptoms of acute and chronic allergic reactions, Lisa Feulner, MD, PhD, reported. While topical therapies are good at providing relief for patients with early-phase allergic flare-ups, a chronic, late-phase reaction might persist.
In contrast, corticosteroids are effective against that late-phase reaction, and intracanalicular drug inserts can provide that continuous relief that patients with ocular allergies need, added Dr. Feulner, in private practice, Bel Air, MD.
“Such modalities allow for one-time administration of a corticosteroid to deliver a tapered, extended-release dose of dexamethasone over about four weeks,” she said.
Phase III clinical trial
Dr. Feulner and colleagues conducted a study to evaluate the safety and efficacy of Dextenza administered, via a 30-day, sustained-release dexamethasone insert. The results were compared with those of a placebo insert in patients with allergic conjunctivitis using a modified conjunctival allergen challenge model (CAC, Ora).
Patients were 18 years of age and older, had a positive history of ocular allergies, and a positive skin test reaction to a perennial allergen, and a seasonal allergen. They also had a positive bilateral CAC reaction to a perennial allergen at the first visit and for at least 2 of 3 time points after the challenge.
Patients were excluded if they had undergone a refractive surgery, including LASIK, or had a history of retinal detachment or diabetic retinopathy, active ocular infections, herpes simplex keratitis, glaucoma, ocular hypertension, or spikes in their intraocular pressure (IOP) values. They also were excluded if they used certain topical or systemic antihistamines, decongestants, and other anti-inflammatory agents.
The study protocol required 13 evaluations during the course of 11 weeks. The primary endpoints at the sixth evaluation (day 8) were ocular itching (symptom) rated on a scale of 0 to 4 at 3, 5, and 7 minutes after CAC and conjunctival redness rated on a scale of 0 to 4 at 7, 15, and 20 minutes after CAC.
Both scales allowed for half-unit increments. The secondary endpoints were ocular itching, eyelid swelling, tearing/watery eyes, rhinorrhea, nasal pruritus, ear or palate pruritus, nasal congestion, conjunctival redness, ciliary and episcleral redness, and chemosis. The safety evaluations included recording of any adverse events, findings on slit-lamp biomicroscopy, IOP evaluations, dilated fundus examination, and visual acuity.
Dr. Feulner explained that to show the drug’s efficacy against ocular itching and conjunctival redness, clinical superiority had to be demonstrated over placebo by at least 0.5 unit on a 5-point scale for all 3 time points after CAC and at least 1 unit for 2 of 3 time points after CAC.
Seventy-three patients were included in the study; 35 were randomized to treatment with the active-treatment insert and the remainder to the placebo insert. The insertion process was not successful in 1 patient in the dexamethasone insert group. Two patients (1 in each group) withdrew consent and did not complete the study.
Dr. Feulner reported that the dexamethasone insert was superior to vehicle for treating ocular itching on day 8, and the responses were significant (P < 0.0001) compared with the placebo group at 3, 5, and 7 minutes after CAC. The treatment differences for the dexamethasone insert were -1.02, -0.87, and -1.04, respectively, at the 3 time points.
However, regarding conjunctival redness on day 8, the drug was not superior to placebo, Dr. Feulner explained. Differences between the groups were significant on only 2 of the 3 time points after CAC, i.e., at 15 and 20 minutes (P ≤ 0.0419), which failed to meet the criteria for clinically meaningfulness at the 7-, 15-, and 20-minute time points with differences of -0.26, -0.32 and -0.41, respectively.
There were no differences between the groups regarding the secondary endpoints.
Regarding safety, a total of 4 adverse events developed in 3 subjects treated with the dexamethasone insert and a total of 7 adverse events developed in 4 subjects treated with placebo. All adverse events were considered mild or moderate, with most affecting the eye.
The most common of these was increased lacrimation, which was reported by 1 subject in the dexamethasone insert group and 2 subjects in the placebo group. No serious adverse events developed in either groups, and no subjects withdrew from the study because of an adverse event.
“Based on these results, (dexamethasone insert) is effective for treating ocular itching but not conjunctival redness associated with allergic conjunctivitis,” Dr. Feulner said. “Treatment with (the dexamethasone insert) is safe and well-tolerated.”