This article discusses some of the new ophthalmic drugs and therapies that have recently come out on the market within the past year for the treatment of allergic conjunctivitis, uveitis and dry eyes.
Zerviate
Zerviate (NicOx; cetirizine ophthalmic solution 0.24%) was approved in May 2017 for the indication of ocular itching associated with allergic conjunctivitis. This drop is a second-generation antihistamine (H1 receptor antagonist) that binds competitively to histamine receptor sites. The drop works to reduce swelling, itching and vasodilation. The recommended dose is one drop in each eye twice daily.
Three randomized, double-masked, placebo-controlled, conjunctival antigen challenge (Ora-CAC model of allergic conjunctivitis) clinical trials were performed for the FDA approval. Patients with allergic conjunctivitis were included. In two of the trials, Zerviate demonstrated a statistically and clinically significant decrease in ocular itching compared to placebo at 15 minutes and eight hours after treatment. Adverse effects associated with the use of Zerviate may include ocular hyperemia, instillation site pain, and reduction in visual acuity.
Humira
Humira (Abbvie; adalimumab) was FDA approved in July 2016 for the treatment of non-infectious intermediate, posterior and panuveitis. This drug is a tumor necrosis factor (TNF) blocker. It is supplied as an injection subcutaneous use. The recommended dose is 80 mg as an initial dose, followed by 40 mg every other week starting one week after the initial dose
Two randomized, double-masked, placebo-controlled studies (UVI and II) were performed for the FDA approval. Patients received placebo or Humira at an initial dose of 80 mg followed by 40 mg every other week starting one week after the initial dose. The primary efficacy endpoint in both studies was time to treatment failure. There were 217 patients in study UVI with active uveitis who were being treated with steroids (oral prednisone 10 to 60 mg/day). All patients received 60 mg /day of prednisone at study entry followed by a mandatory taper schedule, with complete corticosteroid discontinuation by week 15. Study UVII evaluated 226 patients with inactive uveitis who were being treated with steroids (oral prednisone 10 to 35mg/day) at baseline to control their disease. These patients underwent a mandatory taper with complete cessation of steroids by week 19. Results from both studies showed statistically significant reduction of the risk of treatment failure in patients treated with Humira versus patients receiving placebo.
Adverse effects associated with Humira may include infections, injection site reactions, headache and rash. Humira comes with a black box warning of an increased risk of serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants. Humira use may also lead to an increased risk of malignancy.
True Tear Intranasal Tear Neurostimulator
True Tear (Allergan) is the first FDA-cleared device used to increase tear production through neurostimulation in adults. This device is a handheld stimulator that comes with daily disposable tips that are inserted into the nasal cavity causing temporary neurostimulation resulting in tear production.
There were two clinical trials that showed positive safely and effectiveness in 145 aqueous deficient dry eye adult patients. Study 1 was a prospective, randomized, controlled, double-masked, multicenter, cross-over trial. Participants used True Tear to stimulate tear production for 180 days. The primary endpoint of increased tear production was measured by Schirmer tests during application of the device as compared with basal Schirmer score at day 180. Secondary endpoints looked at increased tear production during application of the device compared with basal Schirmer score at days 0, 7, 30 and 90, which were met.
True Tear should not be prescribed for patients with a cardiac pacemaker, implanted metallic or electronic devices in the head or neck, a known hypersensitivity to the hydrogel device material, chronic or recurrent nosebleeds or bleeding disorders/conditions that can lead to increased bleeding. Also, stimulation with the device should not be delivered around electronic monitoring equipment (cardiac monitors, ECG alarms, etc), in the bath and shower, while driving, operating machinery, during activity in which sneezing/watery eyes may cause risk, areas other than the nose, within three feet of the shortwave or microwave therapy equipment, around flammable anesthetics mixture (air, oxygen or nitrous oxygen). If the device is used on irritated nasal tissue, injury may incur.
The safety has not been established in pregnancy, patients under 22 years of age, patients status post nasal or sinus surgery, or significant trauma, severe nasal airway obstruction or vascularized polyp, active severe systemic or chronic seasonal allergies, rhinitis or sinusitis requiring treatment, untreated nasal infection and disabling arthritis, neuropathy, severe dexterity impairment or limited motor coordination.
Xiidra
Xiidra (Shire; lifitegrast) was FDA approved about a year ago in July 2016 for the treatment of dry eye disease. Xiidra is an orally active dual leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) inhibitor. LFA-1 is a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). ICAM-1 may be overexpressed in corneal and conjunctival tissues in dry eye disease. LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell activation and migration to target tissues. LFA-1 antagonists mediate both migration and adhesion of the white blood cells to sites of inflammation. Xiidra is supplied as an ophthalmic solution for topical ophthalmic use. The recommended dose is one drop twice daily in each eye. Adverse effects include instillation site irritation, dysgeusia, and decreased visual acuity.
The FDA approval of Xiidra was based on four 12-week, randomized, multi-center, double-masked, vehicle-controlled studies in a total of 1,181 patients. Patients were randomized to Xiidra or vehicle in a 1:1 ratio and dosed twice daily. Use of artificial tears was not allowed during the studies. Outcome measures include Eye Dryness Score (EDS), which was rated by patients using a visual analogue scale (VAS) (0 = no discomfort, 100 = maximal discomfort) at each study visit. Assessment of signs was based on inferior corneal staining score (ICS; 0-4 scale). In all four studies, a larger reduction in EDS was observed with Xiidra at 6 and 12 weeks. In 2 of the 4 studies, an improvement in EDS was seen with Xiidra at 2 weeks. At week 12, a larger reduction in ICSS favoring Xiidra was observed in 3 of the 4 studies.