Triple Fixed-Combination offers beneficial therapeutic alternative for glaucoma patients
Prostaglandin analogs/prostamides (PGAs) remain the most effective intraocular pressure (IOP)-lowering monotherapies for open-angle glaucoma (OAG) and ocular hypertension (OHT). Nonetheless, use of multiple medications is often required to maintain sufficient IOP lowering, and combination therapies are frequently used to achieve this goal and prevent disease progression. Compared with unfixed combinations, fixed combinations increase convenience, reduce costs, and improve treatment adherence, while minimizing medication washout and lowering exposure to preservatives and adverse event (AE) frequency or severity. PGA-containing dual fixed combinations have been shown to be more effective in lowering IOP than PGA monotherapies.
Few studies have demonstrated superiority of TFC over dual fixed-combination brimonidine 0.2%/timolol 0.5%, following washout of prior therapy in patients with primary OAG and OHT.
The present study, conducted by Menon and Goodkin, was designed to evaluate the efficacy and safety of TFC in patients with glaucoma or OHT who continued to have IOP above target after run-in on fixed or unfixed brimonidine 0.2%/timolol 0.5% dual-combination therapy.
In this multicenter, open-label, phase 3 study, patients who received 4–8 weeks of dual-combination therapy twice daily and had an IOP >18 and <34 mmHg in at least one eye were switched (at baseline) to treatment with TFC twice daily for 12 weeks. At Weeks 4, 8, and 12 on TFC, IOP was assessed at Hours 0, 2, and 8. Primary efficacy variable: mean diurnal IOP change from baseline in the study eye at Week 12 (modified intent-to-treat [mITT] population). Sensitivity (per-protocol [PP] population) and subgroup (≤65 vs >65 years).Safety, including adverse events (AEs), was assessed at each visit.
Of 126 patients enrolled, 121 and 103 formed the mITT/safety and PP populations, including 109 (90.1%) and 94 (91.3%) who completed the study, respectively.
In the mITT/safety population, mean age was 58.6 years.
Patients had open-angle glaucoma (51.2%), angle-closure glaucoma with patent iridotomy (36.4%), and/or OHT (13.2%).
At Week 12, the mean diurnal change in IOP from dual combination-treated baseline was statistically significant (P< 0.001) with TFC in the mITT (–3.98 mmHg) and PP (–4.22 mmHg) populations.
Results were similar at all visits, regardless of the age subgroup. The most frequent treatment-related AEs were conjunctival hyperemia (14.0%) and dry eye (4.1%); 5.8% of the patients discontinued treatment due to ocular AEs.
In this open-label, multicenter, phase 3 study, patients with glaucoma or OHT who continued to have IOP above target after run-in on brimonidine 0.2%/timolol 0.5% therapy (administered as a fixed combination or adjunctive monotherapies) twice daily were switched at baseline to the PGA-containing TFC treatment twice daily. Clinically meaningful and statistically significant IOP lowering from an already dual combination-treated baseline was reported at all follow-up visits. TFC also had an acceptable safety/tolerability profile, consistent with that of its individual components; no additional, unexpected AEs were reported.
In the present study, 32.2% of the patients experienced treatment-related AEs with TFC administered twice daily, all mild or moderate in intensity, highlighting the favorable tolerability profile of this triple fixed combination. As expected with a triple combination containing both bimatoprost and brimonidine, conjunctival hyperemia was the most frequently reported treatment-related AE (14.0%) before and after stratification by age. It is worth noting that other, more recently approved IOP-lowering medications containing fewer (1 or 2) active components than the current triple combination were associated with higher rates of conjunctival hyperemia (≥47%) than reported herein, further supporting tolerability of TFC.
In summary, TFC offers a convenient, beneficial therapeutic alternative to patients with glaucoma or OHT whose IOP is not sufficiently controlled with dual-combination therapy, with the potential to enhance patient adherence to treatment and –consequently– quality of life by including all three medications in one bottle.
Source: Menon and Goodkin; Clinical Ophthalmology 2022:16
https://doi.org/10.2147/OPTH.S369626
