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 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