Topical cyclosporine A yields long-term relief for keratoconjunctivitis

Long-term results of the phase III VEKTIS* trial show that cyclosporine A cationic emulsion (CsA-CE) maintained a favourable safety profile and continued to provide symptomatic relief in children and adolescents with severe active vernal keratoconjunctivitis (VKC).

Though rare, VKC may impair daily activities, interactions, and quality of life (QoL) due to its characteristic ocular surface inflammation and a myriad of other** signs/symptoms. [Am J Ophthalmol 2007;144:557-563] Left untreated, persistent keratitis may lead to vision loss. [Ophthalmol Ther 2013;2:73-88; Br J Ophthalmol 2013;97:9-14]

This current safety phase evaluating longer-term use of CsA-CE extend the initial findings of the study, which showed that the primary endpoint*** was met. [Ophthalmology 2019;126:671-681]. “[Our] results provide further evidence that topical CsA-CE is a viable therapeutic option [in this setting],” said the researchers.

The initial 4-month phase randomized 169 patients 1:1:1 to receive one drop of 0.1% CsA-CE (1 mg/mL) QID or BID plus one drop of CE vehicle BID, or one drop of vehicle QID. An 8-month follow-up phase ensued (n=142; mean age 9.1 years, 78 percent male), wherein CsA-CE recipients remained on their assigned treatments, while vehicle recipients were allocated to either of the two active regimens. Participants used CsA-CE continuously (59 percent) or intermittently (34 percent). [Am J Ophthalmol 2020;212:116-126]

 

Favourable safety

Both CsA-CE arms had numerically lower rates of treatment-emergent adverse events (TEAEs) during follow-up (38 percent [QID] and 33 percent [BID]) compared with baseline to month 12^# (58 percent and 50 percent, respectively). “[These imply that] events predominantly occur early during Csa-CE treatment, and that event rates then decline during continued use,” said the researchers.

Apart from one case of withdrawal in the CsA-CE QID arm, no other TEAE-related withdrawals were reported during follow-up. The current safety data were consistent with the safety profile of topical CsA, they noted.

 

Sustained efficacy, QoL

Mean Corneal Fluorescein Staining score achieved with CsA CE was sustained from month 4 (1.28 [QID] and 1.47 [BID]) until month 12 (1.20 and 1.14, respectively).

Rates of rescue medication use were low in both CsA-CE arms during each 2-month interval from months 4–10 (≤8 percent [QID] and ≤11 percent [BID]). Months 10–12 saw an increase (≤20 percent), owing to patients who used Csa-CE intermittently, the researchers pointed out. “[This] increase … may [also] reflect the initiation of a new VKC season,” they added.

“[M]inimal use of corticosteroid rescue medication … is clinically significant, given the severe AEs associated with chronic, long-term use of corticosteroids, and the fact that even [seasonal] VKC can persist for 6–8 months, and the disease … can last for 5–10 consecutive years,” they stressed.

Visual Analogue Scale scores for the CsA-CE QID/BID regimens at month 4 (28/35 [photophobia], 22/28 [tearing], 23/29 [mucous discharge], and 27/33 [itching]) remained stable until month 12 (24/30, 23/24, 19/20, and 26/28, respectively).

Mean scores in two QoL domains were also sustained with both CsA-CE QID/BID regimens from month 4 (25/26 [Symptoms] and 3/8 [Daily Activities]) to month 12 (26/27 and 5/10, respectively).

 

Continuous vs intermittent

However, inconsistent trends across various efficacy parameters were seen regarding continuous vs intermittent CsA-CE use, they said. “[These may] reflect the underlying VKC type (ie, perennial vs seasonal). Nevertheless, it should be noted that, even seasonal VKC symptoms may persist for >4 months, and many of the seasonal VKC patients completing month 12 … were likely entering the start of a second VKC season,” they explained.

 

Long-term exposure

Despite the various^## treatments for severe VKC, these offer short-term relief and “do not effectively address the complex immune response that initiates and perpetuates the allergic ocular inflammation,” said the researchers. Topical corticosteroids, while effective, tend to trigger severe AEs^###, hence the recommended short-term use, they added.

The findings support long-term CsA-CE use to maintain symptom control, minimize corneal damage, and limit or prevent further seasonal reactivation of VKC. As the follow-up phase focused on long-term safety, comparative studies are needed to validate the efficacy data, they noted.