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Fixed-interval dosing provides individualized treatment for AMD patients
Retina practitioners also discuss the concept of ‘nonresponder’ patients.
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Fixed-interval dosing may be a viable treatment option for patients with age-related macular degeneration, according to a physician who spoke at Kiawah Eye 2013.
W. Lloyd Clark, MD, said in a subsequent interview with Ocular Surgery News that he uses fixed-interval dosing as a version of treat-and-extend dosing to determine a patient’s particular treatment interval.
“It’s not monthly, not PRN, but individualized dosing achieved in a rational way,” Clark said.
Fixed-interval approach
Clark examines patients before every injection to look for signs of recurrent disease activity, such as a hemorrhage, that may not be apparent on an optical coherence tomography scan. At each pre-injection exam, 1 month after injection, he looks for associated complications, such as retinal tears or retinal detachments.
W. Lloyd Clark
“However, most often, OCT is the parameter I use to assess disease activity and assign treatment interval,” he said.
Clark begins by treating monthly until vision is stable and OCT shows the eye is dry. He then extends the treatment interval by 1 week until 12 weeks or until the suggestion of recurrence. Signs of recurrence include a small increase in the central subfield thickness or a few cysts.
When treating a patient’s “better” eye, Clark almost never ends treatment. When he finds a treatment interval for a patient who is not experiencing disease activity, he continues that treatment.
“The goal is not really to stop therapy, but to find [the patient’s] optimal interval,” Clark said.
For patients with unilateral disease, Clark uses the same treat-and-extend approach until there is no disease activity in the eye. Once there is no evidence of disease activity, treatment interval extension begins by 1 week, looking for disease recurrence. In this population, if there is no disease activity after injections spaced 12 weeks apart, he may try to halt therapy with close follow-up. However, most patients are maintained on chronic therapy of some sort to maintain visual acuity gains and limit the risk of complications such as submacular hemorrhage or retinal pigment epithelium tears.
For example, a patient’s treatment could be extended to 9 weeks, but if there is a small subclinical recurrence, the interval would be reduced to 8 weeks and would be considered fixed-interval dosing.
At the meeting, Clark supported fixed-interval dosing with data from the CATT and VIEW 1/VIEW 2 studies. Patients in the VIEW 1/VIEW 2 trials were treated with Eylea (aflibercept, Regeneron) every 8 weeks or monthly during the first year of treatment. There was a decrease in the treatment burden, with patients having minimal to no visual acuity deficits, he said.
Monthly dosage treatment
In trials that involved monthly dosing of Lucentis (ranibizumab, Genentech), patients showed visual acuity stability. Quarterly injections or as-needed injections resulted in vision gains that appeared to decrease with less frequent dosing, as in the ANCHOR, MARINA, PIER, EXCITE and SAILOR trials, according to David M. Brown, MD.
David M. Brown
“Any time you stretch out treatment, you have a risk of recurrence and disease. If you get a hemorrhage or you get a [retinal pigment epithelium] rip, you lose the ball game,” Brown said at Kiawah Eye.
Nonresponders
Brown said he does not think nonresponders is a valid term for patients who do not respond well to treatment. Instead, the interval for treatment should be shortened to accommodate those patients.
“If you don’t adjust the dose … then all you can adjust is the time in between [injections],” Brown said.
Factors that can affect a patient’s response rate are diffusion in the retinal fluid, varying levels of VEGF production in the subretinal space and drug dissipation rate over time.
“It is very uncommon to see nonresponders. We do see patients who become refractory to treatment and need to be switched to another agent, but nearly all have some initial response to anti-VEGF therapy,” Clark told OSN.
A patient may have fluid at 4 weeks after treatment, but that does not mean the patient is a nonresponder. Instead, the patient would be told to return at 3 weeks. Nonresponders are based on the notion of monthly injections or injections every 6 or 8 weeks; shortening the treatment interval will mostly eliminate nonresponders, Brown said.
“It’s not about making lesions dry up for good and go away like with the old thermocoagulation radiation therapy or [photodynamic therapy]. It’s about suppressing leakage long term,” Clark said at Kiawah Eye. – by Cheryl DiPietro