Tailored Treatment Best for Neovascular Age-Related Macular Degeneration

August 29, 2013

By Will Boggs, MD

NEW YORK (Reuters Health) Aug 29 - An individualized approach to treatment offers the best outcomes for patients with wet age-related macular degeneration (wAMD), according to a new review of the literature.

"The theoretical advantages of tailored therapies for neovascular AMD are to avoid over- and under-treatment with a proper benefit/risk balance while maintaining the same outcomes of fixed regimens," said lead author Dr. Paolo Lanzetta from the University of Udine in Italy.

"Key points for reaching optimal outcomes reside in the need for monthly monitoring, aggressive re-treatment criteria, and further patient and lesion characterization," he told Reuters Health by email. "Physician's expertise and patient's compliance are crucial steps of this complex algorithm."

Antivascular endothelial growth factor (anti-VEGF) treatment has markedly improved the prognosis of wAMD, with three drugs currently available: bevacizumab, ranibizumab, and aflibercept.

Dr. Lanzetta and colleagues from Australia and Switzerland reviewed major clinical studies comparing anti-VEGF dosing regimens and therapies. A contract research organization paid by Bayer performed the literature search and helped write the article. Dr. Lanzetta and two of his three co-authors disclosed financial ties to Bayer, in addition to several other drug companies.

The report, online August 8 in the British Journal of Ophthalmology, includes three head-to-head studies comparing different anti-VEGF drugs and four studies comparing alternative dosing regimens with ranibizumab.

The CATT (Comparison of Age-Related Macular Degeneration Treatment Trials) study concluded that treatment once every four weeks was better than as-needed (PRN) treatment with anti-VEGF drugs, suggesting that continuous or more frequent treatment with bevacizumab and ranibizumab is needed to maximize long-term outcomes.

Unlike CATT, 12-month results from IVAN (Inhibit VEGF in Age-Related Choroidal Neovascularization) showed no differences in visual outcomes between dosing regimens of bevacizumab and ranibizumab.

VIEW (VEGF Trap-Eye: Investigation of Efficacy and Safety in wAMD) found outcomes for aflibercept 2 mg every eight weeks to be noninferior to those for ranibizumab 0.5 mg every four weeks. Patients treated with aflibercept required, on average, nearly five fewer injections over the 52-week study.

The four ranibizumab dosing studies (PIER, EXCITE, SUSTAIN, and SAILOR) uniformly concluded that monthly dosing gave superior results compared with PRN or quarterly dosing and that disease measures worsened when dosing was transitioned from monthly to PRN.

The rates of adverse events were low and similar across studies, the researchers note, although there appeared to be excessive serious systemic adverse events in bevacizumab-treated patients in CATT and IVAN.

"A relevant lesson learned from randomized trials and from personal experience is that we should not aim at limiting the number of treatments but rather at improving visual acuity of our patients to the upper limit no matter how many treatments are needed," Dr. Lanzetta said. "Other treatment modalities named treat-and-extend are currently under evaluation."

"Recent experiences with the newer drug, aflibercept, have also shown that it may be beneficial in patients no longer responding to ranibizumab treatment," he added. "In the majority of cases the switching corresponded to dramatic and sudden morphological improvements with disappearance of the intra and sub-retinal fluid although this did not correlate with significant functional improvements."

"In summary, there are currently different agents and treatment regimens available for the cure of neovascular AMD," Dr. Lanzetta said. "This has greatly expanded the therapeutic armamentarium and physicians are now closer to offering the right drug at the right moment."

Dr. Guido Bocci from the University of Pisa in Italy, who was not part of the review, said customizing treatment to each patient is "mandatory."

"Pharmacogenetic studies suggest a possible role of genetic background in the susceptibility to the treatment, even if, to date, a well-defined pharmacogenetic marker has not yet been identified," he told Reuters Health by email.

"In the Ophthalmology Unit of Pisa we administered ranibizumab PRN to neovascular AMD patients," Dr. Bocci explained, adding that based on the review aflibercept 2 mg "seems to be an important new strategy."

Dr. Usha Chakravarthy, who was also not involved in the new research, said the anti-VEGF drugs are similar in action and safety.

"The main difficulty with ensuring optimum outcomes is the intensive continued review schedules which most of us cannot cope with at present," Dr. Chakravarthy, of the Centre for Vision and Vascular Science at Queen's University in Belfast, UK, told Reuters Health by email.

"On the basis of cost I would prefer Avastin (bevacizumab)," she said. "However this is not available to me in the National Health Service as ours is a commissioned service and we can only use licensed preparations."

SOURCE: http://bit.ly/141IwIA

Br J Ophthalmol 2013.

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