U.K. surgeons demand freer access to PDT for wet AMD

Government advisory groups are not convinced of PDT’s efficacy. Surgeons fear the potential consequences of withholding treatment.

ByRod McNeil

British surgeons and health policy groups are at odds over the use of photodynamic therapy for age-related macular degeneration. While proponents of PDT for AMD tout its treatment benefits and argue against its indiscriminate use, they oppose recommended restraints on its routine availability in the National Health Service.

Guidance on the implementation of PDT in the United Kingdom has been issued by two U.K. bodies. The Safety and Efficacy Register of New Interventional Procedures (SERNIP) group has categorized PDT with Visudyne (verteporfin for injection, Novartis Ophthalmics) treatment of classic choroidal neovascularization as ‘B’ — efficacy established, further evaluation required to establish safety. A Royal College of Ophthalmologists working party recommended last year that treatment should commence in centers with retinal expertise and access to stereoscopic angiography as part of a surveillance program registered with SERNIP.

More recently, preliminary recommendations from an independent review commissioned by the National Institute for Clinical Excellence (NICE) advised against the routine use of PDT for AMD. The appraisal committee of the Institute argued that this technology, although clinically effective in wet AMD, should be used only in new or ongoing clinical trials, as overall cost-effectiveness is not established.

If confirmed, these recommendations could condemn thousands to blindness, claims the Royal National Institute for the Blind.

Evidence of benefit unequivocal

According to Novartis, the scope of the NICE appraisal was initially to be confined to predominantly classic subfoveal CNV, the indication for verteporfin, but was then expanded to include all forms of AMD. This dilutes the evidence of benefit and misinterprets available cost-effectiveness data by including nonindicated patients, the company stated.

Physicians have also criticized the NICE appraisal.

“The clinical effectiveness of PDT appears to have been overlooked by the appraisal committee. Current evidence supports the use of PDT with verteporfin for a proportion of patients with subfoveal CNV. However, treatment should be restricted to those patients in whom a treatment benefit has been definitely demonstrated,” said Simon Harding, FRCOphth, consultant ophthalmic surgeon, St. Paul’s Eye Unit, Royal Liverpool Hospital and member of the Royal College of Ophthalmologists working party on PDT for subfoveal CNV.

Results of two randomized, double-masked, placebo-controlled trials of verteporfin for PDT found significantly less deterioration in visual acuity in the treated eye compared with the untreated eye. Subgroup analysis found that the treatment effect was greater in patients whose lesions were composed of at least 50% classic CNV. Overall, verteporfin was found to improve the chance of avoiding appreciable loss of vision (loss of three or more lines of visual acuity) over a period of 2 years.

Data show that patients treated for 3 years still see better than those not treated at 3 months. Also, at 2 years, verteporfin halved the risk of both moderate and severe vision loss and cut the number of eyes reaching legal blindness by one-third.

“Our experience of treating patients with National Health Service-funded PDT for the past year is that it does slow visual loss in selected groups of patients. Results achieved have been encouraging and there is no other treatment that works,” said James Talks, FRCOphth, consultant ophthalmologist at the Royal Victoria Infirmary, Newcastle.

“There is sufficient evidence from well-conducted, appropriately powered studies to justify the routine use of this sight-preserving treatment,” argued Robin Hill, FRCOphth, chief executive of the Macular Disease Society. “It is wrong to withhold a treatment proven to be effective, and we believe that PDT should be available as a right to all patients when indicated. Any diminution in loss of visual acuity is a real gain for those suffering sight loss.”

Advocates question evaluation

While appearing to generally accept the clinical effectiveness of verteporfin PDT, available in 59 countries worldwide, the appraisal committee noted that the cost-effectiveness of this technology has not been established.

Advocates of PDT argue, however, that the Health Economic Model used in the appraisal assessment overestimates the cost per quality-adjusted life year (QALY) by including patients for whom verteporfin is not indicated, ignoring the early benefit of proven stabilization of vision at 1 year and by assuming no benefit persisting beyond year 2 of treatment.

The scope of the NICE appraisal initially was to be confined to predominantly classic subfoveal CNV, the indication for verteporfin PDT, but was then expanded to include all forms of AMD. This had the effect of diluting the evidence of benefit by including nonindicated patients, according to Novartis.

“The cost argument put forward in support of this preliminary decision is shot with holes,” Mr. Hill said. “For example, the true costs of low-vision rehabilitation and low-vision aids remain unknown. It is also disingenuous in our view to think that the proven sight-preserving benefit of PDT is suddenly going to fall off the cliff at 2 years. Anything that can arrest loss of sight for this acute condition should be welcomed.”

Data provided to NICE show sustained benefit during the third year of verteporfin therapy. Combined data from the 2-year randomized control trial and the third-year open labeled extension show that vision loss in verteporfin-treated patients tends to be limited to the first 12 months. Also, vision stabilizes at levels much higher than placebo-treated patients and is maintained for at least 3 years.

Simply factoring in the 1-year vision stabilization benefit to the model used by NICE halves the calculated cost per QALY at 2 years, dramatically changing the cost-utility picture, PDT advocates argue.

Independent economic evaluations appear, however, to support arguments that verteporfin PDT is a cost-effective intervention. The ScHARR model, an alternative evaluation commissioned by Novartis for the NICE appraisal, plots 3-month data, allows for proven stabilization of vision after 1 year and allows for vision benefit persisting after the trial. Arguably a more realistic estimate of cost per QALY, it assumes patients with no vision benefit receive only two treatments and covers only those with predominantly classic subfoveal CNV.

Further research welcomed

“The psychological trauma of going blind is difficult at best to quantify,” said Winfried Amoaku, FRCOphth, consultant ophthalmologist at Queen’s Medical Centre, Nottingham. “PDT treatment with verteporfin is clinically effective, and it is cost-effective if all relevant factors are fully considered. There is insufficient justification for recommending that treatment should be withheld until further long-term clinical trials are carried out. We believe that PDT treatment should continue to be offered in the NHS, with clinical research continuing in a selected cohort of patients to identify the relative benefits of different re-treatment schedules.”

Mr. Talks agreed.

“I would question the validity of conducting another full-scale clinical trial, particularly as there are ongoing surveillance studies that will provide quicker audit results of ongoing PDT treatment within approved centers. However, trials to further refine and better select the group that would most benefit from PDT would be helpful, but this should not be at the expense of denying access to treatment,” he said.

“Further research is welcome, in particular to establish the optimum treatment regime,” Mr. Harding said. “However, I would oppose the suggestion that verteporfin PDT treatment should be restricted solely to the confines of a clinical trial population.”

For Your Information:

Simon Harding, FRCOphth, can be reached at St. Paul’s Eye Unit, Royal Liverpool Hospital, Prescot St., Liverpool L78 XP, England; +(44) 151-706-3971; fax: +(44)151-706-5861; e-mail: SimonPHarding@cs.com.

James Talks, FRCOphth, can be reached at Ophthalmology Department, Claremont Wing, Royal Victoria Infirmary, Queen Victoria Rd., Newcastle upon Tyne NE1 4LP, England; +(44)191-282-5452; fax: +(44) 191-227-5246; e-mail: James.Talks@ncl.ac.uk.

Robin Hill, FRCOphth, Chief Executive, The Macular Disease Society, can be reached at PO Box 16, Denbigh LL16 5ZA, England; +(44) 144-441-7308; fax: +(44) 174-581-3212; e-mail: robindjhill@hotmail.com.

Winfried Amoaku, FRCOphth, can be reached at Eye Department, Queen’s Medical Centre, University Hospital, Derby Rd., Nottingham NG7 2UH, England; +(44) 115-924-9924; fax: +(44) 115-970-9749; e-mail: wma@nottingham.ac.uk.

Novartis Ophthalmics, distributor of Visudyne, can be reached at 11695 Johns Creek Pkwy, Duluth, GA 30097 U.S.A.; +(1) 770-905-1000; fax: +(1) 770-905-1883. Visudyne is a trademark of Novartis AG.