|
Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation |
Colquitt JL, Jones J, Tan SC, Takeda A, Clegg AJ, Price A |
|
|
CRD summary This review evaluated clinical and cost effectiveness of ranibizumab and pegaptanib for subfoveal choroidal neovascularisation associated with wet age-related macular degeneration. Patients with age-related macular degeneration of any type of lesion benefited from treatment with pegaptanib or ranibizumab on measures of visual acuity when compared with sham injection and/or photodynamic therapy. These conclusions are likely to be reliable. Authors' objectives To evaluate the clinical and cost effectiveness of ranibizumab and pegaptanib for subfoveal choroidal neovascularisation associated with wet age-related macular degeneration. Searching Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), DARE, HTA database and NHS EED, MEDLINE, EMBASE, National Research Register, Current Controlled Trials, ISI Proceedings, Web of Science, Science Citation Index and BIOSIS Previews were searched for studies in English (from inception to September 2006). Ophthalmology conferences were searched from 2004. Bibliographies of related papers and submissions to NICE were searched. Experts were contacted to identify additional papers. Study selection Randomised controlled trials (RCTs) of patients with subfoveal choroidal neovascularisation associated with wet age-related macular degeneration were eligible for inclusion if they reported at least one of the outcomes of visual acuity, contrast sensitivity, adverse effects of treatment, adherence to treatment and health-related quality of life. Included studies had to compare ranibizumab, pegaptanib or a combination of the two with photodynamic therapy against best supportive care and photodynamic therapy with verteporfin (in individuals with a confirmed diagnosis of classic with no occult subfoveal wet age-related macular degeneration). If these comparators were not available, sham injection or photodynamic therapy with verteporfin for patients with subfoveal wet age-related macular degeneration with predominantly classic lesions could be used.
The proportions of included patients that exhibited predominantly classic, minimally classic and occult with no classic lesions varied (where reported). Length of follow-up ranged from 12 to 24 months. The doses used were 0.3mg, 1.0mg and 3.0mg (pegaptanib) and 0.3mg and 0.5mg (ranibizumab). Sham injections were also used. A variety of regimens were reported in the included studies. Primary outcomes reported were proportion of patients that lost less than 15 letters (various time points), mean change in best corrected visual acuity and safety and tolerability.
Full papers were selected for inclusion by one reviewer and checked by a second reviewer. Assessment of study quality Methodological quality of primary studies was assessed in terms of randomisation, allocation concealment, baseline characteristics, eligibility, blinding, reporting outcomes, intention-to-treat and withdrawals. This was performed by one reviewer and checked by a second; disagreements were resolved by discussion or consultation with a third reviewer. Data extraction Data were extracted for visual acuity (various measures), compliance with treatment and adverse event outcomes by one reviewer into a standard form and checked by a second reviewer. Methods of synthesis The studies were combined narratively by outcome. Tables of individual study details were available for examination of study differences. Meta-analysis was not used due to heterogeneity in patient groups and comparator treatments. Results of the review Six RCTs were included in the review (the number of participants was unclear, but at least 2,748): two investigated pegaptanib (n=1,208); and four investigated ranibizumab (n appeared to be approximately 1,540). All of the included RCTs were described as good quality.
Pegaptanib and ranibizumab were associated with significantly better visual acuity (loss of fewer than 15 letters) in all dose groups compared with sham injection group and photodynamic therapy. Significantly more patients who received ranibizumab/ranibizumab and photodynamic therapy, and pegaptanib doses of 0.3mg and 1.0mg (but not 3.0mg) gained at least 15 letters of visual acuity, which was significantly greater than photodynamic therapy or sham injection groups. Significantly fewer patients who received pegaptanib or ranibizumab reached visual acuity equivalent to legal blindness compared with control groups. A second year of treatment with pegaptanib (0.3mg) reduced the risk of deterioration to the legal level of blindness.
In subgroup analyses mean change in visual acuity was significantly different between pegaptanib (all doses) and sham injection in patients with minimally classic or occult with no classic lesions. Only the licensed 0.3mg pegaptanib dose was associated with a significantly greater effect than sham injection in reducing visual acuity loss in people with predominantly classic lesions after treatment for one year. The size of the lesion, size of choroidal neovascularisation and size of leakage showed a significantly lower rate of increase from baseline with the 1.0mg dose of pegaptanib compared with sham injection. The difference between ranibizumab and control patients in the proportions losing fewer than 15 letters was significant for every lesion subgroup.
There were several adverse events common for both drugs, but most were reported to be mild to moderate.
Further results were reported in the paper. Cost information The costs estimated for one year of treatment (incorporating NHS and Personal Social Services costs of services for visual impairment) were drug costs of £4,626 for pegaptanib and £9,134 for ranibizumab. Non-drug costs were an additional £2,614 for pegaptanib and £3,120 for ranibizumab. Further costs of £1,200 to £2,100 were associated with the management of injection-related adverse events. The incremental cost-effectiveness ratio for pegaptanib compared with usual care ranged from £163,603 (two-year model) to £30,986 (10-year model). Incremental cost-effectiveness ratios for ranibizumab ranged from £152,464 (two-year model) to £25,098 (10-year model). Authors' conclusions Patients with age-related macular degeneration of any type of lesion benefited from treatment with pegaptanib or ranibizumab on measures of visual acuity when compared with sham injection and/or photodynamic therapy. CRD commentary The inclusion criteria were clear for participants, intervention, outcomes and study design. Several sources of published and unpublished data were searched, which reduced the possibility of publication bias. Only English-language studies were included, which could have introduced language bias into the review. Study selection, data extraction and validity assessment were performed by two reviewers, which reduced the risk of reviewer error and bias. The methodological quality of the primary studies was assessed and taken into account. The studies were synthesised narratively, which appeared to be appropriate due to the differences between primary studies. This appeared to be a generally well-conducted review and the authors' conclusions are likely to be reliable. Implications of the review for practice and research Research: The authors stated that the long-term safety and efficacy of bevacizumab (biologically similar to ranibizumab) needed to be assessed. A trial comparing pegaptanib, ranibizumab and bevacizumab was recommended; the role of verteporfin photodynamic therapy in combination with these drugs should be investigated. The optimal dosing regimens and benefits of re-treatment also required investigation.
Practice: The authors did not state any implications for practice. Funding HTA Programme project number 04/24/01. Bibliographic details Colquitt JL, Jones J, Tan SC, Takeda A, Clegg AJ, Price A. Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation. Health Technology Assessment 2008; 12(16): 1-222 Other publications of related interest Takeda AL, Colquitt J, Clegg AJ, Jones J. Pegaptanib and ranibizumab for neovascular age-related macular degeneration: a systematic review. British Journal of Ophthalmology 2007;91(9):1177-1182. Indexing Status Subject indexing assigned by NLM MeSH Age Factors; Antibodies, Monoclonal /economics /therapeutic use; Antibodies, Monoclonal, Humanized; Aptamers, Nucleotide /economics /therapeutic use; Choroidal Neovascularization /drug therapy /etiology; Contrast Sensitivity /drug effects; Cost-Benefit Analysis; Drug Costs; Humans; Macular Degeneration /complications /drug therapy /economics; Randomized Controlled Trials as Topic; Ranibizumab; Visual Acuity /drug effects AccessionNumber 12008104807 Date bibliographic record published 03/11/2008 Date abstract record published 02/09/2009 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
|
|
|