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VEGF-estäjien kustannukset kosteaa silmänpohjan ikärappeumaa sairastavilla

Näytönastekatsaukset
Jorma Komulainen
25.4.2016

Näytön aste: B

Bevasitsumabi annosteltuna tarvittaessa on ilmeisesti kuukausittain annosteltua bevasitsumabia ja tarvittaessa tai kuukausittain annosteltua ranibitsumabia ja afliberseptiä kustannusvaikuttavampi kostean silmänpohjan ikärappeuman hoitomalli.

In the CATT study «Comparison of Age-related Macular Degeneration Tre...»11185 patients with neovascular AMD were initially enrolled in the clinical trial, whereas 1107 of them were followed-up for 2 years. Patients were randomized in 4 groups: ranibizumab 0.5 mg or bevacizumab 1.25 mg and dosing regimen monthly or as needed. At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. Primary end point was mean change in visual acuity. Secondary end points were: proportion of patients with a change in visual acuity of ≥15 letters, number of injections, drug costs, presence of fluid and change in foveal retinal thickness, change in lesion size on fluorescein angiography and incidence of systemic and ocular adverse events.

Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; p=0.046). After adjusting for baseline predictors of visual acuity in a multivariable longitudinal regression model, the estimated change in visual acuity, averaged over 2 years of follow-up, was 1.7 letters better for patients treated monthly (CI: [−0.1, 3.4]; p=0.07).

The mean (standard deviation) number of injections through year 2 in the as-needed groups, out of a maximum of 26, was 12.6 (6.6) for patients treated with ranibizumab and 14.1 (7.0) for those treated with bevacizumab (p=0.01). The estimated 2-year drug cost per patient varied from $705 in the bevacizumab-as-needed group to $44.800 in the ranibizumab-monthly group. At 2 years, mean retinal thickness was 29 µm less in patients treated monthly than in patients treated with an as-needed regimen (regimen p=0.005).

The proportion of patients without fluid on OCT ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab-monthly group (drug p=0.0003; regimen p<0.0001). Fluorescein dye leakage was absent in a higher percentage of patients treated monthly than in patients treated as needed (regimen p=0.002).

The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; p=0.009). Patients treated as needed had higher rates than patients treated monthly (risk ratio 1.20; CI: [0.98, 1.47]; p=0.08).

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

In the IVAN trial «Dakin HA, Wordsworth S, Rogers CA ym. Cost-effecti...»2 610 patients with untreated neovascular AMD were randomized in 4 groups: 0.5 mg ranibizumab given continuously (monthly) for 2 years; 0.5 mg ranibizumab given continuously (monthly) for 3 months, followed by further courses on 3 monthly injections if clinically indicated; 1.25 mg bevacizumab given continuously (monthly) for 2 years; 1.25 mg bevacizumab given continuously (monthly) for 3 months, followed by further courses on 3 monthly injections if clinically indicated. The primary end points were quality-adjusted life-years (QALYs) assessed with EQ-5D questionnaire and their costs (costs incurred by patients and their families or employers were excluded).

The number of QALYs accrued over the 2-year trial period did not differ significantly between bevacizumab and ranibizumab, or between continuous and discontinuous treatments (p≥0.381). Ranibizumab was significantly more costly than bevacizumab for both continuous (+£14 989/patient [$23 468]; 95%CI £14 522 to £15 456; p<0.001). Using continuous rather than discontinuous treatment increased costs by £7090 ($11 102 (95% CI £6337 to £7844), p<0.001) for ranibizumab and £599 $938 [95% CI £91 to £1107], p=0.021) for bevacizumab. The cost of medication changes, hospitalisations and ambulatory consultations associated with expected SAEs and expected AEs was relatively small (mean: £469 [$735] per patient), but varied substantially between patients (95th centile range: £0, £1401). There was no significant difference in such costs between drugs or between treatment regimens (p≥0.163).

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: kohtalainen

Comment: Exclusion of costs incurred by patients, families and employers may underestimate the difference between continuous and discontinuous regimens. ED-5Q questionnaire does not include parts specific to eye problems, and may thus not be sensitive enough for this purpose.

In a cost-utility study «Elshout M, van der Reis MI, Webers CA ym. The cost...»3 a patient-level, visual acuity-based, 2-eye model was developed to compare the cost-utility of aflibercept, ranibizumab and bevacizumab treatment in patients with wet AMD. Data on effectiveness were derived from randomized controlled trials evaluating the outcomes of aflibercept, bevacizumab, and ranibizumab. Utility and resource utilization were assessed in interviews with AMD patients. Costs were based on standard health care cost prices. Time horizons were two and five years. A societal perspective was employed.

Over five years, costs associated with aflibercept treatment were € 36.030, with 2.15 QALYs. Costs associated with the bevacizumab regimens, ABC study as-needed (PRN); CATT study PRN; and CATT study 1×/month, were € 19.367; € 26.746; and € 30.520, with 2.16; 2.17; and 2.15 QALYs, respectively. Costs associated with ranibizumab PRN and 1×/month were € 45.491 and € 74.837 with 2.16 and 2.15 QALYs, respectively. 'No treatment' was associated with € 9530 and 1.96 QALYs. The incremental cost-effectiveness ratios versus 'no treatment' were: aflibercept- € 140.274; bevacizumab- € 51.062 (ABC PRN), € 83.256 (CATT PRN) and € 110.361 (1×/month); ranibizumab- € 181.667 (PRN) and € 349.773 (1×/month). Results were highly dependent on whether only one or both eyes were included, length of time horizon, and whether the costs of blindness and low-vision were included in the analysis.

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: heikko

In a cost-utility study «Elshout M, van der Reis MI, Webers CA ym. The cost...»3 a patient-level, visual acuity-based, 2-eye model was developed to compare the cost-utility of aflibercept, ranibizumab and bevacizumab treatment in patients with wet AMD. Data on effectiveness were derived from randomized controlled trials evaluating the outcomes of aflibercept, bevacizumab, and ranibizumab. Utility and resource utilization were assessed in interviews with AMD patients. Costs were based on standard health care cost prices. Time horizons were two and five years. A societal perspective was employed.

Using a mathematical model with a 20-year time horizon, a study from the USA compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab [B4]. Data came from the Comparison of Age-related macular degeneration Treatment Trial (CATT), the Medicare Fee Schedule, and the medical literature.

Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242 357/QALY. Monthly ranibizumab gains an additional 0.02 QALYs versus monthly bevacizumab at an incremental cost-effectiveness ratio of more than $10 million/QALY. As-needed ranibizumab was dominated by monthly bevacizumab, meaning it was more costly and less effective. In sensitivity analyses assuming a willingness to pay of $100 000/QALY, the annual risk of serious vascular events would have to be at least 2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100 000/QALY.

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: heikko

Kirjallisuutta

  1. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG ym. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 2012;119:1388-98 «PMID: 22555112»PubMed
  2. Dakin HA, Wordsworth S, Rogers CA ym. Cost-effectiveness of ranibizumab and bevacizumab for age-related macular degeneration: 2-year findings from the IVAN randomised trial. BMJ Open 2014;4:e005094 «PMID: 25079928»PubMed
  3. Elshout M, van der Reis MI, Webers CA ym. The cost-utility of aflibercept for the treatment of age-related macular degeneration compared to bevacizumab and ranibizumab and the influence of model parameters. Graefes Arch Clin Exp Ophthalmol 2014;252:1911-20 «PMID: 24777708»PubMed
  4. Stein JD, Newman-Casey PA, Mrinalini T ym. Cost-effectiveness of bevacizumab and ranibizumab for newly diagnosed neovascular macular degeneration. Ophthalmology 2014;121:936-45 «PMID: 24405740»PubMed