Takaisin

Fotodynaaminen hoito (PDT) yhdistettynä verisuonikasvutekijöiden estäjiin kostean silmänpohjan ikärappeuman (AMD) hoidossa

Näytönastekatsaukset
Raija Sipilä
30.3.2016

Näytön aste: B

Fotodynaamisen hoidon (PDT) yhdistäminen ranibitsumabiin ei näytä parantavan näöntarkkuutta kosteaa AMD:tä sairastavilla potilailla verrattuna yksinomaiseen ranibitsumabihoitoon.

A systematic review and meta-analysis «Si JK, Tang K, Bi HS ym. Combination of ranibizuma...»1compared the efficacy and safety of combination of ranibizumab with photodynamic therapy (PDT) and ranibizumab monotherapy in the treatment of age-related macular degeneration (AMD).

Included were randomized controlled trials comparing ranibizumab with PDT and ranibizumab monotherapy in patients with active choroidal neovascularization secondary to AMD. In addition at least one of the following outcome measures had to report: best-corrected visual acuity (BVCA), central retinal thickness, number of treatmentsand ocular or systemic adverse events. Not published conference abstracts were excluded. The Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Pubmed, and Embase were searched until September 2013. In addition handsearches were conducted. Methodological quality of the literatures was evaluated according to the Jadad Score.

From a total of 181 potential studies 7 were included in the systematic review and of them four were included in meta-analysis. Three studies were performed in USA and one each in UK, Italy, Austria, and Denmark. Mean age varied between 71 and 80 years. Duration of follow up was 12 months except in one study with 6 months follow up. Four of the studies were assessed to be of high quality. Two of the studies had over 100 participants per treatment group, the others had 2 to 30 participants per group. There were clinical heterogeneity among the studies. Dose of ranibizumab was 0.5 mg in all studies but the frequency of the injection varied and dose of PDT varied.

Ranibizumab monotherapy group had a better mean BCVA change vs baseline at month 12 compared with that of the combination treatment group weighted mean difference (WMD) -2.61; 95% CI, -5.08 - -0.13; p=0.04. In sensitivity analysis, after the removal of one study due to clinical heterogenity, the difference between the two groups showed no significant difference WMD -2.29; 95% CI, -4.81 - 0.23; p=0.07. Weighted mean difference for central retinal thickness reduction was -4.13µm; 95% CI, -25.88 - 17.63, p=0.71. As major adverse events, the differences in the number of eye pain, endophthalmitis, hypertension and arterial thromboembolic events were not significant between the two groups, and the incidence of serious adverse events in the two groups was very low. Relative risk (RR) for eye pain was 1.38 (95% CI 0.81-2.35), for endophtalmitis 0.53 (0.05-5.80), and for arterial thromboembolic events 0.81 (0.28-2.28).

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

Kommentti: Tutkimukset olivat heterogeenisia potilasjoukon ja hoitojen suhteen. 5 tutkimusta seitsemästä oli pieniä (n < 30/tutkimusryhmä). Kirjoittajat arvioivat 4 tutkimusta (jotka olivat mukana meta-analyysissä) laadukkaiksi. Haittatapahtumien tulokset perustuivat 2 tutkimukseen.

Randomized, controlled double-blind trial «Hatz K, Schneider U, Henrich PB ym. Ranibizumab pl...»2 compared combination therapy of ranibizumab plus PDT vs ranibizumab monotherapy in the treatment of AMD.

Inclusion criteria were age >50 years, subfoveal choroidal neovascularization (CNV) secondary to AMD, visual acuity Snellen equivalent 20/40–20/320, lesion consisted of >50% active CNV. Exclusion criteria were laser photocoagulation, intravitreal steroids or PDT in the study eye within 30 days, prior external-beam radiation therapy, vitrectomy or transpupillary thermotherapy, surgery in the eye within 2 months prior to intravitreal anti-VEGF treatment.

Consecutive eligible patients from one study center were randomized 1:1 to monotherapy ranibizumab (plus sham PDT, N=21) or combination therapy (ranibizumab plus single standard-fluence verteporfin PDT at baseline, n=19). The ranibizumab dose was 0.3 mg monthly three times and thereafter up to 12 months as needed based on prespecified criteria. Minimum interval was 28 days.

Outcome measures were changes in mean BCVA, retreatment rates, and safety evaluation (all adverse events). Intention-to-treat analysis was performed only for safety data.

Majority of patients were female (monotherapy 67%and combination therapy 68%), mean age was 78 and 79 years, patients with prior PDT was 19% and 36.8%, and percentage of patients with CNV composition of occult without classic was 47.6% vs 78.9%. Dropout rate was 7.5%.

At month 6 the mean improvement in BCVA from baseline was 10.2 ± 1.8 in monotherapy group, and 8.5 ± 2.5 in combination therapy group. At month 12 the corresponding figures were 7.5 ± 2.9 and 9.0 ± 2.8, respectively. There was a trend for lower number of retreatments in combination therapy group but none of the between-group differences reached statistical significance. No serious adverse events were reported, ocular adverse events were reported for 11 patients in monotherapy group and 10 in combination therapy group.

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: kohtalainen

Kommentti: Hoitojen tehon vertailussa käytettiin per protocol lukuja, ei hoitoaieanalyysin (ITT) lukuja. Lähtötilanteessa ryhmät olivat erilaisia: yhdistelmähoitoryhmässä useampi oli saanut aiemmin PDT-hoitoa, ja silmänpohjarappeumatyyppien jakauma oli myös erilainen ryhmissä (yhdistelmähoidossa occult without classic yleisempi). Julkaisussa on nostettu tärkeimmäksi tulokseksi uusintahoitojen määrä, vaikka tämä on clinicaltrials.gov-tietokannan mukaan toissijainen tulosmuuttuja. Tutkimusta sponsoroi Novartis Pharma AG. Sponsori osallistui lääketieteellisen kirjoittamisen rahoittamiseen.

Kirjallisuutta

  1. Si JK, Tang K, Bi HS ym. Combination of ranibizumab with photodynamic therapy vs ranibizumab monotherapy in the treatment of age-related macular degeneration: a systematic review and meta-analysis of randomized controlled trials. Int J Ophthalmol 2014;7:541-9 «PMID: 24967206»PubMed
  2. Hatz K, Schneider U, Henrich PB ym. Ranibizumab plus verteporfin photodynamic therapy in neovascular age-related macular degeneration: 12 months of retreatment and vision outcomes from a randomized study. Ophthalmologica 2015;233:66-73 «PMID: 25471330»PubMed