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UNITA’ OPERATIVA DI OCULISTICA

OSPEDALE SANT’ANTONIO - PADOVA

SOI 2008-CORSO 120

Terapie intravitreali. Razionale


ed effetti terapeutici,
indicazioni cliniche e gestione
delle complicanze

Dott. M. Tavolato
Trattamento: valutazione

 Efficacia: clinical trials

 Costo: farmaco-economia

 Safety: clinical trials


Anti-VEGF
 Pegaptanib sodica: Macugen
– Isoforma 165

 Bevacizumab: Avastin
– Tutte isoforme

 Ranibizumab: Lucentis
– Tutte isoforme
Anti-VEGF
 Pegaptanib sodica: Macugen
– Clinical Trials

 Bevacizumab: Avastin
– NO Clinical Trials

 Ranibizumab: Lucentis
– Clinical Trials
Avastin - Bevacizumab
 Anticorpo monoclonale umanizzato anti-VEGF
che viene utilizzato in campo oncologico per
bloccare la crescita della rete vascolare
anarchica nell’ambito di forme tumorali
metastatiche del colon retto (5mg/Kg)
Avastin
 Effetti collaterali:
– Ipertensione 22.4-32%
– Proteinuria asintomatica 21.7-38%
– Tromboembolia arteriosa 18% (non diversa dal gruppo
controllo…)
– Ritardata cicatrizzazione delle ferite
– Perforazioni gastro-intestinali 1.4-2%
 Causa
– Azione del VEGF a livello del microcircolo
– Alterazione dei normali processi di crescita,
riparazione e di rigenerazione
Lucentis
 MARINA: Minimally classic/occult trial of the
Anti-VEGF antibody Ranizumab In the
treatment of Neovascular AMD
 716 soggetti con CNV minimamente classica,
occulta. No classiche
– Sham injection
– 0.3mg intravitreale mensile
– 0.5mg intravitreale mensile
 Follow up: 2 anni

Rosenfeld PJ NEJM 2006;14:1419-31


Lucentis
 ANCHOR: ANti-VEGF Antibody for the treatment
of Predominant Classic CHORoidal Neovascolarization
in AMD
 423 soggetti con CNV prevalentemente classica
– PDT(2.8)+ shame injection/mese(11.1)
– 0.3mg/mese(11) + shame PDT(1.7)
– 0.5mg/mese(11.2) + shame PDT(1.7)
 Follow up: 1 anno

Brown DM NEJM 2006;14:1432-44


Macugen
 VISION: VEGF Inhibition Study in Ocular
Neovascularization
 586 soggetti con CVN
– 1.0 mg pegaptanib
– 0.3 mg pegaptanib
– 3 mg pegaptanib
– Shame injection Gragoudas S NEJM 2004;27:2805-2816
 Follow up: 1 anno
Criteri di esclusione

 MARINA e ANCHOR: soggetti con


storia di problemi cardio-vascolari
NON sono stati esclusi

 VISION: pazienti con problemi


cardiovascolari o pregressi IMA sono
stati esclusi
Side effects – MARINA & ANCHOR
Side effects
Side effects
Side effects
Side effects
Side effects: SAILOR Study
 "Ranibizumab (Lucentis) Safety in Previously Treated and
Newly Diagnosed Patients with Neovascular Age-related
Macular Degeneration (AMD): The SAILOR Study," was
designed to evaluate the safety of two different doses
of Lucentis (0.5 mg, the FDA-approved dose, and 0.3 mg)
administered once a month for three months and
thereafter as needed based on re-treatment criteria.

 Rates of ocular and non-ocular serious adverse events at


one year were similar in patients receiving either 0.3 mg
or 0.5 mg of Lucentis and consistent with previous
studies, supporting the long-term safety of Lucentis

 Rates of ocular and non-ocular adverse events at one


year were generally low in both dose groups and
consistent with previous studies.
Side effects: SAILOR Study
 One-year results also demonstrated that the FDA-approved
dose of Lucentis (0.5 mg) was not associated with the higher
rate of stroke observed during the planned interim analysis at
six months. The data suggested a trend towards a higher
incidence of stroke in the 0.5 mg dose group (1.2% vs. 0.7% in
the 0.3 mg group), though the results were not statistically
significant (p-value=0.21).

 At one-year, patients with a prior history of stroke had a


higher rate of stroke in the 0.5 group (9.6%) compared to the
0.3 group (2.7%). However, this trend was inconclusive, as the
number of events was small. These data are consistent with
epidemiologic data showing that prior history of stroke
predisposes patients to subsequent stroke.

 One-year SAILOR efficacy data suggested that treating


patients with Lucentis on an as needed basis may be less
effective than monthly dosing.
Side effects: VISION
Side effects: AVASTIN
 1173 pazienti, 4303 iniezioni
 Retrospective study
 Follow up: 12 mesi
 Systemic Adverse Events: 1.5%
– 0.59% IPTS
– 0.5% cerebrovascular accident
– 0.4% myocardial infarction
– 0.17% iliac artery aneurysm
– 0.17% toe amputation
– 0.4% death

PACORES. Graefes Arch Clin Exp Ophthalmol 2008;246(1):81-7


Side effects: AVASTIN
 The international intravitreal bevacizumab
safety survey
 5228 pazienti – 7113 iniezioni
 Retrospective web-based study
 Systemic adverse event
– Blood pressure increase 0.21%
– Deep venous thrombosis 0.01%
– Transient ischaemic attack 0.01%
– Cerebrovascular accident 0.07%
– Myocardial infarction 0%
– Death 0.03%
Ziemssen F Br J Ophthamol 2006;90:1440-1
Lucentis

 Efficacia: clinical trials: SI, efficace

 Costo: farmaco-economia: SI, molto costoso

 Safety: clinical trials: SI, sicuro


Macugen

 Efficacia: clinical trials: SI, ± efficace

 Costo: farmaco-economia: SI, costoso

 Safety: clinical trials: SI, sicuro


Avastin

 Efficacia: clinical trials: NO

 Costo: farmaco-economia: SI, economico

 Safety: clinical trials: NO


Conclusioni

 Iniezioni intravitreali con anti-

VEGF sono sicure ed efficaci

 Età e stato di salute generale del

paziente vanno considerati