Scheduled versus Pro Re Nata Dosing in the VIEW Trials

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• 作者：Gisbert Richard ; MD¹ ; ^{richard@uke.de" class="auth_mail" title="E-mail the corresponding author} ; Jordi Moné ; s ; MD ; PhD² ; Sebastian Wolf ; MD ; PhD³ ; Jean Franç ; ois Korobelnik ; MD⁴ ; ⁵ ; ⁶ ; Robyn Guymer ; MBBS ; PhD⁷ ; Michaella Goldstein ; MD⁸ ; Christiane Norenberg ; MS⁹ ; Rupert Sandbrink ; MD ; PhD⁹ ; ¹⁰ ; Oliver Zeitz ; MD¹ ; ⁹
• 关键词：AMD ; age-related macular degeneration ; BCVA ; best-corrected visual acuity ; CRT ; central retinal thickness ; ETDRS ; Early Treatment Diabetic Retinopathy Study ; OCT ; optical coherence tomography ; PRN ; pro re nata ; Rq4 ; ranibizumab 0.5 mg every 4 weeks ; VA ; visual acuity ; 0.5q4 ; intravitreal aflibercept 0.5 mg every 4 weeks ; 2q4 ; intravitreal aflibercept 2.0 mg every 4 weeks ; 2q8 ; intravitreal aflibercept 2.0 mg every 8 weeks after 3 initial monthly doses
• 刊名：Ophthalmology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：122
• 期：12
• 页码：2497-2503
• 全文大小：847 K

文摘

To analyze visual acuity (VA) outcomes before and after preplanned treatment regimen change in the VIEW studies at week 52 (W52).

Design

Multiple post hoc analyses for retrospectively defined subgroups in 2 multicenter, multinational, double-masked trials.

Participants

Two thousand four hundred fifty-seven neovascular age-related macular degeneration (AMD) patients.

Methods

Patients were randomized to treatment with 0.5 mg ranibizumab given monthly, a 0.5-mg or 2-mg intravitreal aflibercept injection given monthly, or 2 mg intravitreal aflibercept given every other month, after 3 initial monthly doses, up to W52. From W52 through W96, patients received their original dosing assignment using a capped pro re nata (PRN) regimen, with defined retreatment criteria based on VA and morphologic signs of disease activity and mandatory dosing at least every 12 weeks.

Main Outcome Measures

Best-corrected VA (BCVA) and optical coherence tomography assessments were mandatory at all visits from baseline to W96. Outcomes were changes in BCVA and central retinal thickness. Outcomes were evaluated in all patients who completed 2 years of the VIEW studies using the last observation carried forward method for missing data at interim visits.

Results

After W52, approximately 20% of patients lost 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more across all treatment arms with PRN treatment. Patients who met the retreatment criterion of loss of 5 ETDRS letters or more in the first quarter of the PRN dosing phase did not recover; mean final VA loss across the 4 study arms was −4.4 to −5.8 letters. Outcomes of these patients up to W52 were indistinguishable from those of the overall population. There were no differences between groups in serious ocular adverse events or Anti-Platelet Trialists' Collaboration arterial thromboembolic events through W96.

Conclusions

These analyses suggest that there are subgroups of patients for whom VA outcomes in the second year of the VIEW studies were less stable than in the first year and for whom W52 seems to be an important inflection point. Although alternate reasons specific to the nature of the underlying AMD cannot be fully excluded, the switch in treatment regimen at W52 is a plausible explanation.