TY - JOUR
T1 - Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy in the PLANET study a randomized clinical trial
AU - Lee, Won Ki
AU - Iida, Tomohiro
AU - Ogura, Yuichiro
AU - Chen, Shih Jen
AU - Wong, Tien Yin
AU - Mitchell, Paul
AU - Cheung, Gemmy Chui Ming
AU - Zhang, Zhongqi
AU - Leal, Sergio
AU - Ishibashi, Tatsuro
N1 - Funding Information:
Additional Contributions: We thank the Fundus Photograph Reading Center at the Department of Ophthalmology and Visual Sciences of the University of Wisconsin School of Medicine and Public Health for their contributions to the conduct of this study. We thank Leigh Prevost, BSc, and Albert M. Balkiewicz, MSc, of PAREXEL for medical writing and editorial assistance that was funded by Bayer Pharmaceuticals.
Funding Information:
completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lee reports receiving personal fees and nonfinancial support from Bayer during the conduct of the study and personal fees from Bayer, Novartis, Allergan, and Santen outside the submitted work. Dr Iida reports receiving personal fees from Bayer during the conduct of the study; grants and personal fees from Alcon, AMO Japan, Bayer, Novartis, Otsuka Pharmaceutical, Santen Pharmaceutical, Senju Pharmaceutical, and Wakamoto Pharmaceutical; grants from Canon, Hoya, Kowa, Nidek, and Pfizer; and personal fees from Bayer and Chugai Pharmaceutical outside the submitted work. Prof Ogura reports receiving personal fees from Bayer during the conduct of the study and personal fees from Bayer, Alcon, Bausch and Lomb, Janssen Pharma, Kissei Pharma, Kowa, Novartis, Santen, Sanwa Kagaku, Senju, Topcon, and Wakamoto outside the submitted work. Dr Chen reports receiving personal fees and nonfinancial support from Bayer, Novartis, and Allergan and personal fees from Medical Integrating System during the conduct of the study. Dr Wong reports receiving consultancy fees and payments for lectures from Abbott, Allergan, Bayer, and Novartis outside the submitted work. Dr Mitchell reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work. Dr Cheung reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work. Drs Zhang and Leal are employees of Bayer Pharmaceuticals. Dr Ishibashi reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work.
Publisher Copyright:
© 2018 American Medical Association.
PY - 2018/7
Y1 - 2018/7
N2 - IMPORTANCE Polypoidal choroidal vasculopathy (PCV) is common in Asian populations, but an optimal treatment approach remains to be confirmed. OBJECTIVE To evaluate intravitreal aflibercept injection (IAI) in participants with PCV and compare IAI monotherapy with IAI plus rescue photodynamic therapy (PDT). DESIGN, SETTING, AND PARTICIPANTS This 96-week, double-masked, sham-controlled phase 3b/4 randomized clinical trial was conducted at multiple centers in Australia, Germany, Hong Kong, Hungary, Japan, Singapore, South Korea, and Taiwan from May 2014 to August 2016, and included adults 50 years or older with symptomatic macular PCV and a best-corrected visual acuity of 73 to 24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent). INTERVENTIONS Participants received 2mg of IAI at weeks 0, 4, and 8. At week 12, participants with a suboptimal response were randomized 1:1 to receive IAI plus sham PDT (IAI monotherapy) or a "rescue" of IAI plus rescue PDT (IAI/PDT). Participants who did not qualify for rescue received IAI every 8 weeks; those qualifying for rescue received IAI every 4 weeks plus sham/active PDT. When the rescue criteria were no longer met, injection intervals were gradually extended to 8 weeks. MAIN OUTCOMES AND MEASURES Noninferiority of IAI monotherapy to IAI/PDT for mean change in best-corrected visual acuity from baseline to week 52 (95%CI of the difference entirely above-5 letters). RESULTS Of the 318 participants, the mean (SD) age was 70.6 (8.2) years, 96 (30.2%) were women, and 152 (47.8%) were Japanese. Monotherapy with IAI was noninferior to IAI/PDT for the primary end point (+10.7 vs +10.8 letters, respectively; 95%CI,-2.9 to 1.6; P =.55), with few participants requiring rescue therapy (19 [12.1%] vs 23 [14.3%], respectively). Participants in both treatment groups had similar reductions in central subfield thickness from baseline to week 52 (-137.7 [IAI monotherapy] vs-143.5 μm [IAI/PDT]). At week 52, 49 (38.9%) and 60 participants (44.8%) had no polypoidal lesions observed on indocyanine green angiography in the IAI monotherapy and IAI/PDT groups, respectively. Furthermore, 116 (81.7%) and 136 (88.9%), respectively, had no polypoidal lesions with leakage. The most frequent ocular adverse events were conjunctival hemorrhage (IAI monotherapy, 8 [5.1%]) and dry eye (IAI/PDT, 9 [5.6%]). CONCLUSIONS AND RELEVANCE Improvement in visual and/or functional outcomeswas achieved in more than 85%of participants who were treated with IAI monotherapy, with no signs of leakage from polypoidal lesions in more than 80%. As fewer than 15%met the criteria of a suboptimal response to receive PDT, the potential benefit of adding PDT cannot be determined.
AB - IMPORTANCE Polypoidal choroidal vasculopathy (PCV) is common in Asian populations, but an optimal treatment approach remains to be confirmed. OBJECTIVE To evaluate intravitreal aflibercept injection (IAI) in participants with PCV and compare IAI monotherapy with IAI plus rescue photodynamic therapy (PDT). DESIGN, SETTING, AND PARTICIPANTS This 96-week, double-masked, sham-controlled phase 3b/4 randomized clinical trial was conducted at multiple centers in Australia, Germany, Hong Kong, Hungary, Japan, Singapore, South Korea, and Taiwan from May 2014 to August 2016, and included adults 50 years or older with symptomatic macular PCV and a best-corrected visual acuity of 73 to 24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent). INTERVENTIONS Participants received 2mg of IAI at weeks 0, 4, and 8. At week 12, participants with a suboptimal response were randomized 1:1 to receive IAI plus sham PDT (IAI monotherapy) or a "rescue" of IAI plus rescue PDT (IAI/PDT). Participants who did not qualify for rescue received IAI every 8 weeks; those qualifying for rescue received IAI every 4 weeks plus sham/active PDT. When the rescue criteria were no longer met, injection intervals were gradually extended to 8 weeks. MAIN OUTCOMES AND MEASURES Noninferiority of IAI monotherapy to IAI/PDT for mean change in best-corrected visual acuity from baseline to week 52 (95%CI of the difference entirely above-5 letters). RESULTS Of the 318 participants, the mean (SD) age was 70.6 (8.2) years, 96 (30.2%) were women, and 152 (47.8%) were Japanese. Monotherapy with IAI was noninferior to IAI/PDT for the primary end point (+10.7 vs +10.8 letters, respectively; 95%CI,-2.9 to 1.6; P =.55), with few participants requiring rescue therapy (19 [12.1%] vs 23 [14.3%], respectively). Participants in both treatment groups had similar reductions in central subfield thickness from baseline to week 52 (-137.7 [IAI monotherapy] vs-143.5 μm [IAI/PDT]). At week 52, 49 (38.9%) and 60 participants (44.8%) had no polypoidal lesions observed on indocyanine green angiography in the IAI monotherapy and IAI/PDT groups, respectively. Furthermore, 116 (81.7%) and 136 (88.9%), respectively, had no polypoidal lesions with leakage. The most frequent ocular adverse events were conjunctival hemorrhage (IAI monotherapy, 8 [5.1%]) and dry eye (IAI/PDT, 9 [5.6%]). CONCLUSIONS AND RELEVANCE Improvement in visual and/or functional outcomeswas achieved in more than 85%of participants who were treated with IAI monotherapy, with no signs of leakage from polypoidal lesions in more than 80%. As fewer than 15%met the criteria of a suboptimal response to receive PDT, the potential benefit of adding PDT cannot be determined.
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U2 - 10.1001/jamaophthalmol.2018.1804
DO - 10.1001/jamaophthalmol.2018.1804
M3 - Article
C2 - 29801063
AN - SCOPUS:85050893479
VL - 136
SP - 786
EP - 793
JO - JAMA Ophthalmology
JF - JAMA Ophthalmology
SN - 2168-6165
IS - 7
ER -