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. 2018 Sep 13:12:1789-1799.
doi: 10.2147/OPTH.S171015. eCollection 2018.

Efficacy and safety of ranibizumab monotherapy versus ranibizumab in combination with verteporfin photodynamic therapy in patients with polypoidal choroidal vasculopathy: 12-month outcomes in the Japanese cohort of EVEREST II study

Kanji Takahashi  1 , Masahito Ohji  2 , Hiroko Terasaki  3 , Shigeru Honda  4 , Philippe Margaron  5 , Tadhg Guerin  6 , Mitsuko Yuzawa  7
Affiliations

Efficacy and safety of ranibizumab monotherapy versus ranibizumab in combination with verteporfin photodynamic therapy in patients with polypoidal choroidal vasculopathy: 12-month outcomes in the Japanese cohort of EVEREST II study

Kanji Takahashi et al. Clin Ophthalmol. .

Abstract

Purpose: To compare the efficacy and safety of ranibizumab 0.5 mg with or without verteporfin photodynamic therapy in Japanese patients with polypoidal choroidal vasculopathy over 12 months.

Study design: EVEREST II was a 24-month, Phase IV, multicenter, randomized, double-masked study in Asian patients with symptomatic macular polypoidal choroidal vasculopathy.

Methods: Of the 322 enrolled patients, 84 patients, including 46 patients who received ranibizumab + verteporfin photodynamic therapy (combination therapy arm) and 38 patients who received ranibizumab/sham PDT (monotherapy arm), were Japanese who were evaluated in this subanalysis. Mean change in best-corrected visual acuity (BCVA) and complete polyp regression at Month 12, ranibizumab treatment exposure, and safety over 12 months were assessed.

Results: Baseline demographics were well balanced between the arms. At Month 12, mean change in BCVA letter score was +8.5 with combination therapy versus +6.4 with monotherapy. Complete polyp regression was higher with combination therapy than with monotherapy at Month 12 (70.5% vs 27.3%). Over 12 months, patients in the combination arm received a median of 4.0 ranibizumab injections vs 7.0 in the monotherapy arm. Serious adverse events were generally low in both arms, and retinal hemorrhage, an adverse event, was reported in one patient (2.2%).

Conclusion: The results from the Japanese cohort were in agreement with the EVEREST II study. Combination therapy was effective in improving BCVA and achieving a higher rate of complete polyp regression with a lower number of ranibizumab injections than monotherapy. No new safety signals were reported, and safety events were comparable between both arms over 12 months.

Keywords: Japanese; neovascular age-related macular degeneration; polypoidal choroidal vasculopathy; ranibizumab; verteporfin photodynamic therapy.

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Conflict of interest statement

Disclosure Kanji Takahashi received grant, personal fees, and nonfinancial support from Novartis, Santen, Alconpharma, Bayer; grant and personal fees from Senju; personal fees from Ohtsuka and Carl Zeiss; grant from Hoya, Amo, Senjyu and Sun Contact Lens; grant and financial support from Pfizer. Dr Masahito Ohji reported grants and personal fees from Novartis, Bayer, Santen, Pfizer, Senju, Alcon, Otsuka Pharmaceutical, Kowa Pharmaceutical, HOYA Corporation, Topcon; personal fees from Allergan, Carl Zeiss, RE Medical Inc., Bausch + Lomb, Chuo Sangio; and grants from AMO, TOMEY, outside the submitted work. Hiroko Terasaki received grant and personal fees from Nidek Inc., Otsuka Pharmaceutical Co., Ltd., Pfizer, Inc., Santen Inc, Alcon Japan Ltd., Novartis Pharmaceuticals Corporation, Senju Pharmaceutical Co. Ltd., Kowa Pharmaceutical Co. Ltd., Wakamoto Co., Ltd.; personal fees from Rohto Pharmaceutical co., ltd., Takeda Pharmaceutical Company Limited., Mitsubishi Tanabe Pharma Corporation, Graybug Vision, Inc, Alcon Research Surgical Retina R&D, Alcon Laboratories, Inc., Alcon Research Ltd, AbbVie GK, Daiichi Sankyo Company, Limited, Chuo Sangio Co., Sanofi K.K., Nihon Tenganyaku Kenkyusyo Co. Ltd., Alcon Pharma Corporation, Bayer Healthcare Pharmaceuticals; financial grant from HOYA Corporation and Allergan Japan; and personal fees and nonfinancial support from Carl Zeiss Meditec co., Ltd. Shigeru Honda has no conflicts of interest to be disclosed. Philippe Margaron is an employee of Novartis Pharma AG, Basel, Switzerland. Tadhg Guerin is an employee of Novartis Global Service Center, Dublin, Ireland. Mitsuko Yuzawa received grants and personal fees from Alcon Japan; personal fees and nonfinancial support from Novartis, Bayer, Bausch & Lomb Japan; personal fees from Senju, Astelles Pharma, Japan focus company, Janssen Japan. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study design and treatment schedule. Notes: Included Japanese patients. *Ranibizumab was administered PRN as per protocol-specific retreatment criteria if there was a BCVA loss or presence of disease activity as seen in OCT. #vPDT/sham PDT‡ was administered PRN as per protocol-specific retreatment criteria based on presence of active polyp(s) on ICGA with a minimum interval between two PDT treatments of at least 3 months. The interval between two ranibizumab treatments was at least 28 days. Abbreviations: BCVA, best-corrected visual acuity; D, Day; ICGA, indocyanine green angiography; OCT, optical coherence tomography; PRN, pro re nata; vPDT, verteporfin photodynamic therapy.
Figure 2
Figure 2
Randomization and patient disposition in the Japanese cohort. Notes: *Of the 322 patients who were randomized 1:1 in the EVEREST II study, 84 patients identified themselves as belonging to the Japanese ethnicity. Percentages are based on the total number of patients in the randomized set in the respective treatment arm. Abbreviation: vPDT, verteporfin photodynamic therapy.
Figure 3
Figure 3
Assessment of BCVA outcomes over the 12-month study period. Notes: (A) Mean BCVA and mean change at baseline and Month 12 (FAS; LOCF). (B) Proportion of patients with BCVA ≥69 letters at baseline and Month 12 (FAS). The FAS comprised all participants who were assigned to a treatment regimen. The total counts presented are the counts of patients in the specific treatment arm who attended the specific visit. These total counts are used as the denominator for the percentages. Abbreviations: BCVA, best-corrected visual acuity; FAS, full analysis set; vPDT, verteporfin photodynamic therapy; LOCF, last observation carried forward; n, number of patients.
Figure 4
Figure 4
Proportion of participants with complete polyp regression by study visits up to Month 12 (FAS). Notes: Values assessed by the Central Reading Center using ICGA. The FAS comprised all participants who were assigned to a treatment regimen. Number values indicate the total number of participants in the FAS in the respective treatment arm. Percentages are computed by considering the total number of participants in the respective treatment arm who attended the specific visit as a denominator. Abbreviations: FAS, full analysis set; ICGA, indocyanine green angiography; vPDT, verteporfin photodynamic therapy.
Figure 5
Figure 5
Mean change in CSFT and CCT, and proportion of participants with disease activity. Notes: (A) Mean CSFT change from baseline to Month 12 (FAS). (B) Mean reduction in CCT from baseline to Month 12 (FAS). (C) Proportion of participants with disease activity by visit (FAS). The FAS comprised all participants who were assigned to the treatment regimen. Number values indicate the total number of participants in the FAS in the respective treatment arm. Percentages are computed by considering the total number of participants in the respective treatment arm who attended the specific visit as a denominator. Abbreviations: CSFT, central subfield thickness; CCT, central choroidal thickness; FAS, full analysis set; M, month; vPDT, verteporfin photodynamic therapy.
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