Adrian Koh1, Timothy Y Y Lai2, Kanji Takahashi3, Tien Y Wong4, Lee-Jen Chen5, Paisan Ruamviboonsuk6, Colin S Tan7,8, Chrystel Feller9, Philippe Margaron9, Tock H Lim7,8, Won Ki Lee10. 1. Eye and Retina Surgeons, Camden Medical Centre, Singapore, Singapore. 2. Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. 3. Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, Japan. 4. Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, National University of Singapore, Singapore. 5. Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan. 6. Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand. 7. Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore. 8. National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore. 9. Novartis Pharma AG, Basel, Switzerland. 10. Department of Ophthalmology, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Abstract
Importance: Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals. To our knowledge, there are no large randomized clinical trials to evaluate intravitreal ranibizumab, with and without verteporfin photodynamic therapy (vPDT), for the treatment of PCV. Objective: To compare the efficacy and safety of combination therapy of ranibizumab and vPDT with ranibizumab monotherapy in PCV. Design, Setting, and Participants: A double-masked, multicenter randomized clinical trial of 322 Asian participants with symptomatic macular PCV confirmed by the Central Reading Center usingindocyanine green angiography was conducted between August 7, 2013, and March 2, 2017. Interventions: Participants were randomized 1:1 to ranibizumab, 0.5 mg, and vPDT (n = 168; combination therapy group) or ranibizumab, 0.5 mg, and sham PDT (n = 154; monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT/sham PDT on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions. Main Outcomes and Measures: Step 1 assessed whether combination therapy was noninferior (5-letter margin) to monotherapy for change in best-corrected visual acuity from baseline and superior in complete polyp regression. If noninferiority was established, step 2 assessed whether combination therapy was superior to monotherapy measured by best-corrected visual acuity change at month 12. Results: Baseline demographics of the 322 participants were comparable between the treatment groups. Mean (SD) age of the patients was 68.1 (8.8) years, and overall, 69.9% of the patients were men. At baseline, the overall mean best-corrected visual acuity and mean central subfield thickness were 61.1 letters and 413.3 μm, respectively. At 12 months, mean improvement from baseline was 8.3 letters with combination therapy vs 5.1 letters with monotherapy (mean difference, 3.2 letters; 95% CI, 0.4-6.1), indicating that combination therapy met the predefined criterion for noninferiority as well as being superior to monotherapy (P = .01). Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P < .001). Over 12 months, the combination therapy group received a median of 4.0 ranibizumab injections compared with 7.0 in the monotherapy group. Vitreous hemorrhage was the only ocular serious adverse event (combination therapy group, 1 [0.6%]; monotherapy group, 3 [2.0%]). Conclusions and Relevance: After 12 months, combination therapy of ranibizumab plus vPDT was not only noninferior but also superior to ranibizumab monotherapy in best-corrected visual acuity and superior in complete polyp regression while requiring fewer injections. Combination therapy should be considered for eyes with PCV. Trial Registration: clinicaltrials.gov Identifier: NCT01846273.
RCT Entities:
Importance: Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals. To our knowledge, there are no large randomized clinical trials to evaluate intravitreal ranibizumab, with and without verteporfin photodynamic therapy (vPDT), for the treatment of PCV. Objective: To compare the efficacy and safety of combination therapy of ranibizumab and vPDT with ranibizumab monotherapy in PCV. Design, Setting, and Participants: A double-masked, multicenter randomized clinical trial of 322 Asian participants with symptomatic macular PCV confirmed by the Central Reading Center using indocyanine green angiography was conducted between August 7, 2013, and March 2, 2017. Interventions: Participants were randomized 1:1 to ranibizumab, 0.5 mg, and vPDT (n = 168; combination therapy group) or ranibizumab, 0.5 mg, and sham PDT (n = 154; monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT/sham PDT on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions. Main Outcomes and Measures: Step 1 assessed whether combination therapy was noninferior (5-letter margin) to monotherapy for change in best-corrected visual acuity from baseline and superior in complete polyp regression. If noninferiority was established, step 2 assessed whether combination therapy was superior to monotherapy measured by best-corrected visual acuity change at month 12. Results: Baseline demographics of the 322 participants were comparable between the treatment groups. Mean (SD) age of the patients was 68.1 (8.8) years, and overall, 69.9% of the patients were men. At baseline, the overall mean best-corrected visual acuity and mean central subfield thickness were 61.1 letters and 413.3 μm, respectively. At 12 months, mean improvement from baseline was 8.3 letters with combination therapy vs 5.1 letters with monotherapy (mean difference, 3.2 letters; 95% CI, 0.4-6.1), indicating that combination therapy met the predefined criterion for noninferiority as well as being superior to monotherapy (P = .01). Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P < .001). Over 12 months, the combination therapy group received a median of 4.0 ranibizumab injections compared with 7.0 in the monotherapy group. Vitreous hemorrhage was the only ocular serious adverse event (combination therapy group, 1 [0.6%]; monotherapy group, 3 [2.0%]). Conclusions and Relevance: After 12 months, combination therapy of ranibizumab plus vPDT was not only noninferior but also superior to ranibizumab monotherapy in best-corrected visual acuity and superior in complete polyp regression while requiring fewer injections. Combination therapy should be considered for eyes with PCV. Trial Registration: clinicaltrials.gov Identifier: NCT01846273.
Authors: Kai Tang; Jun-Kang Si; Da-Dong Guo; Yan Cui; Yu-Xiang Du; Xue-Mei Pan; Hong-Sheng Bi Journal: Int J Ophthalmol Date: 2015-10-18 Impact factor: 1.779