作者
David M. Brown,David S. Boyer,V. Diana,Charles C. Wykoff,Taiji Sakamoto,Peter H. Win,Sunir Joshi,Hani Salehi-Had,András Seres,Alyson J. Berliner,Sergio Leal,Robert Vitti,Karen Chu,Kimberly Reed,Rohini Rao,Yenchieh Cheng,Wenjie Sun,Delia Voronca,Rafia Bhore,Ursula Maria Schmidt-Ott,Thomas Schmelter,Andrea Schulze,Xin Zhang,Boaz Hirshberg,George D. Yancopouloš,Sobha Sivaprasad,Prema Abraham,Christopher M. Aderman,Kunihiko Akiyama,D. Virgil Alfaro,Fareed Ali,Payam Amini,Andres Emanuelli Anzalotta,György Bátor,Ivan Batlle,Adam S. Berger,Ramanath Bhandari,William Z. Bridges,Christian Brinkmann,Jamin Brown,SC Burgess,Jorge I. Calzada,Antonio Capone,Dana Cervena,Steven T. Charles,Nauman Chaudhry,David R. Chow,W. Lloyd Clark,Paul Conrad,Maureen Cunningham,Hajir Dadgostar,Amr Dessouki,D. M. Deupree,Christopher A. Devine,David Eichenbaum,Jan Ernest,Nicolas Feltgen,M. J. Fenberg,Philip J. Ferrone,Ronald E. P. Frenkel,Scott M. Friedman,Julie Gasperini,Adam T. Gerstenblith,Ghassan Ghorayeb,Michel Giunta,Mitchell J. Goff,Liliya Golas,Joseph M. Googe,Jordana Fein,C.L. Hagedorn,Akira Hagiwara,Paul Hahn,Richard Hairston,Jason M Handza,Vivienne Hau,Ken Hayashi,Jeffrey S. Heier,Vrinda Hershberger,Patrick Higgins,Yoshio Hirano,Shigeru Honda,Yasuko Ikegami,Yusuke Ishida,Isao Ishikawa,Kiyoshi Ishii,Eric P. Jablon,Atul Jain,Yuichi Kaji,Kapil Kapoor,Ágnes Kerényi,Kazuhiro Kimura,Genichiro Kishino,Katalin Kiss,Takashi Kitaoka,James M. Klancnik,Namie Kobayashi,Jiro Kogo,V Korda,Erik Kruger,Sentaro Kusuhara,Wilfredo Lara,Ketan Laud,Seong Lee,James K. Luu,Dennis M. Marcus,Calvin E. Mein,Annal D. Meleth,Tibor Milibák,Yoshinori Mitamura,Toshinori Murata,Sumiyo Noge,Hajime Onoe,James M. Osher,András Papp,Justin Parschauer,Sugat Patel,Sunil Patel,Matthew Pezda,Ashkan Pirouz,Pradeep Prasad,Omar S. Punjabi,Llewelyn Rao,Richard H. Roe,Ramin Schadlu,Eric Schneider,Ankur Shah,Milan Shah,Sandeep N. Shah,Sumit P Shah,Ashish Sharma,Veeral Sheth,Masahiko Shimura,Lawrence J. Singerman,Georg Spital,Robert Stoltz,Eric Suan,Kiyoshi Suzuma,Hidenori Takahashi,Yoshihiro Takamura,Masaru Takeuchi,Jonathan M. Tan,Benjamin Thomas,-Molnár Edit Tóth,Takahiro Ueda,Hiroaki Ushida,Attila Vajas,Deepali Varma,Balázs Varsányi,Miroslav Veith,Pamela Weber,Raymond Wee,Geoff Williams,Haruhiko Yamada,Yoshihiro Yonekawa,Shigeo Yoshida
摘要
Summary
Background
A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. Methods
PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). Findings
Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was –0·57 letters (95% CI –2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and –1·44 letters (–3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). Interpretation
Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. Funding
Regeneron Pharmaceuticals and Bayer.