Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema
Authors: Hutton David W. , Glassman Adam R. , Liu Danni , Sun Jennifer K. ,   DRCR Retina Network, Sneath Mark , Chen Melvin , Jelemensky Peggy A. , Miller Rosa , Basham Samantha R. , Raphael Tara L. , Harara Abla M , Berger Brian B. , Jhaveri Chirag D. , Stovall Christopher C. , Renfroe Cori , Vega Pereira Daniela , Wilson Daniela Mariel , Makkouk Fuad , Jonna Gowtham , Gunderson Ivana , Chexal Saradha , Gatavaski Valerie , Ren Yong , Irons Amber N , Rego Brittany , Weinberg David V. , Dorsey Eleanor , Nelson Erika , Sheppard Hannah , McKenney Kaitlin C , Chen Nickolas , Wirostko William J. , Ghuman A. Thomas , Arevalo Alice , Petersen Amanda J. , Leslie Anita H. , Sharma Ashish G. , Kiesel Cheryl , Peters Crystal Y. , Knips Eileen , Walker Joseph P. , Mears Katrina A. , Maro Kristi , Toleman Lee T , Raskauskas Paul A. , Kiesel Raymond K. , Meeks Ashaki , Rhymes Ginger K. , Gardner Glenn R , Shami Michel , Saldivar Yolanda , Schlossman Deborah K. , Weimann Elizabeth S. , Rhee Jae W , Sun Jennifer K. , Cavallerano Jerry D. , Tran Katie V , Bestourous Leila , Stockman Margaret E. , Sehizadeh Mina , Silva Paolo S. , Cavicchi Robert W. , Shah Sabera T. , Papaconstantinou Steve L. , Olesker Tanya , Murtha Timothy J. , Carli William , Wilson Amanda H. , Antoszyk Andrew N. , Price Angela K. , Gentile Angella K. , Murphy Brittany A , Shore Carol A , Mutch Christina , Fleming Christina J. , Browning David , McClain Donna , Allen John Bradley , Clark Justin , McShea Kaitlin T. , Bratcher Kayla A , Jackson Lisa A. , Clark Loraine M. , Watson Lynn , Nayar Monica D. , Punjabi Omar S. , Ennis Sarah A. , Stobbe Shannon , Fredenberg Sherry L. , Ross Tracy A. , Balasubramaniam Uma M. , Harless Ashley M. , Novak Carolee K. , Harris Charlotte , Brown Erin , Fiscus Holly , White Lorraine , Retrum Myra K , Maturi Raj K. , Morrow Stephanie J. , Saxe Stephen J , Mahesh Vinaya , Sarmiento Yesenia , Gilbreath Caitlin , Griffone Hodge A. , Wheeler Jeff , Googe Joseph M. , Asher Julie , Walsh Justin , Milstead Katie , Oliver Kristina , Anderson Nicholas G. , Shuler R. Keith , Lince Raul E. , Oelrich Sarah M. , Perkins Stephen L. , Morris Steve , McCoy Summer , Seitz Vicky L. , Al Moshmosh Ahmad , Nicholson Ashley M , Tucker Ashley Y , Clow Claudia , Trichonas Georgios , Miranda Geraldo R , Baum-Rawraway Irit , Randhawa Jasmeen K , O'Malley Jennifer , Wash Laura M , Richards Leslie A , Petrosky Margaret N , Allchin Peggy , Kurup Shree K. , Pelton Stephanie , Brewer Alisha N , Hollingshead Amanda M , Hughes Ashley , Cheadle Markeisha , Thomas Myka , Sohl Rachel , Kingsley Ronald M. , Burris Russ , Almeida Shannon R. , Icks Sonny , Shah Vinay A. , Camp Alecia B. , Baker Carl W. , Baker Jil D , Sedberry Kylie S. , Orr Margaret J. , Sharp Mary J. , Kettler Samantha , Alcaraz Sonya L , Caldwell Tracey M. , Listerman Angela D. , Igoe Ashley L , Feehan Christine E. , McLouth Darra S. , Kuitula Donald E. , Truax Elizabeth , Garber Frank W. , Cruz Heather L. , Zheutlin Jeffrey D. , DeHorn Kathleen U. , Glazer Louis C. , Homann Melissa A. , Crown Paul D. , Weatherbee Sue , Hutson Amy , Richter Beau A , Almanza Belinda A. , Wykoff Charles C. , Henry Christopher R. , Garcia David , Kegley Eric N. , Vela Melina , Fish Richard H. , McCoy Tyneisha , Sneed Veronica A. , Alset Adel E , Sierpina David Isaiah , Easterly Marcia , Rauser Michael E. , Tellez Moises , Hernandez Raquel , Ramirez Tina L , Reddy Ashok K. , Gutierrez Bonnie J , Atkinson Janet L , Ramaiya Kamalesh J. , Carter Lorraine J. , Chiu Mark T. , Daniels Marlena A , Miera Michael G , Maerki Shirley , Bunch Debra Paige , Lazarus Howard S. , Moore Jay , Davis Liana C. , Drudge Nick , Bobbitt Brenda J. , Wendel Ceara L , Fagan Damanda F. , Andrews Jacqueline , Seyez Karen L , Holmes Krystal Nikki , Cadieux Lauren , Moinfar Nader , Friedman Scott M. , Williams Shana E , Rehling Shannon M , Marsh Tammi , VandeVelde Amber R , Suiter Beatty G. , Cooper Blake A. , Yeager Frank T. , Fox Gregory M. , Wyrick Holly , Hinkel Holly A , Batlle Ivan R. , Pippin Katherine , Ainley Lexie R. , Singh Ravi S. J. , Perkins Samantha , Guardado Adrian , Patel Apurva K. , Adamo Ashley M , Puckett Brian S , Clark David J , Flato Inessa M , Cohen Joshua , Kopfer Marcia , Cleary Megan M , Lee Michael S. , Connaughton Michele , Tlucek Paul S. , Zhang Wenlan , Durrani Alia K. , Braverman Allan L. , Pulliam Brook G. , Gabel Dana L , Reardon Diana , Nobel Ginny S. , Wehmeier Jarrod , Bockius Kara R , Blinder Kevin J. , Boyd Lynda K. , Stuart Maria A. , Kittleman Nathan A. , Weeks Rhonda F. , Dang Sabin , Schremp Steve A , Ibarra Amber B , Pina Ana L , Garza Angelina , Navarro Elyssa , Villarreal Georgia L. , Cabrera Isaac , Salinas Nancy L , Patel Nehal R. , Flores Rebecca R. , Alonso Samuel , Garza Santos , Gonzalez Victor Hugo , Marcus Dennis M. , Simons Elizabeth W , Ivey Ken , Woodward Michele , Ortiz Siobhan O. , Bailey Thomas , Dunn Courtney J , Heim Elizabeth N. , Stewart Mary C , Varner R. Scott , Lamaster Sarah N. , Rosenthal William N. , Nakoski Brenda , Mein Calvin E. , Belmontes Celeste A , Wienecke Christopher Sean , Baskin Darrell E. , San Roman Jonathan , Castellanos Jorge , Kirschbaum Lita , Adams Lydia , Chica Moises A. , Lane Richard Gary , Bankston Samantha , Cloudt Sara L , Martinez Vanessa D , Lopez Victoria , Joshi Annika S. , Leger April , Chatham Becky R. , Weng Christina Y. , Barnett Dana B. , Leung Ella , Cai Jiping , Morales Joseph F. , Baker Laura A , Scholle Tahira , Volpigno Amy , Niffenegger Arysol , Bentsen Bruce A. , Scully Donna , Richter Elizabeth R. , Niffenegger John H. , Cottrill Marianne , Lopez Marisol , Vyas Avni Patel , Doft Bernard H. , Stout Brittany , Foreman Courtney L. , Diperna Dawn , Knickelbein Jared E. , Walter Julie , Olsen Karl R. , Stepansky Lois , Merlotti Lori A. , Forish Missy A. , Conrad P. William , Ostroska Phyllis P , Bergren Robert L. , Menzel Andrea K. , Klutz Ashley Hinson , Stone Cameron McLure , Machen Donna , Overbey Julia Crokett , Cutshaw Kaitlyn Marie , Raymer Lea R. , Rickman Leslie D. , Hawkins Lisa H. , Hall McCayla Elise , Smith Melissa , Hamrick Monica , Price Paula A. , Vincent Holly L. , Barrett Kimberly , Fredrick Kristyn Jae , Shevchenko Liliya , Pezda Nathan F. , Rainey Olivia P , Westhouse Scott J. , Mohamed Shymaa , Aaberg Thomas M. , Rosberger Daniel F. , Wangmo Phuntsho , Gyaltshen Sonam , Villa Adriana , Workman Karen , Oberlander Mark , Pereda Noel H. , Burgess Stuart K. , Lara Tirso M. , Montesclaros Chris A. , Vargas Corinne C , Mangham Cory , Karsaliya Gopal , Martinez Jose A. , Nixon Peter A. , Le Phillip V. , Wong Robert W. , Young Ryan C. , Cheek Andrew G. , Skea Brian G , Waidelich Dylan C. , Dittman Eileen A. , Erstad Jillian N , Jack Loren S. , Wirthlin Robert S. , Dessouki Amr , Trujillo Carla , Chow Clement , Dinh Danielle , Dang Hienmy , Hernandez Juan , To Kelly , He Lingmin , Cummins Lynise , Montes Paola , Fernandez Pete Donovan , Kelley Tim , Kuang Whitney , Malzahn Anita Kim , DeSilva Demi , Vargo Heidi , Suner Ivan J. , Traynom Janet R. , Henderson Kim , Peden Marc C. , Munoz Stephanie , Ramsey Susan , Wetzel Adelyn , Cook Carlos R. , Weaver Cynthia , McCluskey Jessica D. , Wynne Kathy T. , Kaufman Paul L. , Matloff Sarah , Reynard Ann , Connolly Brian P. , Hall Edward F. , Territo Joe , Goole Malinda , Whelehan Margaret , Yagoda Margaret M. , Doran Mary Jo , Witmer Matthew T. , Burgess Mindy , Nelson Ryan W , Rose Steven J. , Warrington Susan , Rodriguez Alma , Ortiz Carolina Figueroa , Figueroa Dianelis , Rodriguez-Roman Elaine , Mavrofrides Elias C. , Kumar Jaya B. , Haddox Martha , Cunningham Matthew A. , Gomez Ramona , Houston Samuel K. S. , Holle Timothy S , Neyra Ana , Lara David , Shienbaum Gary , Rodriguez Jaziel , Gonzalez Marco A. , Garcia Pamela , Lara Wilfredo C. , Castro Alejandra , Santacruz Cristina , Shaya Fadi S. , Small Kent W. , Jamali Afsoon , Bustamante Denise Joy , Winje Heidi A. , Ricks Helen , Kwan Mae , Miranda Maria , Rofagha Soraya , Aho Amanda , Haight Bethany A. , Pallipeedikayil Chandapilla C. , Girard Crystal , Tedstone Daniel , Johnson Elizabeth I. , Velez Gisela , Larkin Jean , Caro Jhan Carlos , Rand Lawrence I. , Parry Maa Ahema , Ortega Michael D. , Mastrodomenico Nicholas R , Mykhaylyk Oksana , Taylor Thomas , Sweeney Travis , Fox Amanda , Evans Bradley C. , Wessel Caitlyn , Moushon Gaylan W , Shaw Jennifer , Karrick Kris , Bhandari Ramanath , Douglas Dusti D , Jois Latha M , Cummings Molly K. , Morris Rebecca , Webb Rebecca , Grigorian Ruben A. , David Sharoon , Ritchey Treasure , Gerstenblith Adam T. , Goldizen Angie , Stockman April L. , Shirey Jennifer , Stambaugh Kylie , Toomey Leslie , Glaspell Lora , Parnes Robert E. , Watkins Andre , Ortiz Denise , Murillo Diana , Dunn Gregory A , Qureshi Jawad A. , Warminski Johnathan D. , Smith Pualani , Cowart Victoria E. , Carey Annette M. , Oudshoff Bronson , Glover Christina , Handza Jason M. , Chiang Allen , Kenney Brianna , Regillo Carl , Williams Dylon , Gonzales Elaine , Benfield Hannah , Hsu Jason , Grande Lisa , Huntzberry Megan , Millard Michelle , Merchan Ana Maria , Hernandez Annie , Cardoza Cristal , Parque Karen , MacCumber Mathew W. , Merrill Pauline , Montgomery Sara E. , Huertas Cathy , Feinstein Eric , Bell Ginny G. , Kumar Gokul , Fulgencio John , Olson John , Daffron Sarah , Philibin Sonia , Tarabishy Ahmad B. , Blair Dana , Dunn Evan N. , Meyers Jessica , Goff Marcus , Spear Megan , Summerville Alamira B , Hoekzema Aubrey J , Huynh Becky , Thomas Benjamin J. , Carter Heavenly S , Staman James A. , Staman Jonathan A. , Yesensky Karen D. , Montalvo Massiel , Charleus Maxsonne , Pheng Sovanny Brenda , Epperson Steven , Maximin Tiffany , Hunter Allan A. , Beck Roy W. , Baptista Alyssa , Beaulieu Wesley T. , Calhoun Claire T. , Constantine Sharon R. , Correia Isabella , Dale Brian B. , Dupre Simone S. , Franklin Crystal A. , Galusic Sandra , Huggins Meagan , Hunter Brenda L. , Johnson Paula A. , Josic Kristin , Kelly Brittany , Maguire Maureen G. , Meadows Britney , Melia Michele , Preston Carin M. , Stockdale Cynthia R. , Zokruah Alice , Bhargava Sangeeta , Barkmeier Andrew J. , Baskin Darrell , Blodi Barbra , Chew Emily , Ferris Frederick L. , Solomon Sharon D. , Jaffe Glenn J. , Bressler Neil M. , Lujan Brandon , Abrams Gary , Barnbaum Deborah R. , Flynn Harry , Rudser Kyle D. , Sternberg Paul , Weinstock Ruth S. , Wisniewski Stephen 
Published: February 2023

ImportanceThe DRCR Retina Network Protocol AC showed no significant difference in visual acuity outcomes over 2 years between treatment with aflibercept monotherapy and bevacizumab first with switching to aflibercept for suboptimal response in treating diabetic macular edema (DME). Understanding the estimated cost and cost-effectiveness of these approaches is important.ObjectiveTo evaluate the cost and cost-effectiveness of aflibercept monotherapy vs bevacizumab-first strategies for DME treatment.Design, Setting, and ParticipantsThis economic evaluation was a preplanned secondary analysis of a US randomized clinical trial of participants aged 18 years or older with center-involved DME and best-corrected visual acuity of 20/50 to 20/320 enrolled from December 15, 2017, through November 25, 2019.InterventionsAflibercept monotherapy or bevacizumab first, switching to aflibercept in eyes with protocol-defined suboptimal response.Main Outcomes and MeasuresBetween February and July 2022, the incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life-year (QALY) over 2 years was assessed. Efficacy and resource utilization data from the randomized clinical trial were used with health utility mapping from the literature and Medicare unit costs.ResultsThis study included 228 participants (median age, 62 [range, 34-91 years; 116 [51%] female and 112 [49%] male; 44 [19%] Black or African American, 60 [26%] Hispanic or Latino, and 117 [51%] White) with 1 study eye. The aflibercept monotherapy group included 116 participants, and the bevacizumab-first group included 112, of whom 62.5% were eventually switched to aflibercept. Over 2 years, the cost of aflibercept monotherapy was $26 504 (95% CI, $24 796-$28 212) vs $13 929 (95% CI, $11 984-$15 874) for the bevacizumab-first group, a difference of $12 575 (95% CI, $9987-$15 163). The aflibercept monotherapy group gained 0.015 (95% CI, −0.011 to 0.041) QALYs using the better-seeing eye and had an ICER of $837 077 per QALY gained compared with the bevacizumab-first group. Aflibercept could be cost-effective with an ICER of $100 000 per QALY if the price per dose were $305 or less or the price of bevacizumab was $1307 per dose or more.Conclusions and RelevanceVariability in individual needs will influence clinician and patient decisions about how to treat specific eyes with DME. While the bevacizumab-first group costs still averaged approximately $14 000 over 2 years, this approach, as used in this study, may confer substantial cost savings on a societal level without sacrificing visual acuity gains over 2 years compared with aflibercept monotherapy.