Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema
To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab. Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment...
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| Veröffentlicht in: | Ophthalmology (Rochester, Minn.) Minn.), 2018-07, Vol.125 (7), p.1054-1063 |
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| creator | Wells, John A. Price, Angela K. Fredenberg, Sherry L. Fleming, Christina J. Walker, Aimee Shook, Aimee H. Taylor, Mallie M. Miller, Peggy D. Sease, Courtney Huggins, Tyler Shah, Sabera T. Bestourous, Leila Manhart, Ginger J. Putzulo, Charlene K. Cain, Terri Sotirakos, Peter Gardner, Jared C. Astruc, Juan A. Dawson, Katrina L. Knudsen, Victoria L. Taylor, Teresa Brown, Jamin S. Wong, Tien P. Richter, Beau A. Batlle, Ivan R. Yeager, Frank T. Rush, Ryan B. Morley, Michael G. Johnson, Britta Weeks, Rhonda F. Rykena, Cecelia Drury, Kim Lara, Tirso M. Workman, Karen Johnson, Marilyn A. Ellis, Reshial D. Almeida, Shannon R. Milliron, Amanda C. Tongue, Salina M. Hollar, Rachel Daniels, Stewart A. McNeil, Leah M. Listerman, Angela D. Kuitula, Donald E. Grindall, Nicole Walsh, Justin Montesclaros, Chris A. Malone, Rebecca Maple, Abby Lampert, Scott I. Lo, Tammy Eileen Garg, Seema Barnhart, Cassandra J. Mannarelli, Angelica Nagy, Emma A. Kerkstra, Jamie C. Jones, Teri Hernandez, Brenda Stevens, Kirsten Reynard, Ann Powers, Margaret Kincaid, Christa G. Castillo, Elaine Galonsky, Joyce Johnson, Melissa L. Salerno, Jill A. Pavlica, Michael R. Malpica, Beth Drossner, Sheri Berger, Jim M. McCluskey, Jessica D. Watson, Brandun Wirthlin, Robert S. Suner, Ivan J. Shah, Sumit P. Fontecchio, Alison LaPre, Angela Ellerbe, Kevin A. Rusinek, Brian A. Peloquin, Matt D. Forish, Missy A. Fec, Amanda Rath, Susan A. Leslie, James D. Ramirez, Carmen Kaminski, Lori Robinson, Jason Goddard, Shannon Brower, Judy L. Jordan, Debora J. Carlton, Kathy Corso, Linsey Ely, Karen Dale, Brian B. Connor, Crystal Inusah, Seidu Johnson, Paula A. Burns, Russell Ebersohl, Ryan Myers, Justin |
| description | To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab.
Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm.
Participants with available plasma samples (N = 436).
Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects.
Changes in the natural log (ln) of plasma VEGF levels.
Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61 pg/ml, −0.31±0.54 pg/ml, and −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were −0.01 (−0.12 to +0.10; P = 0.89), −0.31 (−0.44 to −0.18; P < 0.001), and −0.30 (−0.43 to −0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (−0.23 [−0.38 to −0.09]; P < 0.001); the difference between aflibercept and ranibizumab was −0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar.
These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant association |
| doi_str_mv | 10.1016/j.ophtha.2018.01.019 |
| format | Article |
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Price, Angela K. ; Fredenberg, Sherry L. ; Fleming, Christina J. ; Walker, Aimee ; Shook, Aimee H. ; Taylor, Mallie M. ; Miller, Peggy D. ; Sease, Courtney ; Huggins, Tyler ; Shah, Sabera T. ; Bestourous, Leila ; Manhart, Ginger J. ; Putzulo, Charlene K. ; Cain, Terri ; Sotirakos, Peter ; Gardner, Jared C. ; Astruc, Juan A. ; Dawson, Katrina L. ; Knudsen, Victoria L. ; Taylor, Teresa ; Brown, Jamin S. ; Wong, Tien P. ; Richter, Beau A. ; Batlle, Ivan R. ; Yeager, Frank T. ; Rush, Ryan B. ; Morley, Michael G. ; Johnson, Britta ; Weeks, Rhonda F. ; Rykena, Cecelia ; Drury, Kim ; Lara, Tirso M. ; Workman, Karen ; Johnson, Marilyn A. ; Ellis, Reshial D. ; Almeida, Shannon R. ; Milliron, Amanda C. ; Tongue, Salina M. ; Hollar, Rachel ; Daniels, Stewart A. ; McNeil, Leah M. ; Listerman, Angela D. ; Kuitula, Donald E. ; Grindall, Nicole ; Walsh, Justin ; Montesclaros, Chris A. ; Malone, Rebecca ; Maple, Abby ; Lampert, Scott I. ; Lo, Tammy Eileen ; Garg, Seema ; Barnhart, Cassandra J. ; Mannarelli, Angelica ; Nagy, Emma A. ; Kerkstra, Jamie C. ; Jones, Teri ; Hernandez, Brenda ; Stevens, Kirsten ; Reynard, Ann ; Powers, Margaret ; Kincaid, Christa G. ; Castillo, Elaine ; Galonsky, Joyce ; Johnson, Melissa L. ; Salerno, Jill A. ; Pavlica, Michael R. ; Malpica, Beth ; Drossner, Sheri ; Berger, Jim M. ; McCluskey, Jessica D. ; Watson, Brandun ; Wirthlin, Robert S. ; Suner, Ivan J. ; Shah, Sumit P. ; Fontecchio, Alison ; LaPre, Angela ; Ellerbe, Kevin A. ; Rusinek, Brian A. ; Peloquin, Matt D. ; Forish, Missy A. ; Fec, Amanda ; Rath, Susan A. ; Leslie, James D. ; Ramirez, Carmen ; Kaminski, Lori ; Robinson, Jason ; Goddard, Shannon ; Brower, Judy L. ; Jordan, Debora J. ; Carlton, Kathy ; Corso, Linsey ; Ely, Karen ; Dale, Brian B. ; Connor, Crystal ; Inusah, Seidu ; Johnson, Paula A. ; Burns, Russell ; Ebersohl, Ryan ; Myers, Justin</creator><creatorcontrib>Wells, John A. ; Price, Angela K. ; Fredenberg, Sherry L. ; Fleming, Christina J. ; Walker, Aimee ; Shook, Aimee H. ; Taylor, Mallie M. ; Miller, Peggy D. ; Sease, Courtney ; Huggins, Tyler ; Shah, Sabera T. ; Bestourous, Leila ; Manhart, Ginger J. ; Putzulo, Charlene K. ; Cain, Terri ; Sotirakos, Peter ; Gardner, Jared C. ; Astruc, Juan A. ; Dawson, Katrina L. ; Knudsen, Victoria L. ; Taylor, Teresa ; Brown, Jamin S. ; Wong, Tien P. ; Richter, Beau A. ; Batlle, Ivan R. ; Yeager, Frank T. ; Rush, Ryan B. ; Morley, Michael G. ; Johnson, Britta ; Weeks, Rhonda F. ; Rykena, Cecelia ; Drury, Kim ; Lara, Tirso M. ; Workman, Karen ; Johnson, Marilyn A. ; Ellis, Reshial D. ; Almeida, Shannon R. ; Milliron, Amanda C. ; Tongue, Salina M. ; Hollar, Rachel ; Daniels, Stewart A. ; McNeil, Leah M. ; Listerman, Angela D. ; Kuitula, Donald E. ; Grindall, Nicole ; Walsh, Justin ; Montesclaros, Chris A. ; Malone, Rebecca ; Maple, Abby ; Lampert, Scott I. ; Lo, Tammy Eileen ; Garg, Seema ; Barnhart, Cassandra J. ; Mannarelli, Angelica ; Nagy, Emma A. ; Kerkstra, Jamie C. ; Jones, Teri ; Hernandez, Brenda ; Stevens, Kirsten ; Reynard, Ann ; Powers, Margaret ; Kincaid, Christa G. ; Castillo, Elaine ; Galonsky, Joyce ; Johnson, Melissa L. ; Salerno, Jill A. ; Pavlica, Michael R. ; Malpica, Beth ; Drossner, Sheri ; Berger, Jim M. ; McCluskey, Jessica D. ; Watson, Brandun ; Wirthlin, Robert S. ; Suner, Ivan J. ; Shah, Sumit P. ; Fontecchio, Alison ; LaPre, Angela ; Ellerbe, Kevin A. ; Rusinek, Brian A. ; Peloquin, Matt D. ; Forish, Missy A. ; Fec, Amanda ; Rath, Susan A. ; Leslie, James D. ; Ramirez, Carmen ; Kaminski, Lori ; Robinson, Jason ; Goddard, Shannon ; Brower, Judy L. ; Jordan, Debora J. ; Carlton, Kathy ; Corso, Linsey ; Ely, Karen ; Dale, Brian B. ; Connor, Crystal ; Inusah, Seidu ; Johnson, Paula A. ; Burns, Russell ; Ebersohl, Ryan ; Myers, Justin ; Diabetic Retinopathy Clinical Research Network</creatorcontrib><description>To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab.
Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm.
Participants with available plasma samples (N = 436).
Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects.
Changes in the natural log (ln) of plasma VEGF levels.
Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61 pg/ml, −0.31±0.54 pg/ml, and −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were −0.01 (−0.12 to +0.10; P = 0.89), −0.31 (−0.44 to −0.18; P < 0.001), and −0.30 (−0.43 to −0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (−0.23 [−0.38 to −0.09]; P < 0.001); the difference between aflibercept and ranibizumab was −0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar.
These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.</description><identifier>ISSN: 0161-6420</identifier><identifier>EISSN: 1549-4713</identifier><identifier>DOI: 10.1016/j.ophtha.2018.01.019</identifier><identifier>PMID: 29525602</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Angiogenesis Inhibitors - therapeutic use ; Bevacizumab - therapeutic use ; Diabetic Retinopathy - blood ; Diabetic Retinopathy - diagnosis ; Diabetic Retinopathy - drug therapy ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Intravitreal Injections ; Macular Edema - blood ; Macular Edema - diagnosis ; Macular Edema - drug therapy ; Male ; Middle Aged ; Ranibizumab - therapeutic use ; Receptors, Vascular Endothelial Growth Factor - therapeutic use ; Recombinant Fusion Proteins - therapeutic use ; Retreatment ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A - antagonists & inhibitors ; Vascular Endothelial Growth Factor A - blood ; Visual Acuity</subject><ispartof>Ophthalmology (Rochester, Minn.), 2018-07, Vol.125 (7), p.1054-1063</ispartof><rights>2018 American Academy of Ophthalmology</rights><rights>Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-2aa7edaeb80ad688b91cb202fac91b4403331caf7097f6004af33c5a6f1e5e333</citedby><cites>FETCH-LOGICAL-c474t-2aa7edaeb80ad688b91cb202fac91b4403331caf7097f6004af33c5a6f1e5e333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0161642017322327$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29525602$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wells, John A.</creatorcontrib><creatorcontrib>Price, Angela K.</creatorcontrib><creatorcontrib>Fredenberg, Sherry 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P.</creatorcontrib><creatorcontrib>Richter, Beau A.</creatorcontrib><creatorcontrib>Batlle, Ivan R.</creatorcontrib><creatorcontrib>Yeager, Frank T.</creatorcontrib><creatorcontrib>Rush, Ryan B.</creatorcontrib><creatorcontrib>Morley, Michael G.</creatorcontrib><creatorcontrib>Johnson, Britta</creatorcontrib><creatorcontrib>Weeks, Rhonda F.</creatorcontrib><creatorcontrib>Rykena, Cecelia</creatorcontrib><creatorcontrib>Drury, Kim</creatorcontrib><creatorcontrib>Lara, Tirso M.</creatorcontrib><creatorcontrib>Workman, Karen</creatorcontrib><creatorcontrib>Johnson, Marilyn A.</creatorcontrib><creatorcontrib>Ellis, Reshial D.</creatorcontrib><creatorcontrib>Almeida, Shannon R.</creatorcontrib><creatorcontrib>Milliron, Amanda C.</creatorcontrib><creatorcontrib>Tongue, Salina M.</creatorcontrib><creatorcontrib>Hollar, Rachel</creatorcontrib><creatorcontrib>Daniels, Stewart A.</creatorcontrib><creatorcontrib>McNeil, Leah M.</creatorcontrib><creatorcontrib>Listerman, Angela D.</creatorcontrib><creatorcontrib>Kuitula, Donald E.</creatorcontrib><creatorcontrib>Grindall, Nicole</creatorcontrib><creatorcontrib>Walsh, Justin</creatorcontrib><creatorcontrib>Montesclaros, Chris A.</creatorcontrib><creatorcontrib>Malone, Rebecca</creatorcontrib><creatorcontrib>Maple, Abby</creatorcontrib><creatorcontrib>Lampert, Scott I.</creatorcontrib><creatorcontrib>Lo, Tammy Eileen</creatorcontrib><creatorcontrib>Garg, Seema</creatorcontrib><creatorcontrib>Barnhart, Cassandra J.</creatorcontrib><creatorcontrib>Mannarelli, Angelica</creatorcontrib><creatorcontrib>Nagy, Emma A.</creatorcontrib><creatorcontrib>Kerkstra, Jamie C.</creatorcontrib><creatorcontrib>Jones, Teri</creatorcontrib><creatorcontrib>Hernandez, Brenda</creatorcontrib><creatorcontrib>Stevens, Kirsten</creatorcontrib><creatorcontrib>Reynard, Ann</creatorcontrib><creatorcontrib>Powers, Margaret</creatorcontrib><creatorcontrib>Kincaid, Christa G.</creatorcontrib><creatorcontrib>Castillo, Elaine</creatorcontrib><creatorcontrib>Galonsky, Joyce</creatorcontrib><creatorcontrib>Johnson, Melissa L.</creatorcontrib><creatorcontrib>Salerno, Jill A.</creatorcontrib><creatorcontrib>Pavlica, Michael R.</creatorcontrib><creatorcontrib>Malpica, Beth</creatorcontrib><creatorcontrib>Drossner, Sheri</creatorcontrib><creatorcontrib>Berger, Jim M.</creatorcontrib><creatorcontrib>McCluskey, Jessica D.</creatorcontrib><creatorcontrib>Watson, Brandun</creatorcontrib><creatorcontrib>Wirthlin, Robert S.</creatorcontrib><creatorcontrib>Suner, Ivan J.</creatorcontrib><creatorcontrib>Shah, Sumit P.</creatorcontrib><creatorcontrib>Fontecchio, Alison</creatorcontrib><creatorcontrib>LaPre, Angela</creatorcontrib><creatorcontrib>Ellerbe, Kevin A.</creatorcontrib><creatorcontrib>Rusinek, Brian A.</creatorcontrib><creatorcontrib>Peloquin, Matt D.</creatorcontrib><creatorcontrib>Forish, Missy A.</creatorcontrib><creatorcontrib>Fec, Amanda</creatorcontrib><creatorcontrib>Rath, Susan A.</creatorcontrib><creatorcontrib>Leslie, James D.</creatorcontrib><creatorcontrib>Ramirez, Carmen</creatorcontrib><creatorcontrib>Kaminski, Lori</creatorcontrib><creatorcontrib>Robinson, Jason</creatorcontrib><creatorcontrib>Goddard, Shannon</creatorcontrib><creatorcontrib>Brower, Judy L.</creatorcontrib><creatorcontrib>Jordan, Debora J.</creatorcontrib><creatorcontrib>Carlton, Kathy</creatorcontrib><creatorcontrib>Corso, Linsey</creatorcontrib><creatorcontrib>Ely, Karen</creatorcontrib><creatorcontrib>Dale, Brian B.</creatorcontrib><creatorcontrib>Connor, Crystal</creatorcontrib><creatorcontrib>Inusah, Seidu</creatorcontrib><creatorcontrib>Johnson, Paula A.</creatorcontrib><creatorcontrib>Burns, Russell</creatorcontrib><creatorcontrib>Ebersohl, Ryan</creatorcontrib><creatorcontrib>Myers, Justin</creatorcontrib><creatorcontrib>Diabetic Retinopathy Clinical Research Network</creatorcontrib><title>Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema</title><title>Ophthalmology (Rochester, Minn.)</title><addtitle>Ophthalmology</addtitle><description>To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab.
Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm.
Participants with available plasma samples (N = 436).
Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects.
Changes in the natural log (ln) of plasma VEGF levels.
Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61 pg/ml, −0.31±0.54 pg/ml, and −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were −0.01 (−0.12 to +0.10; P = 0.89), −0.31 (−0.44 to −0.18; P < 0.001), and −0.30 (−0.43 to −0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (−0.23 [−0.38 to −0.09]; P < 0.001); the difference between aflibercept and ranibizumab was −0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar.
These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.</description><subject>Angiogenesis Inhibitors - therapeutic use</subject><subject>Bevacizumab - therapeutic use</subject><subject>Diabetic Retinopathy - blood</subject><subject>Diabetic Retinopathy - diagnosis</subject><subject>Diabetic Retinopathy - drug therapy</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Intravitreal Injections</subject><subject>Macular Edema - blood</subject><subject>Macular Edema - diagnosis</subject><subject>Macular Edema - drug therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Ranibizumab - therapeutic use</subject><subject>Receptors, Vascular Endothelial Growth Factor - therapeutic use</subject><subject>Recombinant Fusion Proteins - therapeutic use</subject><subject>Retreatment</subject><subject>Tomography, Optical Coherence</subject><subject>Treatment Outcome</subject><subject>Vascular Endothelial Growth Factor A - antagonists & inhibitors</subject><subject>Vascular Endothelial Growth Factor A - blood</subject><subject>Visual Acuity</subject><issn>0161-6420</issn><issn>1549-4713</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxi0EokvhDRDykUuWceL8uyBVS1sqFcGhcLUmzljxKokX21vUW9-hJ16PJ8HRLj1WSCPNyP59M5r5GHsrYC1AVB-2a7cb4oDrHESzBpGifcZWopRtJmtRPGerhImskjmcsFchbAGgqgr5kp3kbZmXFeQr9vvbiGFC_gOD3o_o-fncuzjQaHHkl979igO_QB2d5xs3a5qjx2jdHDiaSJ5fLQ-3Nnpy-8DP5mj_3D_8R7ObgTzu7rhJ9SeLHUWr-Rc8ynqa8DV7YXAM9OaYT9n3i_Obzefs-uvl1ebsOtOyljHLEWvqkboGsK-apmuF7nLIDepWdFJCURRCo6mhrU0FINEUhS6xMoJKSp-n7P2h7867n3sKUU02aBpHnJedVDpvIaCs5YLKA6q9C8GTUTtvJ_R3SoBaTFFbdTBlUTUKRIo2yd4dJ-y7ifpH0T8XEvDxAFDa89aSV0FbStfurScdVe_s0xP-AmlTpAg</recordid><startdate>201807</startdate><enddate>201807</enddate><creator>Wells, John A.</creator><creator>Price, Angela K.</creator><creator>Fredenberg, Sherry L.</creator><creator>Fleming, Christina J.</creator><creator>Walker, Aimee</creator><creator>Shook, Aimee H.</creator><creator>Taylor, Mallie M.</creator><creator>Miller, Peggy D.</creator><creator>Sease, Courtney</creator><creator>Huggins, Tyler</creator><creator>Shah, Sabera T.</creator><creator>Bestourous, Leila</creator><creator>Manhart, Ginger J.</creator><creator>Putzulo, Charlene K.</creator><creator>Cain, Terri</creator><creator>Sotirakos, Peter</creator><creator>Gardner, Jared C.</creator><creator>Astruc, Juan A.</creator><creator>Dawson, Katrina L.</creator><creator>Knudsen, Victoria L.</creator><creator>Taylor, Teresa</creator><creator>Brown, Jamin S.</creator><creator>Wong, Tien P.</creator><creator>Richter, Beau A.</creator><creator>Batlle, Ivan R.</creator><creator>Yeager, Frank T.</creator><creator>Rush, Ryan B.</creator><creator>Morley, Michael G.</creator><creator>Johnson, Britta</creator><creator>Weeks, Rhonda F.</creator><creator>Rykena, Cecelia</creator><creator>Drury, Kim</creator><creator>Lara, Tirso M.</creator><creator>Workman, Karen</creator><creator>Johnson, Marilyn A.</creator><creator>Ellis, Reshial D.</creator><creator>Almeida, Shannon R.</creator><creator>Milliron, Amanda C.</creator><creator>Tongue, Salina M.</creator><creator>Hollar, Rachel</creator><creator>Daniels, Stewart A.</creator><creator>McNeil, Leah M.</creator><creator>Listerman, Angela D.</creator><creator>Kuitula, Donald E.</creator><creator>Grindall, Nicole</creator><creator>Walsh, Justin</creator><creator>Montesclaros, Chris A.</creator><creator>Malone, Rebecca</creator><creator>Maple, Abby</creator><creator>Lampert, Scott I.</creator><creator>Lo, Tammy Eileen</creator><creator>Garg, Seema</creator><creator>Barnhart, Cassandra J.</creator><creator>Mannarelli, Angelica</creator><creator>Nagy, Emma A.</creator><creator>Kerkstra, Jamie C.</creator><creator>Jones, Teri</creator><creator>Hernandez, Brenda</creator><creator>Stevens, Kirsten</creator><creator>Reynard, Ann</creator><creator>Powers, Margaret</creator><creator>Kincaid, Christa G.</creator><creator>Castillo, Elaine</creator><creator>Galonsky, Joyce</creator><creator>Johnson, Melissa L.</creator><creator>Salerno, Jill A.</creator><creator>Pavlica, Michael R.</creator><creator>Malpica, Beth</creator><creator>Drossner, Sheri</creator><creator>Berger, Jim M.</creator><creator>McCluskey, Jessica D.</creator><creator>Watson, Brandun</creator><creator>Wirthlin, Robert S.</creator><creator>Suner, Ivan J.</creator><creator>Shah, Sumit P.</creator><creator>Fontecchio, Alison</creator><creator>LaPre, Angela</creator><creator>Ellerbe, Kevin A.</creator><creator>Rusinek, Brian A.</creator><creator>Peloquin, Matt D.</creator><creator>Forish, Missy A.</creator><creator>Fec, Amanda</creator><creator>Rath, Susan A.</creator><creator>Leslie, James D.</creator><creator>Ramirez, Carmen</creator><creator>Kaminski, Lori</creator><creator>Robinson, Jason</creator><creator>Goddard, Shannon</creator><creator>Brower, Judy L.</creator><creator>Jordan, Debora J.</creator><creator>Carlton, Kathy</creator><creator>Corso, Linsey</creator><creator>Ely, Karen</creator><creator>Dale, Brian B.</creator><creator>Connor, Crystal</creator><creator>Inusah, Seidu</creator><creator>Johnson, Paula A.</creator><creator>Burns, Russell</creator><creator>Ebersohl, Ryan</creator><creator>Myers, Justin</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201807</creationdate><title>Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema</title><author>Wells, John A. ; Price, Angela K. ; Fredenberg, Sherry L. ; Fleming, Christina J. ; Walker, Aimee ; Shook, Aimee H. ; Taylor, Mallie M. ; Miller, Peggy D. ; Sease, Courtney ; Huggins, Tyler ; Shah, Sabera T. ; Bestourous, Leila ; Manhart, Ginger J. ; Putzulo, Charlene K. ; Cain, Terri ; Sotirakos, Peter ; Gardner, Jared C. ; Astruc, Juan A. ; Dawson, Katrina L. ; Knudsen, Victoria L. ; Taylor, Teresa ; Brown, Jamin S. ; Wong, Tien P. ; Richter, Beau A. ; Batlle, Ivan R. ; Yeager, Frank T. ; Rush, Ryan B. ; Morley, Michael G. ; Johnson, Britta ; Weeks, Rhonda F. ; Rykena, Cecelia ; Drury, Kim ; Lara, Tirso M. ; Workman, Karen ; Johnson, Marilyn A. ; Ellis, Reshial D. ; Almeida, Shannon R. ; Milliron, Amanda C. ; Tongue, Salina M. ; Hollar, Rachel ; Daniels, Stewart A. ; McNeil, Leah M. ; Listerman, Angela D. ; Kuitula, Donald E. ; Grindall, Nicole ; Walsh, Justin ; Montesclaros, Chris A. ; Malone, Rebecca ; Maple, Abby ; Lampert, Scott I. ; Lo, Tammy Eileen ; Garg, Seema ; Barnhart, Cassandra J. ; Mannarelli, Angelica ; Nagy, Emma A. ; Kerkstra, Jamie C. ; Jones, Teri ; Hernandez, Brenda ; Stevens, Kirsten ; Reynard, Ann ; Powers, Margaret ; Kincaid, Christa G. ; Castillo, Elaine ; Galonsky, Joyce ; Johnson, Melissa L. ; Salerno, Jill A. ; Pavlica, Michael R. ; Malpica, Beth ; Drossner, Sheri ; Berger, Jim M. ; McCluskey, Jessica D. ; Watson, Brandun ; Wirthlin, Robert S. ; Suner, Ivan J. ; Shah, Sumit P. ; Fontecchio, Alison ; LaPre, Angela ; Ellerbe, Kevin A. ; Rusinek, Brian A. ; Peloquin, Matt D. ; Forish, Missy A. ; Fec, Amanda ; Rath, Susan A. ; Leslie, James D. ; Ramirez, Carmen ; Kaminski, Lori ; Robinson, Jason ; Goddard, Shannon ; Brower, Judy L. ; Jordan, Debora J. ; Carlton, Kathy ; Corso, Linsey ; Ely, Karen ; Dale, Brian B. ; Connor, Crystal ; Inusah, Seidu ; Johnson, Paula A. ; Burns, Russell ; Ebersohl, Ryan ; Myers, Justin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-2aa7edaeb80ad688b91cb202fac91b4403331caf7097f6004af33c5a6f1e5e333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Angiogenesis Inhibitors - therapeutic use</topic><topic>Bevacizumab - therapeutic use</topic><topic>Diabetic Retinopathy - blood</topic><topic>Diabetic Retinopathy - diagnosis</topic><topic>Diabetic Retinopathy - drug therapy</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Intravitreal Injections</topic><topic>Macular Edema - blood</topic><topic>Macular Edema - diagnosis</topic><topic>Macular Edema - drug therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Ranibizumab - therapeutic use</topic><topic>Receptors, Vascular Endothelial Growth Factor - therapeutic use</topic><topic>Recombinant Fusion Proteins - therapeutic use</topic><topic>Retreatment</topic><topic>Tomography, Optical Coherence</topic><topic>Treatment Outcome</topic><topic>Vascular Endothelial Growth Factor A - antagonists & inhibitors</topic><topic>Vascular Endothelial Growth Factor A - blood</topic><topic>Visual Acuity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wells, John A.</creatorcontrib><creatorcontrib>Price, Angela K.</creatorcontrib><creatorcontrib>Fredenberg, Sherry L.</creatorcontrib><creatorcontrib>Fleming, Christina J.</creatorcontrib><creatorcontrib>Walker, Aimee</creatorcontrib><creatorcontrib>Shook, Aimee H.</creatorcontrib><creatorcontrib>Taylor, Mallie M.</creatorcontrib><creatorcontrib>Miller, Peggy D.</creatorcontrib><creatorcontrib>Sease, Courtney</creatorcontrib><creatorcontrib>Huggins, Tyler</creatorcontrib><creatorcontrib>Shah, Sabera T.</creatorcontrib><creatorcontrib>Bestourous, Leila</creatorcontrib><creatorcontrib>Manhart, Ginger J.</creatorcontrib><creatorcontrib>Putzulo, Charlene K.</creatorcontrib><creatorcontrib>Cain, Terri</creatorcontrib><creatorcontrib>Sotirakos, Peter</creatorcontrib><creatorcontrib>Gardner, Jared C.</creatorcontrib><creatorcontrib>Astruc, Juan A.</creatorcontrib><creatorcontrib>Dawson, 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A.</creatorcontrib><creatorcontrib>Peloquin, Matt D.</creatorcontrib><creatorcontrib>Forish, Missy A.</creatorcontrib><creatorcontrib>Fec, Amanda</creatorcontrib><creatorcontrib>Rath, Susan A.</creatorcontrib><creatorcontrib>Leslie, James D.</creatorcontrib><creatorcontrib>Ramirez, Carmen</creatorcontrib><creatorcontrib>Kaminski, Lori</creatorcontrib><creatorcontrib>Robinson, Jason</creatorcontrib><creatorcontrib>Goddard, Shannon</creatorcontrib><creatorcontrib>Brower, Judy L.</creatorcontrib><creatorcontrib>Jordan, Debora J.</creatorcontrib><creatorcontrib>Carlton, Kathy</creatorcontrib><creatorcontrib>Corso, Linsey</creatorcontrib><creatorcontrib>Ely, Karen</creatorcontrib><creatorcontrib>Dale, Brian B.</creatorcontrib><creatorcontrib>Connor, Crystal</creatorcontrib><creatorcontrib>Inusah, Seidu</creatorcontrib><creatorcontrib>Johnson, Paula A.</creatorcontrib><creatorcontrib>Burns, Russell</creatorcontrib><creatorcontrib>Ebersohl, Ryan</creatorcontrib><creatorcontrib>Myers, Justin</creatorcontrib><creatorcontrib>Diabetic Retinopathy Clinical Research Network</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Ophthalmology (Rochester, Minn.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wells, John A.</au><au>Price, Angela K.</au><au>Fredenberg, Sherry L.</au><au>Fleming, Christina J.</au><au>Walker, Aimee</au><au>Shook, Aimee H.</au><au>Taylor, Mallie M.</au><au>Miller, Peggy D.</au><au>Sease, Courtney</au><au>Huggins, Tyler</au><au>Shah, Sabera T.</au><au>Bestourous, Leila</au><au>Manhart, Ginger J.</au><au>Putzulo, Charlene K.</au><au>Cain, Terri</au><au>Sotirakos, Peter</au><au>Gardner, Jared C.</au><au>Astruc, Juan A.</au><au>Dawson, Katrina L.</au><au>Knudsen, Victoria L.</au><au>Taylor, Teresa</au><au>Brown, Jamin S.</au><au>Wong, Tien P.</au><au>Richter, Beau A.</au><au>Batlle, Ivan R.</au><au>Yeager, Frank T.</au><au>Rush, Ryan B.</au><au>Morley, Michael G.</au><au>Johnson, Britta</au><au>Weeks, Rhonda F.</au><au>Rykena, Cecelia</au><au>Drury, Kim</au><au>Lara, Tirso M.</au><au>Workman, Karen</au><au>Johnson, Marilyn A.</au><au>Ellis, Reshial D.</au><au>Almeida, Shannon R.</au><au>Milliron, Amanda C.</au><au>Tongue, Salina M.</au><au>Hollar, Rachel</au><au>Daniels, Stewart A.</au><au>McNeil, Leah M.</au><au>Listerman, Angela D.</au><au>Kuitula, Donald E.</au><au>Grindall, Nicole</au><au>Walsh, Justin</au><au>Montesclaros, Chris A.</au><au>Malone, Rebecca</au><au>Maple, Abby</au><au>Lampert, Scott I.</au><au>Lo, Tammy Eileen</au><au>Garg, Seema</au><au>Barnhart, Cassandra J.</au><au>Mannarelli, Angelica</au><au>Nagy, Emma A.</au><au>Kerkstra, Jamie C.</au><au>Jones, Teri</au><au>Hernandez, Brenda</au><au>Stevens, Kirsten</au><au>Reynard, Ann</au><au>Powers, Margaret</au><au>Kincaid, Christa G.</au><au>Castillo, Elaine</au><au>Galonsky, Joyce</au><au>Johnson, Melissa L.</au><au>Salerno, Jill A.</au><au>Pavlica, Michael R.</au><au>Malpica, Beth</au><au>Drossner, Sheri</au><au>Berger, Jim M.</au><au>McCluskey, Jessica D.</au><au>Watson, Brandun</au><au>Wirthlin, Robert S.</au><au>Suner, Ivan J.</au><au>Shah, Sumit P.</au><au>Fontecchio, Alison</au><au>LaPre, Angela</au><au>Ellerbe, Kevin A.</au><au>Rusinek, Brian A.</au><au>Peloquin, Matt D.</au><au>Forish, Missy A.</au><au>Fec, Amanda</au><au>Rath, Susan A.</au><au>Leslie, James D.</au><au>Ramirez, Carmen</au><au>Kaminski, Lori</au><au>Robinson, Jason</au><au>Goddard, Shannon</au><au>Brower, Judy L.</au><au>Jordan, Debora J.</au><au>Carlton, Kathy</au><au>Corso, Linsey</au><au>Ely, Karen</au><au>Dale, Brian B.</au><au>Connor, Crystal</au><au>Inusah, Seidu</au><au>Johnson, Paula A.</au><au>Burns, Russell</au><au>Ebersohl, Ryan</au><au>Myers, Justin</au><aucorp>Diabetic Retinopathy Clinical Research Network</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema</atitle><jtitle>Ophthalmology (Rochester, Minn.)</jtitle><addtitle>Ophthalmology</addtitle><date>2018-07</date><risdate>2018</risdate><volume>125</volume><issue>7</issue><spage>1054</spage><epage>1063</epage><pages>1054-1063</pages><issn>0161-6420</issn><eissn>1549-4713</eissn><abstract>To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab.
Comparative-effectiveness trial with participants randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm.
Participants with available plasma samples (N = 436).
Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects.
Changes in the natural log (ln) of plasma VEGF levels.
Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61 pg/ml, −0.31±0.54 pg/ml, and −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval [CI]; P value) were −0.01 (−0.12 to +0.10; P = 0.89), −0.31 (−0.44 to −0.18; P < 0.001), and −0.30 (−0.43 to −0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (−0.23 [−0.38 to −0.09]; P < 0.001); the difference between aflibercept and ranibizumab was −0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar.
These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29525602</pmid><doi>10.1016/j.ophtha.2018.01.019</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0161-6420 |
| ispartof | Ophthalmology (Rochester, Minn.), 2018-07, Vol.125 (7), p.1054-1063 |
| issn | 0161-6420 1549-4713 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2013105743 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Angiogenesis Inhibitors - therapeutic use Bevacizumab - therapeutic use Diabetic Retinopathy - blood Diabetic Retinopathy - diagnosis Diabetic Retinopathy - drug therapy Enzyme-Linked Immunosorbent Assay Female Follow-Up Studies Humans Intravitreal Injections Macular Edema - blood Macular Edema - diagnosis Macular Edema - drug therapy Male Middle Aged Ranibizumab - therapeutic use Receptors, Vascular Endothelial Growth Factor - therapeutic use Recombinant Fusion Proteins - therapeutic use Retreatment Tomography, Optical Coherence Treatment Outcome Vascular Endothelial Growth Factor A - antagonists & inhibitors Vascular Endothelial Growth Factor A - blood Visual Acuity |
| title | Plasma Vascular Endothelial Growth Factor Concentrations after Intravitreous Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema |
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