Correspondence
Long-Term Results of Rabbit Antithymocyte Globulin and Basiliximab Induction
N Engl J Med 2008; 359:1736-1738October 16, 2008
- Article
To the Editor:
In our recently reported prospective, randomized, international clinical trial comparing rabbit antithymocyte globulin and basiliximab in renal transplantation (ClinicalTrials.gov number, NCT00235300),1 we observed that induction treatment with rabbit antithymocyte globulin was as safe as and more effective than basiliximab at 1 year in preventing acute rejection in patients who had received kidney transplants from deceased donors and who were at increased risk for acute rejection or delayed graft function. Whether the apparent benefits of rabbit antithymocyte globulin over basiliximab persist is unknown.
The duration of follow-up in a clinical study is limited by whether patients are willing to participate for an extended period and whether investigators can commit the additional time. Additional limitations include the need for additional informed consent and the added costs of further study. Consequently, long-term safety and efficacy data are lacking for many drugs in multiple therapeutic areas.2 Postmarketing surveillance after drug approval is mandated by the Food and Drug Administration to monitor safety but depends on spontaneous reporting by health care professionals. Unfortunately, causality often cannot be ascertained from such reports. Registries of patients, sponsored by the government or pharmaceutical industry, offer an alternative approach to monitoring outcomes.
In the United States, transplantation centers are mandated to enter patient information into a database maintained by the Organ Procurement and Transplantation Network (OPTN). The reliability of this registry with regard to major transplantation outcomes appears to be excellent.3 To obtain 5-year follow-up data on the patients in our study, records for each U.S.-enrolled patient1 were matched with records in the OPTN database for birth date, transplantation date, sex, and transplantation center. Matches were verified on the basis of recipient and donor HLAs and blood groups and cross-referenced with death records from the Social Security Administration.
All 183 U.S. patients from the study were matched to their OPTN records.1 There were no differences in baseline demographic characteristics between the U.S. patients who received rabbit antithymocyte globulin and those who received basiliximab (Table 1Table 1
Baseline Characteristics of the U.S. Patients and 1-Year and 5-Year Outcomes.). The 5-year incidences of acute rejection and of acute rejection requiring antibody treatment were lower among patients treated with rabbit antithymocyte globulin than among those treated with basiliximab (15% vs. 27%, P=0.03; and 3% vs. 12%, P=0.05). Patients treated with rabbit antithymocyte globulin also had a lower incidence of the composite end point of acute rejection, graft loss, and death at 5 years (37% vs. 51%, P=0.04). The incidence of treated cytomegalovirus infection remained lower in the group treated with rabbit antithymocyte globulin (7% vs. 17%, P=0.02), and the incidence of cancer did not differ significantly between the two groups.Thus, the benefits and safety of rabbit antithymocyte globulin over basiliximab for induction therapy were sustained and stable throughout a period of 5 years after transplantation. This strategy is a cost-efficient way to monitor long-term efficacy and safety of patients in clinical studies for which registry data are available and may have implications for other fields.
Daniel C. Brennan, M.D.
Washington University School of Medicine, St. Louis, MO 63110
brennan@wudosis.wustl. edu Mark A. Schnitzler, Ph.D.
Saint Louis University, St. Louis, MO 63104Supported by a grant from Genzyme. The data reported here have been supplied by United Network for Organ Sharing as the contractor for the Organ Procurement Transplant Network. The interpretation of these data is that of the investigators.
Dr. Brennan reports receiving consulting fees, lecture fees, and grant support from Genzyme and Novartis; and Dr. Schnitzler, grant support from Genzyme and Novartis. No other potential conflict of interest relevant to this letter was reported.
3 References1
Brennan DC ,Daller JA ,Lake KD ,Cibrik D ,Del Castillo D . Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med 2006;355:1967-1977
Full Text | Web of Science | Medline2
Strom BL . How the US drug safety system should be changed. JAMA 2006;295:2072-2075
CrossRef | Web of Science | Medline3
Dickinson DM ,Dykstra DM ,Levine GN ,Li S ,Welch JC ,Webb RL . Transplant data: sources, collection and research considerations, 2004. Am J Transplant 2005;5:850-861
CrossRef | Web of Science | Medline
- Citing Articles (20)
Citing Articles
1
Mark A. Schnitzler, Krista L. Lentine, Adrian Gheorghian, David Axelrod, Digisha Trivedi, Gilbert L’Italien. (2012) Renal function following living, standard criteria deceased and expanded criteria deceased donor kidney transplantation: impact on graft failure and death. Transplant International 25:2, 179-191
CrossRef2
Lorenzo Gallon, Darshika Chhabra, Anton I. Skaro. (2012) T-Cell–Depleting Agents in Kidney Transplantation: Is There a Place for Alemtuzumab?. American Journal of Kidney Diseases 59:1, 15-18
CrossRef3
J.M. Kim, H.R. Jang, C.H.D. Kwon, W.S. Huh, G.S. Kim, S.J. Kim, J.W. Joh, H.Y. Oh. (2012) Rabbit Antithymocyte Globulin Compared with Basiliximab in Kidney Transplantation: A Single-Center Study. Transplantation Proceedings 44:1, 167-170
CrossRef4
R. Abou-Ayache, M. Büchler, P. Le Pogamp, P.-F. Westeel, Y. Le Meur, I. Etienne, B. Hurault de Ligny, O. Toupance, S. Caillard, G. Sinnasse-Raymond, G. Touchard. (2011) The Influence of Cytomegalovirus Infections on Patient and Renal Graft Outcome: A 3-year, Multicenter, Observational Study (Post-ECTAZ Study). Transplantation Proceedings 43:7, 2630-2635
CrossRef5
Ben Sprangers, Dirk R. Kuypers, Yves Vanrenterghem. (2011) Immunosuppression: Does One Regimen Fit All?. Transplantation 92:3, 251-261
CrossRef6
Daniel R Getts, Sushma Shankar, Emily ML Chastain, Aaron Martin, Meghann Teague Getts, Kathryn Wood, Stephen D Miller. (2011) Current landscape for T-cell targeting in autoimmunity and transplantation. Immunotherapy 3:7, 853-870
CrossRef7
Martijn WF van den Hoogen, Luuk B Hilbrands. (2011) Use of monoclonal antibodies in renal transplantation. Immunotherapy 3:7, 871-880
CrossRef8
Mark A. Schnitzler, Karissa Johnston, David Axelrod, Adrian Gheorghian, Krista L. Lentine. (2011) Associations of Renal Function at 1-Year After Kidney Transplantation With Subsequent Return to Dialysis, Mortality, and Healthcare Costs. Transplantation 91:12, 1347-1356
CrossRef9
W.H. Marks, J.N. Ilsley, V.R. Dharnidharka. (2011) Posttransplantation Lymphoproliferative Disorder in Kidney and Heart Transplant Recipients Receiving Thymoglobulin: A Systematic Review. Transplantation Proceedings 43:5, 1395-1404
CrossRef10
Hanaway, Michael J., Woodle, E. Steve, Mulgaonkar, Shamkant, Peddi, V. Ram, Kaufman, Dixon B., First, M. Roy, Croy, Richard, Holman, John, . (2011) Alemtuzumab Induction in Renal Transplantation. New England Journal of Medicine 364:20, 1909-1919
Full Text11
M.R. Laftavi, M. Alnimri, E. Weber-Shrikant, R. Kohli, M. Said, S. Patel, O. Pankewycz. (2011) Low-Dose Rabbit Antithymocyte Globulin Versus Basiliximab Induction Therapy in Low-Risk Renal Transplant Recipients: 8-Year Follow-Up. Transplantation Proceedings 43:2, 458-461
CrossRef12
Michael L. Spinner, Georges Saab, Ed Casabar, Lyndsey J. Bowman, Gregory A. Storch, Daniel C. Brennan. (2010) Impact of Prophylactic Versus Preemptive Valganciclovir on Long-Term Renal Allograft Outcomes. Transplantation 90:4, 412-418
CrossRef13
Hans Sollinger, Nikole A. Neidlinger. (2010) Response To Gaber. Transplantation Proceedings 42:5, 1401
CrossRef14
E. Rodrigo, G. Fernandez-Fresnedo, C. Robledo, R. Palomar, C. Cantarell, A. Mazuecos, A. Osuna, A. Mendiluce, A. Alarcon, M. Arias. (2010) Heterogeneity of induction therapy in Spain: changing patterns according to year, centre, indications and results. NDT Plus 3:Supplement 2, ii9-ii14
CrossRef15
A. Osama Gaber, R.J. Knight, S. Patel, L.W. Gaber. (2010) A Review of the Evidence for Use of Thymoglobulin Induction in Renal Transplantation. Transplantation Proceedings 42:5, 1395-1400
CrossRef16
Leah Krischock, Stephen D. Marks. (2010) Induction therapy: Why, when, and which agent?. Pediatric Transplantation 14:3, 298-313
CrossRef17
A. Osama Gaber, Anthony P. Monaco, James A. Russell, Yvon Lebranchu, Mohamad Mohty. (2010) Rabbit Antithymocyte Globulin (Thymoglobulin®). Drugs 70:6, 691-732
CrossRef18
Angela C Webster, Lorenn P Ruster, Richard McGee, Sandra L Matheson, Gail Y Higgins, Narelle S Willis, Jeremy R Chapman, Jonathan C Craig, Angela C Webster. 2010. Interleukin 2 receptor antagonists for kidney transplant recipients. .
CrossRef19
Aparna Padiyar, Joshua J. Augustine, Donald E. Hricik. (2009) Induction Antibody Therapy in Kidney Transplantation. American Journal of Kidney Diseases 54:5, 935-944
CrossRef20
Emma D. Deeks, Gillian M. Keating. (2009) Rabbit Antithymocyte Globulin (Thymoglobulin®). Drugs 69:11, 1483-1512
CrossRef
