Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial

Mario H. Cardiel; James A. Tumlin; Richard A. Furie; Daniel J. Wallace; Tenshang Joh; Matthew D. Linnik; Micha Abeles; Jacob Aelion; Gerald B. Appel; Cynthia Aranow; Stanley Ballou; Michael A. Becker; H. Michael Belmont; Eugene P. Boling; Stefano Bombardieri; James Brodeur; Jill Buyon; John J. Condemi; Mary E. Cronin; John J. Cush; Raphael DeHoratius; Deborah Desir; John Donohue; Michael Edwards; Mohamed A. El-Shahawy; Paul Emery; Stephanie Ensworth; Luis R. Espinoza; Maria Fondal; Paul Fortin; Thomas Geppert; Gary S. Gilkeson; Ellen Ginzler; Peter Gorevic; Jose Granda; Jennifer Grossman; Falk Hiepe; Paul Howard; Claudia E. Hura; Adrian Jaffer; James Jakes; Joachim R. Kalden; Gary M. Kammer; Mariana J. Kaplan; Stanley Kaplan; Robert Katz; Alastair Kennedy; Howard M. Kenney; Munther Khamashta; Alan J. Kivitz; Christine Kovacs; Mahesh Krishnan; Neil A. Kurtzman; Michael Liebling; Seth H. Lourie; James Loveless; Carl V. Manion; Susan Manzi; Kevin Martin; James McKay; Phillip J. Mease; Joan T. Merrill; Larry W. Moreland; Charles Moritz; C. Michael Neuwelt; Michelle Petri; Bryan C. Pogue; Robert J. Quinet; Rosalind Ramsey-Goldman; Arnold Roth; Naomi Rothfield; Nicholas Scarpa; Matthias Schneider; William J. Shergy; Yvonne Sherrer; Jean Sibilia; Moges Sisay; Douglas Smith; Bruce Spinowitz; Moses Spira; Michael P. Stevens; Gunnar Sturfelt; William Surbeck; Elizabeth A. Tindall; Arnaldo Torres; Ronald Van Vollenhoven; Anitha Vijayan; Miguel Vilardell-Tarres; Cynthia Weaver; Gary W. Williams; Michael Zummer

doi:10.1002/art.23673

Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial

Mario H. Cardiel, James A. Tumlin, Richard A. Furie, Daniel J. Wallace, Tenshang Joh, Matthew D. Linnik, Micha Abeles, Jacob Aelion, Gerald B. Appel, Cynthia Aranow, Stanley Ballou, Michael A. Becker, H. Michael Belmont, Eugene P. Boling, Stefano Bombardieri, James Brodeur, Jill Buyon, John J. Condemi, Mary E. Cronin, John J. CushRaphael DeHoratius, Deborah Desir, John Donohue, Michael Edwards, Mohamed A. El-Shahawy, Paul Emery, Stephanie Ensworth, Luis R. Espinoza, Maria Fondal, Paul Fortin, Thomas Geppert, Gary S. Gilkeson, Ellen Ginzler, Peter Gorevic, Jose Granda, Jennifer Grossman, Falk Hiepe, Paul Howard, Claudia E. Hura, Adrian Jaffer, James Jakes, Joachim R. Kalden, Gary M. Kammer, Mariana J. Kaplan, Stanley Kaplan, Robert Katz, Alastair Kennedy, Howard M. Kenney, Munther Khamashta, Alan J. Kivitz, Christine Kovacs, Mahesh Krishnan, Neil A. Kurtzman, Michael Liebling, Seth H. Lourie, James Loveless, Carl V. Manion, Susan Manzi, Kevin Martin, James McKay, Phillip J. Mease, Joan T. Merrill, Larry W. Moreland, Charles Moritz, C. Michael Neuwelt, Michelle Petri, Bryan C. Pogue, Robert J. Quinet, Rosalind Ramsey-Goldman, Arnold Roth, Naomi Rothfield, Nicholas Scarpa, Matthias Schneider, William J. Shergy, Yvonne Sherrer, Jean Sibilia, Moges Sisay, Douglas Smith, Bruce Spinowitz, Moses Spira, Michael P. Stevens, Gunnar Sturfelt, William Surbeck, Elizabeth A. Tindall, Arnaldo Torres, Ronald Van Vollenhoven, Anitha Vijayan, Miguel Vilardell-Tarres, Cynthia Weaver, Gary W. Williams, Michael Zummer

School of Medicine

Research output: Contribution to journal › Article › peer-review

129 Scopus citations

Abstract

Objective. To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. Methods. We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels > 15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. Results. Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced ≥ 50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. Conclusion. Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

Original language	English (US)
Pages (from-to)	2470-2480
Number of pages	11
Journal	Arthritis and rheumatism
Volume	58
Issue number	8
DOIs	https://doi.org/10.1002/art.23673
State	Published - Aug 2008

ASJC Scopus subject areas

Immunology and Allergy
Rheumatology
Immunology
Pharmacology (medical)

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Cardiel, M. H., Tumlin, J. A., Furie, R. A., Wallace, D. J., Joh, T., Linnik, M. D., Abeles, M., Aelion, J., Appel, G. B., Aranow, C., Ballou, S., Becker, M. A., Belmont, H. M., Boling, E. P., Bombardieri, S., Brodeur, J., Buyon, J., Condemi, J. J., Cronin, M. E., ... Zummer, M. (2008). Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial. Arthritis and rheumatism, 58(8), 2470-2480. https://doi.org/10.1002/art.23673

Cardiel, MH, Tumlin, JA, Furie, RA, Wallace, DJ, Joh, T, Linnik, MD, Abeles, M, Aelion, J, Appel, GB, Aranow, C, Ballou, S, Becker, MA, Belmont, HM, Boling, EP, Bombardieri, S, Brodeur, J, Buyon, J, Condemi, JJ, Cronin, ME, Cush, JJ, DeHoratius, R, Desir, D, Donohue, J, Edwards, M, El-Shahawy, MA, Emery, P, Ensworth, S, Espinoza, LR, Fondal, M, Fortin, P, Geppert, T, Gilkeson, GS, Ginzler, E, Gorevic, P, Granda, J, Grossman, J, Hiepe, F, Howard, P, Hura, CE, Jaffer, A, Jakes, J, Kalden, JR, Kammer, GM, Kaplan, MJ, Kaplan, S, Katz, R, Kennedy, A, Kenney, HM, Khamashta, M, Kivitz, AJ, Kovacs, C, Krishnan, M, Kurtzman, NA, Liebling, M, Lourie, SH, Loveless, J, Manion, CV, Manzi, S, Martin, K, McKay, J, Mease, PJ, Merrill, JT, Moreland, LW, Moritz, C, Neuwelt, CM, Petri, M, Pogue, BC, Quinet, RJ, Ramsey-Goldman, R, Roth, A, Rothfield, N, Scarpa, N, Schneider, M, Shergy, WJ, Sherrer, Y, Sibilia, J, Sisay, M, Smith, D, Spinowitz, B, Spira, M, Stevens, MP, Sturfelt, G, Surbeck, W, Tindall, EA, Torres, A, Van Vollenhoven, R, Vijayan, A, Vilardell-Tarres, M, Weaver, C, Williams, GW & Zummer, M 2008, 'Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial', Arthritis and rheumatism, vol. 58, no. 8, pp. 2470-2480. https://doi.org/10.1002/art.23673

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title = "Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial",

abstract = "Objective. To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. Methods. We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels > 15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. Results. Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced ≥ 50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. Conclusion. Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.",

author = "Cardiel, {Mario H.} and Tumlin, {James A.} and Furie, {Richard A.} and Wallace, {Daniel J.} and Tenshang Joh and Linnik, {Matthew D.} and Micha Abeles and Jacob Aelion and Appel, {Gerald B.} and Cynthia Aranow and Stanley Ballou and Becker, {Michael A.} and Belmont, {H. Michael} and Boling, {Eugene P.} and Stefano Bombardieri and James Brodeur and Jill Buyon and Condemi, {John J.} and Cronin, {Mary E.} and Cush, {John J.} and Raphael DeHoratius and Deborah Desir and John Donohue and Michael Edwards and El-Shahawy, {Mohamed A.} and Paul Emery and Stephanie Ensworth and Espinoza, {Luis R.} and Maria Fondal and Paul Fortin and Thomas Geppert and Gilkeson, {Gary S.} and Ellen Ginzler and Peter Gorevic and Jose Granda and Jennifer Grossman and Falk Hiepe and Paul Howard and Hura, {Claudia E.} and Adrian Jaffer and James Jakes and Kalden, {Joachim R.} and Kammer, {Gary M.} and Kaplan, {Mariana J.} and Stanley Kaplan and Robert Katz and Alastair Kennedy and Kenney, {Howard M.} and Munther Khamashta and Kivitz, {Alan J.} and Christine Kovacs and Mahesh Krishnan and Kurtzman, {Neil A.} and Michael Liebling and Lourie, {Seth H.} and James Loveless and Manion, {Carl V.} and Susan Manzi and Kevin Martin and James McKay and Mease, {Phillip J.} and Merrill, {Joan T.} and Moreland, {Larry W.} and Charles Moritz and Neuwelt, {C. Michael} and Michelle Petri and Pogue, {Bryan C.} and Quinet, {Robert J.} and Rosalind Ramsey-Goldman and Arnold Roth and Naomi Rothfield and Nicholas Scarpa and Matthias Schneider and Shergy, {William J.} and Yvonne Sherrer and Jean Sibilia and Moges Sisay and Douglas Smith and Bruce Spinowitz and Moses Spira and Stevens, {Michael P.} and Gunnar Sturfelt and William Surbeck and Tindall, {Elizabeth A.} and Arnaldo Torres and {Van Vollenhoven}, Ronald and Anitha Vijayan and Miguel Vilardell-Tarres and Cynthia Weaver and Williams, {Gary W.} and Michael Zummer",

year = "2008",

month = aug,

doi = "10.1002/art.23673",

language = "English (US)",

volume = "58",

pages = "2470--2480",

journal = "Arthritis and rheumatism",

issn = "0004-3591",

publisher = "John Wiley and Sons Ltd",

number = "8",

}

TY - JOUR

T1 - Abetimus sodium for renal flare in systemic lupus erythematosus

T2 - Results of a randomized, controlled phase III trial

AU - Cardiel, Mario H.

AU - Tumlin, James A.

AU - Furie, Richard A.

AU - Wallace, Daniel J.

AU - Joh, Tenshang

AU - Linnik, Matthew D.

AU - Abeles, Micha

AU - Aelion, Jacob

AU - Appel, Gerald B.

AU - Aranow, Cynthia

AU - Ballou, Stanley

AU - Becker, Michael A.

AU - Belmont, H. Michael

AU - Boling, Eugene P.

AU - Bombardieri, Stefano

AU - Brodeur, James

AU - Buyon, Jill

AU - Condemi, John J.

AU - Cronin, Mary E.

AU - Cush, John J.

AU - DeHoratius, Raphael

AU - Desir, Deborah

AU - Donohue, John

AU - Edwards, Michael

AU - El-Shahawy, Mohamed A.

AU - Emery, Paul

AU - Ensworth, Stephanie

AU - Espinoza, Luis R.

AU - Fondal, Maria

AU - Fortin, Paul

AU - Geppert, Thomas

AU - Gilkeson, Gary S.

AU - Ginzler, Ellen

AU - Gorevic, Peter

AU - Granda, Jose

AU - Grossman, Jennifer

AU - Hiepe, Falk

AU - Howard, Paul

AU - Hura, Claudia E.

AU - Jaffer, Adrian

AU - Jakes, James

AU - Kalden, Joachim R.

AU - Kammer, Gary M.

AU - Kaplan, Mariana J.

AU - Kaplan, Stanley

AU - Katz, Robert

AU - Kennedy, Alastair

AU - Kenney, Howard M.

AU - Khamashta, Munther

AU - Kivitz, Alan J.

AU - Kovacs, Christine

AU - Krishnan, Mahesh

AU - Kurtzman, Neil A.

AU - Liebling, Michael

AU - Lourie, Seth H.

AU - Loveless, James

AU - Manion, Carl V.

AU - Manzi, Susan

AU - Martin, Kevin

AU - McKay, James

AU - Mease, Phillip J.

AU - Merrill, Joan T.

AU - Moreland, Larry W.

AU - Moritz, Charles

AU - Neuwelt, C. Michael

AU - Petri, Michelle

AU - Pogue, Bryan C.

AU - Quinet, Robert J.

AU - Ramsey-Goldman, Rosalind

AU - Roth, Arnold

AU - Rothfield, Naomi

AU - Scarpa, Nicholas

AU - Schneider, Matthias

AU - Shergy, William J.

AU - Sherrer, Yvonne

AU - Sibilia, Jean

AU - Sisay, Moges

AU - Smith, Douglas

AU - Spinowitz, Bruce

AU - Spira, Moses

AU - Stevens, Michael P.

AU - Sturfelt, Gunnar

AU - Surbeck, William

AU - Tindall, Elizabeth A.

AU - Torres, Arnaldo

AU - Van Vollenhoven, Ronald

AU - Vijayan, Anitha

AU - Vilardell-Tarres, Miguel

AU - Weaver, Cynthia

AU - Williams, Gary W.

AU - Zummer, Michael

PY - 2008/8

Y1 - 2008/8

N2 - Objective. To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. Methods. We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels > 15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. Results. Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced ≥ 50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. Conclusion. Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

AB - Objective. To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. Methods. We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels > 15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. Results. Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced ≥ 50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. Conclusion. Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

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Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial

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