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

Research output: Contribution to journalArticle

127 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 languageEnglish (US)
Pages (from-to)2470-2480
Number of pages11
JournalArthritis and rheumatism
Volume58
Issue number8
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

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