To date, studies of alternative regimens to intravenous cyclophosphamide, such as MMF and the ELN protocol, in the past decade have demonstrated comparable efficacy to intravenous cyclophosphamide with reduced treatment-related comorbidities. The addition of biologic therapies to these regimens—in particular rituximab and abatacept—assessed over relatively short periods, has not resulted in improvements above that observed with the NIH cyclophosphamide protocol. Improvements in efficacy have not paralleled improvements in treatment-related morbidities.
Going forward, significant improvements in treatment efficacy will not only be partially realized by clinical trials, but also by a deeper understanding of therapeutics directed against specific features of human pathology.
Elena M. Massarotti, MD, is an associate professor of medicine at Harvard Medical School and director of clinical trials in the Lupus Center at Brigham and Women’s Hospital. She divides her professional time between direct patient care, clinical research in the areas of therapeutics of lupus and rheumatoid arthritis, and medical education.
Peter H. Schur, MD, is professor of medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital, medical director of the Brigham and Women’s Hospital Clinical Immunology Laboratory, editor of UpToDate in Rheumatology, and emeritus director of the Lupus Center at Brigham and Women’s Hospital, where he maintains an active clinical practice, continues to mentor trainees and teaches medical students.
Acknowledgment: The authors wish to thank Dr. Richard Furie for his helpful comments.
References
- Chen YE, Korbet SM, Katz RS, et al. Value of a complete or partial remission in severe lupus nephritis. Clin J Am Soc Nephrol. 2008 Jan;3(1):46–53.
- Dubois EL, Commons RR, Starr P, et al. Corticotropin and cortisone treatment for systemic lupus erythematosus. J Am Med Assoc. 1952 Jul 12;149(11):995–1002.
- Dubois EL. Nitrogen mustard in the treatment of systemic lupus erythematosus. AMA Arch Intern Med. 1954 May;93(5):667–672.
- Dillard MG, Dujovne I, Pollak VE, et al. The effect of treatment with prednisone and nitrogen mustard on the renal lesions and life span of patients with lupus nephritis. Nephron. 1973;10(5):273–291.
- Austin HA, Klippel JH, Balow JE, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986 Mar 6;314(10):614–619.
- Wagner L. Immunosuppressive agents in lupus nephritis: A critical analysis. Medicine (Baltimore). 1976 May;55(3):239–250
- Donadio JV Jr, Holley KE, Wagoner RD, et al. Treatment of lupus nephritis with prednisone and combined prednisone and azathioprine. Ann Intern Med. 1972 Dec;77(6):829–835.
- Felson DT, Anderson J. Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis—Results of a pooled analysis. N Engl J Med. 1984 Dec 13;311(24):1528–1533.
- Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005 Nov 24;353(21):2219–2228.
- Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis. The Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophophamide. Arthritis Rheum. 2002 Aug;46(8):2121–2231.
- Schur PH, Sandson J. Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med. 1968 Mar 7;278(10):533–538.
- Daikh DI, Wofsy D. Cutting edge: Reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. J Immunol. 2001 Mar 1;166(5):2913–2916.
- Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009 May;20(5):1103–1112.
- Wofsy D, Askanase A, Cagnoli PC, et al. Treatment of lupus nephritis with abatacept plus low-dose cyclophophamide followed by azathioprine (the Euro-Lupus Regimen): Twenty-four week data from a double-blind controlled study. Arthritis Rheum. 2013;65(S10):884.
