Abetimus sodium (riquent) for the prevention of nephritic flares in patients with systemic lupus erythematosus.
ABSTRACT Abetimus sodium has been under development for the treatment of systemic lupus erythematosus since the early 1990s. Because its administration results in the selective reduction of circulating double-stranded DNA antibodies, La Jolla Pharmaceutical Company has focused on the agent's ability to prolong time to nephritic flare. Fourteen trials have been initiated since 1994, but the two pivotal registration trials failed to meet primary end points. The US Food and Drug Administration issued a letter in October 2004 that stated abetimus sodium was "approvable" pending the successful completion of a trial demonstrating clinical benefit. The fate of this agent lies in the ability of the company to successfully complete a phase III study.
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ABSTRACT: Although the survival of patients with lupus nephritis (LN) has improved considerably in recent years, refractory LN appears in a substantial proportion of patients and, therefore, treatment of LN remains a real challenge today. We will use the term "refractory" LN, for those cases with none or partial response to first-line therapies. In this sense, numerous epidemiological factors, including racial, socioeconomic, histological and serological parameters, may influence treatment response and, therefore, may have an impact on the outcome of renal involvement. Initial conventional therapy will depend somewhat on these epidemiological factors. If this initial therapy fails, fortunately today we have alternative therapies that include the multitarget therapy and the use of biologics. Published evidence about these therapies is presented in this review. Important terms in the management of LN, such as the definition of complete response, partial response, sustained response and renal flare as well as the discrimination of different types of flare, are also discussed here according to the European consensus statement on the terminology used in the management of lupus glomerulonephritis.Autoimmunity reviews 05/2011; 10(11):655-63. · 6.37 Impact Factor
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ABSTRACT: Lupus nephritis, one of the most severe and therapeutically challenging manifestations of systemic lupus erythematosus (SLE), has been the target of drug development by La Jolla Pharmaceutical Company. Abetimus sodium, an example of the La Jolla Pharmaceutical Company's Tolerance Technology is an intravenously administered tetrameric oligonucleotide conjugate that safely reduces antidouble-stranded DNA (anti-dsDNA) antibodies. Given the importance of anti-dsDNA antibodies in the pathogenesis of lupus nephritis, the Phase II and III trials were designed to evaluate whether treatment with abetimus sodium could prolong the time to renal flare in cohorts of patients at high risk of nephritic flares. The available data regarding abetimus were reviewed and the current status of the drug's development program is reported. Animal studies have demonstrated the ability of abetimus to reduce the titers of anti-dsDNA antibodies as well as of antidsDNA antibody-secreting cells. Administration of abetimus to patients with SLE has uniformly been associated with reductions in circulating anti-dsDNA antibodies. However, two pivotal trials with large numbers of lupus nephritis patients failed to demonstrate statistically signi ficant prolongations in time to renal flare. An event-driven randomized placebo-controlled trial was abruptly terminated in February 2009 after an interim data safety monitoring board determined that achievement of a successful study outcome was futile.Expert Opinion on Pharmacotherapy 07/2009; 10(9):1501-7. · 2.86 Impact Factor
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ABSTRACT: Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE) in childhood affecting more than 80 % of patients. Treatment of this complication has undergone significant evolution in recent years. A series of randomized controlled trials has clarified the role of a variety of immunomodulating regimens including some novel biologic medications. This review touches on the major trials that have influenced practice and shaped current thinking about the treatment of proliferative lupus glomerulonephritis.Pediatric Nephrology 11/2012; · 2.94 Impact Factor