CHICAGO – Newly updated American College of Rheumatology guidelines for the screening and management of lupus nephritis in adults, which are expected to be published in early 2012, focus largely on induction therapy with mycophenolate mofetil or cyclophosphamide and on maintenance therapy with mycophenolate mofetil and azathioprine.

An algorithm for diffuse proliferative nephritis, for example, indicates that in patients with active class III and IV disease without cellular crescents, induction therapy should include mycophenolate mofetil (MMF) at 2-3 g/day for 6 months. Cyclophosphamide is an alternative option in these patients, according to the guidelines, which note that the literature suggests MMF is preferred for initial therapy in African Americans and Hispanics in North America and Latin America.

These recommendations are based on level A evidence from multiple randomized controlled trials or a meta-analysis, Dr. Bevra H. Hahn noted at the annual meeting of the American College of Rheumatology, where she presented the updated guidelines.

In patients who are given cyclophosphamide, the dose should be 500 mg intravenously every 2 weeks for 6 weeks, or 500-1,000 mg/m² of body surface area. This recommendation is based on level B evidence from a single randomized controlled trial or nonrandomized studies. The latter choice has been studied only in Caucasians of European descent, noted Dr. Hahn, a professor of medicine and chair of the rheumatology department at the University of California, Los Angeles, as well as a member of the core working group for the updated guidelines.

Also recommended for class III and IV patients without cellular crescents is a concomitant pulse of steroids for 3 days, then prednisone at a dose of 0.5-1.0 mg/kg to induce improvement, with tapering to the lowest effective dose after a few weeks. Data supporting a specific dose in this range are lacking, and this recommendation, which is based on level C evidence indicating the recommendation is derived from consensus, expert opinion, or a case series, also states that the prednisone should continue for 6 months.

The algorithm for patients with diffuse proliferative disease also addresses patients with cellular crescents. Such patients should receive the higher 1.0-mg/kg per day prednisone dose. Patients who do not respond to induction should be switched from their initial induction regimen, be it MMF or cyclophosphamide, to the other. Maintenance therapy for responders to either MMF or cyclophosphamide should include MMF at 1-2 g/day or azathioprine at 2 mg/kg per day plus low-dose daily glucocorticoids.

The updated guidelines also address renal biopsy, adjunctive treatments, patients with focal disease, patients with class V disease, lupus nephritis in pregnancy, and recommendations for monitoring.

Notably, the guidelines do not advocate use of belimumab, as it has not been studied in active lupus nephritis, Dr. Hahn said, noting that despite the expanded literature on lupus nephritis that led to development of these updated guidelines, there are a number of unmet needs.

Between 20% and 35% of patients do not respond at all to induction therapies, and in many the response is slow, taking up to 52 weeks to determine response. Furthermore, response rates remain low.