This dearth of trial-based evidence has led to the development of consensus treatment plans (CTPs) for cSLE and other pediatric rheumatologic diseases. These CTPs have been created through recognized consensus methodology by the Childhood Arthritis and Rheumatology Research Alliance (CARRA), and for cSLE, provide the physician with a choice of treatment plans for induction and maintenance of proliferative LN.12 Data will be collected from multiple centers using the CTPs for comparative effectiveness research, and in this case, a comparison of MMF versus IV cyclophosphamide with concomitant oral and/or IV corticosteroids. With the high cost of industry-sponsored, randomized controlled trials, using observational data collected in a rigorous prospective manner and analyzed with newer statistical methodologies are the most realistic and cost-effective ways for pediatric rheumatologists to address many of the treatment questions in this relatively rare disease.
Cyclophosphamide has traditionally played a pivotal role in the treatment of severe organ involvement and rare life-threatening complications such as pulmonary hemorrhage. At our center, we have rarely used this drug for induction treatment for LN and instead have reserved its use primarily for patients with severe NPSLE—psychosis, acute confusional state, what was called “lupus cerebritis” or “organic brain syndrome”—and for severe cognitive dysfunction occurring concomitantly with other NPSLE syndromes. Our practice change to cyclophosphamide for NPSLE treatment occurred as more than 50% of patients initially treated with azathioprine (and corticosteroids) required escalation of therapy due to inadequate response.13
The U.S. Food and Drug Administration’s approval of belimumab as “the first new drug for SLE in 50 years” was lauded within the SLE community. However, the drug is indicated for adults with SLE, and as is frequently the case, pediatric rheumatologists are limited to “off-label” prescribing. In Canada as in the U.S., there are many payers who will not cover biologic drugs for off-label therapy. Thus, we await results from the ongoing international randomized controlled trial (RCT) of this drug in cSLE. Although rituximab, an anti-CD20 monoclonal antibody, may be effective in the treatment armamentarium of cSLE, following the disappointing results of the aSLE rituximab trials, no phase III or IV study has been conducted in cSLE. Anecdotally, the pediatric rheumatology community uses rituximab for treatment-resistant cSLE manifestations including refractory CNS disease, renal disease, and cytopenias. At the Hospital for Sick Children in Toronto, 24 patients with cytopenias have received 31 courses of rituximab, with achievement of a rapid and complete response in 23 patients over the past 10 years. This is a selected group of cSLE patients with cytopenias refractory to high-dose systemic corticosteroids, intravenous immunoglobulin, antimalarial drugs, and other immunosuppressants. Clinical response is durable at a median of two years of follow-up, and those patients who flared all responded to repeat courses of rituximab.
