Further Study Needed into Rituxan Use and Its Outcomes in Lupus Patients, Review Suggests
Factors that might be predictive of different responses and outcomes in systemic lupus erythematosus (SLE) patients who are treated with Rituxan (rituximab) still need to be validated in future studies to enable better and more personalized treatment, a literature review suggests.
The study, “Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review,” was published in the journal Seminars in Arthritis and Rheumatism.
Rituxan, an approved therapy for certain lymphomas and rheumatoid arthritis, has long been prescribed to lupus patients in accordance with several guidelines, including that of the American College of Rheumatology, issued in 2012. It is an anti-B-cell therapy, and B-cells play a pivotal role in the development of lupus.
But the treatment has shown variability in terms of clinical outcomes, and two randomized Phase 3 clinical trials, EXPLORER (NCT00137969) and LUNAR (NCT00282347), did not reach their primary endpoints of superior clinical responses compared to placebo. This variability is thought to be a result of both study design and heterogeneity in the lupus population.
In their review, the researchers aimed to identify predictors of differential response and prognostic factors that can be used to assess clinical outcomes in lupus patients following Rituxan treatment.
The study involved 16 research papers, including three papers from the EXPLORER and LUNAR trials, and 13 papers from six cohort studies.
Overall, patients were ages 15 and older, with follow-up evaluations ranging from between six and 18 months for the clinical trials, and between six and 60 months for the cohort studies. The researchers assessed the so-called quality of evidence (QoE) to reflect the reliability of predictive and prognostic factors used in the studies.
Overall, most of the investigated predictive and prognostic factors were of rather poor quality. “Our confidence in the majority of these is very limited,” the researchers wrote.
Main reasons for this finding were publication bias due to a study’s small patient group, and the existence of factors that were reported in one only study. Several studies reported data from the same center or cohort (patient group), and many did not report the size of the effects observed.
Still, some factors showed “some evidence of prognostic value,” the researchers said. These included clinical phenotype and severity, baseline anti-extractable nuclear antigens (ENA) and anti-Ro antibodies, interleukin 2/21, single nucleotide polymorphisms, and complete B-cell depletion after Rituxan use.
While several guidelines recommend the use of Rituxan for the treatment of refractory lupus patients, this study found limited evidence to predict patients’ response to Rituxan in studies that support the drug’s efficacy.
“It is therefore important to validate any predictive or prognostic factors in hypothesis-testing studies and determine whether such markers are associated with SLE outcomes in general or whether they are specific for [Rituxan] therapy,” the research team concluded. “Such an approach will pave the way for more personalised use of this agent in the future.”