How clinical trials into lupus nephritis define their requirements for patient eligibility are too strict, leaving many people with active and severe disease ineligible for participation, according to a study that looked at six lupus trials and how well their “inclusion and exclusion criteria” matched patients in a large U.K. registry.
Its researchers reported that a majority of registry patients, 50.6%, would not have been enrolled under published entry requirements.
These findings were presented at the recent 2019 European Congress of Rheumatology (EULAR 2019), in a poster titled “How Well Do Clinical Trials Represent Real World Lupus Nephritis Patients?”
Lupus nephritis (inflammation of the kidneys) can be a serious complication of systemic lupus erythematosus (SLE).
The standard of care for lupus nephritis is treatment using glucocorticoids or conventional immunosuppressants. Rituxan (rituximab), an antibody that dampens some immune cells, has been used off-label to treat some with lupus nephritis, but has not shown efficacy across several clinical trials.
Finding better treatments for these people requires clinical studies that determine safety and effectiveness. But stringent requirements for trial participation, often done to ensure patient homogeneity in the group studied, can result in criteria that does not accurately reflect real-world patients, the study notes.
Researchers set out to evaluate clinical trial criteria for lupus nephritis by determining how closely they reflected a general population.
They reviewed six recently published clinical trials involving these patients. Then they compared inclusion and exclusion criteria common across the trials to patients with active lupus nephritis in a U.K.-wide database of SLE patients called the BILAG-Biologics Register (BILAG-BR).
Inclusion criteria define the characteristics that potential participants must have to be in a study, while exclusion criteria define those that disqualify from participation.
The registry showed 259 people with active lupus nephritis, corresponding to 28.9% of its population. Among them, 230 had been treated with Rituxan, while the 29 others were given standard of care.
Analysis showed that 70 people (30.4%) in the Rituxan group and 10 (34.5%) in the standard-of-care group that would not meet all inclusion criteria common to the six trials. The requirement that patients most often missed was not having a urine protein/creatinine ratio below 100 mg/mmol. This would exclude people with more severe kidney impairment.
A majority, 118 patients or 51.3%, in the Rituxan group and six patients (20.7%) in standard-of-care also met one or more common exclusion criteria for the trials. Most often, the excluding criteria was active disease in the central nervous system and low levels of antibodies implying an immune system disorder (hypogammaglobulinaemia).
Overall, more than half of registry patients (50.6%) with active lupus nephritis would not satisfy all inclusion and exclusion criteria, and likely be ineligible for clinical trial entry, the study found.
Among patients deemed ineligible, those in the Rituxan group were younger (mean age, 36) compared to those given standard of care (mean age, 49). Most were also minorities (non-Caucasian) and female.
“In a large national cohort of active LN [lupus nephritis] we found that 50.6% of patients would not be eligible for clinical trial entry using published entry criteria,” the researchers wrote.
“This poses significant implications on the study of LN treatment in patients with more severe disease. When designing clinical trials, the stringency of eligibility criteria should be reviewed in order to provide greater representation of the target disease population,” they concluded.