Background: Lupus nephritis (LN) represents a serious manifestation of systemic lupus erythematosus (SLE). LN therapies include glucocorticoids and conventional immunosuppressants as standard of care (SOC) or biological therapies. Rituximab (RTX) is used in some patients but published clinical trials have failed to meet their primary end-points. SLE trials have limitations including stringent eligibility criteria in an attempt to achieve homogeneity, however poor recruitment can lead to early termination as such, clinical trials may not reflect the disease population of interest and outcomes can be difficult to generalise.
Objectives: Our aim was to apply published trial eligibility criteria to patients with LN in a large UK-wide register to quantify how accurately LN clinical trials represent a real-world cohort.
Methods: A literature review of recent major published LN clinical trials was performed (n=6). Inclusion and exclusion criteria common across trials were applied to all patients registered in the BILAG-Biologics Register (BILAG-BR) with active LN, a UK-wide registry of patients with SLE. Active LN was defined as a renal BILAG score A or B. We applied available data to inclusion criteria including ACR/SLICC criteria for SLE diagnosis, positive dsDNA or ANA antibodies and a UPCR>100mg/mmol. Available exclusion criteria were active CNS lupus, a history of hepatitis, malignancy or CKD 4/5, hypogammaglobulinaemia, and cyclophosphamide use within 30 days of entry or previous B cell therapy within 12 months of entry.
Results: As of July 2018, 259/897 (28.9%) patients in BILAG-BR had active LN. In the RTX and SOC groups, 70/230 (30.4%) and 10/29 (34.5%) respectively did not meet all inclusion criteria (Table 1). Meanwhile 118/230 (51.3%) of RTX patients and 6/29 (20.7%) of SOC patients met one or more exclusion criteria. Overall 131/259 (50.6%) did not satisfy all inclusion and exclusion criteria and thus were ineligible for clinical trial entry. Of those patients deemed ineligible, the RTX patients were younger (median age 36 vs. 49 in SOC group, p=0.653) and the majority were non-Caucasian (n=71/121 (58.7%), p=0.251). The majority of patients in both treatment groups were female (p=0.089). UPCR <100mg/mol (n=35) was the most common inclusion criteria missed whilst the commonest exclusion criteria were concomitant active CNS disease (n=22) and hypogammaglobulinaemia (n=24).
Conclusion: In a large national cohort of active LN we found that 50.6% of patients would not be eligible for clinical trial entry using published entry criteria. 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.
British Isles Lupus Assessment Group Biologics Register
Disclosure of Interests: Sophie Collinson: None declared, Ben Parker Grant/research support from: GSK, Consultant for: AZ, UCB, GSK, Eoghan McCarthy: None declared, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GlaxoSmithKline, Consultant for: AstraZeneca, Eli Lilly, GlaxoSmithKline, ILTOO Pharma, MedImmune, Merck Serono, Speakers bureau: GlaxoSmithKline, UCB Pharma
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