Lupus clinical trial eligibility in a real-world setting: results from the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR)

Abstract

ObjectiveTo quantify how well phase III randomised clinical trials in both SLE and lupus nephritis (LN) represents a real-world SLE cohort.MethodsLiterature reviews were performed of major published phase III SLE (n=12) and LN (n=6) clinical trials (ClinicalTrials.gov). Inclusion and exclusion criteria common across these trials were collated for non-renal SLE or LN trials, and applied to patients recruited to the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR) starting either biological or standard-of-care (SOC) therapies.ResultsWe recruited 837 patients to the BILAG-BR from September 2010 to June 2018, starting either SOC (n=125, 15%) or a biological medication (n=712, 85%). Active LN, defined as a BILAG A in the renal domain occurred in 20% (n=166). Overall, 530 (63%) patients were ineligible to participate in non-renal SLE clinical trials and 72 (43%) patients with active LN would be ineligible for LN trials. The most common reasons for ineligibility from the non-renal lupus trials included active renal involvement (n=166, 20%) and low disease activity (n=114, 15%). For LN trials, the most common exclusion met was pre-existing renal impairment (n=15, 9%). Patients with fewer comorbidities were more likely to be eligible to participate in non-renal SLE trials.ConclusionsIn this national register of patients with moderate-to-severe SLE, nearly two-thirds would not be eligible for recruitment to key SLE clinical trials nor would almost half of those with active LN. Eligibility criteria may excessively constrain enrolment and thus, how we can generalise trial results in a real-world setting.

Clinical trial outcomes for SLE: what we have and what we need

“…Indeed, it has been shown that nearly two-thirds of patients are ineligible to participate in non-renal SLE clinical trials. 64 In particular, the inclusion limitations in clinical trials are greatly influenced by authorised standard-of-care treatments, prior treatments and, especially, the washout periods for various treatments. Of note, some trials have suggested that background immunosuppressants could be safely withdrawn in patients with SLE with active but non-organ-threatening flare to support more interpretable trial results.…”

Lupus clinical trials and the promise of future therapies

“…Increasingly complex inclusion/exclusion criteria with many restrictions related to the past medical history, biologic use prior to enrollment, and laboratory tests have led to further reduction in the number of eligible patients in clinical trials. [ 18 ] Inclusion criteria usually specifies a disease activity in the moderate to severe range; however, exclusion criteria restrict the range of disease activity by limiting use of steroids or other immunosuppressive treatments. [ 19 , 20 ] More medications have been approved for SLE and the standard of care treatment is evolving but inclusion/exclusion mostly remains the same, and as such more patients are excluded from studies.…”

Obesity and tobacco smoking are independently associated with poor patient-reported outcomes in SLE: a cross-sectional study

“…Using data from two international RCTs, we previously reported associations between obesity and clinically important impairments in physical aspects of HRQoL, fatigue, and social functioning [ 15 ]. Despite the large sample size and ethnical diversity of the patients included, this does not necessarily resemble the target population in a real-world setting, as most individuals from clinical practices do not meet the eligibility criteria for RCT programmes [ 17 ].…”