Trio of anifrolumab lupus trials show concordant BICLA, SRI(4) responses in most patients
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Most patients with systemic lupus erythematosus across a trio of anifrolumab trials demonstrated concordant outcomes on BILAG-based Composite Lupus Assessment and SLE Responder Index responses, according to data.
In addition, although a subgroup of patients with discordant responses was identified, they were overrepresented among those who received placebo in one of the trials. These participants demontrated lower baseline disease activity, joint counts and glucocorticoid tapering rates than those treated with anifrolumab (Saphnelo, AstraZeneca), the researchers wrote.
“As standard therapies do not always adequately control disease activity, additional effective SLE-targeted therapies are needed, which has led to unprecedented SLE clinical trial activity over the last two decades,” Ian N. Bruce, MD, FRCP, of the University of Manchester, in the United Kingdom, and co-authors wrote in Annals of the Rheumatic Diseases. “Efficacy assessments in these trials often use composite indices of global lupus disease activity, such as the BILAG-based Composite Lupus Assessment (BICLA) and the SLE Responder Index (SRI).
“While BICLA and SRI(4) both evaluate clinically meaningful elements of global SLE disease activity, differences in their metric properties may give rise to inconsistent classification of a patient’s response between these measures,” they added.
To examine the response discordance between BICLA and SRI(4) in patients treated with anifrolumab 300 mg, Bruce and colleagues analyzed data from the TULIP-1, TULIP-2 and MUSE trials. All three trials investigated BICLA and SRI(4) responses at week 52. Glucocorticoid tapering was mandated in TULIP-1 and TULIP-2, but was left to the investigators’ discretion in MUSE, according to the researchers.
BICLA responses were identified when all the criteria were met. Patients needed to show a reduction in all BILAG-2004 A domain scores to B, C or D and all B domain scores to C or D. Additionally, there could be no worsening in other BILAG-2004 organ systems, the authors wrote.
In addition, there could be no increase in SLEDAI-2K scores, from baseline, and no increaser in the Physician’s Global Assessment (PGA) score. SRI(4) responses were defined as achieving a four-point or greater reduction in SLEDAI-2K scores, less than one new BILAG-2004 A or two new BILAG 2004 B organ domain scores and no increase in PGA. In both measurements, no treatment discontinuations or use of restricted medications were allowed.
Patients in all three trials underwent assessments at 52 weeks, regardless of whether they received anifrolumab or placebo. Patients were then grouped by concordance on outcomes, whether they were dual responders or total non-responders. Subgroups were analyzed based on demographics, clinical characteristics, glucocorticoid tapering protocols, responses to organ domains and joint count changes.
In all, between 78% and 85% of patients had concordant responses (P < .001). Across all three studies, dual responses in BICLA and SRI(4) favored patients who received anifrolumab.
According to the researchers, 11% of the TULIP-1 population showed SRI(4) responses, but not BICLA. Among these discordant patients, 28 received placebo and 12 were treated with anifrolumab. In this subgroup, those who received placebo demonstrated lower baseline disease activity, joint counts and glucocorticoid tapering rates. In addition, more placebo-treated patients acheived arthritis response than anifrolumab-treated patients, the researchers wrote.
“In individual patient-level analyses, the majority of patients across the TULIP-1, TULIP-2 and MUSE trials of anifrolumab had concordant outcomes on BICLA and SRI(4),” Bruce and colleagues wrote. “Using a stringent definition of response requiring dual BICLA and SRI(4) response, anifrolumab treatment was associated with efficacy compared with placebo in all three trials. A discordant BICLA non-responder/SRI(4) responder subgroup was identified in all three trials but this subgroup was larger in the TULIP-1 placebo group.
“Discordance was primarily driven by the sensitivity of SRI(4) to single organ (arthritis) improvement as the discordant placebo group was enriched for patients with lower baseline joint counts,” they added. “... For now, we suggest that careful attention to baseline factors and maintaining uniformity in glucocorticoid tapering are essential in future SLE clinical trials to reduce the likelihood of discordant results and maximize the ability to detect efficacy signals.”
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