Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials

Abstract

ObjectivesTo characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups.MethodsWe performed post hoc analyses of pooled data from the 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials of intravenous anifrolumab in moderate-to-severe SLE. Outcomes were assessed in predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age of onset, glucocorticoid use, disease activity and serological markers.ResultsIn pooled data, patients received anifrolumab 300 mg (360/726) or placebo (366/726); 82.6% were IFNGS-high. IFNGS-high patients had greater baseline disease activity and were more likely to have abnormal serological markers versus IFNGS-low patients. In the total population, a greater proportion of patients treated with anifrolumab versus placebo achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 52 (difference 16.6%; nominal p<0.001). BICLA response treatment differences with anifrolumab versus placebo were comparable to the total population across most predefined subgroups, including subgroups for baseline glucocorticoid dosage (<10/≥10 mg/day prednisone/equivalent) and for clinical disease activity (SLE Disease Activity Index 2000 score <10/≥10). Subgroups with larger treatment differences included IFNGS-high patients (18.2%), patients with abnormal baseline serological markers (23.1%) and Asian patients (29.2%). The safety profile of anifrolumab was similar across subgroups.ConclusionsOverall, this study supports the consistent efficacy and safety of anifrolumab across a range of patients with moderate-to-severe SLE. In a few subgroups, small sample sizes limited conclusions from being drawn regarding the treatment benefit with anifrolumab.Trial registration numberNCT02446912, NCT02446899.

Nonlinear Population Pharmacokinetics of Anifrolumab in Healthy Volunteers and Patients With Systemic Lupus Erythematosus

“…34 However, it should be noted that the IFNGS-low group was small, limiting the interpretation of results. 32,33 Similar to the findings in our analyses, IFNGS status was also found to impact the CL of sifalimumab, an anti-IFN-α mAb that exhibits linear PK in patients with SLE. 35 In a phase 1b study of sifalimumab, patients with greater baseline IFNGS score had a slightly higher CL of sifalimumab than those with a low IFNGS score.…”

“…In a separate analysis of the efficacy of anifrolumab across patient subgroups in data pooled from the TULIP‐1 and TULIP‐2 trials, 47.6% of patients with a high IFNGS and 46.8% of patients with a low IFNGS obtained a BICLA response at week 52 following anifrolumab treatment 32,33 . However, the BICLA response treatment difference (for anifrolumab vs placebo) was greater in patients with a high IFNGS vs patients with a low IFNGS 32,33 .…”

“…32,33 However, the BICLA response treatment difference (for anifrolumab vs placebo) was greater in patients with a high IFNGS vs patients with a low IFNGS. 32,33 This was driven by the differences in response rates in the comparator (placebo) group, who just received standard therapy; the response rate in placebo-treated patients was lower in the IFNGShigh group (29.4%) vs IFNGS-low group (37.5%). 32,33 The difference in response to standard therapy was likely due to the association between elevated IFNGS and greater disease activity.…”

“…The difference in response to standard therapy was likely due to the association between elevated IFNGS and greater disease activity 34 . However, it should be noted that the IFNGS‐low group was small, limiting the interpretation of results 32,33 …”

“…32,33 This was driven by the differences in response rates in the comparator (placebo) group, who just received standard therapy; the response rate in placebo-treated patients was lower in the IFNGShigh group (29.4%) vs IFNGS-low group (37.5%). 32,33 The difference in response to standard therapy was likely due to the association between elevated IFNGS and greater disease activity. 34 However, it should be noted that the IFNGS-low group was small, limiting the interpretation of results.…”