Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus

Abstract

Objective: This post hoc analysis compared anifrolumab 300 mg every 4 weeks with placebo on rash and arthritis measures with different stringency in patients with moderate to severe SLE (phase IIb; MUSE; NCT01438489). Subgroups were analysed by type I interferon gene signature (IFNGS test-high or test-low).

Methods: Rash was measured with the SLE Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG) Index and modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI). Arthritis was evaluated using SLEDAI-2K, BILAG and swollen and tender joint counts. Outcomes were measured at week 52.

Results: More anifrolumab-treated patients demonstrated resolution of rash by SLEDAI-2K versus placebo: 39/88 (44.3%) versus 13/88 (14.8%), OR (90% CI) 4.56 (2.48 to 8.39), p<0.001; improvement of BILAG: 48/82 (58.5%) versus 24/85 (28.2%), OR (90% CI) 3.59 (2.08 to 6.19), p<0.001; and ≥50% improvement by mCLASI: 57/92 (62.0%) versus 30/89 (33.7%), OR (90% CI) 3.31 (1.97 to 5.55), p<0.001. More anifrolumab-treated patients had improved arthritis by SLEDAI-2K versus placebo: 55/97 (56.7%) versus 42/99 (42.4%), OR (90% CI) 1.88 (1.16 to 3.04), p=0.032; and BILAG: 65/94 (69.1%) versus 47/95 (49.5%), OR (90% CI) 2.47 (1.48 to 4.12), p=0.003; and mean (SD) swollen and tender joint reductions: -5.5 (6.3) versus -3.4 (5.9), p=0.004. Comparable results were demonstrated in IFNGS test-high patients (n=151). In IFNGS test-low patients (n=50), substantial numerical differences in partial rash and arthritis responses were observed in anifrolumab-treated patients versus placebo, with statistical significance only for rash by BILAG in this small population.

Conclusions: Anifrolumab treatment was associated with improvements versus placebo in specific SLE features of arthritis and rash using measures of different stringency. Although driven by robust data in the prevalent IFNGS test-high population, further evaluation in IFNGS test-low patients is warranted.

Keywords: Arthritis; Interferon; Treatment.

Figure 1

Patients with SLEDAI-2K-defined resolution of rash (A), BILAG-defined improvement in rash (B) and improvement in mCLASI activity score^a (C) in all patients, and IFNGS test–high and IFNGS test–low subgroups at week 52. ^aPatients with mCLASI activity score >0 at baseline who achieved ≥50% improvement from baseline. *p<0.05, **p<0.01, ***p<0.001 compared with placebo. Only patients with baseline involvement for each outcome were included in analyses of rash (as measured by SLEDAI-2K, BILAG and mCLASI). BILAG, British Isles Lupus Assessment Group; IFNGS, interferon gene signature; mCLASI, modified Cutaneous Lupus Erythematosus Disease Area and Severity Index; Q4W, every 4 weeks; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.

Figure 2

Patients with resolution in SLEDAI-2K-defined arthritis (A) and BILAG-defined improvement in arthritis (B) in all patients, and IFNGS test–high and IFNGS test–low subgroups at week 52. *p<0.05, **p<0.01, ***p<0.001 compared with placebo. Only patients with baseline involvement for each outcome were included in analyses of arthritis (by SLEDAI-2K and BILAG). BILAG, British Isles Lupus Assessment Group; IFNGS, interferon gene signature; Q4W, every 4 weeks; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.

Figure 3

Change from baseline to week 52 in swollen and tender joint counts in all patients, and IFNGS test–high and IFNGS test–low subgroups. *p<0.05, **p<0.01, ***p<0.001 compared with placebo. IFNGS, interferon gene signature; Q4W, every 4 weeks.