Objective

To explore long-term safety and tolerability of anifrolumab 300 mg compared with placebo in patients with systemic lupus erythematosus (SLE) who completed a Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP) trial and enrolled in the placebo-controlled 3-year long-term extension (LTE) study (ClinicalTrials.gov identifier: NCT02794285).

Methods

In the blinded LTE study, patients continued anifrolumab 300 mg, switched from anifrolumab 150 mg to 300 mg, or were re-randomized from placebo to receive either anifrolumab 300 mg or to continue placebo, administered every 4 weeks. Primary comparisons in the LTE study were between patients who received anifrolumab 300 mg or placebo throughout the TULIP and LTE studies. For rare safety events, comparisons included patients who received any anifrolumab dose during TULIP or LTE. When exposure differed, exposure-adjusted incidence rates (EAIRs) per 100 patient-years were calculated.

Results

In the LTE study, EAIRs of serious adverse events (SAEs) were 8.5 with anifrolumab compared with 11.2 with placebo; likewise, EAIRs of AEs leading to treatment discontinuation were 2.5 versus 3.2, respectively. EAIRs of non-opportunistic serious infections were comparable between groups (3.7 with anifrolumab versus 3.6 with placebo). Exposure-adjusted event rates of COVID-related AEs, including asymptomatic infections, were 15.5 with anifrolumab compared with 9.8 with placebo. No COVID-related AEs occurred in fully vaccinated individuals. EAIRs of malignancy and major acute cardiovascular events were low and comparable between groups. Anifrolumab was associated with lower cumulative glucocorticoid use and greater mean improvement in the SLE Disease Activity Index 2000, compared with placebo.

Conclusion

This LTE study represents the longest placebo-controlled clinical trial performed in SLE to date. No new safety findings were identified in the LTE study, supporting the favorable benefit-risk profile of anifrolumab for patients with moderate-to-severe SLE receiving standard therapy.

Objectives

To characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups.

Methods

We 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.

Results

In 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.

Conclusions

Overall, 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 number

NCT02446912, NCT02446899.