TY - JOUR
T1 - A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus
AU - Kalunian, Kenneth C.
AU - Furie, Richard
AU - Morand, Eric F.
AU - Bruce, Ian N.
AU - Manzi, Susan
AU - Tanaka, Yoshiya
AU - Winthrop, Kevin
AU - Hupka, Ihor
AU - Zhang, Lijin
AU - Werther, Shanti
AU - Abreu, Gabriel
AU - Hultquist, Micki
AU - Tummala, Raj
AU - Lindholm, Catharina
AU - Al-Mossawi, Hussein
N1 - Publisher Copyright:
© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2023/2
Y1 - 2023/2
N2 - 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. (Figure presented.).
AB - 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. (Figure presented.).
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U2 - 10.1002/art.42392
DO - 10.1002/art.42392
M3 - Article
C2 - 36369793
AN - SCOPUS:85143210495
SN - 2326-5191
VL - 75
SP - 253
EP - 265
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 2
ER -