PMID- 33597205
OWN - NLM
STAT- MEDLINE
DCOM- 20210923
LR  - 20240330
IS  - 2053-8790 (Print)
IS  - 2053-8790 (Electronic)
IS  - 2053-8790 (Linking)
VI  - 8
IP  - 1
DP  - 2021 Feb
TI  - Safety profile of anifrolumab in patients with active SLE: an integrated analysis 
      of phase II and III trials.
LID - 10.1136/lupus-2020-000464 [doi]
LID - e000464
AB  - OBJECTIVE: In phase II and III trials, anifrolumab, a human monoclonal antibody 
      that binds type I interferon receptor subunit 1, has shown efficacy in adults 
      with moderate to severe SLE. We evaluated the safety and tolerability of 
      anifrolumab using data pooled from these trials to more precisely estimate the 
      rate and severity of adverse events (AEs). METHODS: Data were pooled from 
      patients receiving monthly intravenous anifrolumab 300 mg or placebo in MUSE, 
      TULIP-1 and TULIP-2. Key safety endpoints included percentages and 
      exposure-adjusted incidence rates (EAIRs) of patients who experienced AEs, 
      serious AEs (SAEs), AEs leading to discontinuation and AEs of special interest. 
      RESULTS: During treatment, 86.9% of patients receiving anifrolumab 300 mg (n=459) 
      experienced AEs (>/=1) versus 79.4% receiving placebo (n=466), and 4.1% versus 5.2% 
      experienced an AE leading to discontinuation of investigational product. SAEs 
      (>/=1) were experienced by 11.8% and 16.7% of patients receiving anifrolumab and 
      placebo, respectively (EAIR risk difference (95% CI) -7.2 (-12.5 to -1.9)), 
      including lupus exacerbations classified as SAEs (1.5% and 3%, respectively). 
      Infections occurred in 69.7% and 55.4% of patients receiving anifrolumab and 
      placebo, respectively; difference in reported rates was driven by herpes zoster 
      (HZ) and mild and moderate respiratory (excluding pneumonia) infections. The risk 
      of HZ was increased with anifrolumab versus placebo (6.1% vs 1.3%, respectively; 
      EAIR risk difference (95% CI) 5.4 (2.8 to 8.4)); most HZ events were mild or 
      moderate, cutaneous and resolved without treatment discontinuation. Serious 
      infections occurred in 4.8% and 5.6% of patients receiving anifrolumab and 
      placebo, respectively. CONCLUSIONS: In this pooled analysis of 925 patients with 
      moderate to severe SLE, monthly intravenous anifrolumab 300 mg was generally well 
      tolerated over 52 weeks with an acceptable safety profile. Anifrolumab was 
      associated with an increased incidence of HZ and respiratory tract infections and 
      lower reported rate of SLE worsening as SAEs.
CI  - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Tummala, Raj
AU  - Tummala R
AD  - Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA 
      Raj.Tummala@astrazeneca.com.
FAU - Abreu, Gabriel
AU  - Abreu G
AD  - BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
FAU - Pineda, Lilia
AU  - Pineda L
AD  - Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
FAU - Michaels, M Alex
AU  - Michaels MA
AD  - Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
FAU - Kalyani, Rubana N
AU  - Kalyani RN
AD  - Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
FAU - Furie, Richard A
AU  - Furie RA
AD  - Division of Rheumatology, Zucker School of Medicine at Hofstra/Northwell, Great 
      Neck, New York, USA.
FAU - Morand, Eric F
AU  - Morand EF
AD  - Centre for Inflammatory Disease, Monash University, Melbourne, Victoria, 
      Australia.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Lupus Sci Med
JT  - Lupus science & medicine
JID - 101633705
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 38RL9AE51Q (anifrolumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Humans
MH  - *Lupus Erythematosus, Systemic/drug therapy
MH  - Respiratory Tract Infections
PMC - PMC7893670
OTO - NOTNLM
OT  - biological products
OT  - health care
OT  - interferon type I
OT  - lupus erythematosus
OT  - outcome assessment
OT  - systemic
OT  - therapeutics
COIS- Competing interests: RT, GA, LP, MAM and RNK are employees of AstraZeneca. RAF 
      has received grant/research support and consulting fees from AstraZeneca. EM has 
      received grant support from, was a consultant for and was a speaker at a speaker 
      bureau for AstraZeneca; received grant support and consulting fees from AbbVie, 
      BMS, Eli Lilly, GSK, Janssen, Merck Serono and UCB; received grant support from 
      BMS; and received consulting fees from Amgen, Biogen, CSL Inc, Neovacs and Wolf 
      Biotherapeutics.
EDAT- 2021/02/19 06:00
MHDA- 2021/09/24 06:00
PMCR- 2021/02/17
CRDT- 2021/02/18 05:54
PHST- 2020/11/25 00:00 [received]
PHST- 2021/01/11 00:00 [revised]
PHST- 2021/01/11 00:00 [accepted]
PHST- 2021/02/18 05:54 [entrez]
PHST- 2021/02/19 06:00 [pubmed]
PHST- 2021/09/24 06:00 [medline]
PHST- 2021/02/17 00:00 [pmc-release]
AID - 8/1/e000464 [pii]
AID - lupus-2020-000464 [pii]
AID - 10.1136/lupus-2020-000464 [doi]
PST - ppublish
SO  - Lupus Sci Med. 2021 Feb;8(1):e000464. doi: 10.1136/lupus-2020-000464.