PMID- 33871596
OWN - NLM
STAT- MEDLINE
DCOM- 20211230
LR  - 20211230
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
VI  - 60
IP  - 11
DP  - 2021 Nov 3
TI  - Long-term safety and efficacy of sarilumab over 5 years in patients with 
      rheumatoid arthritis refractory to TNF inhibitors.
PG  - 4991-5001
LID - 10.1093/rheumatology/keab355 [doi]
AB  - OBJECTIVE: The objective of this study was to evaluate the long-term safety and 
      efficacy of sarilumab over 5 years in patients with RA refractory to TNF 
      inhibitors (TNFis). METHODS: Patients in the 24-week randomized controlled trial 
      (RCT) TARGET (NCT01709578) who received double-blind placebo or sarilumab 150 or 
      200 mg every 2 weeks (q2w), plus conventional synthetic DMARDs (csDMARDs), were 
      eligible to receive open-label sarilumab 200 mg q2w plus csDMARDs in the 
      open-label extension (OLE), EXTEND (NCT01146652). OLE dose reduction to 150 mg 
      q2w was permitted per investigators' judgement or protocol-mandated safety 
      concerns. Safety and efficacy were assessed through treatment-emergent adverse 
      events (AEs), laboratory abnormalities and clinical DASs. All statistics are 
      descriptive. RESULTS: Of 546 patients, 454 (83%) were treated with sarilumab in 
      the OLE. The cumulative observation period was 1654.8 patient-years (PY; 
      n = 521); 268 patients (51%) had >/=4 years' exposure. Incidence rates per 100 PY 
      of AEs, and AEs leading to discontinuation, infection and serious infection were 
      160.4, 8.1, 57.8 and 3.9, respectively. Neutropenia was the most common AE (15.3 
      per 100 PY). An absolute neutrophil count of <1000 cells/mm3 (Grade 3/4 
      neutropenia) was observed in 74 patients (14.2%) and normalized on treatment in 
      48. Clinical efficacy was sustained through 5 years' follow-up. Efficacy was 
      similar for patients with 1 and >1 TNFi failure, and similar for patients who 
      either remained on 200 mg or reduced to 150 mg. CONCLUSION: In patients with RA 
      refractory to TNFi, sarilumab's long-term term safety profile was consistent with 
      previous clinical studies and post-marketing reports. Efficacy was sustained over 
      5 years. TRIAL REGISTRATION: TARGET, ClinicalTrials.gov, 
      https://clinicaltrials.gov/ct2/show/NCT01709578, NCT01709578; EXTEND, 
      ClinicalTrials.gov, https://www.clinicaltrials.gov/ct2/show/NCT01146652, 
      NCT01146652.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology. All rights reserved. For permissions, please 
      email: journals.permissions@oup.com.
FAU - Fleischmann, Roy
AU  - Fleischmann R
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center 
      and Metroplex Clinical Research Center, Dallas, TX.
FAU - Genovese, Mark C
AU  - Genovese MC
AD  - Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA.
FAU - Maslova, Karina
AU  - Maslova K
AD  - Immunology and Inflammation Clinical Development, Sanofi Genzyme, Cambridge, MA.
FAU - Leher, Henry
AU  - Leher H
AD  - Department of Translational Medicine, Regeneron Pharmaceuticals, Inc., Tarrytown, 
      NY.
FAU - Praestgaard, Amy
AU  - Praestgaard A
AD  - Biostatistics, Sanofi Genzyme, Cambridge, MA, USA.
FAU - Burmester, Gerd R
AU  - Burmester GR
AD  - Department of Rheumatology and Clinical Immunology, Charite - University Medicine 
      Berlin, Berlin, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT01709578
SI  - ClinicalTrials.gov/NCT01146652
GR  - Regeneron Pharmaceuticals, Inc./
GR  - Sanofi and Regeneron Pharmaceuticals, Inc/
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (IL6R protein, human)
RN  - 0 (Receptors, Interleukin-6)
RN  - NU90V55F8I (sarilumab)
SB  - IM
CIN - Rheumatology (Oxford). 2021 Nov 3;60(11):4953-4955. PMID: 33974043
MH  - *Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects
MH  - Antirheumatic Agents/administration & dosage/adverse effects
MH  - *Arthritis, Rheumatoid/blood/diagnosis/drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Monitoring/methods/statistics & numerical data
MH  - Drug Tapering/methods/statistics & numerical data
MH  - Drug-Related Side Effects and Adverse Reactions/diagnosis/epidemiology/etiology
MH  - Female
MH  - Humans
MH  - *Infections/diagnosis/epidemiology
MH  - *Long Term Adverse Effects/chemically induced/diagnosis/epidemiology
MH  - Male
MH  - Middle Aged
MH  - *Neutropenia/chemically induced/diagnosis/epidemiology
MH  - Product Surveillance, Postmarketing
MH  - Receptors, Interleukin-6/*antagonists & inhibitors
MH  - Treatment Outcome
OTO - NOTNLM
OT  - DMARDs
OT  - biologic therapies
OT  - clinical trials and methods
OT  - cytokines and inflammatory mediators
OT  - rheumatoid arthritis
EDAT- 2021/04/20 06:00
MHDA- 2021/12/31 06:00
CRDT- 2021/04/19 12:22
PHST- 2020/11/13 00:00 [received]
PHST- 2021/04/09 00:00 [revised]
PHST- 2021/04/20 06:00 [pubmed]
PHST- 2021/12/31 06:00 [medline]
PHST- 2021/04/19 12:22 [entrez]
AID - 6237932 [pii]
AID - 10.1093/rheumatology/keab355 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2021 Nov 3;60(11):4991-5001. doi: 
      10.1093/rheumatology/keab355.