PMID- 31312844
OWN - NLM
STAT- MEDLINE
DCOM- 20200622
LR  - 20201029
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 59
IP  - 2
DP  - 2020 Feb 1
TI  - Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis 
      with up to 7 years' follow-up.
PG  - 292-302
LID - 10.1093/rheumatology/kez265 [doi]
AB  - OBJECTIVE: Sarilumab is a human monoclonal antibody that blocks IL-6 from binding 
      to membrane-bound and soluble IL-6 receptor-alpha. We assessed the long-term safety 
      of sarilumab in patients from eight clinical trials and their open-label 
      extensions. METHODS: Data were pooled from patients with rheumatoid arthritis who 
      received at least one dose of sarilumab in combination with conventional 
      synthetic disease-modifying antirheumatic drugs (csDMARDs; combination group) or 
      as monotherapy (monotherapy group). Treatment-emergent adverse events (AEs) and 
      AEs and laboratory values of special interest were assessed. RESULTS: 2887 
      patients received sarilumab in combination with csDMARDs and 471 patients 
      received sarilumab monotherapy, with mean exposure of 2.8 years and 1.7 years, 
      maximum exposure 7.3 and 3.5 years, and cumulative AE observation period of 8188 
      and 812 patient-years, respectively. Incidence rates per 100 patient-years in the 
      combination and monotherapy groups, respectively, were 9.4 and 6.7 for serious 
      AEs, 3.7 and 1.0 for serious infections, 0.6 and 0.5 for herpes zoster (no cases 
      were disseminated), 0.1 and 0 for gastrointestinal perforations, 0.5 and 0.2 for 
      major adverse cardiovascular events, and 0.7 and 0.6 for malignancy. Absolute 
      neutrophil counts <1000 cells/mm3 were recorded in 13% and 15% of patients, 
      respectively. Neutropenia was not associated with increased risk of infection or 
      serious infection. Analysis by 6-month interval showed no signal for increased 
      rate of any AE over time. CONCLUSION: The long-term safety profile of sarilumab, 
      either in combination with csDMARDs or as monotherapy, remained stable and 
      consistent with the anticipated profile of a molecule that inhibits IL6 
      signalling.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology.
FAU - Fleischmann, Roy
AU  - Fleischmann R
AD  - Metroplex Clinical Research Center and University of Texas Southwestern Medical 
      Center, Dallas, TX.
FAU - Genovese, Mark C
AU  - Genovese MC
AD  - Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA.
FAU - Lin, Yong
AU  - Lin Y
AD  - Sanofi Genzyme, Bridgewater, NJ.
FAU - St John, Gregory
AU  - St John G
AD  - Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
FAU - van der Heijde, Desiree
AU  - van der Heijde D
AD  - Department of Rheumatology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Wang, Sheldon
AU  - Wang S
AD  - Sanofi Genzyme, Bridgewater, NJ.
FAU - Gomez-Reino, Juan Jose
AU  - Gomez-Reino JJ
AD  - IDIS, Complejo Hospitalario Universitario de Santiago, Santiago, Spain.
FAU - Maldonado-Cocco, Jose Antonio
AU  - Maldonado-Cocco JA
AD  - School of Medicine, Buenos Aires University, Buenos Aires, Argentina.
FAU - Stanislav, Marina
AU  - Stanislav M
AD  - Research Rheumatology Institute n. a. V.A. Nassonova, Moscow, Russia.
FAU - Kivitz, Alan J
AU  - Kivitz AJ
AD  - Altoona Center for Clinical Research, Duncansville, PA, USA.
FAU - Burmester, Gerd R
AU  - Burmester GR
AD  - Charite - University Medicine Berlin, Berlin, Germany.
LA  - eng
PT  - Journal Article
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  - NU90V55F8I (sarilumab)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Antirheumatic Agents/adverse effects/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Drug Therapy, Combination
MH  - Erythema/chemically induced/epidemiology
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Incidence
MH  - Male
MH  - Methotrexate/adverse effects/therapeutic use
MH  - Middle Aged
MH  - Neutropenia/chemically induced/epidemiology
MH  - Respiratory Tract Infections/chemically induced/epidemiology
MH  - Treatment Outcome
PMC - PMC7571482
OTO - NOTNLM
OT  - IL-6 inhibition
OT  - biologic DMARD
OT  - integrated safety analysis
OT  - long-term safety
OT  - sarilumab
EDAT- 2019/07/18 06:00
MHDA- 2020/06/23 06:00
PMCR- 2019/07/15
CRDT- 2019/07/18 06:00
PHST- 2019/03/11 00:00 [received]
PHST- 2019/05/26 00:00 [accepted]
PHST- 2019/07/18 06:00 [pubmed]
PHST- 2020/06/23 06:00 [medline]
PHST- 2019/07/18 06:00 [entrez]
PHST- 2019/07/15 00:00 [pmc-release]
AID - 5532503 [pii]
AID - kez265 [pii]
AID - 10.1093/rheumatology/kez265 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2020 Feb 1;59(2):292-302. doi: 
      10.1093/rheumatology/kez265.