PMID- 29361199
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20191210
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 70
IP  - 5
DP  - 2018 May
TI  - Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor 
      Receptor alpha Monoclonal Antibody: Long-Term Safety and Efficacy in Patients With 
      Rheumatoid Arthritis.
PG  - 679-689
LID - 10.1002/art.40420 [doi]
AB  - OBJECTIVE: Mavrilimumab, a human monoclonal antibody, targets 
      granulocyte-macrophage colony-stimulating factor receptor alpha. We undertook to 
      determine the long-term safety and efficacy of mavrilimumab in rheumatoid 
      arthritis patients in 2 phase IIb studies (1071 and 1107) and in 1 open-label 
      extension study (ClinicalTrials.gov identifier: NCT01712399). METHODS: In study 
      1071, patients with an inadequate response to disease-modifying antirheumatic 
      drugs (DMARDs) received mavrilimumab (30, 100, or 150 mg) or placebo every other 
      week plus methotrexate. In study 1107, patients with an inadequate response to 
      anti-tumor necrosis factor agents and/or DMARDs received 100 mg mavrilimumab 
      every other week or 50 mg golimumab every 4 weeks plus methotrexate. Patients 
      entering the open-label extension study received 100 mg mavrilimumab every other 
      week plus methotrexate. Long-term safety and efficacy of mavrilimumab were 
      assessed. RESULTS: A total of 442 patients received mavrilimumab (14 of 245 
      patients from study 1071, 9 of 70 patients from study 1107, and 52 of 397 
      patients from the open-label extension study discontinued mavrilimumab treatment 
      throughout the studies). The cumulative safety exposure was 899 patient-years; 
      the median duration of mavrilimumab treatment was 2.5 years (range 0.1-3.3 
      years). The most common treatment-emergent adverse events (AEs) were 
      nasopharyngitis (n = 69; 7.68 per 100 patient-years) and bronchitis (n = 51; 5.68 
      per 100 patient-years). At weeks 74 and 104, 3.5% and 6.2% of patients, 
      respectively, demonstrated reduction in forced expiratory volume in 1 second, 
      while 2.9% and 3.4% of patients, respectively, demonstrated reduction in forced 
      vital capacity (>20% reduction from baseline to <80% predicted). Most pulmonary 
      changes were transient and only infrequently associated with AEs. Mavrilimumab at 
      100 mg every other week demonstrated sustained efficacy; at week 122, 65.0% of 
      patients achieved a Disease Activity Score in 28 joints using the C-reactive 
      protein level (DAS28-CRP) of <3.2, and 40.6% of patients achieved a DAS28-CRP of 
      <2.6. CONCLUSION: Long-term treatment with mavrilimumab maintained response and 
      was well-tolerated with no increased incidence of treatment-emergent AEs. Safety 
      data were comparable with those from both phase IIb qualifying studies.
CI  - (c) 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. 
      on behalf of American College of Rheumatology.
FAU - Burmester, Gerd R
AU  - Burmester GR
AD  - Charite - University Medicine Berlin, Berlin, Germany.
FAU - McInnes, Iain B
AU  - McInnes IB
AD  - University of Glasgow, Glasgow, UK.
FAU - Kremer, Joel M
AU  - Kremer JM
AD  - The Albany Medical College, Albany, New York.
FAU - Miranda, Pedro
AU  - Miranda P
AD  - Centro de Estudios Reumatologicos, Santiago, Chile.
FAU - Vencovsky, Jiri
AU  - Vencovsky J
AD  - Institute of Rheumatology, Prague, Czech Republic.
FAU - Godwood, Alex
AU  - Godwood A
AD  - MedImmune, Cambridge, UK.
FAU - Albulescu, Marius
AU  - Albulescu M
AD  - MedImmune, Cambridge, UK.
FAU - Michaels, M Alex
AU  - Michaels MA
AD  - MedImmune, Gaithersburg, Maryland.
FAU - Guo, Xiang
AU  - Guo X
AD  - MedImmune, Gaithersburg, Maryland.
FAU - Close, David
AU  - Close D
AD  - MedImmune, Cambridge, UK.
FAU - Weinblatt, Michael
AU  - Weinblatt M
AD  - Brigham and Women's Hospital, Boston, Massachusetts.
LA  - eng
SI  - ClinicalTrials.gov/NCT01712399
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180331
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 1158JD1P9A (mavrilimumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/*therapeutic use
MH  - Treatment Outcome
PMC - PMC5947536
EDAT- 2018/01/24 06:00
MHDA- 2019/06/25 06:00
PMCR- 2018/05/11
CRDT- 2018/01/24 06:00
PHST- 2017/10/03 00:00 [received]
PHST- 2018/01/11 00:00 [accepted]
PHST- 2018/01/24 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2018/01/24 06:00 [entrez]
PHST- 2018/05/11 00:00 [pmc-release]
AID - ART40420 [pii]
AID - 10.1002/art.40420 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2018 May;70(5):679-689. doi: 10.1002/art.40420. Epub 2018 
      Mar 31.