PMID- 26554876
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20220408
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 68
IP  - 2
DP  - 2016 Feb
TI  - When Is Osteonecrosis Not Osteonecrosis?: Adjudication of Reported Serious 
      Adverse Joint Events in the Tanezumab Clinical Development Program.
PG  - 382-91
LID - 10.1002/art.39492 [doi]
AB  - OBJECTIVE: Tanezumab, a monoclonal antibody against nerve growth factor, has 
      demonstrated efficacy in clinical trials of chronic pain in osteoarthritis (OA) 
      and chronic low back pain. Unexpected adverse events (AEs) described as 
      osteonecrosis (ON) occurred during tanezumab development, leading the US Food and 
      Drug Administration to impose a partial clinical hold for all indications except 
      cancer pain. A blinded Adjudication Committee (AC) including orthopedic surgeons, 
      rheumatologists, and an orthopedic pathologist reviewed and adjudicated 
      joint-related AEs in the tanezumab clinical program. METHODS: The AC adjudicated 
      all reported cases of ON as well as cases of total joint replacements (TJRs) not 
      reported as ON for which radiographs obtained within 9 months of the surgery were 
      available. The AC prespecified categories for joint safety events including 
      primary ON, worsening OA (rapid progression of OA [RPOA], normal progression of 
      OA, insufficient information to distinguish between rapid and normal progression 
      of OA), other, or insufficient information to distinguish between primary ON and 
      worsening OA or another diagnosis. RESULTS: The AC reviewed events in 249 of 386 
      patients with an investigator-reported AE of ON and/or a TJR. Two events were 
      adjudicated as primary ON, 200 events were adjudicated as worsening OA (68 of 
      which were classified as RPOA), 29 events had another diagnosis, 11 had 
      insufficient information to distinguish primary ON from worsening OA, and 7 did 
      not have committee member consensus. CONCLUSION: Despite initial reports, 
      tanezumab treatment was not associated with an increase in ON but was associated 
      with an increase in RPOA. Higher doses of tanezumab, tanezumab administered with 
      nonsteroidal antiinflammatory drugs, and preexisting subchondral insufficiency 
      fractures were risk factors for RPOA in this cohort.
CI  - (c) 2016, American College of Rheumatology.
FAU - Hochberg, Marc C
AU  - Hochberg MC
AD  - University of Maryland School of Medicine, Baltimore.
FAU - Tive, Leslie A
AU  - Tive LA
AD  - Pfizer Inc., New York, New York.
FAU - Abramson, Steven B
AU  - Abramson SB
AD  - New York University Medical Center, New York, New York.
FAU - Vignon, Eric
AU  - Vignon E
AD  - Universite Claude Bernard Lyon 1, Lyon, France.
FAU - Verburg, Kenneth M
AU  - Verburg KM
AD  - Pfizer Inc., Groton, Connecticut.
FAU - West, Christine R
AU  - West CR
AD  - Pfizer Inc., Groton, Connecticut.
FAU - Smith, Michael D
AU  - Smith MD
AD  - Pfizer Inc., Groton, Connecticut.
FAU - Hungerford, David S
AU  - Hungerford DS
AD  - Johns Hopkins University School of Medicine, Johns Hopkins Hospital, and Good 
      Samaritan Hospital, Baltimore, Maryland.
LA  - eng
SI  - ClinicalTrials.gov/NCT00733902
SI  - ClinicalTrials.gov/NCT00744471
SI  - ClinicalTrials.gov/NCT00809354
SI  - ClinicalTrials.gov/NCT00809783
SI  - ClinicalTrials.gov/NCT00864097
SI  - ClinicalTrials.gov/NCT00876187
SI  - ClinicalTrials.gov/NCT00924664
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - EQL0E9GCX1 (tanezumab)
SB  - IM
CIN - Arthritis Rheumatol. 2016 Feb;68(2):270-3. PMID: 26555026
MH  - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Arthroplasty, Replacement/statistics & numerical data
MH  - Chronic Pain/*drug therapy
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Disease Progression
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Low Back Pain/*drug therapy
MH  - Osteoarthritis/*drug therapy
MH  - Osteonecrosis/*chemically induced/surgery
MH  - Proportional Hazards Models
MH  - Randomized Controlled Trials as Topic
EDAT- 2015/11/12 06:00
MHDA- 2016/06/15 06:00
CRDT- 2015/11/12 06:00
PHST- 2014/06/20 00:00 [received]
PHST- 2015/10/20 00:00 [accepted]
PHST- 2015/11/12 06:00 [entrez]
PHST- 2015/11/12 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
AID - 10.1002/art.39492 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2016 Feb;68(2):382-91. doi: 10.1002/art.39492.