PMID- 37852417
OWN - NLM
STAT- MEDLINE
DCOM- 20240325
LR  - 20240325
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Print)
IS  - 0161-6420 (Linking)
VI  - 131
IP  - 4
DP  - 2024 Apr
TI  - Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multicenter Study.
PG  - 458-467
LID - S0161-6420(23)00760-1 [pii]
LID - 10.1016/j.ophtha.2023.10.018 [doi]
AB  - PURPOSE: To assess the duration, incidence, reversibility, and severity of 
      adverse events (AEs) in patients with thyroid eye disease (TED) treated with 
      teprotumumab. DESIGN: Multicenter, retrospective, observational cohort study. 
      PARTICIPANTS: Patients with TED of all stages and activity levels treated with at 
      least 4 infusions of teprotumumab. METHODS: Patients were treated with 
      teprotumumab between February 2020 and October 2022 at 6 tertiary centers. 
      Adverse event metrics were recorded at each visit. MAIN OUTCOME MEASURES: The 
      primary outcomes measure was AE incidence and onset. Secondary outcome measures 
      included AE severity, AE reversibility, AE duration, proptosis response, clinical 
      activity score (CAS) reduction, and Gorman diplopia score improvement. RESULTS: 
      The study evaluated 131 patients. Proptosis improved by 2 mm or more in 77% of 
      patients (101/131), with average proptosis improvement of 3.0 +/- 2.1 mm and 
      average CAS reduction of 3.2 points. Gorman diplopia score improved by at least 1 
      point for 50% of patients (36/72) with baseline diplopia. Adverse events occurred 
      in 81.7% of patients (107/131). Patients experienced a median of 4 AEs. Most AEs 
      were mild (74.0% [97/131]), 28.2% (37/131) were moderate, and 8.4% (11/131) were 
      severe. Mean interval AE onset was 7.9 weeks after the first infusion. Mean 
      resolved AE duration was 17.6 weeks. Forty-six percent of patients (60/131) 
      demonstrated at least 1 persistent AE at last follow-up. Mean follow-up was 70.2 
      +/- 38.5 weeks after the first infusion. The most common type of AEs was 
      musculoskeletal (58.0% [76/131]), followed by gastrointestinal (38.2% [50/131]), 
      skin (38.2% [50/131]), ear and labyrinth (30.5% [40/131]), nervous system (20.6% 
      [27/131]), metabolic (15.3% [20/131]), and reproductive system (12.2% [16/131]). 
      Sixteen patients (12.2%) discontinued therapy because of AEs, including hearing 
      loss (n = 4), inflammatory bowel disease flare (n = 2), hyperglycemia (n = 1), 
      muscle spasms (n = 1), and multiple AEs (n = 8). CONCLUSIONS: Adverse events are 
      commonly reported while receiving teprotumumab treatment. Most are mild and 
      reversible; however, serious AEs can occur and may warrant treatment cessation. 
      Treating physicians should inform patients about AE risk, properly screen 
      patients before treatment, monitor patients closely throughout therapy, and 
      understand how to manage AEs should they develop. FINANCIAL DISCLOSURE(S): 
      Proprietary or commercial disclosure may be found in the Footnotes and 
      Disclosures at the end of this article.
CI  - Copyright (c) 2023 American Academy of Ophthalmology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Shah, Shreya A
AU  - Shah SA
AD  - Department of Ophthalmology, Byers Eye Institute, Stanford University School of 
      Medicine, Palo Alto, California.
FAU - Amarikwa, Linus
AU  - Amarikwa L
AD  - Department of Ophthalmology, Byers Eye Institute, Stanford University School of 
      Medicine, Palo Alto, California.
FAU - Sears, Connie M
AU  - Sears CM
AD  - Department of Ophthalmology, Byers Eye Institute, Stanford University School of 
      Medicine, Palo Alto, California.
FAU - Clauss, Kevin D
AU  - Clauss KD
AD  - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami 
      Miller School of Medicine, Miami, Florida.
FAU - Rajjoub, Raneem D
AU  - Rajjoub RD
AD  - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 
      Minneapolis, Minnesota.
FAU - Kang, Julia Y
AU  - Kang JY
AD  - Clayton Eye Center, Morrow, Georgia.
FAU - Tamhankar, Madhura A
AU  - Tamhankar MA
AD  - Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, Pennsylvania.
FAU - Briceno, Cesar A
AU  - Briceno CA
AD  - Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, Pennsylvania.
FAU - Harrison, Andrew R
AU  - Harrison AR
AD  - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 
      Minneapolis, Minnesota.
FAU - Dosiou, Chrysoula
AU  - Dosiou C
AD  - Department of Medicine, Stanford University School of Medicine, Palo Alto, 
      California.
FAU - Cockerham, Kimberly P
AU  - Cockerham KP
AD  - Senta Clinic, San Diego, California.
FAU - Wester, Sara T
AU  - Wester ST
AD  - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami 
      Miller School of Medicine, Miami, Florida.
FAU - Douglas, Raymond S
AU  - Douglas RS
AD  - Division of Ophthalmology, Cedars-Sinai Medical Center, Los Angeles, California.
FAU - Kossler, Andrea L
AU  - Kossler AL
AD  - Department of Ophthalmology, Byers Eye Institute, Stanford University School of 
      Medicine, Palo Alto, California. Electronic address: akossler@stanford.edu.
LA  - eng
GR  - P30 EY026877/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
DEP - 20231016
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
RN  - Y64GQ0KC0A (teprotumumab)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Humans
MH  - *Graves Ophthalmopathy/drug therapy
MH  - Retrospective Studies
MH  - Diplopia/chemically induced
MH  - *Exophthalmos
MH  - *Antibodies, Monoclonal, Humanized
PMC - PMC10960718
MID - NIHMS1940022
OTO - NOTNLM
OT  - Adverse events
OT  - Insulin-like growth factor 1 receptor (IGF-1R)
OT  - Tepezza
OT  - Teprotumumab
OT  - Thyroid eye disease
COIS- Declaration of interests Dr. Andrea Kossler is a Consultant/Advisor for Horizon 
      Therapeutics, Immunovant Inc, Aceylrin, Kriya Therapeutics, Genentech, and Argenx 
      and performs research with Sling Therapeutics, Horizon Therapeutics, Lassen 
      Therapeutics, and Viridian. Dr. Raymond Douglas is the Chief Scientific Officer 
      at Sling and is a Consultant/Advisor for Horizon Therapeutics, Immunovant 
      Corporation, and Viridian Corporation. Dr. Sara Wester is a Consultant/Advisor 
      for Horizon Therapeutics, Immunovant, and Sling. Dr. Cesar Briceno is a 
      Consultant/Advisor for Horizon Therapeutics. Dr. Madhura Tamhankar is a 
      Consultant/Advisor for Horizon Therapeutics. Dr. Chrysoula Dosiou is a member of 
      Sling Therapeutics Scientific Advisory Board and has served as Consultant for 
      Third Rock Ventures and The Column Group. Dr. Kimberly Cockerham is a 
      Consultant/Advisor for Horizon Therapeutics and Viridian Pharmaceuticals. Dr. 
      Andrew Harrison is a Consultant/Speaker for Horizon therapeutics and RVL 
      pharmaceuticals. Dr. Julia Kang is a speaker for Horizon Therapeutics. Shreya 
      Shah, Dr. Linus Amarikwa, Dr. Connie Sears, Dr. Kevin Clauss, and Dr. Raneem 
      Rajjoub have no disclosures. Conflict of Interest: All authors have completed and 
      submitted the ICMJE disclosures form. Authors with financial interests or 
      relationships to disclose are listed prior to the references.
EDAT- 2023/10/19 00:46
MHDA- 2024/03/25 06:42
PMCR- 2025/04/01
CRDT- 2023/10/18 19:26
PHST- 2023/07/13 00:00 [received]
PHST- 2023/09/26 00:00 [revised]
PHST- 2023/10/11 00:00 [accepted]
PHST- 2025/04/01 00:00 [pmc-release]
PHST- 2024/03/25 06:42 [medline]
PHST- 2023/10/19 00:46 [pubmed]
PHST- 2023/10/18 19:26 [entrez]
AID - S0161-6420(23)00760-1 [pii]
AID - 10.1016/j.ophtha.2023.10.018 [doi]
PST - ppublish
SO  - Ophthalmology. 2024 Apr;131(4):458-467. doi: 10.1016/j.ophtha.2023.10.018. Epub 
      2023 Oct 16.