PMID- 28689898
OWN - NLM
STAT- MEDLINE
DCOM- 20171127
LR  - 20220409
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Linking)
VI  - 124
IP  - 12
DP  - 2017 Dec
TI  - Corticosteroid-Related Adverse Events Systematically Increase with Corticosteroid 
      Dose in Noninfectious Intermediate, Posterior, or Panuveitis: Post Hoc Analyses 
      from the VISUAL-1 and VISUAL-2 Trials.
PG  - 1799-1807
LID - S0161-6420(17)30359-7 [pii]
LID - 10.1016/j.ophtha.2017.06.017 [doi]
AB  - PURPOSE: Chronic use of corticosteroids for the treatment of uveitis has been 
      linked with drug-associated toxicity and adverse events (AEs). This study 
      examines the association between corticosteroid dosage and incidence rates of 
      corticosteroid-related AEs. DESIGN: A post hoc analysis of the VISUAL-1 and 
      VISUAL-2 placebo-controlled clinical trials. PARTICIPANTS: The clinical trials 
      consisted of adults with active (VISUAL-1) and inactive (VISUAL-2) noninfectious 
      intermediate, posterior, and panuveitis. Patients were randomized to receive 
      adalimumab or placebo and underwent a protocol-defined mandatory taper to 
      discontinue their oral corticosteroids. METHODS: Adverse event data were 
      collected at each visit and included an assessment of the corticosteroid 
      relationship by the investigator. A longitudinal Poisson regression model was 
      estimated controlling for time-dependent corticosteroid dose, age, sex, prior 
      oral corticosteroid dose, prior topical corticosteroid use, and concomitant 
      immunosuppressive drug use. Only patients randomized to placebo were considered. 
      MAIN OUTCOME MEASURES: The primary outcome measure was the frequency of AEs. 
      RESULTS: The incidence rates of corticosteroid-related AEs among placebo patients 
      during the prednisone treatment period in VISUAL-1 was statistically higher than 
      after discontinuation (454.2 per 100 patient-years [PY] vs. 36.1 per 100 PY, 
      incident rate ratio = 12.6, P < 0.001). Incidence rate ratios among VISUAL-2 
      patients were similarly high (317.5 per 100 PY vs. 41.1 per 100 PY, incident rate 
      ratio = 7.7, P < 0.001). Based on the Poisson multivariate longitudinal 
      Generalized Estimating Equation (GEE) model, each 10 mg increase in prednisone 
      dose is associated with a 1.5- and 2.6-fold increase (P < 0.001 and P < 0.001) in 
      the rate of corticosteroid-related AEs in VISUAL-1 and VISUAL-2, respectively. 
      This implies in turn that a patient with active uveitis taking 60 mg/day of 
      prednisone will experience, on average, an additional 10.1 (95% confidence 
      interval (CI), 6.3-14.5; P < 0.001) corticosteroid-related AEs per year compared 
      with a patient taking 10 mg/day, whereas a patient with inactive uveitis taking 
      35 mg/day of prednisone will experience, on average, an additional 23.5 (95% CI, 
      7.6-52.7; P = 0.05) corticosteroid-related AEs per year compared with a patient 
      taking 10 mg/day. CONCLUSIONS: Evidence from VISUAL-1 and VISUAL-2 suggests that 
      the incidence rates of corticosteroid-related AEs increase systematically with 
      corticosteroid dose.
CI  - Copyright (c) 2017 American Academy of Ophthalmology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Suhler, Eric B
AU  - Suhler EB
AD  - VA Portland Health Care System, Portland, Oregon; Oregon Health and Science 
      University, Portland, Oregon.
FAU - Thorne, Jennifer E
AU  - Thorne JE
AD  - Johns Hopkins School of Medicine, Baltimore, Maryland; Johns Hopkins Bloomberg 
      School of Public Health, Baltimore, Maryland.
FAU - Mittal, Manish
AU  - Mittal M
AD  - AbbVie Inc, North Chicago, Illinois.
FAU - Betts, Keith A
AU  - Betts KA
AD  - Analysis Group, Inc, Los Angeles, California. Electronic address: 
      Keith.Betts@analysisgroup.com.
FAU - Tari, Samir
AU  - Tari S
AD  - AbbVie Inc, North Chicago, Illinois.
FAU - Camez, Anne
AU  - Camez A
AD  - AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany.
FAU - Bao, Yanjun
AU  - Bao Y
AD  - AbbVie Inc, North Chicago, Illinois.
FAU - Joshi, Avani
AU  - Joshi A
AD  - AbbVie Inc, North Chicago, Illinois.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170706
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Glucocorticoids)
RN  - FYS6T7F842 (Adalimumab)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Adalimumab/administration & dosage/adverse effects
MH  - Administration, Oral
MH  - Adult
MH  - Anti-Inflammatory Agents/administration & dosage/*adverse effects
MH  - Double-Blind Method
MH  - Drug Combinations
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/*etiology
MH  - Female
MH  - Glucocorticoids/administration & dosage/*adverse effects
MH  - Humans
MH  - Incidence
MH  - Male
MH  - Panuveitis/*drug therapy
MH  - Prednisone/administration & dosage/adverse effects
MH  - Uveitis, Intermediate/*drug therapy
MH  - Uveitis, Posterior/*drug therapy
MH  - Visual Acuity
EDAT- 2017/07/12 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/07/11 06:00
PHST- 2017/02/01 00:00 [received]
PHST- 2017/05/09 00:00 [revised]
PHST- 2017/06/13 00:00 [accepted]
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/07/11 06:00 [entrez]
AID - S0161-6420(17)30359-7 [pii]
AID - 10.1016/j.ophtha.2017.06.017 [doi]
PST - ppublish
SO  - Ophthalmology. 2017 Dec;124(12):1799-1807. doi: 10.1016/j.ophtha.2017.06.017. 
      Epub 2017 Jul 6.