Model-based Meta-analysis to Compare Primary Efficacy-endpoint, Efficacy-time Course, Safety, and Tolerability of Opioids Used in the Management of Osteoarthritic Pain in Humans.
Opioids
efficacy-time course
model-based meta-analysis
osteoarthritis
safety
tolerability
Journal
Current drug metabolism
ISSN: 1875-5453
Titre abrégé: Curr Drug Metab
Pays: Netherlands
ID NLM: 100960533
Informations de publication
Date de publication:
2020
2020
Historique:
received:
05
12
2019
revised:
19
02
2020
accepted:
26
03
2020
pubmed:
15
5
2020
medline:
2
6
2021
entrez:
15
5
2020
Statut:
ppublish
Résumé
Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need for a study to integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA). To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using a nonlinear mixed-effects modeling approach. The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate doses. This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone, oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.
Sections du résumé
BACKGROUND
BACKGROUND
Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need for a study to integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA).
METHODS
METHODS
To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using a nonlinear mixed-effects modeling approach.
RESULTS
RESULTS
The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate doses.
CONCLUSION
CONCLUSIONS
This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone, oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.
Identifiants
pubmed: 32407270
pii: CDM-EPUB-106629
doi: 10.2174/1389200221666200514130441
pmc: PMC9670863
mid: NIHMS1846846
doi:
Substances chimiques
Analgesics, Opioid
0
Tramadol
39J1LGJ30J
Oxymorphone
9VXA968E0C
Oxycodone
CD35PMG570
Types de publication
Journal Article
Meta-Analysis
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
390-399Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES005605
Pays : United States
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Références
Osteoarthritis Cartilage. 2008 Feb;16(2):137-62
pubmed: 18279766
Clin J Pain. 2005 Nov-Dec;21(6):524-35
pubmed: 16215338
J Pain Symptom Manage. 2004 Jul;28(1):59-71
pubmed: 15223085
Pain Physician. 2012 Jul;15(3 Suppl):ES9-38
pubmed: 22786464
J Pain Symptom Manage. 2007 Sep;34(3):328-38
pubmed: 17583466
Sci Rep. 2016 Sep 12;6:32790
pubmed: 27616273
Pain Res Manag. 2008 Mar-Apr;13(2):93-102
pubmed: 18443671
Am J Ther. 2011 May;18(3):216-26
pubmed: 20215961
BMJ. 2004 Jul 3;329(7456):15-9
pubmed: 15231615
MMWR Recomm Rep. 2016 Mar 18;65(1):1-49
pubmed: 26987082
Pain Med. 2005 Sep-Oct;6(5):357-66
pubmed: 16266356
Clin Ther. 2006 Mar;28(3):352-64
pubmed: 16750450
Am Fam Physician. 2012 Jan 1;85(1):49-56
pubmed: 22230308
Arch Phys Med Rehabil. 2014 May;95(5):986-995.e1
pubmed: 24462839
Clin Pharmacol Ther. 2012 Sep;92(3):283-6
pubmed: 22910485
Pain Ther. 2014 Jun;3(1):31-44
pubmed: 25135386
Arch Gerontol Geriatr. 2009 Nov-Dec;49(3):378-82
pubmed: 19150139
Curr Med Res Opin. 2006 Jul;22(7):1391-401
pubmed: 16834838
Osteoarthritis Cartilage. 2013 Sep;21(9):1145-53
pubmed: 23973124
Arch Intern Med. 2000 Mar 27;160(6):853-60
pubmed: 10737286
Pain. 2013 Sep;154(9):1603-1612
pubmed: 23707270
J Pain. 2005 Jun;6(6):392-9
pubmed: 15943961
Clin Drug Investig. 2010;30(8):489-505
pubmed: 20586515
Clin Ther. 2007 Jul;29(7):1381-9
pubmed: 17825689
Am J Ther. 2005 Mar-Apr;12(2):106-12
pubmed: 15767827
Clin Ther. 2009 Feb;31(2):260-71
pubmed: 19302899
Hippokratia. 2010 Dec;14(Suppl 1):29-37
pubmed: 21487488
J Arthroplasty. 1996 Oct;11(7):841-4
pubmed: 8934324
J Rheumatol. 2004 Jan;31(1):150-6
pubmed: 14705234
Pain Res Manag. 2008 Mar-Apr;13(2):103-10
pubmed: 18443672
Clin Ther. 2002 Feb;24(2):282-97
pubmed: 11911558
Clin Transl Sci. 2018 Mar;11(2):218-225
pubmed: 29168990
Clin J Pain. 2005 Nov-Dec;21(6):471-7
pubmed: 16215331
J Opioid Manag. 2007 Sep-Oct;3(5):273-80
pubmed: 18181382
Clin Ther. 2004 Nov;26(11):1774-82
pubmed: 15639689
J Rheumatol. 1999 Apr;26(4):862-9
pubmed: 10229408
Clin Ther. 2007 May;29(5):874-888
pubmed: 17697906
Pain Med. 2009 Jan;10(1):35-42
pubmed: 18721170
Curr Med Res Opin. 2009 May;25(5):1095-104
pubmed: 19301989