Sethi, Vidhu;
Qin, Li;
Cox, Eugene;
Troconiz, Inaki F;
Della Pasqua, Oscar;
(2024)
Model-Based Meta-Analysis Supporting the Combination of Acetaminophen and Topical Diclofenac in Acute Pain: A Therapy for Mild-to-Moderate Osteoarthritis Pain?
Pain and Therapy
, 13
(1)
pp. 145-159.
10.1007/s40122-023-00569-z.
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Abstract
Introduction: Acetaminophen and topical diclofenac (AtopD) have complementary mechanisms of action and are therefore candidates for combination use in osteoarthritis (OA) pain. However, an evidence gap exists on their combination use in OA pain. This study aimed to assess the effects of this combination and compare its performance relative to monotherapies on pain score reduction and opioid-sparing effect by leveraging evidence from acute pain setting using a model-based meta-analysis (MBMA). Methods: A literature search was conducted using the MEDLINE database to identify randomized controlled trials (RCTs) studying the combination for acute pain. Subsequently, an MBMA of RCTs was implemented in conjunction with extrapolation principles to infer efficacy in the population of interest. Pain score reduction and opioid-sparing effect (OSE) were selected as the measures of efficacy. Results: A total of 11 RCTs encompassing 1396 patients were included. Exploratory evaluation revealed AtopD combination to show greater pain score reduction versus acetaminophen monotherapy. However, pain score reduction was more susceptible to confounding by opioid patient-controlled analgesia (PCA) than OSE. Therefore, a parsimonious MBMA evaluating OSE was developed from 5 of the 11 RCTs (n = 353 patients). The analysis revealed a statistically significant interaction coefficient, suggesting a reduction of 32% in opioid use with the combination versus acetaminophen monotherapy. Differences in the effect size of the combination were less conclusive versus diclofenac monotherapy. Conclusion: Our results indicate greater pain reduction and opioid-sparing efficacy for the AtopD combination versus acetaminophen monotherapy. Given the similar pain pathways and mechanisms of action of the two drugs in acute and mild-to-moderate OA pain, comparable beneficial effects from the combination therapy may be anticipated following extrapolation to chronic OA pain. Prospective RCTs and real-world studies in OA pain are needed to confirm the differences in the efficacy of the combination treatment observed in our study.
| Type: | Article |
|---|---|
| Title: | Model-Based Meta-Analysis Supporting the Combination of Acetaminophen and Topical Diclofenac in Acute Pain: A Therapy for Mild-to-Moderate Osteoarthritis Pain? |
| Location: | New Zealand |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s40122-023-00569-z |
| Publisher version: | http://dx.doi.org/10.1007/s40122-023-00569-z |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, Acetaminophen, Diclofenac, Combination therapy, Model-based meta-analysis, Osteoarthritis, Acute pain, NONSTEROIDAL ANTIINFLAMMATORY DRUGS, RANDOMIZED CONTROLLED-TRIAL, POSTOPERATIVE PAIN, ANALGESIC EFFICACY, PARACETAMOL ACETAMINOPHEN, MANAGEMENT, SAFETY, NSAIDS, RELIEF, PROPACETAMOL |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10187864 |
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