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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

4 Issues per year


CiteScore 2017: 0.84

SCImago Journal Rank (SJR) 2017: 0.401
Source Normalized Impact per Paper (SNIP) 2017: 0.452

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1877-8879
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Volume 16, Issue 1

Efficacy and safety of diclofenac in osteoarthritis: Results of a network meta-analysis of unpublished legacy studies

Patricia Guyot / Shaloo Pandhi / Richard M. Nixon / Asif Iqbal / Ricardo L. Chaves / R. Andrew Moore
  • Corresponding author
  • Department of Pain Research, Nuffield Division of Anaesthetics, University of Oxford, The Churchill, Oxford, United Kingdom
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Published Online: 2017-07-01 | DOI: https://doi.org/10.1016/j.sjpain.2017.03.006

Abstract

Background and aim

Diclofenac is widely prescribed for the treatment of pain. Several network meta-analyses (NMA), largely of published trials have evaluated the efficacy, tolerability, and safety of nonsteroidal anti-inflammatory drugs (NSAIDs). The present NMA extends these analyses to unpublished older (legacy) diclofenac trials.

Methods

We identified randomised controlled trials (RCTs) of diclofenac with planned study duration of at least 4 weeks for the treatment of osteoarthritis (OA) from ‘legacy’ studies conducted by Novartis but not published in a peer reviewed journal or included in any previous pooled analyses. All studies reporting efficacy and/or safety of treatment with diclofenac or other active therapies or placebo were included. We used a Bayesian NMA model, and estimated relative treatment effects between pairwise treatments. Main outcomes included pain relief measured using visual analogue scale at 2, 4 and 12 weeks and patient global assessment (PGA) at 4 and 12 weeks for efficacy, all-cause withdrawals, and adverse events.

Results

A total of 19 RCTs (5030 patients) were included; 18 of which were double-blind and one singleblind. All studies were conducted before cyclooxygenase 2 inhibitors (COXIBs) became commercially available. Data permitted robust efficacy comparison between diclofenac and ibuprofen, but the amount of data for other comparators was limited. Diclofenac 150 mg/day was more efficacious than ibuprofen 1200 mg/day and had likely favourable outcomes for pain relief compared to ibuprofen 2400 mg/day. Diclofenac 100 mg/day had likely favourable outcomes compared to ibuprofen 1200 mg/day in alleviating pain. Based on PGA, diclofenac 150 mg/day was more efficacious and likely to be favourable than ibuprofen 1200 mg/day and 2400 mg/day, respectively. Risk of withdrawal due to all causes with diclofenac and ibuprofen were comparable. Diclofenac 150 mg/day was likely to have favourable efficacy and comparable tolerability with diclofenac 100 mg/day. Results comparing diclofenac and ibuprofen were similar to those from NMAs of published trials.

Conclusions

Results from these unpublished ‘legacy’ studies were similar to those from NMAs of published trials. The favourable efficacy results of diclofenac compared to ibuprofen expand the amount of available evidence comparing these two NSAIDs. The overall benefit-risk profile of diclofenac was comparable to that of ibuprofen in OA.

Implications

The present NMA results reassures that the older unpublished blinded trials have similar results compared to more recently published trials and also contributes to increase the transparency of clinical trials performed with diclofenac further back in the past.

This article offers supplementary material which is provided at the end of the article.

Keywords: Bayesian network meta-analysis; Diclofenac; Ibuprofen; Osteoarthritis; Patient global assessment; Randomised controlled trials; Visual analogue scale

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About the article

Department of Pain Research, Nuffield Division of Anaesthetics, University of Oxford, The Churchill, Oxford OX3 7LE, United Kingdom.


Received: 2017-02-14

Accepted: 2017-03-28

Published Online: 2017-07-01

Published in Print: 2017-07-01


Authors’ contributions: RMN conceptualised and designed the study.The study was conducted and the data were analysed by RMN and PG.PG was involved in data collection.Interpretation of data was done by RMN, PG, RAM, SP and RLC. All the authors drafted the manuscript and revised the contents. They also approved the final version and were responsible for the integrity of data analysis.

Conflict of interest: This study was conducted by Mapi on behalf of Novartis Pharma AG (Basel, Switzerland) who funded the study. PG is an employee of Mapi and served as paid consultant to Novartis during the conduct of this study and the preparation of this manuscript. SP, RN, AI, and RLC are employees of Novartis and are thus eligible for Novartis stock and stock options. RAM has no competing interests to declare in this work.

Funding: The study was funded by Novartis Pharma AG.


Citation Information: Scandinavian Journal of Pain, Volume 16, Issue 1, Pages 74–88, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1016/j.sjpain.2017.03.006.

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