AB0808 COMBINATION OF ORAL PARACETAMOL AND TOPICAL NSAIDS FOR OSTEOARTHRITIS PAIN: A SYSTEMATIC SCOPING REVIEW OF THE LITERATURE
Authors: John Bell, Vidhu Sethi, Kamran Siddiqui, Philip G. Conaghan
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Topical NSAIDs and paracetamol (APAP) are frequently used for osteoarthritis (OA) pain.<sup>1,2</sup> In real-world settings, combination treatment is common,<sup>3,4</sup> with more than one-quarter of patients using topical NSAIDs with oral non-opioid analgesics such as APAP.<sup>4</sup> <h3>Objectives</h3> We conducted a systematic scoping review to: understand current recommendations on concomitant use of topical NSAIDs and APAP for OA pain; evaluate the extent of supporting evidence for this practice; and identify literature gaps. <h3>Methods</h3> We searched PubMed and the Cochrane Library for clinical studies (database inception to January 2019) of topical NSAIDs in OA in which APAP was given concomitantly, either regularly (combination treatment) or as needed (rescue treatment). Grey literature searches were conducted to identify clinical practice guidelines for management of OA from leading organizations. <h3>Results</h3> After removing duplicates, the literature searches returned 375 articles, of which 66 were clinical studies of topical NSAIDs in OA and were reviewed further. Of these, we identified 1 randomized controlled trial (RCT) evaluating efficacy and safety of combination treatment with APAP and a topical NSAID, in which 43 patients with knee OA currently treated with APAP were randomly assigned to double-blind treatment with ketoprofen plaster or placebo for 4 weeks.<sup>5</sup> Results showed that the combination of APAP/topical ketoprofen was statistically significantly more effective in pain reduction (<i>P</i>=0.03) and physician's global assessments (<i>P</i>=0.01) compared with APAP/placebo. Of the remaining 65 topical NSAID studies, another 37 (57%) allowed rescue treatment with APAP during the treatment period (including 34 RCTs; 1 open-label extension of 2 RCTs; 1 patient preference study; and 1 single-arm open clinical trial). Because none of these studies randomly assigned patients to the combination, it was not possible to evaluate efficacy or safety of the combination based on these data. Review of OA guidelines identified 3 major organizations—EULAR, NICE, and ESCEO—that recommend or allow concomitant use of topical NSAIDs and APAP for specific joints.<sup>6-8</sup> <h3>Conclusion</h3> In clinical practice, drug combinations are frequently used to manage OA pain, and some OA treatment guidelines allow the use of topical NSAIDs concomitantly with APAP. Very limited supporting data are available, with only a single small RCT demonstrating the efficacy and safety of the combination. However, it may be inferred from the fact that more than half of the topical NSAID studies identified allowed APAP rescue therapy that this combination is generally perceived to be efficacious and well tolerated. Additional, larger RCTs are needed to confirm the benefit of this commonly used analgesic combination in managing OA pain. <h3>References</h3> [1] Conaghan PG, et al. Clin Rheumatol. 2015;34:1581-8. [2] Jackson H, et al. BMJ Open. 2017;7:e019694. [3] Gupta R, et al. Int J Res Med Sci. 2018;6:985-9. [4] Wilson N, et al. Rheumatology. 2015;54:860-7. [5] Yoo B, et al. J Korean Rheum Assoc. 1996;3:70-5. [6] Bruyere O, et al. Semin Arthritis Rheum. 2014;44:253-63. [7] Geenen R, et al. Ann Rheum Dis. 2018;77:797-807. [8] NICE. Guideline CG177. 2014. <h3>Disclosure of Interests</h3> John Bell Consultant for: John Bell has acted as consultant for Bayer, GlaxoSmithKline, Mylan, Novartis, Pfizer and Reckitt Benckiser., Speakers bureau: John Bell has received payment for speaking from GlaxoSmithKline, Pfizer and Reckitt Benckiser., Vidhu Sethi Employee of: Vidhu Sethi is an employee of GlaxoSmithKline Consumer Healthcare, Singapore., Kamran Siddiqui Employee of: Kamran Siddiqui is an employee of GlaxoSmithKline Consumer Healthcare, Singapore., Philip G Conaghan Consultant for: Flexion Therapeutics, AbbVie, Medivir, Merck Serono, Novartis, GlaxoSmithKline