THU0447 THE RELATIVE EFFICACY OF TOPICAL NON-STEROIDAL ANTI-INFLAMMATORY DRUGS AND CAPSAICIN IN OSTEOARTHRITIS: MOVING FROM AVERAGE TREATMENT EFFECTS TO INDIVIDUAL TREATMENT PREFERENCES
Authors: Monica Persson, Joanne Stocks, Aliya Sarmanova, Gwen Fernandes, Gyula Varadi, Mohammad Hashem Hashempur, Robbert van Haselen, David Walsh, Michael Doherty, Weiya Zhang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Pain is an important issue for people with osteoarthritis (OA). Topical non-steroidal anti-inflammatory drugs (tNSAIDs) and capsaicin are recommended treatments, but reduce OA pain by different mechanisms. <h3>Objectives:</h3> To [1] determine the relative efficacy of tNSAIDs and capsaicin in OA and [2] identify predictors of response that may allow tailoring of topical therapy to the individual. <h3>Methods:</h3> Systematic literature searches were conducted up to 16/11/2015 for randomised controlled trials (RCTs) of tNSAIDs or capsaicin in OA. Placebo-controlled RCTs were pooled in conventional meta-analyses (CMA) for specific (difference between treatment and placebo) and overall (pain reduction in treatment arm) treatment effects. Bayesian network meta-analysis (NMA) compared treatments via placebo. RCT data custodians were contacted and an individual patient data meta-analysis (IPDMA) examined for predictors of response. A pilot n-of-1 trial series (PNTS) examined treatment effects, patient preferences, and predictors of response. Participants with painful radiographic knee OA were allocated to three treatment cycles, each comprising four weeks treatment with 5% ibuprofen gel and 0.025% capsaicin cream in a random order. Effect sizes (ES) are Hedges' g and 95% confidence interval (CI) or credible interval (CrI). Predictors of response were identified in regression modelling for treatment-by-covariate interactions (specific effect) or covariate associations (overall effect). 9 and 25 predictors were examined in IPDMA and PNTS, respectively. <h3>Results:</h3> Of 63 tNSAID and 10 capsaicin RCTs identified, CMA and NMA analysed 21 tNSAID (n=6191) and five capsaicin (n=415) RCTs. The quality of evidence was moderate for tNSAIDs and very low for capsaicin. Overall treatment effects were large and likely clinically significant (tNSAIDs ES 1.23, 95%CI 1.06-1.41; capsaicin ES 1.05, 95%CI 0.52-1.57). tNSAIDs (all drugs/doses grouped) were superior to placebo (ES 0.31, 95%CI 0.20-0.41), but capsaicin was only effective at 0.025% concentration (ES 0.41, 95%CI 0.17-0.64; ES of all capsaicin RCTs 0.28, 95%CI -0.04-0.60). On average, tNSAIDs and capsaicin were equally effective (ES 0.04, 95%CrI -0.29-0.37). IPD were provided for 15 (n=3889) tNSAID RCTs, including 11 (n=3140) placebo-controlled RCTs. No IPD were obtained for capsaicin. A significant but small interaction was observed between sex and tNSAID use for pain relief, with women reporting greater effect (11 RCTs, n=2939, p=0.023). 22 participants enrolled in the PNTS and completed 104 treatment periods. Clinically important pain relief (≥1 on 0-10 numeric rating scale) was achieved in 64% of periods, with no difference in efficacy between treatments overall (p=0.271). Individual responses to treatment varied, with c.60% of people preferring one treatment over the other, but without clear predictors for the preference. Conclusion: tNSAIDs and capsaicin may relieve OA pain, but treatment effects from group comparisons do not directly translate to treatment outcomes at an individual level. No baseline characteristics robustly determine which treatment is more likely to benefit an individual. Patients may benefit from trying both treatments to determine which is better for them. <h3>Acknowledgement:</h3> M Underwood (Warwick University), A Suter (Bioforce AG/A.Vogel Produkte), GR Mautone (IBSA Institut Biochimique SA), and GSK for sharing IPD; D Burke for statistical advice; and D McWilliams for trial randomisation <h3>Disclosure of Interests:</h3> Monica Persson: None declared, Joanne Stocks Grant/research support from: Co-I on research grant from Pfizer/Eli Lilly, Aliya Sarmanova: None declared, Gwen Fernandes: None declared, Gyula Varadi Employee of: Inpellis, Inc. (previous); BioPhysics Pharma, Inc (current), Mohammad Hashem Hashempur: None declared, Robbert van Haselen Consultant for: Consultancy services for homeopathic pharmaceutical companies, David Walsh Consultant for: Pfizer, GlaxoSmithKline. Consultancies on arthritis pain, Speakers bureau: Pfizer Ltd for a talk at OARSI 2018, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant for: Advisory Boards on Grunenthal and Mallinckrodt, Weiya Zhang Consultant for: Grunenthal for advice on gout management, Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium