THU0469 QUANTIFYING THE PLACEBO EFFECT AFTER INTRA-ARTICULAR INJECTIONS: IMPLICATIONS FOR TRIALS AND PRACTICE
Authors: S. C. Rodriguez-García, R. Castellanos-Moreira, J. Uson Jaeger, E. Naredo, L. Carmona
Journal: Annals of the Rheumatic Diseases (2020)

Background: In recent years, diverse compounds for intra-articular administration were brought into the market with a subsequent significant and heterogeneous literature production. Understanding the efficacy of intra-articular therapies (IAT) on pain implies bearing in mind the related placebo (PBO) effect. To date, most studies analyzing it were focused on the compound being administered rather than the route of administration. Objectives: We aimed at evaluating the size of the PBO effect after intra-articular injections. Methods: We conducted an overview of systematic reviews (SRs) including randomized-controlled trials (RCTs) of frequently used IAT. SRs with a saline solution PBO arm and high-confidence results according to the AMSTAR-2 tool were selected for analysis. Data on the change in pain in the PBO arms from baseline to 3-6 and 12-16 weeks after the IA procedure was extracted. The standardized mean differences (SMD) from baseline were calculated as the ratio between the size of the intervention effect in each study and the variability observed in that study. A meta-analysis was then performed using an inverse-variance random-effects model in Review Manager 5.3. The overall effect sizes obtained refer to versions of the SMD, which corresponds to the Hedges’ (adjusted) g. e.g. a “g” of 1 indicates the two groups being compared differ by 1 standard deviation and so on. Results: Two SR were included comprising 50 RCTs, 44 not meeting inclusion criteria were excluded so pain, measured by visual analogue scale (VAS) and Lequesne index, was retrieved from 6 RCT. At 3-6 weeks, an SMD [95%CI] = 0.74 [0.47-1.00] was found. One study showing too large an effect was excluded after conducting sensitivity analysis resulting in a significant reduction of heterogeneity with an SMD = 0.62 [0.45-0.79] (Fig.1). At 12-16 weeks, we found a SMD = 0.33 [0.13-0.52] (Fig.2) Figure 1. Forest plot for intra-articular PBO effect at 3-6 weeks after injection. Figure 2. Forest plot for intra-articular PBO effect at 12-16 weeks after injection. Using the interpretation suggested by Cohen 1 , our results would confirm a moderate to large effect of IA saline (PBO) at 3-6 weeks with a subsequent reduction to a small but persistent effect at 12-16 weeks. Conclusion: Our results showed a moderate to large short-term effect of intra-articular PBO that persisted on the mid-term although reduced. Based on these findings we suggest this effect should be considered when assessing the efficacy of IAT in RCTs and also in clinical practice where it could be maximized as well. References: [1]Cohen J. Statistical Power Analysis in the Behavioural Sciences (2nd edition). Hillsdale (NJ): Lawrence Erlbaum Associates, Inc., 1988. Disclosure of Interests: : Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp &amp; Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp &amp; Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)