Dataset Information

Predictors of placebo response to local (intra-articular) therapy in osteoarthritis: an individual patient data meta-analysis protocol.

ABSTRACT:

Introduction

Osteoarthritis (OA) is a highly prevalent and disabling condition with limited safe and effective treatment options. Intra-articular therapies are increasingly being used, however whether the effect of these agents is due to active treatment or placebo remains unclear. As the placebo response can be attributed to multiple factors, assessment of the placebo response using individual patient data (IPD) meta-analysis will give insight into the different modifiers of response to placebo. The aim of this IPD meta-analysis is to investigate the predictors of placebo response in intra-articular injection trials in OA. IPD meta-analysis is considered to be superior to conventional meta-analysis, as it combines multiple trial data, facilitates the standardisation of analyses across different studies and allows measuring derivation of the desired information.

Method and analysis

A systematic literature search will be conducted for randomised clinical trials comparing corticosteroid and viscosupplementation/hyaluronic acid intra-articular injections with placebo for knee and hip OA. Pubmed (Medline), EMBASE, Web of Science, Cochrane Central and SCOPUS will be searched from inception to September 2018. Corresponding authors of the original trials will be contacted to obtain IPD. Risk of bias will be assessed using the Cochrane Collaboration's tool. The primary outcome will be change in pain from baseline. Secondary outcomes will be change in function and patient's global assessment. Potential predictors of placebo response assessed will include patient's characteristics, pain mechanism characteristics, radiographic severity, pain severity, intervention characteristics and trial design characteristics. A multilevel logistic regression analyses will be applied. Results will be reported using the Preferred Reporting Items for Systematic review and Meta-Analysis -IPD guidelines.

Ethics and dissemination

This study does not include identifiable data and ethical approval was obtained by the original investigators. Results of the IPD meta-analysis will be disseminated for publication in peer-reviewed journals and conference presentations.

Prospero registration number

CRD42018095188.

SUBMITTER: Yu SP

PROVIDER: S-EPMC6537977 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Predictors of placebo response to local (intra-articular) therapy in osteoarthritis: an individual patient data meta-analysis protocol.

Yu Shirley Pei-Chun SP Ferreira Manuela L ML van Middelkoop Marienke M Bierma-Zeinstra Sita M A SMA Zhang Weiya W Deveza Leticia A LA Hunter David J DJ

BMJ open 20190524 5

<h4>Introduction</h4>Osteoarthritis (OA) is a highly prevalent and disabling condition with limited safe and effective treatment options. Intra-articular therapies are increasingly being used, however whether the effect of these agents is due to active treatment or placebo remains unclear. As the placebo response can be attributed to multiple factors, assessment of the placebo response using individual patient data (IPD) meta-analysis will give insight into the different modifiers of response to ...[more]

PMID: 31129588

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Project description:ObjectiveTo evaluate the efficacy of intra--articular (IA) glucocorticoid for knee or hip osteoarthritis (OA) in specific subgroups of patients according to the baseline severity of pain and inflammatory signs using individual patient data (IPD) from existing trials. Furthermore, this study aims to assess if a baseline pain cut-off was associated with clinically important effectiveness of IA glucocorticoid. This is an update of an IA glucocorticoid IPD meta-analysis by the OA Trial Bank.MethodRandomized trials evaluating one or more IA glucocorticoid preparations in hip and knee OA, published to May 2018 were selected. IPD of patient and disease characteristics and outcome measures were acquired. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). Potential interaction effect of severe pain (≥70 points, 0-100 scale) and signs of inflammation at baseline were studied using a two-stage approach with general liner model followed by random effects model. Analysis of trend was conducted, assessing if a baseline pain cut-off was associated with the threshold for clinically important treatment effect of IA glucocorticoid compared to placebo.ResultsFour out of 16 eligible randomized clinical trials (n = 641) were combined with the existing OA Trial Bank studies (n = 620), yielding 1261 participants from eleven studies. Participants with severe baseline pain compared to those with less severe pain had greater pain reduction at mid-term (around 12 weeks) (mean reduction: -6.90 (95%CI -10.91; -2.90)), but not at short- and long-term. No interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo at all follow-up time-points. Analysis of trend demonstrated treatment response to IA glucocorticoid from baseline pain levels >50 (0-100 scale) and above.ConclusionThis updated IPD meta-analysis demonstrated that participants with severe pain compared to those with less severe pain at baseline experienced significantly more pain relief with IA glucocorticoid compared with placebo at mid-term.

Project description:BackgroundIntra-articular (IA) corticosteroid (CS) injections are the mainstay of treatment for symptomatic management in knee osteoarthritis (OA), particularly in the UK. IA platelet-rich plasma (PRP) injections are a promising alternative, but no systematic reviews to date have compared them to the current standard of care, IA CS injections. We aim to investigate the effect of IA PRP injections versus IA corticosteroid injections for the symptomatic management of knee OA.MethodsAll published trials comparing IA PRP and CS injections for knee OA were included. MEDLINE, EMBASE, Scopus and Web of Science were searched through June 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool. A random effects model was used to calculate standardized mean difference with 95% confidence interval in WOMAC/VAS score (or subscores), comparing IA PRP to CS injections across studies.ResultsIncluded were eight studies and 648 patients, 443 (68%) were female, mean age 59 years, with a mean BMI of 28.4. Overall, the studies were considered at low risk of bias. Compared with CS injections, PRP was significantly better in reducing OA symptoms (pain, stiffness, functionality) at 3, 6 and 9 months post-intervention (P < 0.01). The greatest effect was observed at 6 and 9 months (- 0.78 (- 1.34 to - 0.23) standard mean deviations (SMD) and - 1.63 (- 2.14 to - 1.12) SMD respectively). At 6 months, this equates to an additional reduction of 9.51 in WOMAC or 0.97 on the VAS pain scales. At 6 months PRP allowed greater return to sporting activities than CS, measured by the KOOS subscale for sporting activity, of magnitude 9.7 (- 0.45 to 19.85) (P = 0.06). Triple injections of PRP, generally separated by a week, were superior to single injections over 12 months follow-up (P < 0.01).ConclusionsIA-PRP injections produce superior outcomes when compared with CS injections for symptomatic management of knee OA, including improved pain management, less joint stiffness and better participation in exercise/sporting activity at 12 months follow-up. Giving three IA-PRP, with injections separated by a week, appears more effective than 1 IA-PRP injection.Prospero trial registration numberCRD42020181928 .

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Project description:Knee osteoarthritis (KOA) is a debilitating disease characterized by chronic pain, stiffness, and decreased mobility. Intra-articular injectable therapies show good clinical efficacy in improving symptoms; however, these therapies and their comparators (intra-articular saline) have been associated with a large underlying placebo effect. We aimed to describe the existing evidence on the challenges, hypotheses, and potential solutions to mitigate the intra-articular placebo effect in clinical trials in KOA. A targeted literature review was conducted by searching Embase, MEDLINE®, and CENTRAL using predefined study selection criteria. All eligible studies identified were extracted for relevant data, and results were narratively summarized. Forty-three studies were included following screening. Challenges associated with the intra-articular placebo effect included its ability to mask the comparative efficacy of active treatments in trials (n = 7 studies), long-lasting effects (up to 6 months; n = 3), and substantial variation of placebo effect sizes across populations (n = 3). Hypotheses for the mechanism of the placebo effect included aspiration of synovial fluid during administration (n = 6) and dilution of inflammatory mediators (n = 2). Factors affecting the placebo effect size were more invasive routes of administration (e.g., injection versus oral; n = 4) and patient expectations (n = 2). Proposed solutions included the suggestion for readers to weigh the relevance of clinical trial evidence against the presence of large underlying placebo effects (n = 9), discontinuation of intra-articular saline as an appropriate placebo (n = 5), and inclusion of 'no treatment' or sham injection as a control (n = 4). The intra-articular placebo effect is a well-documented occurrence in KOA clinical trials, and it is suggested that it be accounted for when designing randomized controlled trials. Awareness and understanding of the intra-articular placebo effect in KOA are required for fair interpretation of clinical trial evidence.

Dataset Information

Predictors of placebo response to local (intra-articular) therapy in osteoarthritis: an individual patient data meta-analysis protocol.

Introduction

Method and analysis

Ethics and dissemination

Prospero registration number

Publications

Predictors of placebo response to local (intra-articular) therapy in osteoarthritis: an individual patient data meta-analysis protocol.

Similar Datasets

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