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Is it possible to predict which patients are most likely to benefit from intra-articular corticosteroid injections? A systematic review

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Journal International journal of rheumatic diseases
Year 2024
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This article includes 8 Primary studies 8 Primary studies (8 references)

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Aim: Intra-articular corticosteroid injections (IACIs) can reduce osteoarthritis-related pain, with differing levels of response across patient groups. This systematic review investigates what is known about the positive and negative predictors of outcomes in patients with osteoarthritis who undergo IACIs. Methods: We systematically searched the Medline, Embase, and Cochrane databases to May 2023 for studies that evaluated patients undergoing IACIs for osteoarthritis and reported on predictors of outcomes in these patients. Results: Eight studies were included. Two were placebo-controlled trials, six were observational studies. Due to the heterogeneity of outcomes and variables between the studies, it was not possible to pool the results for formal meta-analysis. Higher baseline pain, older age, higher BMI, lower range of movement, higher Kellgren-Lawrence radiographic score, joint effusion, and aspiration were shown to be predictors of a positive response to IACIs in some of the included studies. However, other studies showed no difference in response with these variables, or a negative correlation with response. Sex, smoking, mental health status, hypertension/ischaemic heart disease, diabetes mellitus, duration of symptoms, and socioeconomic status did not demonstrate any correlation with the prediction of positive or negative outcomes after IACIs. Conclusion: Several patient features have been identified as positive predictors of outcomes following IACIs. However, this systematic review has identified inconsistent and variable findings across the existing literature. Further research with standardization of IACI administration and outcome measures is required to facilitate further analysis of the reliability and significance of predictive factors for response to IACIs. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Systematic review

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Intra-articular corticosteroids for the treatment of osteoarthritis: A systematic review and meta-analysis on the comparison of different molecules and doses

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Journal Journal of experimental orthopaedics
Year 2024
Links Pubmed DOI PubMed Central

This article includes 16 Primary studies 16 Primary studies (16 references)

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PURPOSE: The purpose of this study was to quantify and compare the clinical relevance of the different intra-articular corticosteroids (CS) effects in vivo for osteoarthritis (OA) treatment. METHODS: The search was conducted on PubMed, Cochrane, and Web of Science in October 2023. The PRISMA guidelines were used. Inclusion criteria: animal or human randomized controlled trials (RCTs), English language and no time limitation, on the comparison of different intra-articular CS for OA treatment. The articles' quality was assessed using the Cochrane RoB2 and GRADE guidelines for human RCTs, and SYRCLE's tool for animal RCTs. RESULTS: Eighteen RCTs were selected (16 human and 2 animal studies), including 1577 patients (1837 joints) and 31 animals (51 joints). The CS used were triamcinolone (14 human and 2 animal studies), methylprednisolone (7 human and 1 animal study), betamethasone (3 human studies) and dexamethasone (1 human study). All studies addressed knee OA except for three human and one animal study. A meta-analysis was performed on the comparison of methylprednisolone and triamcinolone in humans with knee OA analysing VAS pain at very short- (≤2 weeks), short- (>2 and ≤4 weeks), mid- (>4 and ≤8 weeks), long- (>8 and ≤ 12 weeks), and very long-term (>12 and ≤24 weeks). Triamcinolone showed better post-injection values compared to methylprednisolone at very short-term (p = 0.028). No difference in terms of VAS improvement was observed at any follow-up. CONCLUSIONS: The available preclinical and clinical literature provides limited evidence on the comparison of different CS, hindering the possibility of determining the best CS approach in terms of molecule and dose for the intra-articular injection of OA joints. LEVEL OF EVIDENCE: Level I.

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The OA Trial Bank: Update of individual patient data meta-analysis of intra-articular glucocorticoids in persons with knee and hip osteoarthritis

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Journal Osteoarthritis and cartilage open
Year 2023
Links Pubmed DOI PubMed Central

This article includes 11 Primary studies 11 Primary studies (11 references)

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OBJECTIVE: To 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. METHOD: Randomized 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. RESULTS: Four 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. CONCLUSION: This 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.

Systematic review

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Comparison of Minimally Invasive Procedures to Treat Knee Pain Secondary to Osteoarthritis: A Systematic Review and Meta-Analysis.

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Journal Journal of vascular and interventional radiology
Year 2022
Links Pubmed DOI www.epistemonikos.org

This article includes 46 Primary studies 46 Primary studies (46 references)

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ABSTRACT: PURPOSE: To review and indirectly compare the outcomes of genicular artery embolization (GAE), radiofrequency (RF) ablation, and intra-articular (IA) injection for the treatment of knee pain secondary to osteoarthritis (OA). MATERIALS AND METHODS: A literature review of the MEDLINE and Cochrane databases was conducted with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement in June 2020. The visual analog scale (VAS) was recorded at baseline and at all available time points for each therapy. Standard mean differences were calculated at each time point and compared between treatments to assess the magnitude of the treatment effect. RESULTS: All 3 treatments demonstrated significant differences in VAS scores after therapy. RF ablation produced the greatest significant mean reduction in relative VAS score from baseline at 1 year of follow-up (mean, 0.49; 95% confidence interval, 0.4-0.59; P = .03). GAE reported the most significant reductions in VAS scores across all measured time points. Overall, the comparison did not demonstrate a significant difference in VAS scores among patients receiving IA injections, RF ablation, and GAE. CONCLUSIONS: The current evidence does not suggest a significant difference in outcomes among IA injection, RF ablation, and GAE for knee pain secondary to OA.

Systematic review

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Effects of recurrent intra-articular corticosteroid injections for osteoarthritis at 3 months and beyond: a systematic review and meta-analysis in comparison to other injectables

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Journal Osteoarthritis and cartilage
Year 2022
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This article includes 10 Primary studies 10 Primary studies (10 references)

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Objective: Intra-articular corticosteroid injections (IACIs) provide temporary symptom relief in osteoarthritis (OA). This meta-analysis investigated the effects of recurrent IACIs at 3 months and beyond. Design: We searched Medline, Embase and Cochrane from inception to January 2021 for randomised controlled trials (RCTs) of patients with OA who received recurrent IACIs compared with other injectables, placebo or no treatment (primary outcomes: pain, function). Mean differences (MDs) with 95% confidence intervals were reported. Results: Ten RCTs were included (eight knee OA (n = 763), two trapeziometacarpal OA (n = 121)). Patients received between 2 and 8 injections, varying by trial. Trials compared recurrent IACIs with hyaluronic acid (HA), platelet-rich plasma (PRP), saline or orgotein (follow-up 3–24 months). Greater improvements in pain, function and QoL at 3–24 months were noted for the comparators than with IACIs, with comparators demonstrating an equal or superior effect, or the intervention effect attenuated during follow-up. Recurrent IACIs demonstrated no benefits in pain or function over placebo at 12–24 months. No serious adverse events were recorded. No studies reported on time-to-future interventions, risk of future prosthetic joint infection or other adverse events associated with subsequent joint replacement. Conclusions: Recurrent IACIs often provide inferior (or non-superior) symptom relief compared with other injectables (including placebo) at 3 months and beyond. Other injectables (HA, PRP) often yielded greater improvements in pain and function up to 24 months post-injection. Existing RCTs on recurrent IACIs lack sufficient follow-up data to assess disease progression and time-to-future interventions. © 2022 The Author(s)

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Efficacy and safety of multiple intra-articular corticosteroid injections for osteoarthritis-a systematic review and meta-analysis of randomized controlled trials and observational studies.

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Journal Rheumatology (Oxford, England)
Year 2021
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This article includes 16 Primary studies 16 Primary studies (16 references)

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OBJECTIVES: To investigate the efficacy and safety of multiple intra-articular corticosteroid (IACS) injections for the treatment of OA. METHODS: We conducted electronic searches of several databases for randomized controlled trials (RCTs) and observational studies. Standard mean difference was calculated for efficacy, whereas hazard ratio (HR) was used for adverse effects. Results were combined using the random effects model. Heterogeneity was measured using I2 statistics. RESULTS: Six RCTs were included for efficacy assessment. The use of multiple IACS appeared to be better than comparator (standard mean difference for pain -0.47, 95% CI -0.62, 0.31). However, there was considerable heterogeneity (I2 92.6%) and subgroup analysis by comparator showed no separation of regular IACS from placebo, though timing of pain assessments was questionable. Fourteen RCTs and two observational studies were assessed for the safety of multiple IACS. Minor local adverse events were similar in both groups. One RCT found that regular IACS every 3 months for 2 years caused greater cartilage loss compared with saline injection (-0.21 vs 0.10 mm). One cohort study found that multiple IACS injections associated with worsening of joint space narrowing (HR 3.02, 95% CI 2.25, 4.05) and increased risk of joint replacement (HR 2.54, 95% CI 1.81, 3.57). CONCLUSION: Multiple IACS injections are no better than placebo for OA pain according to current evidence. The preliminary finding of a detrimental effect on structural OA progression warrants further investigation. Efficacy and safety of multiple IACS reflecting recommended best practice has yet to be assessed.

Systematic review

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Efficacy of intra-articular corticosteroid injections in knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials

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Journal Joint bone spine
Year 2021
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This article includes 23 Primary studies 23 Primary studies (23 references)

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Systematic review

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THE MAGNITUDE AND DURATION OF THE EFFECT OF INTRA-ARTICULAR CORTICOSTEROID INJECTIONS ON PAIN SEVERITY IN KNEE OSTEOARTHRITIS - A SYSTEMATIC REVIEW AND META-ANALYSIS.

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Journal American journal of physical medicine & rehabilitation
Year 2020
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This article includes 8 Primary studies 8 Primary studies (8 references)

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OBJECTIVE: To clarify the evidence on the magnitude and duration of treatment effect of intra-articular corticosteroid (IAC) injections for knee osteoarthritis (OA) compared to placebo, to evaluate a treatment effect by steroid type, and to describe the reported adverse effects. DESIGN: Cochrane Controlled Trials Register, Medline, Embase, CINAHL, Scopus, and Web of Science databases were searched. The risk of systematic bias was assessed according to the Cochrane Collaboration's domain-based evaluation framework. RESULTS: The final sample included eight RCTs with follow-ups from 1 to 26 weeks. The risk of systematic bias was considered low in five and high in three studies. The pooled SMD was -0.58 (95% CI -0.88 to -0.27) and NNT 5.1 (95% CI 10.0 to 3.7). The heterogeneity was considerable. The pooled effect size approached the level of statistical insignificance at four months. The pooled risk ratio of adverse effects was insignificant 0.95 (95% CI 0.34 to 2.55). CONCLUSION: The IAC had a mild to moderate effect on pain severity up to three months after the injection - much longer than it had previously been reported. The effect may vary substantially in different patient groups and appropriate patient selection is important. The risk of adverse effects was low.

Systematic review

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Mixed Treatment Comparisons for Nonsurgical Treatment of Knee Osteoarthritis: A Network Meta-analysis.

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Journal The Journal of the American Academy of Orthopaedic Surgeons
Year 2018
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This article includes 52 Primary studies 54 Primary studies (52 references)

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INTRODUCTION: Knee osteoarthritis (KOA) is a significant health problem with lifetime risk of development estimated to be 45%. Effective nonsurgical treatments are needed for the management of symptoms. METHODS: We designed a network meta-analysis to determine clinically relevant effectiveness of nonsteroidal anti-inflammatory drugs, acetaminophen, intra-articular (IA) corticosteroids, IA platelet-rich plasma, and IA hyaluronic acid compared with each other as well as with oral and IA placebos. We used PubMed, EMBASE, and Cochrane Central Register of Controlled Trials to perform a systematic search of KOA treatments with no date limits and last search on October 7, 2015. Article inclusion criteria considered the following: target population, randomized controlled study design, English language, human subjects, treatments and outcomes of interest, ≥30 patients per group, and consistent follow-up. Using the best available evidence, two abstractors independently extracted pain and function data at or near the most common follow-up time. RESULTS: For pain, all active treatments showed significance over oral placebo, with IA corticosteroids having the largest magnitude of effect and significant difference only over IA placebo. For function, no IA treatments showed significance compared with either placebo, and naproxen was the only treatment showing clinical significance compared with oral placebo. Cumulative probabilities showed naproxen to be the most effective individual treatment, and when combined with IA corticosteroids, it is the most probable to improve pain and function. DISCUSSION: Naproxen ranked most effective among conservative treatments of KOA and should be considered when treating pain and function because of its relative safety and low cost. The best available evidence was analyzed, but there were instances of inconsistency in the design and duration among articles, potentially affecting uniform data inclusion.

Systematic review

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Intra-articular injection of methylprednisolone for reducing pain in knee osteoarthritis: A systematic review and meta-analysis.

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Authors Tian K , Cheng H , Zhang J , Chen K
Journal Medicine
Year 2018
Links Pubmed DOI PubMed Central

This article includes 4 Primary studies 4 Primary studies (4 references)

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BACKGROUND: To evaluate the efficacy and safety of intra-articular methylprednisolone for reducing pain in patients with knee osteoarthritis. METHODS: We conduct electronic searches of Medline (1966-2017.11), PubMed (1966-2017.11), Embase (1980-2017.11), ScienceDirect (1985-2017.11), and the Cochrane Library (1900-2017.11) for randomized clinical trials comparing the use of methylprednisolone to treat knee osteoarthritis. The primary outcomes are Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores and WOMAC function scores. Each outcome was combined and calculated using the statistical software STATA 12.0. Fixed/random effect model was adopted based on the heterogeneity tested by I statistic. RESULTS: A total of 739 patients were analyzed across 4 randomized controlled trials (RCTs). The present meta-analysis revealed that there were significant differences between groups regarding the WOMAC pain scores at 4 weeks (WMD = -1.384, 95% CI: -1.975 to -0.793, P = .000), 12 weeks (WMD = -1.587, 95% CI: -2.489 to -0.685, P = .001), and 24 weeks (WMD = -1.563, 95% CI: -2.245 to -0.881, P = .000). Significant differences were identified in terms of physical function at 4 weeks (WMD = -7.925, 95% CI: -13.359 to -2.491, P = .004), 12 weeks (WMD = -7.314, 95% CI: -13.308 to -1.320, P = .117), and 24 weeks (WMD = -6.484, 95% CI: -11.256 to -1.711, P = .008). CONCLUSION: Intra-articular methylprednisolone injection was associated with an improved pain relief and physical function in patients with knee osteoarthritis. Additionally, no severe adverse effects were observed. Due to the limited quality of the evidence currently available, higher quality RCTs were required.