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.
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.
Purpose. The aim of this current review was to confirm the efficacy of intra-articular steroid therapy (IAST) for patients with hip osteoarthritis (OA) and discuss the duration and influential factors of IAST. Methods. Online databases (Medline, EMBASE, and Web of Science) were searched from inception to May 2019. Both randomized controlled trials (RCTs) and noncontrolled trials assessing the efficacy of hip IAST on pain were included. Common demographics data were extracted using a standardized form. Quality was assessed on the basis of Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. Results. 12 trials met the inclusion criteria. According to data from individual trials, IAST had significant efficacy on hip OA in both immediate and delay pain reduction, which persisted up to 12 weeks after IAST. The influences of the baseline severity of hip OA or synovitis and injection dose or volume on the clinical outcome of IAST were still controversial. The IAST appeared to be well tolerant by most of the participants. Conclusion. IAST was proved to be an efficacious therapy in both immediate and delay pain reduction for hip OA patients within 12 weeks. The longer follow-up data of efficacy and safety and potentially influential factors are still unclear and needed further confirmation.
Objective To assess the efficacy of viscosupplementation (hyaluronic acid [HA]) on the pain and disability caused by hip osteoarthritis, and to determine the occurrence of adverse events. Data Sources PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov database, and specific journals up to March 2017. Study Selection Randomized controlled trials (RCTs) comparing HA with any other intra-articular injection. Data Extraction Performed according to Cochrane/Grades of Recommendation, Assessment, Development, and Evaluation criteria. Two authors extracted data and assessed the risk of bias and quality of evidence. A random-effects meta-analysis was conducted. Data Synthesis Eight RCTs were retrieved (n=807): 4 comparing HA to placebo; 3 to platelet-rich plasma (PRP); 3 to methylprednisolone; and 1 to mepivacaine. Some RCTs had 3 arms. There is very low evidence that HA is not superior to placebo for pain at 3 months (standardized mean difference [SMD]=−.06; 95% CI, −.38 to .25; P =.69), and high evidence that it is not superior in adverse events (risk ratio [RR]=1.21; 95% CI, .79–1.86; P =.38). There is low evidence that HA is not superior to PRP for pain at 1 month. There is very low evidence that HA is not superior to PRP for pain at 6 and 12 months (mean difference in visual analog scale [in cm]: −.05 [95% CI, −.81 to .71], 1.0 [95% CI, −1.5 to 3.50], and .81 [95% CI, −1.11 to 2.73], respectively). There is high evidence that HA is no different from methylprednisolone for pain at 1 month (SMD=.02; 95% CI, −.18 to .22; P =.85). There is low evidence that HA is no different from methylprednisolone for Outcome Measures in Rheumatoid Arthritis Clinical Trials–Osteoarthritis Research Society International Responders Index at 1 month (RR=.44; 95% CI, .10–1.95; P =.28). There is high evidence that HA is no different from methylprednisolone for adverse events (RR=1.21; 95% CI, .79–1.87; P =.38). Conclusions We do not recommend viscosupplementation for hip osteoarthritis. Compared with placebo, data show scarce evidence of its efficacy up to 3 months, and suggest no difference at 6 months. However, future RCTs could present HA as an alternative to methylprednisolone for short-term symptom relief.
OBJECTIVE: The aims of this study were to systematically review clinimetrics of commonly assessed ultrasound pathologies in knee, hip and hand osteoarthritis (OA), and to conduct a meta-analysis for each clinimetric.
METHODS: MEDLINE, EMBASE, and Cochrane Library databases were searched from their inceptions to September 2016. According to the OMERACT Instrument Selection Algorithm, data extraction focused on ultrasound technical features and performance metrics. Methodological quality was assessed with modified 19-item Downs and Black score and 11-item Quality Appraisal of Diagnostic Reliability (QAREL) score. Separate meta-analyses were performed for clinimetrics: 1)inter-rater/intra-rater reliability; 2)construct validity; 3)criteria validity; and 4)internal/external responsiveness. SPSS, Excel and Comprehensive Meta-analysis were used.
RESULT: Our search identified 1126 records; of these, 100 were eligible, including a total of 8542 patients and 32373 joints. The average Downs and Black score was 13.01, and average QAREL was 5.93. The stratified meta-analysis was performed only for knee OA, which demonstrated moderate to substantial reliability [minimum kappa>0.44(0.15,0.74), minimum ICC>0.82(0.73-0.89)], weak construct validity against pain(r=0.12 to 0.27), function(r=0.15 to 0.23), and blood biomarkers(r=0.01 to 0.21), but weak to strong correlation with plain radiography(r=0.13 to 0.60), strong association with MRI [minimum r=0.60(0.52,0.67)] and strong discrimination against symptomatic patients(OR=3.08 to 7.46). There was strong criterion validity against cartilage histology [r=0.66(-0.05,0.93), and small to moderate internal(SMD=0.20 to 0.58) and external(r=0.35 to 0.43) responsiveness to interventions.
CONCLUSION: Ultrasound demonstrated strong criterion validity with cartilage histology, poor to strong correlation with patient findings and MRI, moderate reliability, and low responsiveness to interventions.
There is less credible evidence of using of intra-articular injections of hyaluronic acid (HA) to treat hip osteoarthritis (OA). This study is to determine the therapeutic effects and risk of adverse events of HA administration for hip OA. The MEDLINE, Cochrane of Systematic Reviews, Cochrane Clinical Trial Register and EMBASE, were searched for articles published. Eligible studies were limited to trials of HA with a randomized design. A total of six studies were included in this the meta-analysis. The pooled effect size of improved pain scores from pretreatment was -0.72 (95%CI; -1.06 to -0.39; P < 0.05). The standardized mean difference (SMD) of improved Lequesne's index and McMaster Universities Osteoarthritis Index (WOMAC) was -0.74 (95%CI, -1.42 to -0.51; P < 0.05) and -7.75 (95%CI, -14.28 to -1.21; P < 0.05), respectively. The pooled effect size of improved pain scores compared HA with different controls was 0.03 (95%CI; -0.20 to 0.26; P < 0.05). The SMD of improved Lequesne's index and WOMAC was -0.24 (95%CI, -0.50 to 0.02; P > 0.05) and -0.13 (95%CI, 0.64 to 0.37; P > 0.05). There were no significant differences between HA and control group in adverse events (RR: 0.94; 95%CI, 0.41 to 2.20; P > 0.05). Intra-articular HA in hip OA can significantly reduce pain and improve functional recovery when compared with the condition before treatment. However, there seems no significant difference between HA and saline or other treatments. Currently, available evidence indicated that intra-articular HA in hip OA would not be increased risk of adverse events.
OBJECTIVE: To assess the efficacy of viscosupplementation (HA) in hip osteoarthritis (OA) pain, disability and adverse events.
DATA SOURCES: Pubmed, EMBASE, Cochrane Library, ClinicalTrials.gov database and specific journals up to March 2017.
STUDY SELECTION: Randomized controlled trials comparing HA with any other intra-articular injection.
DATA EXTRACTION: Performed according to Cochrane/GRADE criteria. Two authors extracted data, assessed risk of bias and quality of evidence. Random-effects meta-analysis was conducted. Protocol registered on PROSPERO under CRD42015017312 DATA SYNTHESIS: Eight RCTs were retrieved (n=807): four comparing HA to placebo (PBO); three with platelet-rich plasma (PRP), three with methylprednisolone (MPA), and one mepivacaine (MPV). Some RCTs had three arms. There is VERY LOW evidence that HA is not superior to PBO in pain at 3 months (SMD=-0.06 [95% CI -0.38; 0.25], p=0.69), and HIGH evidence that is not superior in adverse events (RR=1.21 [95%CI 0.79; 1.86], p=0.38). There is LOW evidence that HA is not superior to PRP for pain at 1 month. There is VERY LOW evidence that HA is not superior to PRP for pain at 6 and 12 months (mean difference in VAS in cm= -0.05 [95%CI -0.81, 0.71]; 1.0 [95%CI -1.5, 3.50]; 0.81 [95%CI -1.11, 2.73], respectively). There is HIGH evidence that HA is no different from MPA for pain at 1 month (SMD=0.02 [95% CI -0.18; 0.22], p=0.85). There is LOW evidence HA is no different from MPA for OMERACT-OARSI responders index at 1 month (RR=0.44 [95%CI 0.10; 1.95], p=0.28; There is HIGH evidence HA is no different from MPA for adverse events (RR=1.21 [95%CI 0.79; 1.87], p=0.38).
CONCLUSIONS: We do not recommend viscosupplementation for hip OA. Compared to placebo, data shows scarce evidence of its efficacy up to 3 months, and suggests no difference at 6 months. However, future RCTs could present HA as an alternative to MPA for short-term symptom relief.
OBJECTIVE: To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials.
DESIGN: Randomized trials evaluating one or more IA glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). The subgroup factors assessed included severe pain (≥70 points, 0-100 scale) and signs of inflammation (dichotomized in present or not) at baseline. Multilevel regression analyses were applied to estimate the magnitude of the effects in the subgroups with the individuals nested within each study.
RESULTS: Seven out of 43 published randomized clinical trials (n = 620) were included. Patients with severe baseline pain had a significantly larger reduction in short-term pain, but not in mid- and long-term pain, compared to those with less severe pain at baseline (Mean Difference 13.91; 95% Confidence Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points.
CONCLUSIONS: This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short-term follow-up than those with less severe pain at baseline.
El ácido hialurónico (HA) inyecciones se utilizan para tratar la osteoartritis de la cadera, pero su eficacia no se ha establecido claramente. El propósito de este meta-análisis fue determinar el efecto de las inyecciones de HA en dolor de la cadera. Había veintitrés estudios que cumplieron con los criterios y la disminución media en las puntuaciones analógicas visuales (EAV) fue - 1.97 (95% CL, 2,83 a - 1,12, p <0,0001). Sin embargo, la relevancia clínica de este cambio es difícil de determinar ya que la disminución de la EVA fue sólo - 0,27 en los seis ensayos aleatorizados en el estudio y la duración del seguimiento en la mayoría de estudios fue de menos de seis meses. Se necesitan ensayos aleatorios multicéntrico para determinar la verdadera eficacia de las inyecciones de HA para reducir el dolor asociado con la osteoartritis de cadera.
OBJETIVOS: Variaciones en el grado de alivio del dolor informado por los pacientes con osteoartritis después de inyecciones intraarticulares de corticosteroides son bien reconocidos pero las razones de esto no son ampliamente entendidas y factores que podrían predecir variaciones en la respuesta no han sido objeto de revisión sistemática. Nos propusimos realizar una revisión sistemática de la literatura en relación con los predictores de la reducción del dolor después de inyecciones intraarticulares de corticosteroides en pacientes con artrosis de rodilla y cadera.
MÉTODOS: Se realizaron búsquedas en Medline, EMBASE, Web of Knowledge y la búsqueda MeSH de PubMed, la última búsqueda se realizó en agosto de 2012. Los términos de búsqueda incluyeron artrosis de rodilla, artrosis de cadera, términos corticosteroides y productos relacionados, y la inyección intra-articular. Los trabajos fueron seleccionados y revisados por 2 colaboradores. Para la inclusión, se requieren papeles para describir estudios en los que los pacientes con osteoartritis de la rodilla o cadera recibieron la inyección de corticosteroides intraarticular como una intervención, contienen claros indicadores de medidas de resultado relacionadas con el dolor y contener el análisis en relación con predictores de la respuesta clínica al tratamiento.
RESULTADOS: Veintiún estudios cumplieron los criterios de inclusión de un total de 54 artículos revisados en su totalidad. Ocho de ellos relacionados con la artrosis de cadera y 13 en relación con OA de rodilla. No hay factores que fueron investigados como posibles factores predictivos de respuesta, incluyendo la evidencia radiográfica de grado y clínica o ecográfica de la inflamación o hipertrofia sinovial fueron apoyados por pruebas sólidas. El estudio también identificó que varios predictores potenciales plausibles no habían sido estudiados hasta la fecha.
CONCLUSIONES: La investigación previa no ha identificado predictores confiables de respuesta a las inyecciones de corticosteroides IA, una intervención ampliamente practicada en la OA de rodilla y cadera. Se requieren estudios adicionales si esta pregunta se responde.
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.
