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.
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.
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.
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.
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.
Both epidemiologic and clinical research continues to be performed in osteoarthritis (OA). While epidemiologic studies identify risk factors for incident and progressive disease, clinical studies explore the role of both non-pharmacologic and pharmacologic treatments, including oral and intra-articular therapies. We performed a systematic review of the literature using PubMed for the time period between April 1, 2015 to February 22, 2016. Selected publications in the areas of both epidemiology and treatment are reviewed in this article.
BACKGROUND: Intra-articular normal saline (IA-NS) injections have been utilized as a placebo in a number of randomized controlled trials pertaining to the management of knee osteoarthritis (OA); however, it is believed that these “placebo” injections may have a therapeutic effect that has not been quantified in the literature. PURPOSE: To (1) quantify the effect of IA-NS injections on patient-reported outcomes (PROs) and (2) compare postinjection PROs to established minimal clinically important difference (MCID) criteria to demonstrate a potential therapeutic effect. STUDY DESIGN: Meta-analysis. METHODS: A review was conducted to identify all randomized, placebo-controlled trials on injection therapy for knee OA between 2006 and 2016. Patient demographics and PROs before the injection and at 3 and 6 months after the injection were collected for patients in the IA-NS injection group in each study. A random-effects model was used to compare preinjection scores and scores at each postinjection time point in a pairwise fashion. RESULTS: In total, there were 14 placebo cohorts in 13 studies that were analyzed after meeting inclusion criteria for this meta-analysis. This included 1076 patients (Kellgren-Lawrence grade 1-4), with a weighted mean age of 62.53 years and mean body mass index of 28.67 kg/m2. There was only sufficient information to perform analyses of visual analog scale (VAS) pain and Western Ontario and McMaster Universities Arthritis Index (WOMAC) total scores. At 3 months after the IA-NS placebo injection, there was a significant improvement in VAS pain scores (mean difference [MD], 12.10 [95% CI, 3.27 to 20.93]; P = .007), whereas improvement in the WOMAC total scores approached but did not reach statistical significance (MD, 19.75 [95% CI, –0.50 to 40.09]; P = .06). At 6 months, both VAS pain scores (MD, 16.62 [95% CI, 12.13-21.10]; P < .00001) and WOMAC total scores (MD, 11.34 [95% CI, 7.03-15.65]; P < .00001) were significantly improved in comparison to preinjection values. Furthermore, improvements in both the VAS pain and WOMAC total scores at 6 months were clinically significant (MCID, 1.37 and 9, respectively). CONCLUSION: The administration of an IA-NS placebo injection yields a statistically and clinically meaningful improvement in PROs up to 6 months after the injection in patients with knee OA. This observation supports the notion that the so-called placebo effect for IA-NS injections achieves a clinically meaningful response in patients with OA when provided during comparison studies to an active treatment group (ie, hyaluronic acid).
OBJETIVOS: El ácido hialurónico y los corticosteroides son terapias intraarticulares (IA) comúnmente utilizadas para el tratamiento de la osteoartritis de rodilla leve a moderada (OA). Muchos ensayos que evalúan la eficacia de las terapias administradas con IA usan comúnmente las inyecciones salinas IA como brazo comparador de placebo. Utilizando una revisión sistemática y metanálisis, nuestro objetivo fue evaluar el beneficio clínico asociado con el uso de solución salina IA en ensayos de terapias IA en el tratamiento de pacientes con OA dolorosa de rodilla. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE y Embase para artículos publicados hasta el 14 de agosto de 2014. Dos revisores evaluaron la elegibilidad de reportes potenciales y el riesgo de sesgo de los ensayos incluidos. Se analizó la reducción del dolor corto (≤ 3 meses) ya largo plazo (6-12 meses) del grupo salino de los ensayos incluidos utilizando diferencias de medias estandarizadas (SMDs, estimadas asumiendo un efecto nulo en un grupo de comparación) que fueron combinadas y ponderadas usando Un modelo de efectos aleatorios. Los eventos adversos relacionados con el tratamiento (AE) se tabularon y se presentaron utilizando estadísticas descriptivas. Resultados: De 40 ensayos controlados aleatorios (ECA) elegibles para inclusión sólo 38 proporcionaron datos suficientes para ser incluidos en el metanálisis. Basándose en datos con moderada incoherencia, se encontró que la solución salina de IA mejoraba significativamente el dolor de rodilla a corto plazo en 32 estudios con 1705 pacientes (DMS = -0,68; IC del 95%: -0,78 a -0,57; P <0,001; I (2) = 50 %). El dolor de rodilla a largo plazo disminuyó significativamente después de la inyección de IA con solución salina en 19 estudios con 1445 pacientes (DME = -0,61; IC del 95%: -0,76 a -0,45; P <0,001) con un grado sustancial de inconsistencia (I 2) = 74%). En total, 29 de los ensayos incluidos informaron sobre eventos adversos, ninguno de los cuales encontró serias AE relacionados con el tratamiento después de la inyección de IA con solución salina. CONCLUSIONES: El alivio del dolor observado con solución salina IA debe inducir a los proveedores de atención médica a considerar la eficacia adicional de los tratamientos actuales de IA que usan comparadores salinos en estudios clínicos y los desafíos de identificar la inyección salina IA como un "placebo".
ANTECEDENTES: los controles con placebo son esenciales en la evaluación de la eficacia de los tratamientos médicos. Aunque no está claro si las diferentes intervenciones placebo para la osteoartritis varían en eficacia, las diferencias sistemáticas afectarían sustancialmente interpretación de los resultados de los ensayos controlados con placebo.
Objetivo: Evaluar los efectos de los tipos alternativos de placebo en los resultados de dolor en la artrosis de rodilla.
FUENTES DE INFORMACIÓN: MEDLINE, EMBASE, Web of Science, Google Scholar, y Base de Datos Cochrane desde el comienzo hasta 1 de junio de 2015 y no publicados datos.
SELECCIÓN DE ESTUDIOS: 149 ensayos aleatorios de adultos con osteoartritis de rodilla que informaron los resultados de dolor y se compararon fármacos ampliamente usados contra oral, intraarticular, tópica y oral más placebos tópicos.
EXTRACCIÓN DE DATOS: Se forma independiente doble extrajeron los datos del estudio; la calidad del estudio se evaluó utilizando el riesgo de Cochrane herramienta de sesgo.
SÍNTESIS: El efecto placebo que se evaluaron mediante el uso de una red metanálisis con 4 nodos con placebo separadas (modelo diferencial) mostraron que el placebo intraarticular (tamaño del efecto, 0,29 [95% intervalo de credibilidad, 0,09 a la 0,49]) y placebo tópico ( el tamaño del efecto, 0,20 [intervalo de credibilidad, 0,02 a la 0,38]) tenían significativamente mayores tamaños del efecto que el placebo oral. Este modelo diferencial mostró marcadas diferencias en las eficacias relativas y la jerarquía de los tratamientos activos en comparación con un modelo de red que considera todos los placebos equivalente. En el modelo para la contabilidad efectos diferenciales, intra-articular y terapias tópicas fueron superiores a los tratamientos orales en la reducción del dolor. Cuando se ignoraron estos efectos diferenciales, fármacos anti-inflamatorios no esteroides orales eran superiores.
LIMITACIONES: Pocos estudios compararon diferentes placebos directamente. El estudio no pudo concluir si decisivamente gravedad de la enfermedad y las co-intervenciones difieren sistemáticamente entre los ensayos que evalúan diferentes placebos.
Conclusión: Todos los placebos no son iguales, y algunos pueden desencadenar respuestas clínicamente relevantes. efectos placebo diferenciales pueden alterar sustancialmente las estimaciones de la eficacia relativa de los tratamientos activos, una consideración importante para el diseño de ensayos clínicos y la interpretación de sus resultados.
PRIMARIA FUENTE DE FINANCIACIÓN: Agencia para la Investigación y Calidad.
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.
