OBJECTIVE: This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis.
PATIENTS AND METHODS: Randomized clinical trials evaluating ultramicronised diclofenac, diclofenac, celecoxib, etodolac and placebo in patients with osteoarthritis were identified. A search was conducted in May 2021 through PubMed, Scopus and Web of Science databases. A network meta-analysis was developed for efficacy outcome related to analgesia measured by the pain subscale of the Western Ontario and McMaster Universities tool. In addition, surface under the cumulative ranking was performed to rank the drugs in relation to this outcome.
RESULTS: Twelve randomized clinical trials were included. Overall, ultramicronised diclofenac 105 mg/day (UD105) was better than all the others, including ultramicronised diclofenac 70 mg/day (UD70). In addition, surface under the cumulative ranking resulted in the following order: 1) ultramicronised diclofenac 105 mg/day (100%), 2) ultramicronised diclofenac 70 mg/day (80%), 3) celecoxib 200 mg/day (49%), 4) diclofenac 100 mg/day (48%), 5) placebo (19%) and 6) diclofenac 150 mg/day (6%).
CONCLUSIONS: Ultramicronised diclofenac demonstrated superior efficacy compared to other conventional anti-inflammatory drugs and placebo in relieving osteoarthritis pain.
OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.
DESIGN: Systematic review and network meta-analysis of randomised trials.
DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.
OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.
REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.
RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).
CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656.
OBJECTIVE: Current global guidelines regarding the first-line analgesics (acetaminophen, topical or oral non-steroidal anti-inflammatory drugs [NSAIDs]) for knee osteoarthritis remain controversial and their comparative risk-benefit profiles have yet to be adequately assessed.
DESIGN: Pubmed, Embase, Cochrane Library, and Web of Science were searched from database inception to March 2021 for randomized controlled trials (RCTs) comparing acetaminophen, topical NSAIDs and oral NSAIDs directly or indirectly in knee osteoarthritis. Bayesian network meta-analyses were conducted. A propensity-score matched cohort study was also conducted among patients with knee osteoarthritis in The Health Improvement Network database.
RESULTS: 122 RCTs (47,113 participants) were networked. Topical NSAIDs were superior to acetaminophen (standardized mean difference [SMD]=-0.29, 95% credible interval [CrI]: -0.52 to -0.06) and not statistically different from oral NSAIDs (SMD=0.03, 95% CrI: -0.16 to 0.22) for function. It had lower risk of gastrointestinal adverse effects (AEs) than acetaminophen (relative risk [RR]=0.52, 95%CrI: 0.35 to 0.76) and oral NSAIDs (RR=0.46, 95%CrI: 0.34 to 0.61) in RCTs. In real-world data, topical NSAIDs showed lower risks of all-cause mortality (hazard ratio [HR]=0.59, 95% confidence interval [CI]: 0.52 to 0.68), cardiovascular diseases (HR=0.73, 95%CI: 0.63 to 0.85) and gastrointestinal bleeding (HR=0.53, 95%CI: 0.41 to 0.69) than acetaminophen during the one-year follow-up (n=22,158 participants/group). A better safety profile was also observed for topical than oral NSAIDs (n=14,218 participants/group).
CONCLUSIONS: Topical NSAIDs are more effective than acetaminophen but not oral NSAIDs for function improvement in people with knee osteoarthritis. Topical NSAIDs are safer than acetaminophen or oral NSAIDs in trials and real-world data.
OBJECTIVE: Despite an extensive body of research on NSAIDs in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.
METHODS: We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. RCTs assessing the efficacy and/or safety of FDA-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences and risk ratios with 95% confidence intervals.
RESULTS: We included 72 RCTs (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [-0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of GI AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [1.21, 1.57]). The incidence of CV AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.
CONCLUSION: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen. This article is protected by copyright. All rights reserved.
OBJECTIVE: Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.METHODS: We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs).RESULTS: We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [95% CI -0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.CONCLUSION: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.
OBJECTIVE: Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.
METHODS: A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once).
RESULTS: Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09-1.46; I2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03-1.38; I2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08-1.80; I2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01-2.10; I2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80-1.83; I2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22-2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21-2.29; 0%).
CONCLUSIONS: In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.
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.
OBJECTIVES: To compare the efficacies of oral glucosamine, chondroitin, the combination of glucosamine and chondroitin, acetaminophen and celecoxib on the treatment of knee and/or hip osteoarthritis.
METHODS: We searched electronic databases including PubMed, Embase, and Cochrane Library and the reference lists of relevant articles published from inception to October 23, 2017. A Bayesian hierarchical random effects model was used to examine the overall effect size among mixed multiple interventions.
RESULTS: We identified 61 randomised controlled trials of patients with knee and/or hip osteoarthritis. There was no obvious difference in the results between the traditional meta-analysis and the network meta-analysis. The network meta-analysis demonstrated that celecoxib was most likely the best option (SMD, -0.32 [95% CI, -0.38 to -0.25]) for pain, followed by the combination of glucosamine and chondroitin. For physical function, all interventions were significantly superior to oral placebo except for acetaminophen. In terms of stiffness, glucosamine (SMD, -0.36 [95% CI, -0.67 to -0.06]) and celecoxib (SMD, -0.29 [95% CI, -0.51 to -0.08]) were significantly better compared to placebo. In view of safety, compared to placebo only, celecoxib and acetaminophen presented significant differences.
CONCLUSIONS: Given the effectiveness of these non-steroidal anti-inflammatory drugs and symptomatic slow-acting drugs, oral celecoxib is more effective than placebo on relieving pain and improving physical function, followed by the combination of glucosamine and chondroitin. Acetaminophen is likely the least efficacious intervention option. This information, accompanied by the tolerability and economic costs of the included treatments, would be conducive to making decisions for clinicians.
OBJECTIVES: To explore the relative efficacy of oral pharmacologic interventions in the treatment of knee OA.
METHODS: A systematic literature review was conducted using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases to identify trials conducted in patients with knee OA with a minimum 6 weeks of follow-up. The standardized mean differences of the change from baseline to week 6 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain between the treatment groups were estimated using Bayesian random-effects network meta-analyses. Subgroup analyses of baseline pain status (high, pain score ≥ 60 mm; low, pain score < 60 mm) were performed.
RESULTS: Of 4,067 manuscripts, 44 were included in the evidence synthesis. Etoricoxib had the highest ranking for improving WOMAC pain (probability of being top ranked, P (best)=0.43) followed by naproxen (P (best)=0.12), acetaminophen (P (best)=0.04), and celecoxib (P (best)=0.02). The top 3 ranked interventions were etoricoxib, celecoxib, and aceclofenac in the higher pain group, and tramadol, celecoxib, and diclofenac in the lower pain group.
CONCLUSIONS: In the overall analysis, etoricoxib, celecoxib, and aceclofenac had the highest rankings for improving WOMAC pain. The ability to improve knee OA symptoms may differ depending on baseline pain and radiologic features.
Antecedentes: La artritis reumatoide es un trastorno autoinmune sistémico que causa inflamación extensa y persistente del revestimiento sinovial de las articulaciones y vainas del tendón. En la actualidad, no hay cura para la artritis reumatoide y el tratamiento se centra en la gestión de síntomas como dolor, rigidez y movilidad, con el objetivo de lograr una remisión estable y mejorar la movilidad. Celecoxib es un fármaco antiinflamatorio no esteroideo selectivo (AINE) utilizado para el tratamiento de personas con artritis reumatoide. OBJETIVOS: Evaluar los beneficios y los daños del celecoxib en personas con artritis reumatoide. Métodos de búsqueda: Se realizaron búsquedas en los registros de Ensayos Controlados (CENTRAL), MEDLINE, Embase y ensayos clínicos de Cochrane Central (ClinicalTrials.gov y el portal de ensayos de la Organización Mundial de la Salud) hasta el 18 de mayo de 2017. También se realizaron búsquedas en las listas de referencias y citas de Incluidos los estudios. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos controlados aleatorios prospectivos (ECA) que compararon celecoxib oral (200 mg y 400 mg al día) versus ninguna intervención, placebo o AINE tradicional (tNSAID) en personas con artritis reumatoide confirmada, de cualquier edad y sexo. Se excluyeron los estudios con menos de 50 participantes en cada brazo o tuvieron una duración de menos de cuatro semanas de tratamiento. Recopilación y análisis de datos: Se utilizaron los procedimientos metodológicos estándar esperados por The Cochrane Collaboration. Se incluyeron ocho ECA con una duración de 4 a 24 semanas, publicados entre 1998 y 2014, que incluyeron un total de 3988 adultos (edad media = 54 años), la mayoría mujeres (73%). Los participantes tuvieron artritis reumatoide por un promedio de 9,2 años. Todos los estudios se evaluaron con riesgo alto o poco claro de sesgo en al menos un dominio. En general, la evidencia se evaluó como de moderada a baja calidad. Cinco estudios fueron financiados por compañías farmacéuticas. Celecoxib versus placebo Se incluyeron dos estudios (N = 873) en los que los participantes recibieron 200 mg diarios o 400 mg al día o placebo. Los participantes que recibieron celecoxib mostraron mejoría clínica significativa en comparación con los que recibieron placebo (15% de mejoría absoluta, 95% IC 7% a 25%, RR 1,53, IC 95% 1,25 a 1,86, número necesario para tratar el beneficio = 7, IC del 95% 5 a 13, 2 estudios, 873 participantes, evidencia de moderada a baja calidad) .Los participantes que recibieron celecoxib reportaron menos dolor que las personas tratadas con placebo (mejoría absoluta del 11%, IC del 95% 8% a 14%, NNTB = 4 , 95% IC 3 a 6, 1 estudio, 706 participantes), pero los resultados no fueron concluyentes para la mejora de la función física (MD -0,10, IC del 95%: 0,29 a 0,10; 1 estudio, 706 participantes). En el grupo celecoxib, 15/293 Los participantes desarrollaron úlceras, en comparación con 4/99 en el grupo placebo (Peto OR 1,26, IC del 95%: 0,44 a 3,63, 1 estudio, 392 participantes, evidencia de baja calidad). Nueve (de 475) participantes en el grupo de celecoxib desarrollaron eventos adversos graves a corto plazo, en comparación con cinco (de 231) en el grupo placebo (Peto OR 0,87 (0,28 a 2,69, 1 estudio, 706 participantes, evidencia de baja calidad). Fueron menos retiradas entre las personas que recibieron celecoxib (163/475) en comparación con placebo (130/231) (22% cambio absoluto, IC 95% 16% a 27%, RR 0,61, IC 95% 0,52 a 0,72, 1 estudio, 706 Celecoxib vs tNSAIDseven estudios (N = 2930) en comparación celecoxib y tNSAIDs (amtolmetin guacyl, diclofenac, ibuprofen, y otros fármacos) Meloxicam, nabumetona, naproxeno, pelubiprofeno), un estudio incluyó comparaciones tanto de placebo como de tNSAID (N = 1149). Hubo una pequeña mejora, que puede no ser clínicamente significativa, en el número de participantes que alcanzaron la respuesta de criterios ACR20 en el grupo de celecoxib com En comparación con los antiinflamatorios no esteroideos (4% de mejoría absoluta; IC del 95% 0% menos mejoría a 8% más mejoría; RR 1,10; IC del 95%: 0,99 a 1,23; 4 estudios, 1981 participantes). Hubo una falta de evidencia de la diferencia entre los participantes en los grupos de celecoxib y tNSAID en términos de dolor o función física. Los pacientes que recibieron celecoxib tuvieron una menor incidencia de úlceras gastroduodenales ≥ 3 mm (34/870) en comparación con los que recibieron tNSAID (116 / 698). Esto equivale a un 12% de cambio absoluto (95% IC 11% a 13%, RR 0,22, IC del 95% 0,15 a 0,32, 5 estudios, 1568 participantes). Hubo un 7% menos de retiros entre las personas que recibieron celecoxib (95% IC 4% a 9%, RR 0,73, IC del 95%: 0,62 a 0,86, 6 estudios, 2639 participantes). Los resultados no fueron concluyentes para eventos adversos graves a corto plazo y cardiovascular (Evidencia de baja calidad). Hubo 17/918 eventos adversos graves en personas que tomaron celecoxib en comparación con 42/1236 entre las personas que recibieron placebo (Peto OR 0.71; IC del 95%: 0.39 a 1.28; 5 estudios, 2154 participantes). En un estudio se informaron eventos cardiovasculares en los grupos celecoxib y placebo (149 participantes). Conclusiones de los autores: Celecoxib puede mejorar los síntomas clínicos, aliviar el dolor y contribuir a la poca o ninguna diferencia en la función física en comparación con el placebo. Celecoxib se asoció con un menor número de retiros de los participantes. Los resultados para la incidencia de úlceras gastroduodenales (≥ 3 mm) y eventos adversos graves a corto plazo fueron inciertos; Sin embargo, hubo pocos eventos reportados para cualquiera.Celecoxib puede mejorar ligeramente los síntomas clínicos en comparación con tNSAIDs. Los resultados para reducir el dolor y mejorar la función física eran inciertos. Los participantes que tomaron celecoxib tuvieron menor incidencia de úlceras gastroduodenales (≥ 3 mm) y hubo menos retiros de los ensayos. Los resultados de eventos cardiovasculares y eventos adversos graves a corto plazo también fueron inciertos. La incertidumbre acerca de la tasa de eventos cardiovasculares entre celecoxib y tNSAIDs podría deberse al riesgo de sesgo; Otro factor es que se trata de pequeños ensayos a corto plazo. Se ha informado previamente que tanto celecoxib como tNSAIDs aumentan las tasas de eventos cardiovasculares. Nuestra confianza en los resultados sobre los daños es por lo tanto baja. Se necesitan ensayos clínicos más amplios comparando celecoxib con otros tNSAIDs para informar mejor a la práctica clínica.
This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis.
PATIENTS AND METHODS:
Randomized clinical trials evaluating ultramicronised diclofenac, diclofenac, celecoxib, etodolac and placebo in patients with osteoarthritis were identified. A search was conducted in May 2021 through PubMed, Scopus and Web of Science databases. A network meta-analysis was developed for efficacy outcome related to analgesia measured by the pain subscale of the Western Ontario and McMaster Universities tool. In addition, surface under the cumulative ranking was performed to rank the drugs in relation to this outcome.
RESULTS:
Twelve randomized clinical trials were included. Overall, ultramicronised diclofenac 105 mg/day (UD105) was better than all the others, including ultramicronised diclofenac 70 mg/day (UD70). In addition, surface under the cumulative ranking resulted in the following order: 1) ultramicronised diclofenac 105 mg/day (100%), 2) ultramicronised diclofenac 70 mg/day (80%), 3) celecoxib 200 mg/day (49%), 4) diclofenac 100 mg/day (48%), 5) placebo (19%) and 6) diclofenac 150 mg/day (6%).
CONCLUSIONS:
Ultramicronised diclofenac demonstrated superior efficacy compared to other conventional anti-inflammatory drugs and placebo in relieving osteoarthritis pain.
Pregunta de la revisión sistemática»Revisión sistemática de intervenciones
