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: 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.
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.
