Dataset Information

Relative Efficacy and Safety of Anti-Inflammatory Biologic Agents for Osteoarthritis: A Conventional and Network Meta-Analysis.

ABSTRACT: Previous studies have consistently revealed that both local and systemic inflammations are the key to the onset and progression of osteoarthritis (OA). Thus, anti-inflammatory biologic agents could potentially attenuate the progression of OA. We conducted this meta-analysis to examine the efficacy and safety of ant-inflammatory biologic agents among OA patients.

Methods

Five databases were searched for randomized controlled trials (RCTs) comparing biologics with placebo or each other in OA patients. Data of pain, physical function, stiffness, and adverse events (AEs) were extracted for a conventional and a Bayesian network meta-analysis.

Results

15 studies with data for 1566 patients were analyzed. In the conventional meta-analysis, etanercept (SMD -0.47; 95% CI -0.89, -0.05) and infliximab (SMD -2.04; CI -2.56, -1.52) were superior to placebo for knee pain. In the network meta-analysis, infliximab was superior to all the other biologic agents in improving pain (vs. hyaluronic acid (SMD -22.95; CI -34.21, -10.43), vs. adalimumab (SMD -21.71; CI -32.65, -11.00), vs. anakinra (SMD -24.63; CI -38.79, -10.05), vs. canakinumab (SMD -32.83; CI -44.45, -20.68), vs. etanercept (SMD -18.40; CI -29.93, -5.73), vs. lutikizumab (SMD -25.11; CI -36.47, -14.78), vs. naproxen (SMD -30.16; CI -41.78, -17.38), vs. tocilizumab (SMD -24.02; CI -35.63, -11.86) and vs. placebo (SMD -25.88; CI -34.87, -16.60)). No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs.

Conclusions

The findings suggest that infliximab may relieve pain more than other biological agents in OA patients. No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. The results must be interpreted cautiously; therefore, further randomized controlled trials are warranted.

SUBMITTER: Li Y

PROVIDER: S-EPMC9317938 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background: With the growing importance of research about the association between neuroinflammation and major depressive disorder (MDD), anti-inflammatory agents have been used as a new antidepressant therapy in clinical practice. We conducted a network meta-analysis (NMA) with up-to-date evidence to compare different anti-inflammatory agents for improving the treatment of MDD patients. Methods: To identify eligible randomized clinical trials, four databases (i.e, the Cochrane Library, Web of Science, PubMed and Embase) were searched from inception date to May 31, 2020. Anti-inflammatory agents were defined as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, cytokine inhibitors, statins, pioglitazone, minocycline, N-acetylcysteine (NAC) and omega-3 fatty acid (Omega-3 FA). The main outcomes of this NMA were efficacy, acceptability and remission rate. Risk ratio (RR) was adopted for dichotomous outcomes, and the confidence interval (CI) was set at 95%. STATA 14.0 and R 3.6.3 were used to conduct the NMA. The study protocol was registered with PROSPERO (CRD42020182531). Results: A total of 39 studies, involving 2871 participants, were included in quantitative data synthesis. For efficacy, NSAIDs (RR=0.50, 95%CI: 0.26-0.73) and pioglitazone (RR=0.45, 95%CI: 0.20-0.84) were more favorable than placebo. With respect to acceptability, NSAIDs were more acceptable than placebo (RR=0.89, 95%CI: 0.77-0.99) and minocycline (RR=1.22, 95%CI: 1.03-1.49). For remission, NSAIDs were more superior than placebo (RR=0.48, 95%CI: 0.27-0.79) and Omega-3 FA (RR=2.01, 95%CI: 1.09-3.90), while NACs were more favorable than placebo (RR=0.39, 95%CI: 0.13-0.99). Based on the surface under the cumulative ranking curve (SUCRA) value, corticosteroids (0.86) were the best anti-inflammatory agent for MDD patients in terms of efficacy, but the head-to-head comparisons for the efficacy of glucocorticoids and other agents were not statistically significant. As for acceptability, NSAIDs (0.81) were much better than other anti-inflammatory agents. Besides, NAC (0.80) was the best anti-inflammatory agent in the terms of remission. Conclusions: In summary, we found that corticosteroids were more superior than other agents in terms of efficacy according to the SUCRA value. However, this result must be interpreted with caution because the head-to-head comparisons for the efficacy of glucocorticoids and other agents did not reach statistical significance. NSAIDs were recommended for acceptability and NAC for remission rate.

Project description:Inhibitors of tumor necrosis factor (anti-TNF agents) are the most effective therapy for Crohn's disease (CD). We evaluated the real-world comparative effectiveness and safety of different anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) in biologic-naive patients with CD in a retrospective, propensity-matched cohort study using a national administrative claims database (Optum Labs Data Warehouse).We identified 3205 biologic-naive patients with CD (mean age, 41 ± 15 years; 45% male; median follow-up period after anti-TNF therapy, 19 months; 44.5% on infliximab and 38.9% on adalimumab) who received their first prescription for an anti-TNF agent (infliximab, adalimumab, or certolizumab pegol) after a 12-month period without any anti-TNF treatment (baseline), and with a minimum follow-up period of 6 months after their initial anti-TNF prescription, between 2006 and 2014. The primary outcomes were all-cause and CD-related hospitalization, abdominal surgery, corticosteroid use, and serious infections. We performed a propensity-matched, Cox proportional hazards analysis, accounting for baseline demographics, health care use, comorbidities, and use of CD-related medication.Compared with adalimumab-treated patients, infliximab-treated patients had a lower risk of CD-related hospitalization (adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.66-0.98), abdominal surgery (aHR, 0.76; 95% CI, 0.58-0.99), and corticosteroid use (aHR, 0.85; 95% CI, 0.75-0.96). Compared with certolizumab pegol-treated patients, infliximab-treated patients had a lower risk of all-cause hospitalization (aHR, 0.70; 95% CI, 0.52-0.95) and CD-related hospitalization (aHR, 0.59; 95% CI, 0.39-0.90). Adalimumab-treated patients had outcomes comparable with those of certolizumab pegol-treated patients. All agents had comparable risk of serious infections.In a retrospective analysis of a large cohort of biologic-naive patients with CD, we found infliximab to be superior to adalimumab and certolizumab pegol for patient-relevant outcomes, without increased risk of serious infections.

Project description:Objective Non-steroidal anti-inflammatory drugs are used as first-line treatment of primary dysmenorrhea, but there has been no optimal clinical choice among non-steroidal anti-inflammatory drugs yet. The present study was to assess the relative benefits of different common non-steroidal anti-inflammatory drugs for primary dysmenorrhea patients with a network meta-analysis. Methods Randomized controlled trials were screened by our criteria and included in the network meta-analysis. Pain relief was considered as primary outcomes and adverse effect was supplied as a safety outcome, while additional rescue, assessment score, and pain intensity difference were secondary outcomes. All the indexes were evaluated with odds ratio or standardized mean difference. Surface under cumulative ranking curve result was used to calculate the ranking of each treatment. Results Totally, 72 randomized controlled trials of 5723 patients and 13 drugs were included in our study after screening. As for pain relief, all drugs except nimesulide, rofecoxib, and waldecoxib were superior to aspirin (odds ratio with 95% credible intervals, diclofenac: 0.28 (0.08, 0.86), flurbiprofen: 0.10 (0.03, 0.29), ibuprofen: 0.32 (0.14, 0.73), indomethacin: 0.21 (0.07, 0.58), ketoprofen: 0.25 (0.10, 0.64), mefenamic acid: 0.28 (0.09, 0.87), naproxen: 0.31 (0.15, 0.64), piroxicam: 0.15 (0.03, 0.59), and tiaprofenic acid: 0.17 (0.04, 0.63)). Aspirin also required additional rescue when compared with the majority of other drugs (flurbiprofen: 3.46 (1.15, 11.25), ibuprofen: 6.30 (2.08, 20.09), mefenamic acid: 7.32 (1.51, 37.71), naproxen: 2.66 (1.17, 6.55), and tiaprofenic acid: 9.58 (1.43, 94.63)). As for assessment of the whole treatment, ketoprofen, naproxen, rofecoxib, and ibuprofen got higher score significantly than placebo. In addition, ibuprofen performed better than placebo in pain intensity difference. Considering the safety, tiaprofenic acid and mefenamic acid were noticeable in low risk, and indomethacin revealed higher risk than any other drugs. According to the results of network analysis and surface under cumulative ranking curve, flurbiprofen was considered to be the best one among all the treatments in efficacy, and aspirin was worse than most of others. On the other hand, tiaprofenic acid and mefenamic acid were indicated as the safest drugs. Conclusion Considering the efficacy and safety, we recommended flurbiprofen and tiaprofenic acid as the optimal treatments for primary dysmenorrhea.

Project description:BackgroundSignificant blood loss is still one of the most frequent complications in spinal surgery, which often necessitates blood transfusion. Massive perioperative blood loss and blood transfusion can create additional risks. Aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The aim of this study was to evaluate the efficacy and safety of aprotinin, EACA, and low/high doses of TXA in spinal surgery, and assess the use of which agent is the most optimal intervention using the network meta-analysis (NMA) method.MethodsFive electronic databases were searched, including PubMed, Cochrane Library, ScienceDirect, Embase, and Web of Science, from the inception to March 1, 2018. Trials that were randomized and compared results between TXA, EACA, and placebo were identified. The NMA was conducted with software R 3.3.2 and STATA 14.0.ResultsThirty randomized controlled trial (RCT) studies were analyzed. Aprotinin (standardized mean difference [SMD]=-0.65, 95% credibility intervals [CrI;-1.25, -0.06]), low-dose TXA (SMD = -0.58, 95% CrI [-0.92, -0.25]), and high-dose TXA (SMD = -0.70, 95% CrI [-1.04, -0.36]) were more effective than the respective placebos in reducing intraoperative blood loss. Low-dose TXA (SMD = -1.90, 95% CrI [-3.32, -0.48]) and high-dose TXA (SMD = -2.31, 95% CrI [-3.75, -0.87]) had less postoperative blood loss. Low-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) and high-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) significantly reduced total blood loss. However, only high-dose TXA (SMD = -2.07, 95% CrI [-3.26, -0.87]) was more effective in reducing the amount of transfusion, and was significantly superior to low-dose TXA in this regard (SMD = -1.67, 95% CrI [-3.20, -0.13]). Furthermore, aprotinin (odds ratio [OR] = 0.16, 95% CrI [0.05, 0.54]), EACA (OR = 0.46, 95% CrI [0.22, 0.97]) and high dose of TXA (OR = 0.34, 95% CrI [0.19, 0.58]) had a significant reduction in transfusion rates. Antifibrinolytics did not show a significantly increased risk of postoperative thrombosis. Results of ranking probabilities indicated that high-dose TXA had the greatest efficacy and a relatively high safety level.ConclusionsThe antifibrinolytic agents are able to reduce perioperative blood loss and transfusion requirement during spine surgery. And the high-dose TXA administration might be used as the optimal treatment to reduce blood loss and transfusion.

Project description:BACKGROUND:Network meta-analyses (NMAs) provide comparative treatment effects estimates in the absence of head-to-head randomized controlled trials (RCTs). This NMA compared the efficacy and safety of dolutegravir (DTG) with other recommended or commonly used core antiretroviral agents. METHODS:A systematic review identified phase 3/4 RCTs in treatment-naïve patients with HIV-1 receiving core agents: ritonavir-boosted protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand inhibitors (INSTIs). Efficacy (virologic suppression [VS], CD4+ cell count change from baseline) and safety (adverse events [AEs], discontinuations, discontinuation due to AEs, lipid changes) were analyzed at Week 48 using Bayesian NMA methodology, which allowed calculation of probabilistic results. Subgroup analyses were conducted for VS (baseline viral load [VL] ≤/> 100,000copies/mL, ≤/> 500,000copies/mL; baseline CD4+ ≤/>200cells/μL). Results were adjusted for the nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) combined with the core agent (except subgroup analyses). RESULTS:The NMA included 36 studies; 2 additional studies were included in subgroup analyses only. Odds of achieving VS with DTG were statistically superior to PIs (odds ratios [ORs] 1.78-2.59) and NNRTIs (ORs 1.51-1.86), and similar but numerically higher than other INSTIs. CD4+ count increase was significantly greater with DTG than PIs (difference: 23.63-31.47 cells/μL) and efavirenz (difference: 34.54 cells/μL), and similar to other core agents. INSTIs were more likely to result in patients achieving VS versus PIs (probability: 76-100%) and NNRTIs (probability: 50-100%), and a greater CD4+ count increase versus PIs (probability: 72-100%) and NNRTIs (probability: 60-100%). DTG was more likely to result in patients achieving VS (probability: 94-100%), and a greater CD4+ count increase (probability: 53-100%) versus other core agents, including INSTIs (probability: 94-97% and 53-93%, respectively). Safety outcomes with DTG were generally similar to other core agents. In patients with baseline VL > 100,000copies/mL or ≤ 200 CD4+cells/μL (18 studies), odds of achieving VS with DTG were superior or similar to other core agents. CONCLUSION:INSTI core agents had superior efficacy and similar safety to PIs and NNRTIs at Week 48 in treatment-naïve patients with HIV-1, with DTG being among the most efficacious, including in patients with baseline VL > 100,000copies/mL or ≤ 200 CD4+cells/μL, who can be difficult to treat.