Systemic treatments for eczema: a network meta-analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Sawangjit R
PROVIDER: S-EPMC8128359 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC6486272 | biostudies-literature
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| S-EPMC6956468 | biostudies-literature
Project description:BackgroundMany onychomycosis treatments have not been directly compared in head-to-head clinical trials.ObjectiveTo determine the relative efficacy of onychomycosis treatments using network meta-analysis (NMA).MethodsWe conducted a systematic review and NMA of mycological cure rates.ResultsNineteen trials were included in the network. Terbinafine 250 mg was significantly superior to all treatments except itraconazole 400 mg pulse therapy. The itraconazole 400 mg pulse regimen was significantly superior to all topicals except efinaconazole 10% nail solution. Itraconazole 200 mg was significantly superior to all topical treatments, while fluconazole 150-450 mg, efinaconazole 10% nail solution, tavaborole 5% nail solution, ciclopirox nail lacquer 8%, terbinafine nail solution, and amorolfine 5% nail lacquer were significantly superior to placebo.ConclusionsNewly developed topicals have improved the odds ratios (ORs) of mycological cure, yet these ORs were not significantly greater than preexisting topical treatments. Further experience with these agents will reveal their clinical significance, and head-to-head trials are warranted. © 2015 S. Karger AG, Basel.
| S-EPMC4857825 | biostudies-literature
Project description:INTRODUCTION:There are numerous new systemic treatments for atopic dermatitis in various stages of development and most are being compared with placebo rather than active comparators. In order to understand the relative efficacy and safety of existing and new treatments for atopic dermatitis, robust mixed comparisons (ie, direct and indirect) would be beneficial. To address this gap, this protocol describes methods for a systematic review and network meta-analysis of systemic treatments for atopic dermatitis. METHODS AND ANALYSIS:We will update the search of a previous systematic review, including searches of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database and the Global Resource of EczemA Trials database in addition to clinical trial protocol registries. Title, abstract and full paper screening as well as data extraction will be conducted in duplicate by independent researchers. Primary outcomes include efficacy with regards to clinician-reported signs and patient-reported symptoms and safety with regards to withdrawal from treatment due to adverse events and the occurrence of serious adverse events. Secondary outcomes will include change in quality of life and itch severity. Where possible and appropriate, network meta-analysis will be performed for each outcome using a random-effects model within a Bayesian framework. If appropriate, the review will be transitioned to a living review with continuous updating of the analysis. ETHICS AND DISSEMINATION:Dissemination in a peer-reviewed scientific journal is planned. PROSPERO REGISTRATION NUMBER:CRD42018088112; Pre-results.
| S-EPMC6119412 | biostudies-literature
Project description:ImportanceMost clinical trials assessing systemic immunomodulatory treatments for patients with atopic dermatitis are placebo-controlled.ObjectiveTo compare the effectiveness and safety of systemic immunomodulatory treatments for patients with atopic dermatitis in a systematic review and network meta-analysis.Data sourcesThe Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of Eczema Trials database, and clinical trial registries were searched from inception to October 28, 2019.Study selectionEnglish-language randomized clinical trials of 8 weeks or more of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis were included. Titles, abstracts, and articles were screened in duplicate. Of 10 324 citations, 39 trials were included.Data extraction and synthesisData were extracted in duplicate, and the review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-Analyses guidelines. Random-effects bayesian network meta-analyses were performed and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria.Main outcomes and measuresPrespecified outcomes were change in signs of disease, symptoms, quality of life, itch, withdrawals, and serious adverse events.ResultsA total of 39 trials with 6360 patients examining 20 medications and placebo were included. Most trials were conducted for adults receiving up to 16 weeks of therapy. Dupilumab, 300 mg every 2 weeks, was associated with improvement in the Eczema Area and Severity Index score vs placebo (mean difference, 11.3-point reduction; 95% credible interval [CrI], 9.7-13.1 [high certainty]). Cyclosporine (standardized mean difference, -1.1; 95% CrI, -1.7 to -0.5 [low certainty]) and dupilumab (standardized mean difference, -0.9; 95% CrI, -1.0 to -0.8 [high certainty]) were similarly effective vs placebo in clearing clinical signs of atopic dermatitis and may be superior to methotrexate (standardized mean difference, -0.6; 95% CrI, -1.1 to 0.0 [low certainty]) and azathioprine (standardized mean difference, -0.4; 95% CrI, -0.8 to -0.1 [low certainty]). Several investigational medications for atopic dermatitis are promising, but data to date are limited to small early-phase trials. Safety analyses were limited by low event rates.Conclusions and relevanceDupilumab and cyclosporine may be more effective for up to 16 weeks of treatment than methotrexate and azathioprine for treating adult patients with atopic dermatitis. More studies directly comparing established and novel treatments beyond 16 weeks are needed and will be incorporated into future updates of this review.
| S-EPMC7177646 | biostudies-literature
Project description:BackgroundCurrently, 6-month oxaliplatin-based chemotherapy has been recommended as the preferred adjuvant treatment against high-risk stage 2 and stage 3 colon cancer patients.MethodsRecord retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology and European Society for Medical Oncology meeting libraries from inception to November 2019. Regarding survival and tolerability, randomized controlled trials comparing different adjuvant systemic regimens against high-risk stage 2 and stage 3 colon cancer were eligible. Disease-free survival was primary endpoint. Network calculation was based on a random-effects model, and relative ranking of each node was numerically indicated by p score.ResultsA total of 30 trials were included, corresponding to 54,109 patients. Regarding disease-free survival, none of the analyzed regimens displayed significant superiority against common comparator 6-month capecitabine plus oxaliplatin (XELOX), while 12-month [network hazard ratio (HR) 0.81 (0.60-1.10); 0.79 (0.57-1.10)] and 3-month XELOX [0.95 (0.86-1.04); 0.93 (0.83-1.05)] were top-ranking regimens showing non-inferiority among overall and stage 3 patients. Moreover, by pairwise meta-analysis, 3-month XELOX demonstrated significant superiority against 6-month XELOX among low-risk stage 3 patients [pairwise HR 0.78 (0.63-0.97)]. Concerning adverse events, 3-month oxaliplatin-based chemotherapy was significantly better than the 6-month counterpart with respect to peripheral sensory neuropathy, thrombocytopenia and fatigue. The 12-month capecitabine monotherapy failed to display non-inferiority among other major adverse events.ConclusionsThe 3-month XELOX treatment could be an alternative option of the 6-month regimen among low-risk stage 3 patients. Among high-risk stage 3 patients, 6-month oxaliplatin-based regimens still seem more competitive. In addition, clinical application of 12-month capecitabine monotherapy should be cautious, despite its top rankings, especially among non-Asian countries.
| S-EPMC7739130 | biostudies-literature
Project description:ImportanceMultiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with unclear comparative effectiveness and safety and widely varied costs.ObjectiveTo compare the effectiveness and safety determined in randomized clinical trials of systemic treatments for mCSPC.Data sourcesBibliographic databases (MEDLINE, Embase, and Cochrane Central), regulatory documents (US Food and Drug Administration and European Medicines Agency), and trial registries (ClinicalTrials.gov and European Union clinical trials register) were searched from inception through November 5, 2019.Study selection, data extraction, and synthesisEligible studies were randomized clinical trials evaluating the addition of docetaxel, abiraterone acetate, apalutamide, or enzalutamide to androgen-deprivation therapy (ADT) for treatment of mCSPC. Two investigators independently performed screening. Discrepancies were resolved through consensus. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by bayesian network meta-analysis and survival models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used.Main outcomes and measuresOverall survival, radiographic progression-free survival, and serious adverse events (SAEs).ResultsSeven trials with 7287 patients comparing 6 treatments (abiraterone acetate, apalutamide, docetaxel, enzalutamide, standard nonsteroidal antiandrogen, and placebo/no treatment) were identified. Ordered from the most to the least effective determined by results of clinical trials, treatments associated with improved overall survival when added to ADT included abiraterone acetate (hazard ratio [HR], 0.61; 95% credible interval [CI], 0.54-0.70), apalutamide (HR, 0.67; 95% CI, 0.51-0.89), and docetaxel (HR, 0.79; 95% CI, 0.71-0.89); treatments associated with improved radiographic progression-free survival when added to ADT included enzalutamide (HR, 0.39; 95% CI, 0.30-0.50), apalutamide (HR, 0.48; 95% CI, 0.39-0.60), abiraterone acetate (HR, 0.51; 95% CI, 0.45-0.58), and docetaxel (HR, 0.67; 95% CI 0.60-0.74). Docetaxel was associated with substantially increased SAEs (odds ratio, 23.72; 95% CI, 13.37-45.15), abiraterone acetate with slightly increased SAEs (odds ratio, 1.42; 95% CI, 1.10-1.83), and other treatments with no significant increase in SAEs. Risk of bias was noted for 4 trials with open-label design, 3 trials with missing data, and 2 trials with potential unprespecified analyses.Conclusions and relevanceIn this network meta-analysis, as add-on treatments to ADT, abiraterone acetate and apalutamide may provide the largest overall survival benefits with relatively low SAE risks. Although enzalutamide may improve radiographic progression-free survival to the greatest extent, longer follow-up is needed to examine the overall survival benefits associated with enzalutamide.
| S-EPMC7809610 | biostudies-literature
Project description:Although various drugs are currently used for restless legs syndrome (RLS) in clinic, selecting appropriate drugs for patients is difficult. This network meta-analysis (NMA) aimed to compare the efficacy and safety of different drugs. After literature searching and screening, 46 trials, including 10,674 participants are included in this NMA. The pooled results showed that, compared with placebo, only levodopa is inefficient to relieve symptoms of RLS. Cabergoline decreases IRLS scores to the greatest extent among all drugs (MD -11.98, 95% CI -16.19 to -7.78). Additionally, pramipexole is superior to ropinirole in alleviating symptoms of RLS (MD -2.52, 95% CI -4.69 to -0.35). Moreover, iron supplement alleviates RLS symptoms significantly compared with placebo in patient with iron deficiency (MD -5.15, 95% CI -8.99 to -1.31), but not for RLS patients with normal serum ferritin level (MD -2.22, 95% CI -6.99 to 2.56). For primary RLS, these drugs are also effective, while there is insufficient data to analyze drug efficacy in secondary RLS. We analyzed risk of common adverse effects of drugs including nausea, somnolence, fatigue, headache and nasopharyngitis. Alpha-2-delta ligands and DAs are favorable choices for both primary and secondary RLS because of their significant efficacy and good tolerability. Iron supplement can significantly alleviate symptoms of RLS patients with iron deficiency than placebo. We recommend gabapentin, gabapentin enacarbil, and pregabalin for clinicians for first consideration mainly because that they rarely cause augmentation. Oxycodone-naloxone could be considered in patients with severe or very severe RLS who failed in treatment with above drugs.
| S-EPMC8576256 | biostudies-literature
Project description:Multiple treatments for early-moderate grade symptomatic haemorrhoids currently exist, each associated with their respective efficacy, complications, and risks. The aim of this study was to compare the relative clinical outcomes and effectiveness of interventional treatments for grade II-III haemorrhoids. A systematic review was conducted according to PRISMA criteria for all the RCTs published between 1980 and 2020; manuscripts were identified using the MEDLINE, Embase, and CENTRAL databases. Inclusion criteria were RCTs comparing procedural interventions for grade II-III haemorrhoids. Primary outcomes of interest were: symptom recurrence at a minimum follow-up of 6 weeks, postprocedural pain measured on a visual analogue scale (VAS) on day 1, and postprocedural complications (bleeding, urinary retention, and bowel incontinence). After bias assessment and heterogeneity analysis, a Bayesian network meta-analysis was performed. Seventy-nine RCTs were identified, including 9232 patients. Fourteen different treatments were analysed in the network meta-analysis. Overall, there were 59 RCTs (73 per cent) judged as being at high risk of bias, and the greatest risk was in the domain measurement of outcome. Variable amounts of heterogeneity were detected in direct treatment comparisons, in particular for symptom recurrence and postprocedural pain. Recurrence of haemorrhoidal symptoms was reported by 54 studies, involving 7026 patients and 14 treatments. Closed haemorrhoidectomy had the lowest recurrence risk, followed by open haemorrhoidectomy, suture ligation with mucopexy, stapled haemorrhoidopexy, and Doppler-guided haemorrhoid artery ligation (DG-HAL) with mucopexy. Pain was reported in 34 studies involving 3812 patients and 11 treatments. Direct current electrotherapy, DG-HAL with mucopexy, and infrared coagulation yielded the lowest pain scores. Postprocedural bleeding was recorded in 46 studies involving 5696 patients and 14 treatments. Open haemorrhoidectomy had the greatest risk of postprocedural bleeding, followed by stapled haemorrhoidopexy and closed haemorrhoidectomy. Urinary retention was reported in 30 studies comparing 10 treatments involving 3116 participants. Open haemorrhoidectomy and stapled haemorrhoidopexy had significantly higher odds of urinary retention than rubber band ligation and DG-HAL with mucopexy. Nine studies reported bowel incontinence comparing five treatments involving 1269 participants. Open haemorrhoidectomy and stapled haemorrhoidopexy had the highest probability of bowel incontinence. Open and closed haemorrhoidectomy, and stapled haemorrhoidopexy were associated with worse pain, and more postprocedural bleeding, urinary retention, and bowel incontinence, but had the lowest rates of symptom recurrence. The risks and benefits of each treatment should be discussed with patients before a decision is made.
| S-EPMC8504447 | biostudies-literature
Project description:Network meta-analysis of randomized controlled trials is increasingly used to combine both direct evidence comparing treatments within trials and indirect evidence comparing treatments across different trials. When the outcome is binary, the commonly used contrast-based network meta-analysis methods focus on relative treatment effects such as odds ratios comparing two treatments. As shown in a recent report, when using contrast-based network meta-analysis, the impact of excluding a treatment in the network can be substantial, suggesting a methodological limitation. In addition, relative treatment effects are sometimes not sufficient for patients to make decisions. For example, it can be challenging for patients to trade off efficacy and safety for two drugs if they only know the relative effects, not the absolute effects. A recently proposed arm-based network meta-analysis, based on a missing-data framework, provides an alternative approach. It focuses on estimating population-averaged treatment-specific absolute effects. This article examines the influence of treatment exclusion empirically using 14 published network meta-analyses, for both arm- and contrast-based approaches. The difference between these two approaches is substantial, and it is almost entirely due to single-arm trials. When a treatment is removed from a contrast-based network meta-analysis, it is necessary to exclude other treatments in two-arm studies that investigated the excluded treatment; such exclusions are not necessary in arm-based network meta-analysis, leading to substantial gain in performance.
| S-EPMC4892976 | biostudies-literature