Mixed Treatment Comparison Research Articles

PSY19 A COST PER RESPONDER ANALYSIS OF SECUKINUMAB COMPARED TO OTHER BIOLOGICS FOR TREATMENT OF MODERATE TO SEVERE PSORIASIS PATIENTS OVER 1 YEAR IN MOROCCO

Secukinumab 300 mg, a fully human interleukin-17A antibody, has demonstrated superior and sustained efficacy in treatment of adults with moderate to severe psoriasis over other biologic treatments. The analysis compared the cost per responder of secukinumab (SEC) as first-line biologic treatment versus adalimumab (ADA), etanercept (ETN), infliximab (INF), ustekinumab (UST) and placebo. A 52-week decision-tree model reflecting response to treatment defined as Psoriasis Area Severity Index (PASI) reduction of ≥90%, from a mixed-treatment comparison, led into a Markov model to evaluate the cost per response for each treatment. Responders (PASI≥90) at week 16 continued the initial treatment. Non-responders and drop-outs were switched to standard of care. Analyses were conducted for responders at week 16, week 52 and for sustained responders between weeks 16 and 52, from the perspective of the National Agency of Social Security in Morocco (ANAM) over a 1-year time horizon. Costs for each treatment included the drug and resource costs, published in the Moroccan Official National Gazette and available at the level of the National Agency of Social Security. SEC 300 mg had the lowest cost per PASI≥90 responder rate at 16 and 52 weeks (MAD 56 795; MAD 210 660), compared with UST (MAD 128 603; MAD 298 702), INF (MAD 92 142; MAD 289 400), ADA (MAD 133 888; MAD 347 414) or ETN (MAD 121 024; MAD 309 013). Likewise, SEC had the lowest cost per sustained 52-week PASI≥90 responder (MAD 153 151) and ADA the highest (MAD 200 778). Sensitivity analysis supported the robustness of the results. Secukinumab as a first-line biologic treatment for adults with moderate to severe Psoriasis has the lowest cost per PASI>90 compared with other biologics in Morocco over 1 year.

PND24 COST-EFFECTIVENESS ANALYSIS OF DIMETHYL FUMARATE IN THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS IN ITALY

Delayed-release dimethyl fumarate (also known as gastro-resistant dimethyl fumarate, DMF) is an oral disease-modifying therapy used for the treatment of relapsing-remitting multiple sclerosis (RRMS). Aim of this economic analysis was to evaluate the cost effectiveness of DMF compared with teriflunomide in first-line treatment of RRMS in Italy, adopting both National Healthcare Service (NHS) and societal perspectives. Cost-effectiveness analysis (CEA) was developed through a Markov model with lifetime horizon. Outcomes were measured in terms of life years (LYs), quality-adjusted life years (QALYs), lifetime costs and incremental cost-effectiveness ratio (ICER). Efficacy of treatments, expressed as reduction of disability progression and relapse rate, were derived from an elaboration of a mixed treatment comparison. Utilities were retrieved from DMF clinical trials and MS survey. Relapses, adverse events, progression to secondary progressive MS were associated with disutilities. Both direct and indirect costs were captured. Unit costs were based on current Italian prices, tariffs, published literature. An annual 3.5% discount rate was applied to costs and outcomes. One-way deterministic and probabilistic sensitivity analyses were conducted, a cost-effectiveness acceptability curve was generated. DMF was more efficacious than teriflunomide for both LYs (19.63 vs. 19.55) and QALYs (6.53 vs. 5.95). From NHS perspective, total costs per patient treated with DMF (€ 348,216) were slightly higher than with teriflunomide (€ 336,896). Resulting ICER was € 19,741 per QALY gained, significantly below the Italian willingness-to-pay threshold (€ 50,000 per QALY). From societal perspective, total costs per patient treated with DMF (€ 1.01 M) were lower than with teriflunomide (€ 1.03 M). DMF was dominant because more effective in terms of QALYs and less costly. Both sensitivity analyses confirmed robustness and reliability of base-case results. Results of this CEA confirm that DMF may be an optimal first-line treatment for RRMS in both Italian NHS and societal perspectives.

A Meta-Analysis Comparing Aspirin Alone Versus Dual Antiplatelet Therapy for the Prevention of Venous Graft Failure Following Coronary Artery Bypass Surgery

BackgroundAspirin (ASA) monotherapy is the current standard of care after coronary artery bypass grafting (CABG) to prevent saphenous vein graft (SVG) failure. Several small, randomized clinical trials (RCTs) have suggested that dual antiplatelet therapy (DAPT) may be more effective at preventing SVG failure than ASA alone; however, it is unclear whether some P2Y12 inhibitors are more effective than others for the prevention of SVG failure. MethodsScientific databases and websites were searched to find RCTs. Both traditional pairwise meta-analysis using random-effect model and network meta-analysis using mixed-treatment comparison models were performed to compare the efficacy of various anti-platelet strategies for the prevention of SVG failure. ResultsNine RCTs, which included a total of 1677 patients, were analyzed. Compared to ASA alone, DAPT decreased the risk of graft failure by 37% (RR: 0.63, 95% CI: 0.47–0.86; p = 0.003). In the moderator analysis, the decreased risk of graft failure with DAPT was not significantly different in the ASA + clopidogrel group than in the ASA + ticagrelor group (P-interaction = 0.17). The results of the network meta-analysis were consistent with those from pairwise analyses. The risk of major bleeding was not statistically significantly different between DAPT and ASA alone (RR: 1.35, 95% CI: 0.62–2.94; p = 0.45). ConclusionIn post-CABG patients, DAPT seems to be more effective at preventing graft failure than ASA alone. This strategy does not seem to significantly increase major bleeding risk. Clopidogrel- and ticagrelor-based DAPT seem to be equally effective for this indication.

Does X(a) mark the spot? An indirect mixed treatment comparison of Xa inhibitors compared to warfarin for patients with atrial fibrillation

The study sets out to compare the safety and efficacy of oral Non-vitamin K antagonists and warfarin in patients with atrial fibrillation. BackgroundPatients with atrial fibrillation carry a higher than normal risk for stroke, thus making them dependent on long-term anticoagulation treatment. While warfarin is considered to be the gold standard, several of its attributes, hinder adherence of patients to the therapeutic regimen. A new therapeutic category, the oral Non-vitamin K antagonist oral anticoagulants, aims to provide better and safer care to patients presenting with atrial fibrillation. MethodAn indirect mixed treatment comparison using data from published randomised controlled trials. ResultsLooking at the primary efficacy endpoint of stroke or systematic embolism, apixaban, rivaroxaban and dabigatran, demonstrated significant superiority compared to warfarin, while a trend exists for edoxaban [OR: 0.84 (95% CI 0.74–1.02)]. At the primary safety endpoint of major bleeding, evidence suggest that apixaban and edoxaban are superior to warfarin. Warfarin proved to be safer regarding gastrointestinal bleeding, compared to rivaroxaban, dabigatran and edoxaban. At the secondary efficacy endpoints of hemorrhagic and intracranial stroke, all Non-vitamin K antagonists oral anticoagulants were related to reduced risk versus warfarin. ConclusionsThe Non-vitamin K antagonist oral anticoagulants constitute a new and promising category in the field of atrial fibrillation, even in the context of uncertainty, which an indirect comparison yields.

Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective

BACKGROUND: Delayed-release dimethyl fumarate (also known as gastro-resistant dimethyl fumarate, hereafter dimethyl fumarate) is an oral disease-modifying therapy used for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS), an autoimmune chronic inflammatory condition of the central nervous system.OBJECTIVE: The objective of this economic analysis was to compare cost-effectiveness of dimethyl fumarate with the alternatives used as first-line treatment of RRMS in Italy.METHODS: The analysis was conducted from the Italian societal perspective. Health outcomes and costs were evaluated over a 50-year time horizon (equivalent to a lifetime horizon). Both health outcomes and costs were discounted at 3.5%. The cost-effectiveness analysis was conducted by adapting a Markov model, already used in previous similar economic analyses conducted in RRMS, to the Italian context. The Markov model estimated the clinical and economic consequences of treating RRMS patients with the following therapeutic options: dimethyl fumarate; interferon (IFN) beta-1a subcutaneous (SC) at two different doses, 22 mcg and 44 mcg; IFN beta-1b SC; glatiramer acetate (GA) SC 20 mg; oral teriflunomide. Clinical efficacy data were retrieved from an elaboration of an already published mixed treatment comparison (MTC). Both direct and indirect costs (disability, treatment acquisition, administration, monitoring, relapses, adverse events) were included in the analysis. One-way and probabilistic sensitivity analyses were carried out and cost-effectiveness acceptability curves generated.RESULTS: In the base-case analysis, dimethyl fumarate was more efficacious than alternatives, in terms of both survival (19.634 vs. 19.440-19.600 life years for alternatives), and quality-of-life-adjusted survival (6.526 vs. 5.143- 6.189 QALYs for alternatives). The total lifetime cost per patient treated with dimethyl fumarate (€ 954,286) was lower than that of the other DMTs included in the analysis. Therefore, dimethyl fumarate was dominant compared with all analyzed alternatives. Dimethyl fumarate was also the therapeutic option with the highest benefit on disease burden. In fact, costs of disability management were lower than those of all the other first-line drugs included in the analysis. The results of one-way deterministic sensitivity analysis and probabilistic sensitivity analysis confirmed the reliability of base-case results.CONCLUSIONS: The results of the cost-effectiveness analysis confirm that dimethyl fumarate is an optimal first-line treatment for RRMS in Italy, compared with the other first-line alternatives included in the economic analysis, when evaluated from the societal perspective.

Adverse pregnancy outcomes between the anti-malarial drugs: Is there a difference between the drugs recommended by World Health Organization? Results of a mixed treatment comparison analysis of randomized clinical trials and cohort studies.

Data regarding the relative safety profile of anti-malarial drugs in pregnancy is sparse mainly limited by the absence of head-to-head clinical trials. The present study is a network meta-analysis of safety of anti-malarial drugs used to treat malaria in pregnant women. A thorough literature search using the search strategy "Malaria [tiab] AND (Pregnant [tiab] OR Pregnancy [tiab])" was carried out for either randomized controlled trials or prospective cohort studies in pregnant malarial women prescribed any of the recommended anti-malarial drugs by World Health Organization (WHO) and that have reported adverse pregnancy outcomes such as miscarriage, still birth, and neonatal deaths. Odds ratio with 95% confidence interval was used as the effect estimate. Random-effects model and Markov Chain Monte Carlo simulation method was used to generate pooled estimates. Sensitivity analysis was performed excluding data from first trimester and GRADE approach was used to categorize the quality of evidence. A total of 1242 papers were obtained with the search strategy, of which seven evaluating 10 treatment arms in a total of 5510 participants were included in the present meta-analysis. The pooled estimates revealed significantly lower risks of abortion with quinine and artemisinin-lumefantrine compared to dihydroartemisinin-piperaquine, artesunate with mefloquine and artesunate with amodiaquine. But when a cohort study that was conducted in the first trimester of pregnancy was excluded, no significant differences were observed in the risk of abortion between the anti-malarial drugs. No significant differences in the risk of either stillbirths or neonatal deaths were observed with any of the drugs. The quality of evidence was found to be very low due to serious limitations in both the precision and indirectness. WHO recommended anti-malarials in pregnancy have similar risk profiles with regard to abortion, stillbirth and neonatal deaths.

Cost Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in Colombia.

ObjectivesThe aim of this study was to evaluate the cost effectiveness of mirabegron relative to two antimuscarinics, oxybutynin extended release (ER) and tolterodine ER, in patients with overactive bladder (OAB) from the perspective of a third-party payer in Colombia.MethodsA Markov model simulated the therapeutic management, disease course, and complications in hypothetical cohorts of OAB patients over a 5-year period. The model predicted costs and three outcomes: quality-adjusted life-years (QALYs), micturition state improvement (MSI), and incontinence state improvement (ISI). In each 1-month cycle, patients could transition between different health states reflecting symptom severity. Transition probabilities were estimated from a published mirabegron trial and mixed treatment comparison. Other inputs such as treatment discontinuation based on treatment-specific rates of persistence, resource use and costs, anticholinergic burden, comorbidity treatment, and drug acquisition were obtained from Società Italiana Scienze Mediche, Instituto de Seguros Sociales Tariff Manual, published literature, and expert opinion. Deterministic and probabilistic sensitivity analyses were conducted. Costs are presented in 2017 Colombia Pesos (COP).ResultsMirabegron was cost effective for all outcome measures at a willingness-to-pay threshold of 124,919,725 COP, which is three times the per capita gross domestic product (GDP). Using QALYs as the measure of effect, mirabegron had an incremental cost-effectiveness ratio (ICER) of 85,802,036 COP/QALY (26,365 USD/QALY) and 66,360,134 COP/QALY (20,384 USD/QALY) versus oxybutynin and tolterodine, respectively. Probabilistic sensitivity analyses showed that mirabegron was cost effective in 99.5% and 100% of simulations compared with oxybutynin and tolterodine, respectively. Using MSI and ISI as the measure of effects yielded ICERs below one GDP.ConclusionsMirabegron is a cost effective alternative to oxybutynin and tolterodine from the perspective of a third-party payer in Colombia.Electronic supplementary materialThe online version of this article (10.1007/s41669-019-0149-9) contains supplementary material, which is available to authorized users.

148-LB: Efficacy and Safety of Adding an Oral Hypoglycemic Agent or a GLP-1 Receptor Agonist to Insulin in Patients with Type 1 Diabetes: A Network Meta-analysis

Objective: Despite intensive insulin treatment in patients with type 1 diabetes (T1D), their glycemic levels often do not reach the recommended target goal. We performed a network meta-analysis to evaluate the efficacy and safety of additional therapy to insulin in patients with T1D. Methods: We searched CENTRAL, MEDLINE, and Embase from 1970 until January 2019 to identify randomized controlled trials (RCTs) in T1D patients treated with insulin and oral hypoglycemic agents or glucagon-like peptide-1 receptor agonists. We performed network meta-analyses using Bayesian models and generated rankings of the different hypoglycemic agents by generation mixed treatment comparison. Results: With 23 RCTs (n =3,839), we performed the network meta-analysis using eight groups; 1) insulin alone, 2) insulin and metformin, 3) insulin and canagliflozin, 4) insulin and dapagliflozin, 5) insulin and empagliflozin, 6) insulin and sotagliflozin, 7) insulin and liraglutide, and 8) insulin and exenatide. Compared with insulin alone, HbA1c was significantly lower in the group treated with insulin and sotagliflozin (mean difference: -0.43%; 95% Crl: -0.66, -0.20). Total daily insulin dose was significantly lower in the insulin and sotagliflozin group by 6.4 U/day than other groups. Compared with insulin alone, body weight was decreased in the group with insulin and canagliflozin by 4.5 kg, insulin and sotagliflozin by 2.8 kg, insulin and liraglutide by 4.5kg, and insulin and exenatide by 5.1 kg, respectively. Severe hypoglycemic episodes did not differ between the groups. Conclusions: In patients with T1D, sotagliflozin treatment combined with insulin decreased HbA1c levels, insulin dose, and body weight without hypoglycemia compared with insulin monotherapy. Combined treatment of canagliflozin, liraglutide, or exenatide with insulin was also effective in weight loss compared with insulin alone in these patients. Disclosure Y. Kim: None. S. Hwang: None. S. Lim: None.

Can cerebral microbleeds predict stroke recurrence?

Can cerebral microbleeds predict stroke recurrence?

Systematic review and network meta-analysis of first-line treatments in mRCC.

e16086 Background: The approval of newer agents in metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm in first-line settings. The aim of this review was to compare pazopanib against current first-line treatments in RCC. Methods: A systematic review was conducted that assessed pazopanib against first-line agents in treatment naïve patients with mRCC. Relevant databases and conferences were searched to identify randomized controlled trials (RCTs) assessing treatment naïve adult patient (≥18 years). Frequentist mixed treatment comparison (MTC) method was applied for the pairwise comparisons among treatments for ITT population and favorable, intermediate, and poor risk subgroups. Results: Twenty-three RCTs met the eligibility criteria. The MTC results showed that pazopanib was comparable to sunitinib in terms of progression free survival (PFS) and overall survival (OS) in ITT population. Cabozantinib was significantly better compared to pazopanib for PFS; however, there was heterogeneity in the patient population. Pazopanib was comparable to nivolumab + ipilimumab when assessed for PFS in ITT population; although, favorable risk patients treated with pazopanib achieved significantly higher PFS compared to nivolumab + ipilimumab (HR: 0.46, 95% CI: [0.37, 0.57]). Atezolizumab + bevacizumab and avelumab + axitinib were associated with significantly higher PFS compared to pazopanib. Cabozantinib and nivolumab + ipilimumab were associated with better OS compared to pazopanib. Conclusions: The newer agents i.e. cabozantinib and nivolumab + ipilimumab are approved for intermediate/poor risk patients. The results suggests that pazopanib is still a reliable option for treatment of patients in first-line settings, especially for favorable/intermediate risk patients.[Table: see text]

PND18 CLINICAL AND ECONOMIC IMPACT OF INITIATING DIMETHYL FUMARATE VERSUS OTHER DISEASE MODYFING THERAPIES IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS IN GERMANY

To evaluate the economic impact among relapsing-remitting multiple sclerosis (RRMS) patients in Germany initiating treatment with dimethyl fumarate (DMF) versus the initiation of DMF following treatment failure of glatiramer acetate (GA), teriflunomide (TER), or a mixed market combination of interferons (IFNs). A Markov model of 10 health states (EDSS scores from 0 to 9) and death over a lifetime horizon in MS patients using annual cycles was used to compare the outcomes of treated RRMS patients from a societal perspective. The model incorporates the ability to fail the initial DMT and subsequently switch to another DMT based on incurring ≥ 2 relapses within a 12-month period. Efficacy inputs were estimated from a mixed treatment comparison, including hazard ratios for 6-month confirmed disability progression, and risk ratios for annual relapse rates. Economic inputs included the costs of treatment, relapse, and disability status. All estimates are analyzed using the eligible cohort of DMF patients overall and per patient and reflect costs in 2018 Euros. The model results showed that among RRMS patients initially treated with DMF in Germany, average time on initial therapy was 11.1 years as compared to GA (6.7 years), TERI (5.6 years) and IFNs (6.8 years). Initiating treatment with DMF resulted in relapse offsets of 2.3 compared to GA, 2.2 compared to TERI, and 1.9 compared to IFNs. When initiating DMF as first-line therapy, the total costs per patient were reduced by €46,414 versus GA, €25,583 versus TERI, and €60,124 versus IFNs. The total cost savings for all DMF patients in Germany (n = 10,510) were ∼€1B versus GA, ∼€570M versus TERI, and ∼€1.3B versus IFNs. Initiating DMF as the initial treatment for German RRMS patients before initiating and failing on GA, TERI, or IFNs results improved economic benefits. Supported by: Biogen.

PMH13 ESTIMATING THE BENEFIT OF LONG-ACTING INJECTABLES FOR SCHIZOPHRENIA TREATMENT IN RWANDA USING A ONE-YEAR COST-CONSEQUENCE MODEL

A one-year cost-consequence model was developed to estimate health and economic impact of paliperidone palmitate long-acting formulations, 1-monthly (PP1M) and 3-monthly (PP3M), compared to current standard of care for the treatment of schizophrenia in Rwanda The model measures key goals and outcomes of schizophrenia treatment including hospitalization, relapse, and treatment persistence as well as key adverse events with direct and indirect costs specific to Rwanda. Clinical inputs were based on mixed treatment comparisons of pivotal phase III clinical trials while cost inputs were based on local standard of care data collected by a blinded randomized audit of schizophrenia patients conducted at Ndera Neuropsychiatric Hospital in Kigali. Supplemental data was collected from the annual report and other documents on hospital tariffs, travel costs to the hospital, cost of medicines on formulary, and distribution of patients by insurance category. The great majority of patients received first-generation antipsychotics, mainly in oral form. Risperidone and Olanzapine were the only available second-generation antipsychotics. Patients from across Rwanda are required to visit a health facility (usually Ndera Neuropsychiatric Hospital in the capital, Kigali) once a month to refill their prescriptions. The average patient has 1.2 hospitalisations per year. Travel costs, in addition to traditional direct medical costs, make up a significant proportion of patient costs associated with schizophrenia treatment. Using the model to compare PP3M to haloperidol, the predominant standard of care, over the course of one year, patients on long-acting injectables spent more months on treatment (10.7 vs 9.8 months), had fewer relapses (0.20 vs 0.43 relapses) and needed fewer days in hospital (8 vs 16 days). Schizophrenia imposes significant health and economic burden on schizophrenia patients and caregivers. The improved outcomes suggest there may be a role for second generation LAIs for the treatment of schizophrenia patients in Rwanda.

Economic evaluation of sunitinib versus pazopanib and best supportive care for the treatment of metastatic renal cell carcinoma in Chile: cost-effectiveness analysis and a mixed treatment comparison

ABSTRACTBackground: Sunitinib and Pazopanib are two metastatic renal cell carcinoma (MRCC) treatment alternatives, however the health system in Chile does not consider coverage for any. The cost-effectiveness versus relevant comparator was assessed to support evidence-based decision making.Methods: A four health states Markov model was built: first, second line treatments, BSC and death. Benefits were measured in QALYs, and efficacy estimates were obtained from an indirect treatment comparison. A 10-year time horizon and a 3% undifferentiated discount rate were considered. Deterministic and probabilistic sensitivity analyses were performed.Results: The costs of treating MRCC with Sunitinib were higher than Pazopanib and BSC. When comparing Sunitinib versus Pazopanib, the incremental benefit is small favoring Sunitinib (0.03 QALYs). The base case scenario shows an average ICER of PA versus BSC of US$62,327.11/QALY and of US$85,885/QALY for Sunitinib versus Pazopanib. The ICER was most sensitive to the OS relative to BSC, where evidence was associated to important bias.Conclusions: Sunitinib or Pazopanib can be considered cost-effective if a 3 GDP per-capita threshold is assumed. The decision between SU or PA is highly sensitive to the price of the drugs, rather than the outcomes. Therefore, the decision might be made based on cost-minimization exercise.

Vasoactive Agents for the Management of Variceal Bleeding: A Mixed Treatment Comparison Network Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials.

Vasoactives such as terlipressin, somatostatin, vasopressin, octreotide and nitrates are commonly used to treat variceal bleeding. The present study is a network meta-analysis comparing the efficacy and safety of the above vasoactive agents for treating variceal bleeding. Electronic databases were searched for appropriate randomized clinical trials evaluating vasoactives in cirrhotic patients with variceal bleeding. Random-effects model was used to generate the pooled estimates. Mortality was the primary outcome and bleeding control, re-bleeding rate, hospital stay, blood transfusion requirements and adverse events were the secondary outcome measures. Fifty randomized clinical trials were included of which 37 were included for the primary outcome. The overall analysis did not reveal any significant difference in the mortality risk between any of the vaso-active drugs except for terlipressin that had statistically significant benefits from direct pooled estimates. Somatostatin and terlipressin showed significant reduction in the mortality risks at 24 h. Terlipressin significantly reduced re-bleeding rate; somatostatin and vasopressin were associated with better hemostasis; and terlipressin and vasopressin significantly reduced the requirement for blood transfusion. Terlipressin, vasopressin and glyceryltrinitrate/vasopressin were also associated with increased risk of adverse events. Terlipressin could be the best agent in the vasoconstrictor category for managing variceal bleeding. Somatostatin and vasopressin can serve as alternatives.

A Bayesian mixed treatment comparison of efficacy of biologics and small molecules in early rheumatoid arthritis.

The current paradigm in the management of rheumatoid arthritis (RA) is to treat patients in the early stage of the disease (ERA). Previous meta-analysis-based mixed treatment comparisons (MTCs), aimed to identify the most effective drugs in ERA, are biased by the wide "window" of early definition, ranging from 6months to 2years. The aim of this study was to estimate through a Bayesian Network Meta-Analysis which biologics or small molecules are more likely to achieve a 1-year good clinical response in ERA patients with disease duration < 1year. According to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, randomized controlled trials (RCTs) of biologic agents and small molecules in combination with MTX to treat patients affected with ERA lasting < 1year were searched through MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov between 1990 and September 2017. The outcome of interest was the achievement of American College of Rheumatology (ACR) 50 and ACR 70 response at 1year. WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK) was used to perform the analyses, using a fixed effect model. Fourteen studies were included in the analysis. Tofacitinib (64.83%) followed by Etanercept (23.26%) were the drugs with the highest probability of achieving ACR50 response. Rituximab showed the highest probability of inducing ACR70 response (52.81%) followed by Etanercept (26.85%). This is the first MTC involving only RCTs on ERA patients with disease duration < 1year. Tofacitinib and rituximab were the drugs ranked first in inducing 1-year ACR50 and ACR70 response, respectively.

Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis

Background: Clinical practice guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) currently recommend pirfenidone and nintedanib. However, there is a lack of evidence from head-to-head comparisons.Objectives: To perform a systematic review and network meta-analysis (NMA) to access the efficacy and tolerability of two new treatments for IPF, pirfenidone and nintedanib.Methods: Randomized controlled trials (RCTs) selection (CENTRAL, MEDLINE, Embase), data extraction, risk of bias analysis, and GRADE assessment were carried out by two authors separately. Direct estimates were calculated using standard pairwise meta-analysis. A Bayesian mixed treatment comparison approach for NMA estimates, with 95% confidence intervals (CI), was used to compare the treatments, calculating odds ratios (OR) and number needed to treat (NNTB) or harm (NNTH).Results: The NMA on 10 randomized controlled trials showed that each drug had a positive effect on percentage of forced vital capacity (FVC) decline ≥ 10% (pirfenidone OR = 0.54 [95% CI = 0.37–0.80], NNTB = 9 [95% CI = 7–22]; nintedanib OR = 0.59 [95% CI = 0.41–0.84], NNTB = 9 [95% CI = 6–23]), but no significant differences were noted when comparing pirfenidone and nintedanib with respect to acute exacerbations, mortality, and serious adverse events (FVC decline OR = 0.91 [95% CI = 0.45–2.03]) or dropouts (OR = 0.75 [95% CI = 0.33–1.27]). Nintedanib showed an effect on dropouts, OR = 1.61 (1.13–2.28) and NNTH = 14 (8–61).Conclusions: Based on RCTs of 12 month duration in patients with IPF, a positive effect on FVC decline was noted for both treatments and on dropouts for nintedanib, but no significant differences were noted between treatments.

Aproximación a los metanálisis de comparación de múltiples tratamientos: una revisión de la literatura

Multiple treatment comparison meta-analyses are systematic reviews that allow to make direct or indirect comparisons of different interventions from the data collection results of randomized clinical trials, grouping them in a common outcome or conglomerate which is expressed quantitatively. Other names given are network meta-analyses, or mixed treatment comparison meta-analyses or indirect meta-analyses. The use of the comparison of several treatments allows a greater estimation of the intervention effect. This is a guide for the physician to make more accurate decisions and to apply better care criteria to their patients. This literature review should help the reader to perform an organized and adequate critical reading (according to the JAMA recommendations) of the multiple treatment comparison meta-analyses. The article is addressed to authors and editors, and it contains information on how this type of studies should be interpreted and communicated.

Ranking crop species using mixed treatment comparisons.

The mixed treatment comparison (MTC) method has been proposed to combine results across trials comparing several treatments. MTC allows coherent judgments on which of the treatments is the most effective. It produces estimates of the relative effects of each treatment compared with every other treatment by pooling direct and indirect evidence. In this article, we explore how this methodological framework can be used to rank a large number of agricultural crop species from yield data collected in field experiments. Our approach is illustrated in a meta-analysis of yield data obtained in 67 field studies for 36 different bioenergy crop species. The considered dataset defines a network of comparisons of crop species. We introduce several Bayesian MTC models based on baseline treatment contrasts and evaluate the practical advantages of these models to produce yield ratio estimates. We explore the consistency of some estimates by node-splitting and compare our results to those obtained with a classical two-way linear mixed model. Results reveal that the model showing the lowest deviance information criterion (DIC) includes both study random effects and study-specific residual variances. But all the tested models including study random effects lead to similar yield ratio estimates. The proposed Bayesian framework allows an in-depth analysis of the uncertainty in the species ranking.

Effectiveness of contrast-associated acute kidney injury prevention methods; a systematic review and network meta-analysis

BackgroundDifferent methods to prevent contrast-associated acute kidney injury (CA-AKI) have been proposed in recent years. We performed a mixed treatment comparison to evaluate and rank suggested interventions.MethodsA comprehensive Systematic review and a Bayesian network meta-analysis of randomised controlled trials was completed. Results were tabulated and graphically represented using a network diagram; forest plots and league tables were shown to rank treatments by the surface under the cumulative ranking curve (SUCRA). A stacked bar chart rankogram was generated. We performed main analysis with 200 RCTs and three analyses according to contrast media and high or normal baseline renal profile that includes 173, 112 & 60 RCTs respectively.ResultsWe have included 200 trials with 42,273 patients and 44 interventions. The primary outcome was CI-AKI, defined as ≥25% relative increase or ≥ 0.5 mg/dl increase from baseline creatinine one to 5 days post contrast exposure. The top ranked interventions through different analyses were Allopurinol, Prostaglandin E1 (PGE1) & Oxygen (0.9647, 0.7809 & 0.7527 in the main analysis). Comparatively, reference treatment intravenous hydration was ranked lower but better than Placebo (0.3124 VS 0.2694 in the main analysis).ConclusionMultiple CA-AKI preventive interventions have been tested in RCTs. This network evaluates data for all the explored options. The results suggest that some options (particularly allopurinol, PGE1 & Oxygen) deserve further evaluation in a larger well-designed RCTs.

Supraglottic airway devices as a strategy for unassisted tracheal intubation: A network meta-analysis.

We aimed to compare the effectiveness of supraglottic airway devices as a strategy for unassisted tracheal intubation. Accordingly, we searched the OVID-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, KoreaMed, and Google Scholar databases to identify all relevant randomized controlled trials (RCTs) on supraglottic airway devices as a strategy for tracheal intubation published until May 2017. The primary outcome was the overall success rate of intubation by the intention to treat (ITT) strategy. The secondary outcomes of the study were the overall success rate of tracheal intubation by the per protocol (PP) strategy and the success rate of tracheal intubation at first attempt by ITT and PP. We conducted a network meta-analysis with a mixed-treatment comparison method to combine direct and indirect comparisons among supraglottic airway devices. Of 1396 identified references, 16 RCTs (2014 patients) evaluated unassisted intubation with supraglottic airway devices. Patients were grouped according to the type of device used: LMA-CTrach, LMA-Fastrach, Air-Q, i-gel, CobraPLA, Ambu-Aura, or single-use LMA devices. Based on the surface under the cumulative ranking curve, the three best supraglottic airway devices for use as a strategy for unassisted tracheal intubation were LMA-CTrach (which included video-assisted tracheal tube guidance), single-use LMA-Fastrach, and LMA-Fastrach. LMA-Fastrach showed a higher success rate of intubation than did i-gel, CobraPLA, Air-Q, and Ambu-Aura. However, this study was limited by the small number of eligible RCTs. Therefore, well-designed RCTs performed on large patient populations are required to increase the confidence of the results.