Background and Objective Clostridium difficile infection (CDI) is associated with high management costs, particularly in recurrent cases. Fidaxomicin treatment results in lower recurrence rates than vancomycin and metronidazole, but has higher acquisition costs in Europe and the USA. This systematic literature review summarises economic evaluations (EEs) of fidaxomicin, vancomycin and metronidazole for treatment of CDI.MethodsElectronic databases (MEDLINE®, Embase, Cochrane Library) and conference proceedings (ISPOR, ECCMID, ICAAC and IDWeek) were searched for publications reporting EEs of fidaxomicin, vancomycin and/or metronidazole in the treatment of CDI. Reference bibliographies of identified manuscripts were also reviewed. Cost-effectiveness was evaluated according to the overall population of patients with CDI, as well as in subgroups with severe CDI or recurrent CDI, or those at higher risk of recurrence or mortality.ResultsOverall, 27 relevant EEs, conducted from the perspective of 12 different countries, were identified. Fidaxomicin was cost-effective versus vancomycin and/or metronidazole in 14 of 24 EEs (58.3%), vancomycin was cost-effective versus fidaxomicin and/or metronidazole in five of 27 EEs (18.5%) and metronidazole was cost-effective versus fidaxomicin and/or vancomycin in two of 13 EEs (15.4%). Fidaxomicin was cost-effective versus vancomycin in most of the EEs evaluating specific patient subgroups. Key cost-effectiveness drivers were cure rate, recurrence rate, time horizon, drug costs and length and cost of hospitalisation.ConclusionsIn most EEs, fidaxomicin was demonstrated to be cost-effective versus metronidazole and vancomycin in patients with CDI. These results have relevance to clinical practice, given the high budgetary impact of managing CDI and increasing restrictions on healthcare budgets.OtherThis analysis was initiated and funded by Astellas Pharma Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-017-0540-2) contains supplementary material, which is available to authorized users.

Background Tofacitinib and other new treatments approved for use in psoriatic arthritis have only recently been included in psoriatic arthritis treatment guidelines, and studies evaluating the relative efficacy of available therapies are important to inform treatment decisions by healthcare professionals. Objective To perform a network meta-analysis to evaluate the efficacy and safety profiles of tofacitinib, biologic disease-modifying antirheumatic drugs (bDMARDs), and apremilast in patients with psoriatic arthritis naïve to tumor necrosis factor inhibitor therapy (TNFi-naïve) or with an inadequate response (TNFi-IR). Methods A systematic literature review used searches of MEDLINE, Embase, and The Cochrane Library on October 9, 2017. Randomized controlled trials including adult patients with psoriatic arthritis receiving treatment administered as monotherapy or with conventional synthetic DMARDs were selected. Efficacy outcomes included American College of Rheumatology 20 response, change from baseline in Health Assessment Questionnaire-Disability Index, ≥75% improvement in Psoriasis Area and Severity Index, and change from baseline in Dactylitis Severity Score and Leeds Enthesitis Index. Treatment effects were evaluated during placebo-controlled phases, using a binomial logit model for binary outcomes and a normal identify link model for other outcomes. Discontinuations due to adverse events and serious infection events were assessed as safety outcomes. Results The network meta-analysis included 24 published randomized controlled trials, of which 13 enrolled TNFi-naïve patients only, 3 enrolled TNFi-IR patients only, and 8 enrolled both TNFi-naïve and TNFi-IR patients. Placebo-controlled treatment durations ranged from 12 to 24 weeks. Indirect comparisons showed tofacitinib 5 and 10 mg BID to have similar efficacy compared with most bDMARDs and apremilast in improving joint symptoms (based on American College of Rheumatology 20 response), and with some bDMARDs in improving skin symptoms (based on Psoriasis Area and Severity Index) (tofacitinib 10 mg BID only in TNFi-IR) in patients with psoriatic arthritis who were TNFi-naïve or TNFi-IR. Results also showed that, compared with placebo, the improvement in physical functioning (based on Health Assessment Questionnaire-Disability Index) with tofacitinib 5 and 10 mg BID was similar to that observed with most bDMARDs and apremilast in TNFi-naïve patients, and similar to that observed with all bDMARDs with available data in the TNFi-IR population. Improvements in Dactylitis Severity Score and Leeds Enthesitis Index scores were comparable between treatments. Tofacitinib 5 and 10 mg BID were median-ranked 8 and 15, respectively, for discontinuation due to any adverse events, and 5 and 16, respectively, for a serious infection event out of a total of 20 treatments in the network (lower numbers are more favorable). Conclusions Tofacitinib p...

BackgroundUricosurics (benzbromarone, probenecid, or sulfinpyrazone) are recommended for second-line treatment of gout if treatment target cannot be achieved with allopurinol or if allopurinol cannot be tolerated. While some uricosurics have been available since the 1970s, only two head-to-head trials have been conducted, both of which compared benzbromarone with probenecid. A new uricosuric, lesinurad, has recently been developed, but also has no head-to-head data against current uricosurics. There is therefore a need to compare the efficacy of uricosurics relative to each other via network meta-analysis (NMA), which requires high-quality evidence from well conducted trials, and also for evidence-based recommendations.ObjectivesTo identify and assess the quality of the randomised controlled trial (RCT) evidence for uricosurics currently licensed for the treatment of gout, and to assess the feasibility of developing an NMA based on these trials.MethodsA systematic review was conducted to identify RCT evidence for uricosurics, followed by an assessment of the quality of the comparisons possible based on this evidence using the GRADE system. This assessment was then used in a feasibility assessment for NMA based on the comparability of the trials in terms of population, comparators, and outcomes.ResultsIn total, 21 publications reporting on 13 unique studies were identified by the SR, two of which had no common comparator arm with other trials and were excluded from further assessment. Eleven studies were included in the quality assessment informing comparisons between treatments for two outcomes: proportion of patients achieving sUA <6 mg/dL (or 0.36 mMol/L) and change from baseline in sUA. Issues with two or more elements of the methodological quality of the studies were present in all comparisons other than lesinurad plus allopurinol vs placebo plus allopurinol, including open-label design, incomplete reporting and sparse data mainly of safety assessment, and inadequate randomisation. The outcomes assessed in these RCTs were generally comparable across trials, but follow-up time ranged from 1 week to a mean of 19.6 months and few trials reported data at the same endpoint. In addition, line of therapy was unclear/not reported in four trials, with uricosurics used in a first-line population in two trials. The final GRADE quality rating was 5 (high) for lesinurad plus allopurinol vs placebo plus allopurinol and –1 to 1 (very low) for all other comparisons (febuxostat plus lesinurad was not included in comparisons). Based on this assessment, it was concluded that a NMA or other statistical comparison is not possible because of substantial heterogeneity between trials for methodological quality, outcomes, and population.ConclusionsThe quality of the randomised controlled trial evidence supporting the use of uricosurics other than lesinurad for gout is poor, and there is substantial heterogeneity in reported follow-up times and study populations. It is therefore not possible to make valid comparisons between these trea...

BackgroundTofacitinib is an oral JAK inhibitor for the treatment of psoriatic arthritis (PsA).ObjectivesTo perform a systematic literature review (SLR) and network meta-analysis (NMA) to evaluate the efficacy of tofacitinib 5 and 10 mg BID relative to biologic disease-modifying antirheumatic drugs (bDMARDs) or a targeted synthetic DMARD (apremilast [APR]) in tumour necrosis factor inhibitor-naïve (TNFi-N) patients with active PsA.MethodsThe SLR identified randomised controlled clinical trials (RCTs) evaluating tofacitinib, bDMARDs or APR to treat patients with active PsA who were TNFi-N. Outcomes included American College of Rheumatology (ACR)20 response and change from baseline in Health Assessment Questionnaire-Disability Index (ΔHAQ-DI), Dactylitis Severity Score (ΔDSS) and Leeds Enthesitis Index (ΔLEI). Treatment effects were only evaluated during placebo (PBO)-controlled trial phases. The Bayesian NMA (with non-informative priors) was conducted using WinBUGs. The binomial logit model was used for ACR20. ΔHAQ-DI, ΔDSS and ΔLEI were analysed using the normal identify link model. A fixed-effect model was fitted to the data. Median treatment rankings represent data from each iteration of the model from which inferences are based, following model convergence.ResultsThe SLR identified 25 RCTs and 21 were included in the NMA (see treatments in table 1). All trials allowed methotrexate use. PBO-controlled treatment durations ranged from 12–24 weeks. In general, patient characteristics were similar across trials. All treatments were associated with improvements in ACR20 and ΔHAQ-DI vs PBO. Tofacitinib 5 mg BID was associated with substantially decreased odds ratios (ORs) for ACR20 vs golimumab 50 and 100 mg Q4W, etanercept 25 mg BW, infliximab 5 mg/kg and secukinumab 150 mg QW-Q4W (table 1); ORs for all remaining comparators were not substantially different. Tofacitinib 10 mg BID was associated with a substantially increased OR for ACR20 vs APR 20 mg BID. Etanercept was associated with an improvement in ΔHAQ-DI vs tofacitinib 5 and 10 mg BID. There was no difference in ΔHAQ-DI for tofacitinib vs other bDMARDs. For ACR20, tofacitinib 5 and 10 mg BID were median ranked 14 (95% credible interval: 8, 17) and 9,5, 14 respectively, among 18 comparators. For ΔHAQ-DI, tofacitinib 5 and 10 mg BID were median ranked 114, 13 and 8,2, 13 respectively, among 14 comparators. Two studies evaluated ΔDSS and ΔLEI; there were no substantial differences in ΔDSS and ΔLEI for tofacitinib 5 and 10 mg BID vs adalimumab 40 mg Q2W and ixekizumab 80 mg Q2W and Q4W.Abstract THU0300 – Table 1Fixed-effect NMA data for ACR20 and ΔHAQ-DI in TNFi-N patients with PsA – comparison of bDMARDs or apremilast vs tofacitinib 5 and 10 mg BIDa,bConclusionsBased on the NMA of published RCTs in TNFi-N patients with PsA, tofacitinib 5 and 10 mg BID had similar efficacy vs many, but not all, bDMARDs and APR in improving ACR20 and ΔHAQ-DI.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by P Scutt of CMC and funded by Pfizer Inc...

One-way univariate sensitivity analysis showed that the threshold price was most sensitive to varying the ambulatory reporting factor and least sensitive to the vaccine administration cost and coverage rate for catch-up cohorts. ConClusions: Dengue vaccination significantly reduced the health and economic burden in Malaysia. It is a potentially value for money investment if the purchaser could negotiate a price at or below the cost-effective threshold price for the vaccination programs.