Rheumatoid arthritis treated with 6-months of first-line biologic or biosimilar therapy: an updated systematic review and network meta-analysis.

OBJECTIVES: The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses. METHODS: Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical. RESULTS: Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs. CONCLUSIONS: In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.

Erratum: Validity and reliability of an online self-report 24-hour dietary recall method (Intake24): A doubly-labelled water study and repeated measures analysis - CORRIGENDUM.

[This corrects the article DOI: 10.1017/jns.2019.20.].

Validity and reliability of an online self-report 24-h dietary recall method (Intake24): a doubly labelled water study and repeated-measures analysis.

Online self-reported 24-h dietary recall systems promise increased feasibility of dietary assessment. Comparison against interviewer-led recalls established their convergent validity; however, reliability and criterion-validity information is lacking. The validity of energy intakes (EI) reported using Intake24, an online 24-h recall system, was assessed against concurrent measurement of total energy expenditure (TEE) using doubly labelled water in ninety-eight UK adults (40-65 years). Accuracy and precision of EI were assessed using correlation and Bland-Altman analysis. Test-retest reliability of energy and nutrient intakes was assessed using data from three further UK studies where participants (11-88 years) completed Intake24 at least four times; reliability was assessed using intra-class correlations (ICC). Compared with TEE, participants under-reported EI by 25 % (95 % limits of agreement -73 % to +68 %) in the first recall, 22 % (-61 % to +41 %) for average of first two, and 25 % (-60 % to +28 %) for first three recalls. Correlations between EI and TEE were 0·31 (first), 0·47 (first two) and 0·39 (first three recalls), respectively. ICC for a single recall was 0·35 for EI and ranged from 0·31 for Fe to 0·43 for non-milk extrinsic sugars (NMES). Considering pairs of recalls (first two v. third and fourth recalls), ICC was 0·52 for EI and ranged from 0·37 for fat to 0·63 for NMES. EI reported with Intake24 was moderately correlated with objectively measured TEE and underestimated on average to the same extent as seen with interviewer-led 24-h recalls and estimated weight food diaries. Online 24-h recall systems may offer low-cost, low-burden alternatives for collecting dietary information.

The Cost-effectiveness of Sequences of Biological Disease-modifying Antirheumatic Drug Treatment in England for Patients with Rheumatoid Arthritis Who Can Tolerate Methotrexate.

OBJECTIVE: To ascertain whether strategies of treatment with a biological disease-modifying antirheumatic drug (bDMARD) are cost-effective in an English setting. Results are presented for those patients with moderate to severe rheumatoid arthritis (RA) and those with severe RA. METHODS: An economic model to assess the cost-effectiveness of 7 bDMARD was developed. A systematic literature review and network metaanalysis was undertaken to establish relative clinical effectiveness. The results were used to populate the model, together with estimates of Health Assessment Questionnaire (HAQ) score following European League Against Rheumatism response; annual costs, and utility, per HAQ band; trajectory of HAQ for patients taking bDMARD; and trajectory of HAQ for patients using nonbiologic therapy (NBT). Results were presented as those associated with the strategy with the median cost-effectiveness. Supplementary analyses were undertaken assessing the change in cost-effectiveness when only patients with the most severe prognoses taking NBT were provided with bDMARD treatment. The costs per quality-adjusted life-year (QALY) values were compared with reported thresholds from the UK National Institute for Health and Care Excellence of £20,000 to £30,000 (US$24,700 to US$37,000). RESULTS: In the primary analyses, the cost per QALY of a bDMARD strategy was £41,600 for patients with severe RA and £51,100 for those with moderate to severe RA. Under the supplementary analyses, the cost per QALY fell to £25,300 for those with severe RA and to £28,500 for those with moderate to severe RA. CONCLUSION: The cost-effectiveness of bDMARD in RA in England is questionable and only meets current accepted levels in subsets of patients with the worst prognoses.

Sipuleucel-T for the Treatment of Metastatic Hormone-Relapsed Prostate Cancer: A NICE Single Technology Appraisal; An Evidence Review Group Perspective.

The National Institute for Health and Care Excellence (NICE) invited Dendreon, the company manufacturing sipuleucel-T, to submit evidence for the clinical and cost effectiveness of sipuleucel-T for asymptomatic or minimally symptomatic, metastatic, non-visceral hormone-relapsed prostate cancer patients in whom chemotherapy is not yet clinically indicated, as part of NICE's single technology appraisal process. The comparator was abiraterone acetate (AA) or best supportive care (BSC). The School of Health and Related Research at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper describes the company submission (CS), ERG review, and subsequent decision of the NICE Appraisal Committee (AC). The ERG produced a critical review of the clinical and cost-effectiveness evidence of sipuleucel-T based upon the CS. Clinical-effectiveness data relevant to the decision problem were taken from three randomised controlled trials (RCTs) of sipuleucel-T and a placebo (PBO) comparator of antigen-presenting cells (APC) being re-infused (APC-PBO) (D9901, D9902A and D9902B), and one RCT (COU-AA-302) of AA plus prednisone vs. PBO plus prednisone. Two trials reported a significant advantage for sipuleucel-T in median overall survival compared with APC-PBO: for trial D9901, an adjusted hazard ratio (HR) 0.47; (95 % confidence interval [CI] 0.29, 0.76) p < 0.002; for D9902B, adjusted HR 0.78 (95 % CI 0.61, 0.98) p = 0.03. There was no significant difference between groups in D9902A, unadjusted HR 0.79 (95 % CI 0.48, 1.28) p = 0.331. Sipuleucel-T and APC-PBO groups did not differ significantly in time to disease progression, in any of the three RCTs. Most adverse events developed within 1 day of the infusion, and resolved within 2 days. The CS included an indirect comparison of sipuleucel-T (D9902B) and AA plus prednisone (COU-AA-302). As trials differed in prior use of chemotherapy, an analysis of only chemotherapy-naïve patients was included, in which the overall survival for sipuleucel-T and AA was not significantly different, HR 0.94 (95 % CI 0.69, 1.28) p = 0.699. The ERG had several concerns regarding the data and assumptions incorporated within the company's cost-effectiveness analyses and conducted exploratory analyses to quantify the impact of making alternative assumptions or using alternative data inputs. The deterministic incremental cost-effectiveness ratio (ICER) for sipuleucel-T vs. BSC when using the ERG's preferred data and assumptions was £ 108,585 per quality-adjusted life-year (QALY) in the whole licensed population and £ 61,204/QALY in the subgroup with low prostate-specific antigen at baseline. The ERG also conducted an incremental analysis comparing sipuleucel-T with both AA and BSC in the chemotherapy-naïve subgroup. Sipuleucel-T had a deterministic ICER of £ 111,682/QALY in this subgroup, when using the ERG's preferred assumptions, and AA was extendedly dominated. The ERG also concluded that estimates of costs and benefits for AA should be interpreted with caution given the limitations of the indirect comparison. The AC noted that the ICER for sipuleucel-T was well above the range usually considered cost effective, and did not recommend sipuleucel-T for the treatment of asymptomatic or minimally symptomatic, metastatic, non-visceral hormone-relapsed prostate cancer.

Enhancements to angioplasty for peripheral arterial occlusive disease: systematic review, cost-effectiveness assessment and expected value of information analysis.

BACKGROUND: There have been rapid technological developments aimed at improving short- and long-term results of percutaneous transluminal balloon angioplasty (PTA) in peripheral arterial occlusive disease (PAD). OBJECTIVES: To assess current clinical effectiveness and cost-effectiveness evidence of additional techniques to standard PTA for PAD, develop a health economic model to assess cost-effectiveness and to identify where further research is needed. DATA SOURCES: Relevant electronic databases, including MEDLINE, EMBASE and The Cochrane Library were searched from inception to 2011, between May and October 2011. METHODS: Systematic reviews were conducted of clinical effectiveness and cost-effectiveness. The population was participants with symptomatic PAD undergoing endovascular treatment for disease distal to the inguinal ligament. Interventions were modifications of and adjuncts to PTA in the peripheral circulation, compared with conventional PTA. Outcomes included measures of clinical effectiveness and costs. Data were extracted from randomised controlled trials (RCTs), which were quality assessed using standard criteria. Where appropriate, meta-analyses using fixed- and random-effects methods produced relative risks (RRs). A discrete-event simulation model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The patient populations of intermittent claudication (IC) and critical limb ischaemia (CLI) were modelled separately. Univariate and probabilistic sensitivity analyses were undertaken. RESULTS: In total, 40 RCTs were included, many of which had small sample sizes. Significantly reduced restenosis rates were shown in meta-analyses of self-expanding stents (SES) {RR 0.67 [95% confidence interval (CI) 0.52 to 0.87]}, endovascular brachytherapy (EVBT) [RR 0.63 (95% CI 0.48 to 0.83)] at 12 months and drug-coated balloons (DCBs) at 6 months [RR 0.40 (95% CI 0.23 to 0.69)], and single studies of stent-graft or drug-eluting stent (DES), compared with PTA; a single study showed improvements with DES versus bare-metal stents (BMSs). Compared with PTA, walking capacity was not significantly affected by cutting balloon, balloon-expandable stents or EVBT; in SES, there was evidence of improvement in walking capacity after up to 12 months. The use of DCBs dominated both the assumed standard practice of PTA with bailout BMS and all other interventions because it lowered lifetime costs and improved quality of life (QoL). These results were seen for both patient populations (IC and CLI). Sensitivity analyses showed that the results were robust to different assumptions about the clinical benefits attributable to the interventions, suggesting that the use of DCBs is cost-saving. LIMITATIONS: Differing definitions of restenosis made direct comparison across trials difficult. There were few data available for walking capacity and QoL. CONCLUSIONS: The evidence showed a significant benefit to reducing restenosis rates for self-expanding and DESs, stent-graft, EVBT and DCBs. If it is assumed that patency translates into beneficial long-term clinical outcomes, then DCB and bail-out DES are most likely to be the cost-effective enhancements to PTA. A RCT comparing current recommended practice (PTA with bail-out BMS) with DCB and bail-out DES could assess long-term follow-up and cost-effectiveness. Data relating patency status to the need for reintervention and to the probability of symptoms returning should be collected, as should health-related QoL measures [European Quality of Life-5 Dimensions (EQ-5D) and maximum walking distance]. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002014. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Oseltamivir, zanamivir and amantadine in the prevention of influenza: a systematic review.

OBJECTIVE: To systematically review evidence relating to the clinical efficacy of oseltamivir, zanamivir and amantadine in the prevention of influenza. METHODS: RCTs evaluating these interventions in seasonal prophylaxis and post-exposure prophylaxis were identified using electronic bibliographic databases and handsearching of retrieved articles. RESULTS: Oseltamivir was effective in preventing symptomatic laboratory-confirmed influenza (SLCI) in seasonal prophylaxis in healthy adults and at-risk elderly subjects and in post-exposure prophylaxis within households of mixed composition. Post-exposure prophylaxis using oseltamivir for paediatric contacts was observed to prevent SLCI. Zanamivir prevented SLCI in seasonal prophylaxis in healthy adults, at-risk adults and adolescents and in post-exposure prophylaxis within mixed households, with a trend for seasonal and post-exposure preventative effects in elderly subjects. Evidence for amantadine prophylaxis across subgroups was very limited. However, amantadine prevented SLCI in seasonal prophylaxis in healthy adults and in outbreak control amongst adolescent subjects. Interventions were reported to be well tolerated by subjects, with a relatively low proportion of subjects experiencing drug-related adverse events and drug-related withdrawals. CONCLUSIONS: Evidence was identified for the efficacy of oseltamivir and zanamivir in preventing influenza in a range of population subgroups. The evidence base for amantadine was considerably more limited.

Involving users in the delivery and evaluation of mental health services: systematic review.

OBJECTIVES: To identify evidence from comparative studies on the effects of involving users in the delivery and evaluation of mental health services. DATA SOURCES: English language articles published between January 1966 and October 2001 found by searching electronic databases. STUDY SELECTION: Systematic review of randomised controlled trials and other comparative studies of involving users in the delivery or evaluation of mental health services. DATA EXTRACTION: Patterns of delivery of services by employees who use or who used to use the service and professional employees and the effects on trainees, research, or clients of mental health services. RESULTS: Five randomised controlled trials and seven other comparative studies were identified. Half of the studies considered involving users in managing cases. Involving users as employees of mental health services led to clients having greater satisfaction with personal circumstances and less hospitalisation. Providers of services who had been trained by users had more positive attitudes toward users. Clients reported being less satisfied with services when interviewed by users. CONCLUSIONS: Users can be involved as employees, trainers, or researchers without detrimental effect. Involving users with severe mental disorders in the delivery and evaluation of services is feasible.