Best step-up treatments for children with uncontrolled asthma: a systematic review and network meta-analysis of individual participant data.

BACKGROUND: There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines make different recommendations. We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients age <18 years on ICS. METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, Web of Science, National Institute for Health and Care Excellence Technology Appraisals, National Institute for Health and Care Research Health Technology Assessment series, World Health Organization International Clinical Trials Registry, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants age <18 years with uncontrolled asthma on any ICS dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting ß2-agonists (LABA) or combined with leukotriene receptor antagonists (LTRA), LTRA alone, theophylline or placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (low/medium/high dose), ICS+LABA, ICS+LTRA, LTRA alone, theophylline and placebo. RESULTS: Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials and aggregate data were obtained from 19 trials. Compared with ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44, 95% credibility interval (95% CrI) 0.19-0.90) and with an increased forced expiratory volume in 1 s (mean difference 0.71, 95% CrI 0.35-1.06). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control. CONCLUSIONS: Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.

A "Bundle of Care" to Improve Anticoagulation Control in Patients Receiving Warfarin in Uganda and South Africa: Protocol for an Implementation Study.

BACKGROUND: The quality of warfarin anticoagulation among Sub-Saharan African patients is suboptimal. This is due to several factors, including a lack of standardized dosing algorithms, difficulty in providing timely international normalized ratio (INR) results, a lack of patient feedback on their experiences with treatment, a lack of education on adherence, and inadequate knowledge and training of health care workers. Low quality of warfarin anticoagulation, expressed as time in therapeutic range (TTR), is associated with higher adverse event rates, including bleeding and thrombosis, and ultimately, increased morbidity and mortality. Processes and interventions that improve this situation are urgently needed. OBJECTIVE: This study aims to evaluate the implementation of the "warfarin bundle," a package of interventions to improve the quality of anticoagulation and thereby clinical outcomes. The primary outcome for this study is TTR over the initial 3 months of warfarin therapy. METHODS: Patients aged 18 years or older who are newly initiated on warfarin for venous thromboembolism, atrial fibrillation, or valvular heart disease will be enrolled and followed up for 3 months at clinics in Cape Town, South Africa, and Kampala, Uganda, where the warfarin bundle is implemented. A retrospective review of the clinical records of patients on warfarin treatment before implementation (controls) will be used for comparison. This study uses a mixed methods approach of the implementation of patient- and process-centered activities to improve the quality of anticoagulation. Patient-centered activities include the use of clinical dosing algorithms, adherence support, and root cause analysis, whereas process-centered activities include point-of-care INR testing, staff training, and patient education and training. We will assess the impact of these interventions by comparing the TTR and safety outcomes across the 2 groups, as well as the cost-effectiveness and acceptability of the package. RESULTS: We started recruitment in June 2021 and stopped in August 2022, having recruited 167 participants. We obtained ethics approval from the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee, the Provincial Health Research Committees in South Africa, the Joint Clinical Research Centre Institutional Review Board, Kampala, and the University of Liverpool Research Ethics Committee. As of February 2023, data cleaning and formal analysis are underway. We expect to publish the full results by December 2023. CONCLUSIONS: We anticipate that the "bundle of care," which includes a clinical algorithm to guide individualized dosing of warfarin, will improve INR control and TTR of patients in Uganda and South Africa. We will use these findings to design a larger, multisite clinical trial across several Sub-Saharan African countries. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46710.

Novel oral iron therapy for iron deficiency anaemia: How to value safety in a new drug?

AIMS: Novel oral iron supplements may be associated with a reduced incidence of adverse drug reactions compared to standard treatments of iron deficiency anaemia. The aim was to establish their value-based price under conditions of uncertainty surrounding their tolerability. METHODS: A discrete-time Markov model was developed to assess the value-based price of oral iron preparations based on their incremental cost per quality-adjusted life year (QALY) gained from the perspective of the NHS in the UK. Primary and secondary care resource use and health state occupancy probabilities were estimated from routine electronic health records; and unit costs and health state utilities were derived from published sources. Patients were pre-menopausal women with iron deficiency anaemia who were prescribed oral iron supplementation between 2000 and 2014. RESULTS: The model reflecting current use of iron salts yielded a mean total cost to the NHS of £779, and 0.84 QALYs over 12 months. If a new iron preparation were to reduce the risk of adverse drug reactions by 30-40%, then its value-based price, based on a threshold of £20 000 per QALY, would be in the region of £10-£13 per month, or about 7-9 times the average price of basic iron salts. CONCLUSIONS: There are no adequate, direct comparisons of new oral iron supplements to ferrous iron salts, and therefore other approaches are needed to assess their value. Our modelling shows that they are potentially cost-effective at prices that are an order of magnitude higher than existing iron salts.

Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in Childhood Polyarteritis Nodosa: An Open-Label, Randomized, Bayesian Noninferiority Trial.

OBJECTIVE: Cyclophosphamide (CYC) is used in clinical practice off-label for the induction of remission in childhood polyarteritis nodosa (PAN). Mycophenolate mofetil (MMF) might offer a less toxic alternative. This study was undertaken to explore the relative effectiveness of CYC and MMF treatment in a randomized controlled trial (RCT). METHODS: This was an international, open-label, Bayesian RCT to investigate the relative effectiveness of CYC and MMF for remission induction in childhood PAN. Eleven patients with newly diagnosed childhood PAN were randomized (1:1) to receive MMF or intravenous CYC; all patients received the same glucocorticoid regimen. The primary end point was remission within 6 months while compliant with glucocorticoid taper. Bayesian distributions for remission rates were established a priori for MMF and CYC by experienced clinicians and updated to posterior distributions on trial completion. RESULTS: Baseline disease activity and features were similar between the 2 treatment groups. The primary end point was met in 4 of 6 patients (67%) in the MMF group and 4 of 5 patients (80%) in the CYC group. Time to remission was shorter in the MMF group compared to the CYC group (median 7.1 weeks versus 17.6 weeks). No relapses occurred in either group within 18 months. Two serious infections were found to be likely linked to MMF treatment. Physical and psychosocial quality-of-life scores were superior in the MMF group compared to the CYC group at 6 months and 18 months. Combining the prior expert opinion with results from the present study provided posterior estimates of remission of 71% for MMF (90% credibility interval [90% CrI] 51, 83) and 75% for CYC (90% CrI 57, 86). CONCLUSION: The present results, taken together with prior opinion, indicate that rates of remission induction in childhood PAN are similar with MMF treatment and CYC treatment, and MMF treatment might be associated with better health-related quality of life than CYC treatment.

EstablishINg the best STEp-up treatments for children with uncontrolled asthma despite INhaled corticosteroids (EINSTEIN): protocol for a systematic review, network meta-analysis and cost-effectiveness analysis using individual participant data (IPD).

INTRODUCTION: Asthma affects millions of children worldwide-1.1 million children in the UK. Asthma symptoms cannot be cured but can be controlled with low-dose inhaled corticosteroids (ICSs) in the majority of individuals. Treatment with a low-dose ICS, however, fails to control asthma symptoms in around 10%-15% of children and this places the individual at increased risk for an asthma attack. At present, there is no clear preferred treatment option for a child whose asthma is not controlled by low-dose ICS and international guidelines currently recommend at least three treatment options. Herein, we propose a systematic review and individual participant data network meta-analysis (IPD-NMA) aiming to synthesise all available published and unpublished evidence from randomised controlled trials (RCTs) to establish the clinical effectiveness of pharmacological treatments in children and adolescents with uncontrolled asthma on ICS and help to make evidence-informed treatment choices. This will be used to parameterise a Markov-based economic model to assess the cost-effectiveness of alternative treatment options in order to inform decisions in the context of drug formularies and clinical guidelines. METHODS AND ANALYSIS: We will search in MEDLINE, the Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, NICE Technology Appraisals and the National Institute for Health Research (NIHR) Health Technology Assessment series for RCTs of interventions in patients with uncontrolled asthma on ICS. All studies where children and adolescents were eligible for inclusion will be considered, and authors or sponsors will be contacted to request IPD on patients aged <18. The reference lists of existing clinical guidelines, along with included studies and relevant reviews, will be checked to identify further relevant studies. Unpublished studies will be located by searching across a range of clinical trial registries, including internal trial registers for pharmaceutical companies. All studies will be appraised for inclusion against predefined inclusion and exclusion criteria by two independent reviewers with disagreements resolved through discussion with a third reviewer. We will perform an IPD-NMA-eventually supplemented with aggregate data for the RCTs without IPD-to establish both the probability that a treatment is best and the probability that a particular treatment is most likely to be effective for a specific profile of the patient. The IPD-NMA will be performed for each outcome variable within a Bayesian framework, using the WinBUGS software. Also, potential patient-level characteristics that may modify treatment effects will be explored, which represents one of the strengths of this study. ETHICS AND DISSEMINATION: The Committee on Research Ethics, University of Liverpool, has confirmed that ethics review is not required. The dissemination plan consists of publishing the results in an open-access medical journal, a plain-language summary available for parents and children, dissemination via local, national and international meetings and conferences and the press offices of our Higher Education Institutions (HEIs). A synopsis of results will be disseminated to NICE and British Thoracic Society/Scottish Intercollegiate Guidelines Network (SIGN) as highly relevant to future clinical guideline updates. PROSPERO REGISTRATION NUMBER: CRD42019127599.

Silver-impregnated, antibiotic-impregnated or non-impregnated ventriculoperitoneal shunts to prevent shunt infection: the BASICS three-arm RCT.

BACKGROUND: Insertion of a ventriculoperitoneal shunt to treat hydrocephalus is one of the most common neurosurgical procedures worldwide. Shunt infection affects up to 15% of patients, resulting in long hospital stays, multiple surgeries and reduced cognition and quality of life. OBJECTIVES: The aim of this trial was to determine whether or not antibiotic-impregnated ventriculoperitoneal shunts (hereafter referred to as antibiotic shunts) (e.g. impregnated with rifampicin and clindamycin) or silver-impregnated ventriculoperitoneal shunts (hereafter referred to as silver shunts) reduce infection compared with standard ventriculoperitoneal shunts (hereafter referred to as standard shunts). DESIGN: This was a three-arm, superiority, multicentre, parallel-group randomised controlled trial. Patients and a central primary outcome review panel, but not surgeons or operating staff, were blinded to the type of ventriculoperitoneal shunt inserted. SETTING: The trial was set in 21 neurosurgical wards across the UK and the Republic of Ireland. PARTICIPANTS: Participants were patients with hydrocephalus of any aetiology who were undergoing insertion of their first ventriculoperitoneal shunt. INTERVENTIONS: Participants were allocated 1 : 1 : 1 by pressure-sealed envelope to receive a standard non-impregnated, silver-impregnated or antibiotic-impregnated ventriculoperitoneal shunt at the time of insertion. Ventriculoperitoneal shunts are medical devices, and were used in accordance with the manufacturer's instructions for their intended purpose. MAIN OUTCOME MEASURES: The primary outcome was time to ventriculoperitoneal shunt failure due to infection. Secondary outcomes were time to failure for any cause, reason for failure (infection, mechanical), types of ventriculoperitoneal shunt infection, rate of infection after first clean (non-infected) revision and health economics. Outcomes were analysed by intention to treat. RESULTS: Between 26 June 2013 and 9 October 2017, 1605 patients from neonate to 91 years of age were randomised to the trial: n = 36 to the standard shunt, n = 538 to the antibiotic shunt and n = 531 to the silver shunt. Patients who did not receive a ventriculoperitoneal shunt (n = 4) or who had an infection at the time of insertion (n = 7) were not assessed for the primary outcome. Infection occurred in 6.0% (n = 32/533) of those who received the standard shunt, in 2.2% (n = 12/535) of those who received the antibiotic shunt and in 5.9% (n = 31/526) of those who received the silver shunt. Compared with the standard shunt, antibiotic shunts were associated with a lower rate of infection (cause-specific hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80) and a decreased probability of infection (subdistribution hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80). Silver shunts were not associated with a lower rate of infection than standard shunts (cause-specific hazard ratio 0.99, 97.5% confidence interval 0.56 to 1.74). The ventriculoperitoneal shunt failure rate attributable to any cause was 25.0% overall and did not differ between arms. Antibiotic shunts save £135,753 per infection avoided. There were no serious adverse events. LIMITATIONS: It was not possible to blind treating neurosurgeons to the ventriculoperitoneal shunt type. The return rate for patient-reported outcomes was low. Limitations to the economic evaluation included failure to obtain Hospital Episode Statistics data from NHS Digital, as per protocol. Reliance on patient-level information and costing systems data mitigated these limitations. CONCLUSIONS: Antibiotic shunts have a reduced infection rate compared with standard shunts, whereas silver shunts do not. Antibiotic shunts are cost-saving. FUTURE WORK: A sample collection has been established that will enable the study of surrogate markers of ventriculoperitoneal shunt infection in cerebrospinal fluid or blood using molecular techniques. A post hoc analysis to study factors related to shunt failure will be performed as part of a future study. An impact analysis to assess change in practice is planned. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49474281. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 17. See the NIHR Journals Library website for further project information.

Hydrocephalus (commonly known as 'water on the brain') is a condition that can affect all age groups, from babies to the elderly. In hydrocephalus, there is an accumulation of the normal brain fluid in the fluid cavities (ventricles) of the brain. Untreated, hydrocephalus can be life-threatening. The most common treatment involves an operation to insert a tube into the swollen ventricles to drain off the excess fluid. This is called a ventriculoperitoneal shunt. In the UK, 3000­3500 shunt operations are performed each year. The main risks of a shunt operation are infection (surgical meningitis) and blockage without infection. Infection results in the need for at least two further surgeries, antibiotic treatment and a prolonged hospital stay (minimum of 2 weeks). Shunt infections can affect mental abilities and can be life-threatening. People who have blockages without infection, on the other hand, usually need only a single operation to replace the blocked part and only a few days in hospital. Two new types of shunt catheter have been introduced to try to reduce shunt infection: antibiotic-impregnated shunts and silver-impregnated shunts. This study was designed to assess whether or not either of these new shunts reduce infection compared with standard shunts. This study also included an analysis of the cost and health benefits of the different shunts used. A total of 1605 children and adults, who were treated in neurosurgical units across the UK and the Republic of Ireland, participated in this study. Consent was provided by all participants in the trial. Each participant had an equal chance of receiving one of the three shunt types. Shunt infection occurred in 6% of participants receiving standard shunts, 5.9% of participants receiving silver-impregnated shunts and 2.2% of participants receiving antibiotic-impregnated shunts. This study has demonstrated a major reduction in shunt infections in new shunts when using antibiotic-impregnated shunts compared with standard or silver-impregnated shunts. A health economic analysis has indicated that antibiotic-impregnated shunts are cost-saving.

Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation.

BACKGROUND: Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection. METHODS: In this parallel, multicentre, single-blind, randomised controlled trial, we included patients with hydrocephalus of any aetiology undergoing insertion of their first ventriculoperitoneal shunt irrespective of age at 21 regional adult and paediatric neurosurgery centres in the UK and Ireland. Patients were randomly assigned (1:1:1 in random permuted blocks of three or six) to receive standard shunts (standard shunt group), antibiotic-impregnated (0·15% clindamycin and 0·054% rifampicin; antibiotic shunt group), or silver-impregnated shunts (silver shunt group) through a randomisation sequence generated by an independent statistician. All patients and investigators who recorded and analysed the data were masked for group assignment, which was only disclosed to the neurosurgical staff at the time of operation. Participants receiving a shunt without evidence of infection at the time of insertion were followed up for at least 6 months and a maximum of 2 years. The primary outcome was time to shunt failure due the infection and was analysed with Fine and Gray survival regression models for competing risk by intention to treat. This trial is registered with ISRCTN 49474281. FINDINGS: Between June 26, 2013, and Oct 9, 2017, we assessed 3505 patients, of whom 1605 aged up to 91 years were randomly assigned to receive either a standard shunt (n=536), an antibiotic-impregnated shunt (n=538), or a silver shunt (n=531). 1594 had a shunt inserted without evidence of infection at the time of insertion (533 in the standard shunt group, 535 in the antibiotic shunt group, and 526 in the silver shunt group) and were followed up for a median of 22 months (IQR 10-24; 53 withdrew from follow-up). 32 (6%) of 533 evaluable patients in the standard shunt group had a shunt revision for infection, compared with 12 (2%) of 535 evaluable patients in the antibiotic shunt group (cause-specific hazard ratio [csHR] 0·38, 97·5% CI 0·18-0·80, p=0·0038) and 31 (6%) of 526 patients in the silver shunt group (0·99, 0·56-1·74, p=0·96). 135 (25%) patients in the standard shunt group, 127 (23%) in the antibiotic shunt group, and 134 (36%) in the silver shunt group had adverse events, which were not life-threatening and were mostly related to valve or catheter function. INTERPRETATION: The BASICS trial provides evidence to support the adoption of antibiotic shunts in UK patients who are having their first ventriculoperitoneal shunt insertion. This practice will benefit patients of all ages by reducing the risk and harm of shunt infection. FUNDING: UK National Institute for Health Research Health Technology Assessment programme.

Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT.

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. OBJECTIVE: To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. DESIGN: This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost-utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. SETTING: The setting was tertiary care centres throughout the UK. PARTICIPANTS: Patients aged 2-18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). INTERVENTIONS: All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. MAIN OUTCOME MEASURES: Primary outcome - time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome - incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. RESULTS: A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. CONCLUSIONS: Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. FUTURE WORK: A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10065623 and European Clinical Trials Database number 2010-021141-41. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 15. See the NIHR Journals Library website for further project information. This trial was also funded by Arthritis Research UK (grant reference number 19612). Two strengths of adalimumab (20 mg/0.8 ml and 40 mg/0.8 ml) and a matching placebo were manufactured by AbbVie Inc. (the Marketing Authorisation holder) and supplied in bulk to the contracted distributor (Sharp Clinical Services, Crickhowell, UK) for distribution to trial centres.

Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in children and young people, who are at risk of developing inflammation in an area of the eye called the uvea (called uveitis). The purpose of the study was to look at how effective the use of adalimumab in combination with methotrexate (MTX) is compared with using MTX alone to treat JIA-associated uveitis. A total of 90 children (aged 2­18 years) taking MTX with JIA-associated uveitis took part in the study. If the inflammation in a patient's eye or eyes was not getting better during the 18 months, the patient was told to stop taking the study drug. It was found that those patients who were taking placebo and MTX in the trial stopped taking the study drug sooner than those who were taking adalimumab and MTX. This means that adalimumab and MTX was better at treating uveitis than MTX alone. It was found that more patients taking adalimumab and MTX together either reduced or stopped taking topical steroids than the patients taking placebo and MTX. It was found that patients taking adalimumab and MTX together experienced more side effects than those taking placebo with MTX. However, these were expected based on what was already known about adalimumab's side effects. An economic evaluation was conducted to estimate whether or not adalimumab would represent value for money for the NHS for this condition. This included long-term effects based on information about patients' clarity of vision. The analysis showed that adalimumab may not be cost-effective, as the additional costs of treatment may not be justified by the benefits. The final results show that although adalimumab used in combination with MTX does help to treat patients with JIA and uveitis, it may not represent good value for the NHS.

Cost-Effectiveness Analysis of Adalimumab for the Treatment of Uveitis Associated with Juvenile Idiopathic Arthritis.

PURPOSE: To investigate the cost effectiveness of adalimumab in combination with methotrexate, compared with methotrexate alone, for the management of uveitis associated with juvenile idiopathic arthritis (JIA). DESIGN: A cost-utility analysis based on a clinical trial and decision analytic model. PARTICIPANTS: Children and adolescents 2 to 18 years of age with persistently active uveitis associated with JIA, despite optimized methotrexate treatment for at least 12 weeks. METHODS: The SYCAMORE (Randomised controlled trial of the clinical effectiveness, SafetY and Cost effectiveness of Adalimumab in combination with MethOtRExate for the treatment of juvenile idiopathic arthritis associated uveitis) trial (identifier, ISRCTN10065623) of methotrexate (up to 25 mg weekly) with or without fortnightly administered adalimumab (20 or 40 mg, according to body weight) provided data on resource use (based on patient self-report and electronic records) and health utilities (from the Health Utilities Index questionnaire). Surgical event rates and long-term outcomes were based on data from a 10-year longitudinal cohort. A Markov model was used to extrapolate the effects of treatment based on visual impairment. MAIN OUTCOME MEASURES: Medical costs to the National Health Service in the United Kingdom, utility of defined health states, quality-adjusted life-years (QALYs), and incremental cost per QALY. RESULTS: Adalimumab in combination with methotrexate resulted in additional costs of £39 316, with a 0.30 QALY gain compared with methotrexate alone, resulting in an incremental cost-effectiveness ratio of £129 025 per QALY gained. The probability of cost effectiveness at a threshold of £30 000 per QALY was less than 1%. Based on a threshold analysis, a price reduction of 84% would be necessary for adalimumab to be cost effective. CONCLUSIONS: Adalimumab is clinically effective in uveitis associated with JIA; however, its cost effectiveness is not demonstrated compared with methotrexate alone in the United Kingdom setting.