Search

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., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The systemic autoimmune/inflammatory condition systemic lupus erythematosus (SLE) manifests before the age of 16 years in 10-20% of all cases. Clinical courses are more severe, and organ complications are more common in patients with juvenile SLE. Varying gender distribution in different age groups and increasing severity with younger age and the presence of monogenic disease in early childhood indicate distinct differences in the pathophysiology of juvenile versus adult-onset SLE. Regardless of these differences, classification criteria and treatment options are identical. In this article, we discuss age-specific pathomechanisms of juvenile-onset SLE, which are currently available and as future treatment options, and propose reclassification of different forms of SLE along the inflammatory spectrum from autoinflammation to autoimmunity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Evidence from clinical trials, ideally using randomisation and allocation concealment, is essential for informing clinical decisions regarding the benefits and harms of treatments for patients. Where diseases are rare, such as in paediatric rheumatic diseases, patient recruitment into clinical trials can be a major obstacle, leading to an absence of evidence and patients receiving treatments based on anecdotal evidence. There are numerous trial designs and modifications that can be made to improve efficiency and maximise what little data may be available in a rare disease clinical trial. These are discussed and illustrated with examples from paediatric rheumatology. Regulatory incentives and support from research networks have helped to deliver these trials, but more can be done to continue this important research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Adolescence is a time of profound biological and psychosocial change. The management of a complex chronic condition such as systemic lupus erythematosus (SLE) during this period is a challenging but rewarding task for the clinician. Early diagnosis and optimal disease control is essential in order to facilitate normal adolescent development and minimize long-term disease sequelae. Current treatment regimens are associated with significant toxicity in young people, and there is a need for new, less toxic regimens. There are currently no controlled therapeutic studies in adolescents with SLE. Those involved in the care of these young people must ensure that they have appropriate access to specialist medical services while ensuring that their specific needs as adolescents in the health-care system are addressed.

Background: Exogenous surfactant preparations vary in their constitution and biophysical properties. Synthetic and animal-derived preparations lower the rate of death compared with controls. No significant differences in mortality or important long-term clinical outcomes have been shown between them in randomised trials. We did a randomised controlled trial to compare pumactant, a synthetic surfactant, with poractant alfa, an animal-derived surfactant, both of which are widely used in the UK., Methods: We enrolled 212 neonates born between 25 weeks' and 29 weeks and 6 days' gestation who were intubated for presumed surfactant deficiency and were free from life-threatening malformations. We randomly assigned 105 neonates poractant alfa, and 107 pumactant. The primary outcome was duration of high-dependency care and mortality was a secondary outcome. Analysis was by intention to treat., Findings: Outcome data were analysed for 199 babies. The trial was stopped on the recommendation of the data and safety monitoring committee because mortality assumed a greater importance than the primary outcome. Predischarge mortality differed significantly between groups, in favour of poractant alfa (14.1 vs 31.0%, p=0.006; odds ratio 0.37 [95% CI 0.18-0.76). This difference was sustained after adjustment for centre, gestation, birthweight, sex, plurality, and use of antenatal steroids., Interpretation: Mortality was unexpectedly lower among neonates who received poractant alfa than among those who received pumactant, and was independent of all the variables we investigated. Stopping the trial early may have widened the difference between the treatment groups.