BACKGROUNDAdalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis. METHODSIn this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria. RESULTSThe prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; P<0.0001 [the prespecified stopping boundary]). Adverse events were reported more frequently in patients receiving adalimumab than in those receiving placebo ( CONCLUSIONSAdalimumab therapy controlled inflammation and was associated with a lower rate of treatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebo.

BackgroundJuvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Children with JIA are at risk of inflammation of the uvea in the eye (uveitis). Overall, 20% to 25% of paediatric uveitis is associated with JIA. Major risk factors for development of uveitis in JIA are oligoarticular pattern of arthritis, an age at onset of arthritis of less than seven years of age, and antinuclear antibody positivity. In the initial stages of mild to moderate inflammation the uveitis is asymptomatic. This has led to current practice of screening all children with JIA for uveitis. Approximately 12% to 38% of patients with JIA develop uveitis in seven years following onset of arthritis. In 30% to 50% of children with JIA-associated uveitis structural complications are present at diagnosis. Furthermore about 50% to 75% of those with severe uveitis will eventually develop visual impairment secondary to ocular complications such as cataract and glaucoma. Defining the severity of inflammation and structural complications in uveitis patients is now possible following Standardised Uveitis Nomenclature (SUN) guidelines, and modified to incorporate the consensus of end point and outcome criteria into the design of randomised trials. Despite current screening and therapeutic options (pre-biologics) 10% to 15% of children with JIA-associated uveitis may develop bilateral visual impairment and certified legally blind. To date, there remains no controlled trial evidence of benefits of biologic therapy.Methods/designThis study will randomise 154 patients aged 2 to 18 years with active JIA-associated uveitis (despite methotrexate (MTX) treatment for at least 12 weeks). All participants will be treated for 18 months, with follow up of 3 years from randomisation (continuing on MTX throughout). All participants will receive a stable dose of MTX and in addition either adalimumab (20 mg/0.8 ml for patients <30 kg or 40 mg/0.8 ml for patients weighing 30 kg or more, subcutaneous (s/c) injection every 2 weeks based on body weight), or placebo (0.8 ml as appropriate according to body weight) s/c injection every 2 weeks.DiscussionThis is the first randomised controlled trial that will assess the clinical effectiveness, safety and cost effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis.Trial registrationISRCTN10065623

BackgroundUveitis associated with Juvenile Idiopathic Arthritis (JIA) is a major cause of morbidity with potentially sight-threatening complications. Despite current screening and (pre-biologic) therapeutic options, 10–15% of children develop bilateral visual impairment. Tumour necrosis factor alpha plays a pathogenic role in JIA-uveitis. No controlled trials have determined the impact of biologic therapy in JIA-associated uveitis.ObjectivesTo compare the clinical effectiveness of adalimumab in combination with methotrexate (MTX) versus MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA.MethodsPatients aged 2 to 18 years with active JIA-associated uveitis, despite stable methotrexate (MTX) treatment for at least 12 weeks, were randomly assigned to adalimumab or placebo in a ratio of 2:1. All patients were treated up to a maximum period of 18 months, with follow up of 2 years from randomisation. All patients received a stable dose of MTX and in addition either adalimumab (20 mg for patients weighing <30 kg or 40 mg for patients weighing ≥30 kg, subcutaneous injection every 2 weeks) or placebo.Primary endpoint was “time to treatment failure” defined by the “Standardisation of the Uveitis Nomenclature” criteria. Ten secondary efficacy endpoints were assessed including quality of life variables and arthritis disease activity measures. Adverse events from both arms were collected. Post-hoc analyses investigated “time to treatment response” and the proportion of responders, failures or those who had no change at three and six months. Statistical analysis of the primary outcome used the log rank test to compare treatment groups with a hazard ratio and 95% confidence interval also being reported.ResultsThe trial was stopped early for reasons of efficacy after 90 patients had been randomised and the interim analysis met the pre-specified statistical stopping guidelines. The final analysis of the primary outcome showed a positive treatment effect in favour of adalimumab: hazard ratio (HR) 0.25 (95% CI 0.12–0.49); p<0.0001. Adverse events were experienced by 88.3% (53/60, 694 events) of patients in the adalimumab group and 90% (27/30, 144 events) of patients in the placebo group. Events were consistent with the known adalimumab profile. Post-hoc analyses showed significant differences showing favourable response to Adalimumab with respect to both the time to treatment response HR 3.15 (95% CI 1.42 to 7.00); p<0.0027 and the proportion of responders at both three and six months (p=0.0014 for each timepoint).ConclusionsThis trial, the largest of its kind to be conducted in JIA-associated uveitis, provides evidence of efficacy of adalimumab treatment used in addition to methotrexate in this population. The safety profile of adalimumab was consistent with that previously reported for adalimumab.AcknowledgementThis project was funded by the National Institute for Health Research Health Technology Assessment Programme (project 09/51/01) and Arthritis Research UK (grant reference 19612)...

No abstract

1565 Background: Cancer is a cause of health inequalities, and nationally, patients from deprived communities have lower participation rates in cancer research. Equitable access to research benefits patients, healthcare organisations and improves applicability of research. Methods: We undertook a health equity audit of participation in cancer research (trials and non-trials based) in Bristol, North Somerset and South Gloucestershire (BNSSG), England from 1.4.2019-30.3.2020 using data from the Acute Trust patient datasets. Comparison cohorts were extracted from a regional primary care dataset (the system wide dataset). Firstly, an incident cancer cohort: diagnosed from 1.11.2019-1.10.2020. Secondly a “living with cancer” cohort: cancer flag in the 5 years prior to 1.7.2021. Deprivation is measured by IMD of home postcode small area (LSOA). Results: Results are presented for the audit in the table below, with 95% confidence intervals where appropriate. Compared to people newly diagnosed with cancer, adults aged 70 or older were 56% less likely to take part in research (OR 0.44, 95% CI 0.39-0.51), and adults aged 80 or older were 77% less likely to take part in research (OR 0.23, 95% CI 0.18-0.29). Compared to people newly diagnosed with cancer, people from the most deprived 20% of the population were 27% less likely to take part in research (OR 0.73, 95% CI 0.88-0.92). The most deprived research participants were more likely to be younger, have one or more comorbidities and a recent emergency admission. Patients from outside BNSSG (18%) appear similar in profile to those from within BNSSG, including for deprivation. Better data are needed for other factors relevant to equity, including ethnicity and Inclusion Health. Conclusions: This health equity audit confirms and quantifies inequities in access to cancer research in our region. Under-representation of deprived and older patients appeared multifactorial in this audit, but further work to understand facilitators and barriers to recruitment is needed. These results are a call to action. [Table: see text]