دورية أكاديمية
Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT
| العنوان: | Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT |
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| المؤلفون: | Ramanan, Athimalaipet V., Dick, A.D., Jones, Ashley P., Hughes, Dyfrig, McKay, Andrew, Rosala_Hanna, Anna, Williamson, P.R., Hardwick, Ben, Hickey, Helen, Rainford, N, Kolamunnage-Dona, R, Culeddu, Giovanna, Plumpton, Catrin, Wood, Eifiona, Compeyrot-Lacassagne, Sandrine, Woo, P., Eldesten, C, Beresford, Michael W. |
| المصدر: | Ramanan , A V , Dick , A D , Jones , A P , Hughes , D , McKay , A , Rosala_Hanna , A , Williamson , P R , Hardwick , B , Hickey , H , Rainford , N , Kolamunnage-Dona , R , Culeddu , G , Plumpton , C , Wood , E , Compeyrot-Lacassagne , S , Woo , P , Eldesten , C & Beresford , M W 2019 , ' Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT ' , Health Technology Assessment .... |
| سنة النشر: | 2019 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.3310/hta23150 |
| الإتاحة: | https://doi.org/10.3310/hta23150Test https://research.bangor.ac.uk/portal/en/researchoutputs/adalimumab-in-combination-with-methotrexate-for-refractory-uveitis-associated-with-juvenile-idiopathic-arthritis-a-rctTest(e71f87ca-6293-4d9a-a94a-cc45fd7e3b59).html https://research.bangor.ac.uk/ws/files/22989972/3028866.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6D8908D9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3310/hta23150 |
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