Skip to content

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

Research output: Contribution to journalArticle

Standard

Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis : a RCT. / Ramanan, Athimalaipet V; Dick, Andrew D; Jones, Ashley P; Hughes, Dyfrig A; McKay, Andrew; Rosala-Hallas, Anna; Williamson, Paula R; Hardwick, Ben; Hickey, Helen; Rainford, Naomi; Hickey, Graeme; Kolamunnage-Dona, Ruwanthi; Culeddu, Giovanna; Plumpton, Catrin; Wood, Eifiona; Compeyrot-Lacassagne, Sandrine; Woo, Patricia; Edelsten, Clive; Beresford, Michael W.

In: Health Technology Assessment, Vol. 23, No. 15, 01.04.2019, p. 1-140.

Research output: Contribution to journalArticle

Harvard

Ramanan, AV, Dick, AD, Jones, AP, Hughes, DA, McKay, A, Rosala-Hallas, A, Williamson, PR, Hardwick, B, Hickey, H, Rainford, N, Hickey, G, Kolamunnage-Dona, R, Culeddu, G, Plumpton, C, Wood, E, Compeyrot-Lacassagne, S, Woo, P, Edelsten, C & Beresford, MW 2019, 'Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT', Health Technology Assessment, vol. 23, no. 15, pp. 1-140. https://doi.org/10.3310/hta23150

APA

Ramanan, A. V., Dick, A. D., Jones, A. P., Hughes, D. A., McKay, A., Rosala-Hallas, A., ... Beresford, M. W. (2019). Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT. Health Technology Assessment, 23(15), 1-140. https://doi.org/10.3310/hta23150

Vancouver

Author

Ramanan, Athimalaipet V ; Dick, Andrew D ; Jones, Ashley P ; Hughes, Dyfrig A ; McKay, Andrew ; Rosala-Hallas, Anna ; Williamson, Paula R ; Hardwick, Ben ; Hickey, Helen ; Rainford, Naomi ; Hickey, Graeme ; Kolamunnage-Dona, Ruwanthi ; Culeddu, Giovanna ; Plumpton, Catrin ; Wood, Eifiona ; Compeyrot-Lacassagne, Sandrine ; Woo, Patricia ; Edelsten, Clive ; Beresford, Michael W. / Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis : a RCT. In: Health Technology Assessment. 2019 ; Vol. 23, No. 15. pp. 1-140.

Bibtex

@article{356902da7734402f8b851a610f9de46b,
title = "Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT",
abstract = "BACKGROUND: Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira{\circledR}; 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.",
keywords = "ADALIMUMAB, JUVENILE IDIOPATHIC ARTHRITIS, METHOTREXATE, OPHTHALMOLOGY, PAEDIATRIC, RANDOMISED CONTROLLED TRIAL, RHEUMATOLOGY, SAFETY, UVEITIS",
author = "Ramanan, {Athimalaipet V} and Dick, {Andrew D} and Jones, {Ashley P} and Hughes, {Dyfrig A} and Andrew McKay and Anna Rosala-Hallas and Williamson, {Paula R} and Ben Hardwick and Helen Hickey and Naomi Rainford and Graeme Hickey and Ruwanthi Kolamunnage-Dona and Giovanna Culeddu and Catrin Plumpton and Eifiona Wood and Sandrine Compeyrot-Lacassagne and Patricia Woo and Clive Edelsten and Beresford, {Michael W}",
year = "2019",
month = "4",
day = "1",
doi = "10.3310/hta23150",
language = "English",
volume = "23",
pages = "1--140",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "NIHR Journals Library",
number = "15",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis

T2 - a RCT

AU - Ramanan, Athimalaipet V

AU - Dick, Andrew D

AU - Jones, Ashley P

AU - Hughes, Dyfrig A

AU - McKay, Andrew

AU - Rosala-Hallas, Anna

AU - Williamson, Paula R

AU - Hardwick, Ben

AU - Hickey, Helen

AU - Rainford, Naomi

AU - Hickey, Graeme

AU - Kolamunnage-Dona, Ruwanthi

AU - Culeddu, Giovanna

AU - Plumpton, Catrin

AU - Wood, Eifiona

AU - Compeyrot-Lacassagne, Sandrine

AU - Woo, Patricia

AU - Edelsten, Clive

AU - Beresford, Michael W

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

KW - ADALIMUMAB

KW - JUVENILE IDIOPATHIC ARTHRITIS

KW - METHOTREXATE

KW - OPHTHALMOLOGY

KW - PAEDIATRIC

KW - RANDOMISED CONTROLLED TRIAL

KW - RHEUMATOLOGY

KW - SAFETY

KW - UVEITIS

UR - http://www.scopus.com/inward/record.url?scp=85065413083&partnerID=8YFLogxK

U2 - 10.3310/hta23150

DO - 10.3310/hta23150

M3 - Article

VL - 23

SP - 1

EP - 140

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 15

ER -