Elsevier

Ophthalmology

Volume 126, Issue 3, March 2019, Pages 415-424
Ophthalmology

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

https://doi.org/10.1016/j.ophtha.2018.09.043Get rights and content

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.

Section snippets

SYCAMORE Trial Data

The SYCAMORE trial was a multicenter, double-blind, randomized, placebo-controlled trial to assess the clinical effectiveness of adalimumab in refractory uveitis associated with JIA.9, 15 The trial recruited children and adolescents 2 to 18 years of age with active JIA-associated uveitis, despite stable methotrexate treatment for at least 12 weeks, from 14 United Kingdom centers. Ninety participants between 2 and 18 years of age who were taking methotrexate without improvement in uveitis were

Utilities and Quality-Adjusted Life-Years

Baseline utility scores were 0.83 (95% CI, 0.76–0.89) and 0.87 (95% CI, 0.78–0.96) for the adalimumab and placebo groups, respectively. Based on a complete case analysis of 25 participants (42%) randomized to adalimumab and 3 participants (10%) randomized to placebo, the number of QALYs over the 18-month trial period was 1.40 (95% CR, 1.35–1.45) and 1.45 (95% CR, 1.41–1.50), respectively. After imputation, the mean QALY scores were numerically higher for adalimumab at 1.35 (95% CI, 1.30–1.41)

Principal Findings

This analysis suggested that adalimumab in combination with methotrexate for JIA-associated uveitis is associated with appreciably higher healthcare costs than methotrexate alone and exceeds the threshold for cost-effectiveness operated by the NHS in the United Kingdom by a significant margin. The results are robust to changes in parameter estimates and some alternative modeling assumptions (although we had limited scope for assessing structural uncertainty) and are consistent with the

Acknowledgments

The authors thank the trial participants, members of the Medicine for Children Research Network young person’s advisory group, Drs. Colin Ridyard and Lorna Tuersley for their contributions to the economic evaluation, and Dr. Megan Cann for help in collating data from the Bristol Regional Tertiary Paediatric Uveitis clinic that contributed to the analysis.

References (31)

  • Joint Formulary Committee. British National Formulary. (online) London: BMJ Group and Pharmaceutical Press; Available...
  • H. Squires et al.

    A systematic review and economic evaluation of adalimumab and dexamethasone for treating non-infectious intermediate uveitis, posterior uveitis or panuveitis in adults

    Health Technol Assess

    (2017)
  • Specialised Commissioning Team NHS England. Interim clinical commissioning policy: adalimumab for children with severe...
  • All Wales Medicines Advisory Group. Final appraisal recommendation. Advice no: 2717. Adalimumab (Humira®) 40 mg...
  • Scottish Medicines Consortium. Statement of advice: adalimumab 40mg/0.4mL pre-filled syringe and pre-filled pen /...
  • Financial Disclosure(s): The author(s) have made the following disclosure(s): A.D.D.: Consultant – AbbVie (UK).

    A.P.J.: Drug supply – AbbVie (UK).

    A.M.: Drug supply – AbbVie (UK).

    P.R.W.: Drug supply – AbbVie (UK).

    S.C.L.: Drug supply – AbbVie (UK).

    B.H.: Drug supply – AbbVie (UK).

    H.H.: Drug supply – AbbVie (UK).

    P.W.: Drug supply – AbbVie (UK).

    A.V.R.: Consultant – UCB (USA); Eli Lilly (USA); Lecturer – SOBI (UK), AbbVie (UK).

    Supported by the National Institute for Health Research Health Technology Assessment Programme (project no.: 09/51/01); and Arthritis Research United Kingdom (grant no.: 19612). The University Hospitals Bristol NHS Foundation Trust, as sponsor of study, has a data sharing agreement with AbbVie in support of regulatory purposes. AbbVie had no role in the funding, trial management, or data analysis or writing of the manuscript but have licensed use of the data resulting from the study for regulatory purposes. AbbVie was given the opportunity to review the final draft of the manuscript, but the authors maintained complete control over the content of the article.

    HUMAN SUBJECTS: Human subjects were included in this study. The SYCAMORE trial was approved by the NHS National Research Ethics Service Committee (Hampstead, London) 11/LO/0425, and written, informed consent was given by a parent or guardian of each trial participant. The study was conducted according to the principles of the World Medical Association Declaration of Helsinki and its amendments since 1964. All participants provided informed consent.

    No animal subjects were included in this study.

    Author Contributions:

    Conception and design: Hughes, Culeddu, Plumpton, Wood, Dick, Beresford, Ramanan

    Analysis and interpretation: Hughes, Culeddu, Plumpton, Wood, Dick, Jones, McKay, Williamson, Compeyrot Lacassagne, Hardwick, Hickey, Woo, Beresford, Ramanan

    Data collection: Hughes, Culeddu, Plumpton, Wood, Dick, Jones, McKay, Williamson, Compeyrot Lacassagne, Hardwick, Hickey, Woo, Beresford, Ramanan

    Obtained funding: Ramanan, Beresford, Jones, Hughes, Woo, Hickey, Dick

    Overall responsibility: Hughes, Culeddu, Plumpton, Wood, Dick, Beresford, Ramanan

    Both authors contributed equally.

    View full text