Note from the National Guideline Clearinghouse (NGC): The National Institute for Health and Clinical Excellence (NICE) commissioned an independent academic centre to perform a systematic literature review on the technology considered in this appraisal and prepare an assessment report. The assessment report for this technology appraisal was prepared by the West Midlands Health Technology Assessment Collaboration (see the "Companion Documents" field).
Search Strategy
The following electronic bibliographic databases were searched with a stop date of 1st November 2002:
Cochrane Library, Medline, Embase, Science Citation Index (SCI), National Research Register (NRR), NHS Database of Reviews of Effectiveness (DARE), Index to Scientific and Technical Proceedings (ISTP), NHS Economic Evaluation Database (NHS EED), Health Economic Evaluation Database (HEED).
Search terms included the text words: anakinra; kineret; interleukin-1 receptor antagonist; IL- 1ra; rhu-IL-1Ra; and the index terms; arthritis, rheumatoid; receptors, interleukin-1; interleukin-1.
Studies were limited to humans. No language, date or age restrictions were applied. A metasearch engine was used to search the Internet, and links followed up. Proceedings from the American College of Rheumatology and European Congress of Rheumatology meetings were searched electronically for the years 2001 and 2002.
Scrip, Food and Drug Administration (FDA) submissions for new drug applications, European Medicines Agency (EMEA) reports and the pharmaceutical company submission to the National Institute for Clinical Excellence (NICE) were hand searched. The reference lists of identified publications were reviewed to identify any additional studies and/or citations.
Inclusion and Exclusion Criteria
Two reviewers independently applied the following inclusion/exclusion criteria to all potential studies. Disagreements were resolved by discussion, referring to a third party when necessary. Reviewers were not blinded to any features of the report including authorship however inclusion/exclusion decisions were made prior to detailed scrutiny of the results.
Inclusion Criteria
The criteria for inclusion related to the population, intervention and comparator considered and the publication status of the report were applicable to both the clinical effectiveness and cost-effectiveness parts of the review.
Population: Adults aged 18 years and above with rheumatoid arthritis
Intervention: Anakinra (Kineret®) alone or in combination with other drugs
Comparator: Placebo, or other drug treatments for rheumatoid arthritis (RA)
Publication All data to be included irrespective of publication status.
Studies were included in the final analysis of the review if they met the above criteria and the additional criteria for study design and outcomes as specified below for the clinical and cost-effectiveness parts of the review.
Clinical Effectiveness Review
Study design: Randomised or quasi-randomised controlled trials
Outcomes: To include: mortality, morbidity (e.g. disability/mobility, disease progression, joint damage, pain, adverse events), response rates and quality of life.
Cost-Effectiveness Review
Study design: Economic evaluation studies: cost analysis, cost-effectiveness, cost-utility and cost-benefit studies. Existing health economic reviews were also assessed.
Outcomes: To include: quality of life, costs, and incremental cost-effectiveness ratio.
Exclusion Criteria
- Trials only recruiting children with juvenile idiopathic arthritis.
- Trials with no comparator arm.
- Trials which were not randomised. (clinical effectiveness part of review only)
- Articles reporting solely on laboratory measures aimed at investigating disease or treatment mechanisms.