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 Centre for Reviews and Dissemination/ Centre for Health Economics (CRD/CHE) Technology Assessment Group, University of York (see the "Availability of Companion Documents" field.)
Search Strategy
Searches were undertaken on the following databases to identify relevant clinical and cost-effectiveness literature. Full details of the search strategies are reported in Appendix 10.1 of the Assessment Report (see "Availability of Companion Documents" field). Searches took place over a period of time from April to July 2004
All databases were searched from their inception to the date of the search. Searches were also undertaken on several Internet resources, which are documented in Appendix 10.1 of the Assessment Report (see "Availability of Companion Documents" field).
Terminology
The terms for the search strategies were identified through discussion between an Information Officer and the research team, by scanning the background literature, and by browsing the Medline Thesaurus (MeSH). No language or other restrictions were applied.
Management of References
As several databases were searched, some degree of duplication resulted. In order to manage this issue, the titles and abstracts of bibliographic records were downloaded and imported into Endnote bibliographic management software to remove duplicate records.
Handsearching
The bibliographies of all included studies and industry submissions made to NICE were reviewed to identify further relevant studies. Handsearching continued throughout the project.
Inclusion and Exclusion of Studies
Study Selection
Two reviewers selected the studies for the review. Discrepancies were resolved by consensus and a third reviewer was consulted when necessary.
All titles and abstracts identified by the search were screened and any references that were considered relevant by either reviewer were obtained.
No language restrictions were applied to study selection. Trials reported as full publications or unpublished full reports were included in the review. Trials reported as abstracts only were to be included if adequate information was provided. All of the data submitted by Wyeth and Serono were considered in the review.
Inclusion/Exclusion Criteria
Efficacy of Interventions
The review addressed the following questions about the efficacy of etanercept and efalizumab in the treatment of moderate to severe psoriasis:
- Is the drug effective at all?
- How effective is it?
- Can the drugs be used long-term?
- How long is remission and is there any rebound if active treatment is replaced with passive treatment?
- How effective is retreatment in patients who have relapsed following an earlier treatment period?
Studies were included in the review according to the inclusion criteria described in the following paragraphs.
Intervention
Etanercept and efalizumab administered by subcutaneous injection were the interventions of interest. Comparisons with either placebo or any other active agent were eligible for inclusion.
Participants
Studies of adults with moderate to severe psoriasis were included. These patients are usually defined as having an inadequate response to topical treatments alone and to have either received prior systemic therapy or phototherapy or are candidates for such therapy.
Study Design
Only randomised controlled trials were included in the evaluation of efficacy.
Outcomes
The outcomes of primary interest were those derived from the Psoriasis Area and Severity Index (PASI). Data on the following outcomes were also eligible in the review of efficacy: Physician's Global assessment (PGA); patient-centred outcome measures; Self Administered Psoriasis Area and Severity Index (SAPASI); Psoriasis Disability Index (PDI); Total Severity Score (TSS); Investigator's Assessment of Global Improvement (IAGI); quality of life (QoL); Dermatology Life Quality Index (DLQI); duration of remission.
Adverse Effects of Interventions
Adverse events data was summarised from key sources and existing reviews. This was supplemented by a systematic review of adverse events data from clinical studies. See section 3.2.2.2 of the Assessment Report (see "Availability of Companion Documents" field) for a description of the inclusion criteria. The reference details and reasons for exclusion of studies are presented in Appendix 10.3 of the Assessment Report (see "Availability of Companion Documents" field).
Other Treatments for Moderate to Severe Psoriasis
In an attempt to put into context the evidence base for the efficacy of etanercept and efalizumab we investigated the evidence available for other treatments for moderate to severe psoriasis. See section 3.2.2.3 of the Assessment Report (see "Availability of Companion Documents" field) for a description of the inclusion criteria.
Economic Evaluations – Systematic Review
Studies were eligible for inclusion if they assessed both the costs and benefits of either efalizumab or etanercept and compared findings with an appropriate comparator treatment.