• National Institute for Health and Clinical Excellence (NICE). Etanercept and efalizumab for the treatment of adults with psoriasis. London (UK): National Institute for Health and Clinical Excellence (NICE); 2006 Jul. 35 p. (Technology appraisal guidance; no. 103).

This is the current release of the guideline.

Psoriasis

Assessment of Therapeutic Effectiveness
Management
Treatment

Dermatology
Family Practice

Advanced Practice Nurses
Nurses
Pharmacists
Physician Assistants
Physicians

To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and efalizumab for the treatment of moderate to severe chronic plaque psoriasis

Adults with moderate to severe chronic plaque psoriasis

1. Etanercept
2. Efalizumab

• Clinical effectiveness

  Outcomes of primary interest were 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
• Cost effectiveness of treatment

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Searches of Unpublished Data

Clinical Effectiveness

• Three randomized controlled trials (RCTs) related to the efficacy of etanercept were included in the review.
• Five randomised controlled trials related to the efficacy of efalizumab were included in the review.

Cost Effectiveness

• One study of etanercept met the inclusion criteria.
• No economic evaluation of efalizumab was found.

Expert Consensus

Not applicable

Meta-Analysis of Randomized Controlled Trials
Systematic Review with Evidence Tables

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.)

Methods

A systematic review evaluated the clinical efficacy and adverse effects of etanercept and efalizumab. The efficacy of other treatments for moderate to severe psoriasis was also reviewed and, where data allowed, all treatments were compared in an evidence synthesis utilising a mixed treatment comparison implemented as a Bayesian hierarchical model. Following evaluation of existing economic evaluations of etanercept and efalizumab in moderate to severe psoriasis, a new economic model was developed (the York Model), which directly utilised the results from the evidence synthesis.

Evidence Synthesis

To enable indirect comparisons between all treatments for moderate to severe psoriasis, a meta-analysis of the Psoriasis Area and Severity Index (PASI) 50, 75 and 90 response rates from the randomised trials was performed. The endpoints were jointly modelled using an ordered probit model. The available data permitted the inclusion of etanercept (25 mg and 50 mg), efalizumab, infliximab, ciclosporin, methotrexate, Fumaderm and placebo in this mixed-treatment comparison which was implemented as a Bayesian hierarchical model.

For a full discussion of the methods used to analyze the evidence, see sections 3.2.3, 3.2.4, and 3.2.5 in the Assessment Report (see "Availability of Companions Documents" field).

Expert Consensus

Considerations

Technology appraisal recommendations are based on a review of clinical and economic evidence.

Technology Appraisal Process

The National Institute for Health and Clinical Excellence (NICE) invites 'consultee' and 'commentator' organisations to take part in the appraisal process. Consultee organisations include national groups representing patients and carers, the bodies representing health professionals, and the manufacturers of the technology under review. Consultees are invited to submit evidence during the appraisal and to comment on the appraisal documents.

Commentator organisations include manufacturers of the products with which the technology is being compared, the National Health Service (NHS) Quality Improvement Scotland and research groups working in the area. They can comment on the evidence and other documents but are not asked to submit evidence themselves.

NICE then commissions an independent academic centre to review published evidence on the technology and prepare an 'assessment report'. Consultees and commentators are invited to comment on the report. The assessment report and the comments on it are then drawn together in a document called the evaluation report.

An independent Appraisal Committee then considers the evaluation report. It holds a meeting where it hears direct, spoken evidence from nominated clinical experts, patients and carers. The Committee uses all the evidence to make its first recommendations, in a document called the 'appraisal consultation document' (ACD). NICE sends all the consultees and commentators a copy of this document and posts it on the NICE website. Further comments are invited from everyone taking part.

When the Committee meets again it considers any comments submitted on the ACD; then it prepares its final recommendations in a document called the 'final appraisal determination' (FAD). This is submitted to NICE for approval.

Consultees have a chance to appeal against the final recommendations in the FAD. If there are no appeals, the final recommendations become the basis of the guidance that NICE issues.

Who is on the Appraisal Committee?

NICE technology appraisal recommendations are prepared by an independent committee. This includes health professionals working in the NHS and people who are familiar with the issues affecting patients and carers. Although the Appraisal Committee seeks the views of organisations representing health professionals, patients, carers, manufacturers and government, its advice is independent of any vested interests.

Not applicable

Published Economic Evaluations

The Assessment Group did not identify any published economic evaluations that considered efalizumab. The Assessment Group identified only one published economic evaluation of etanercept that met its inclusion criteria. The base-case analysis found ultraviolet B (UVB) phototherapy to be the most cost-effective option, followed by methotrexate. Of the three biological therapies examined (infliximab, etanercept and alefacept), infliximab was found to be the most cost effective, although it was still less cost effective than non-biological treatments. The analysis, however, had limited usefulness for decision making primarily because it was United States (US)-based and the results were not expressed as incremental costs per quality-adjusted life year (QALY).

See sections 4.2.2 and 4.2.3 in the original guideline document for information about manufacturers' models of cost-effectiveness for etanercept and efalizumab.

The Assessment Group Model

The Assessment Group developed its own model for assessing the cost effectiveness of etanercept and efalizumab. The main analysis compared etanercept (intermittent 25 mg and 50 mg, and continuous 25 mg), efalizumab (continuous) and supportive care without disease-modifying anti-rheumatic drugs (DMARDs) or biological therapies. Utilities were estimated by mapping the mean change in Dermatology Life Quality Index (DLQI) score (conditional on Psoriasis Area and Severity Index [PASI] response) to changes in EuroQol-5D (EQ-5D) (a non-disease specific instrument for describing and valuing health-related quality of life [HRQoL]). When modelling intermittent etanercept treatment, it was assumed that the time between 12 week treatment cycles would be 29 days, resulting in 3.2 treatment cycles per year. This was based on the median duration of PASI 75 response as reported in an unpublished etanercept re-treatment study. Annual discount rates of 6% on costs and 1.5% on outcomes were applied in the analyses. Adverse events were not directly modelled. Decision uncertainty was examined using probabilistic sensitivity analysis.

The base-case analysis showed that supportive care is the only cost-effective strategy until the threshold reaches 70,000 pounds sterling per QALY. The ICER for intermittent low-dose (25 mg) etanercept was found to be £65,320 per QALY gained. The incremental cost-effectiveness ratio (ICER) for intermittent high-dose (50 mg) etanercept treatment was substantially higher. Efalizumab was dominated in the analysis by intermittent etanercept 25 mg. The results of several alternative scenarios presented indicated that the cost effectiveness of efalizumab and etanercept varied considerably according to baseline DLQI and whether it was assumed that all non-responders were hospitalised for 21 days annually. In all cases, the ICERs of the biological agents were found to be lower than in the base-case; but efalizumab was less cost-effective than intermittent etanercept 25 mg. In the scenario that considered both poor baseline quality of life and hospitalisation for non-responders, the ICER for intermittent etanercept 25 mg was £14,460 per QALY gained.

External Peer Review

Consultee organizations from the following groups were invited to comment on the draft scope, Assessment Report and the Appraisal Consultation Document (ACD) and were provided with the opportunity to appeal against the Final Appraisal Determination.

• Manufacturer/sponsors
• Professional/specialist and patient/carer groups
• Commentator organisations (without the right of appeal)

In addition, individuals selected from clinical expert and patient advocate nominations from the professional/specialist and patient/carer groups were also invited to comment on the ACD.

1. Etanercept, within its licensed indications, administered at a dose not exceeding 25 mg twice weekly is recommended for the treatment of adults with plaque psoriasis only when the following criteria are met.
   • The disease is severe as defined by a total Psoriasis Area Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10.
   • The psoriasis has failed to respond to standard systemic therapies including ciclosporin, methotrexate, and psoralen and long-wave ultraviolet radiation (PUVA); or the person is intolerant to, or has a contraindication to, these treatments.
2. Etanercept treatment should be discontinued in patients whose psoriasis has not responded adequately at 12 weeks. Further treatment cycles are not recommended in these patients. An adequate response is defined as either:
   • A 75% reduction in the PASI score from when treatment started (PASI 75), or
   • A 50% reduction in the PASI score (PASI 50) and a five-point reduction in DLQI from when treatment started
3. Efalizumab, within its licensed indications, is recommended for the treatment of adults with plaque psoriasis under the circumstances detailed in section 1 (above) only if their psoriasis has failed to respond to etanercept or they are shown to be intolerant of, or have contraindications to, treatment with etanercept.
4. Further treatment with efalizumab is not recommended in patients unless their psoriasis has responded adequately at 12 weeks as defined in section 2 (above).
5. It is recommended that the use of etanercept and efalizumab for psoriasis should be initiated and supervised only by specialist physicians experienced in the diagnosis and treatment of psoriasis. If a person has both psoriasis and psoriatic arthritis their treatment should be managed by collaboration between a rheumatologist and a dermatologist.
6. Patients who have begun a course of treatment with efalizumab at the date of publication of this guidance should have the option of continuing to receive treatment until the patients and their clinicians consider it is appropriate to stop.

None provided

The type of evidence supporting the recommendations is not specifically stated.

Appropriate use of efalizumab and etanercept in the treatment of adults with psoriasis

This guidance represents the view of the Institute, which was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. The guidance does not, however, override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.

Notes on the Generalisability of the Findings

For both etanercept and efalizumab, the trial populations may not truly reflect the difficult-to-treat patients for whom these two biologics are licensed. In addition, the results of both the clinical and economic evaluations relate to induction of remission rather than long-term effectiveness in the treatment of psoriasis.

Living with Illness

Effectiveness
Patient-centeredness

• National Institute for Health and Clinical Excellence (NICE). Etanercept and efalizumab for the treatment of adults with psoriasis. London (UK): National Institute for Health and Clinical Excellence (NICE); 2006 Jul. 35 p. (Technology appraisal guidance; no. 103).

Not applicable: The guideline was not adapted from another source.

2006 Jul

National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]

National Institute for Health and Clinical Excellence (NICE)

Appraisal Committee

Committee Members: Ms Julie Acred, Chief Executive Officer, Derby Hospitals; Dr Darren Ashcroft, Senior Clinical Lecturer, School of Pharmacy and Pharmaceutical Sciences, University of Manchester; Professor David Barnett (Chair) Professor of Clinical Pharmacology, University of Leicester; Dr Peter Barry, Consultant in Paediatric Intensive Care and Honorary Senior Lecturer, Department of Child Health, Leicester Royal Infirmary; Mr Brian Buckley, Vice Chairman, InContact; Professor Mike Campbell, Statistician, Institute of General Practice & Primary Care, Sheffield; Dr Mark Chakravarty, Head of Government Affairs and NHS Policy, Procter and Gamble Pharmaceuticals (UK) Ltd, Egham, Surrey; Dr Peter I Clark, Consultant Medical Oncologist, Clatterbridge Centre for Oncology, Wirral, Merseyside; Ms Donna Covey, Chief Executive, Asthma UK; Dr Mike Davies, Consultant Physician, University Department of Medicine & Metabolism, Manchester Royal Infirmary; Mr Richard Devereaux-Phillips, Public Affairs Manager, Medtronic Ltd; Professor Jack Dowie, Health Economist, London School of Hygiene; Professor Gary A Ford (Vice Chair) Professor of Pharmacology of Old Age/Consultant Physician, Newcastle upon Tyne Hospitals NHS Trust; Dr Fergus Gleeson,  Consultant Radiologist, The Churchill Hospital, Oxford; Ms Sally Gooch, Former Director of Nursing, Mid-Essex Hospital Services NHS Trust, Chelmsford; Professor Trisha Greenhalgh, Professor of Primary Health Care, University College London; Miss Linda Hands, Clinical Reader in Surgery, University of Oxford; Professor Peter Jones, Professor of Statistics & Dean Faculty of Natural Sciences, Keele University; Professor Robert Kerwin, Professor of Psychiatry and Clinical Pharmacology, Institute of Psychiatry, London; Ms Rachel Lewis, Nurse Advisor to the Department of Health; Professor Jonathan Michaels, Professor of Vascular Surgery, University of Sheffield; Dr Ruairidh Milne, Senior Lecturer in Public Health, National Coordinating Centre for Health Technology Assessment, University of Southampton; Dr Neil Milner, General Medical Practitioner, Sheffield; Dr Rubin Minhas, General Practitioner with a Special Interest in Coronary Heart Disease, Primary Care CHD Lead, Medway PCT & Swale PCT; Mr Miles Scott, Chief Executive, Harrogate Health Care NHS Trust; Professor Mark Sculpher, Professor of Health Economics, University of York; Dr Ken Stein, Senior Lecturer, Peninsula Technology Assessment Group (PenTAG), University of Exeter; Professor Andrew Stevens, Professor of Public Health, University of Birmingham; Ms Jayne Wilson, Systematic Reviewer, WMHTAC, Department of Public Health and Epidemiology

Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal.

This is the current release of the guideline.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.