• National Institute for Health and Clinical Excellence (NICE). Etanercept and infliximab for the treatment of adults with psoriatic arthritis. London (UK): National Institute for Health and Clinical Excellence (NICE); 2006 Jul. 33 p. (Technology appraisal guidance; no. 104).

This is the current release of the guideline.

Psoriatic arthritis (PsA, psoriatic arthropathy)

Assessment of Therapeutic Effectiveness
Management
Treatment

Dermatology
Family Practice
Pharmacology
Rheumatology

Advanced Practice Nurses
Nurses
Pharmacists
Physician Assistants
Physicians

To evaluate the clinical effectiveness, safety, tolerability, and cost effectiveness of etanercept and infliximab for the treatment of active and progressive psoriatic arthritis

Adults with active and progressive psoriatic arthritis who have inadequate response to standard treatment (including disease modifying antirheumatic drug [DMARD] therapy)

1. Etanercept
2. Infliximab

• Clinical effectiveness
  • Measures of disease activity
    • The American College of Rheumatology (ACR) joint count
    • The Psoriatic Arthritis Response Criteria (PsARC)
    • The Psoriasis Area and Severity Index (PASI)
  • Function and quality of life (Health Assessment Questionnaire [HAQ])
  • Radiological assessment of disease progression
  • Adverse events
• 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Searches of Unpublished Data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

Etanercept

Two randomised controlled trials (RCTs, n = 265) were included in the Assessment Report.

Infliximab

One RCT was included in the Assessment Report.

Cost Effectiveness

The search strategy for published economic evaluations yielded 117 potentially relevant studies. Of these, none fulfilled the inclusion criteria of being a full economic evaluation of etanercept or infliximab for the treatment of psoriatic arthritis.

Two cost-effectiveness models were received from manufacturers, one for etanercept (from Wyeth) and one for infliximab (from Schering Plough).

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.)

For details of the data extraction and quality assessment strategies, see sections 3.2.3 and 3.2.4 in the Assessment Report (see "Availability of Companion Documents" field).

Data Analysis

Efficacy of Interventions

Full data extraction and quality assessment have been presented for each efficacy trial of etanercept and infliximab.

Results have been summarised in tables and the effect of trial quality on the efficacy findings is discussed. Relative risks (RRs) and mean differences were calculated for the primary outcomes with 95% confidence intervals (CIs); the primary outcome variables were American College of Rheumatology response criteria (ACR) 20, ACR 50, ACR 70, Psoriatic Arthritis Response Criteria (PsARC), Health Assessment Questionnaire (HAQ), and Psoriasis Area and Severity Index (PASI).

Clinical diversity of the trials regarding adult status, minimum PASI score, and concomitant medication was considered. Where the trials were not clinically diverse (heterogeneous) the data were pooled. Statistical heterogeneity was investigated using the Chi-Squared test; where it was statistically significant data were not pooled. Where pooling was appropriate, pooled RRs (95% CI) or weighted mean differences (WMD) (95% CI) were calculated using a fixed effect model. A fixed effect model was selected because a small number of trials were included in the meta-analysis, and a fixed effect model was therefore considered most appropriate due to the smaller estimation of between-study variance.

In order to generate appropriately pooled estimates of clinical parameters for the cost-effectiveness modelling an evidence synthesis was conducted. The exact specification of the synthesis depended on the nature of the trial evidence and the details of the cost-effectiveness models; unless head-to-head trials comparing etanercept and infliximab are identified, the synthesis would be likely to take the form of a mixed treatment comparison. The detailed methods of the evidence synthesis are described in Section 4.2.3 of the Assessment Report (see the "Availability of Companion Documents" field).

Adverse Effects of Interventions

Results have been summarised in tables and the findings are discussed in a narrative synthesis. Adverse events data have been grouped by duration of follow-up.

DMARDs for Treatment of Psoriatic Arthritis

Data extraction has been presented for each comparator trial. Results have been summarised in tables and the findings are discussed. Relative risks (RRs) and mean differences were calculated for the primary outcomes with 95% confidence intervals (CIs); the primary outcome variables were ACR 20, ACR 50, ACR 70, PsARC, Tender Joint Score (mean change from baseline), Erythrocyte sedimentation rate (ESR) (mean change from baseline mm/h), Pain (mean change from baseline, visual analog scale [VAS]), Swollen Joint Score (mean change from baseline), Patient Global Assessment (mean change from baseline), Physician Global Assessment (mean change from baseline), HAQ (mean change from baseline) and PASI (mean change from baseline).

The findings were not pooled statistically due to the clinical diversity of the trials and the small numbers of studies investigating the same treatment comparison.

Economic Evaluations –Systematic Review

Any published economic evaluations were to be described but no formal synthesis was planned. This also applied to submitted analyses from manufacturers, although additional analyses using their electronic models was to have been considered. In the event no published economic evaluation on anti-TNF drugs for the treatment of psoriatic arthritis was identified.

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

Cost-effectiveness models were submitted by Wyeth and Schering Plough. Wyeth's model estimated the incremental cost per quality adjusted life years (QALY) gained for etanercept (compared to a composite comparator) to range from 28,189 pounds sterling for a 10-year time horizon to 66,580 pounds sterling for a 6-month time horizon. Schering Plough presented two models. The "Active Joint" model estimated an incremental cost per QALY gained for infliximab of 36,786 pounds sterling (5-year time horizon). The "Chronic Active Joint" model estimated an incremental cost-effectiveness ratio (ICER) of 33,877 pounds sterling (30-year time horizon).

Given some potential limitations of the manufacturers' models and their failure to compare the two biological therapies directly and with palliative care, a new model was developed (the York Model). Results were estimated over a range of time horizons and based on a number of alternative assumptions. Infliximab is consistently dominated by etanercept because of its higher acquisition and administration costs without superior effectiveness. The incremental cost per QALY gained of etanercept compared with palliative care ranges from 14,806 pounds sterling (females, 40-year time horizon) to 49,299 pounds sterling (males, 1-year time horizon) if it is assumed that, when patients eventually fail on biological therapy, their disability (in terms of Health Assessment Questionnaire [HAQ] score) deteriorates by the same amount as it improved when they initially respond to treatment (rebound equal to gain). The ICERs of etanercept range from 25,403 pounds sterling (females, 40-year time horizon) to 49,408 pounds sterling (males, 1-year time horizon) if it is assumed that, when patients fail on therapy, their disability level returns to what it would have been had they never responded (rebound equal to natural history).

See section 4.2 in the original guideline document for a full discussion of cost effectiveness.

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, is recommended for the treatment of adults with severe active psoriatic arthritis only when the following criteria are met.
   • The person has peripheral arthritis with three or more tender joints and three or more swollen joints.
   • The psoriatic arthritis has not responded to adequate trials of at least two standard disease-modifying anti-rheumatic drugs (DMARDs), administered either individually or in combination.
2. Etanercept treatment should be discontinued in patients whose psoriatic arthritis has not shown an adequate response when assessed using the Psoriatic Arthritis Response Criteria (PsARC) at 12 weeks. An adequate response is defined as:
   • An improvement in at least two of the four PsARC criteria, one of which has to be joint tenderness or swelling score, with no worsening in any of the four criteria
3. Infliximab, within its licensed indications, is recommended for the treatment of adults with severe active psoriatic arthritis if, under the circumstances outlined in section 1 (above), treatment with an anti-tumour necrosis factor (TNF) agent is considered appropriate and the person has been shown to be intolerant of, or have contraindications to, treatment with etanercept or has major difficulties with self administered injections.
4. Infliximab treatment should be discontinued in patients whose psoriatic arthritis has not responded adequately at 12 weeks. An adequate response is defined in section 2 (above).
5. It is recommended that the use of etanercept or infliximab for psoriatic arthritis should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of psoriatic arthritis. If a person has both psoriatic arthritis and psoriasis their treatment should be managed by collaboration between a rheumatologist and a dermatologist.

None provided

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

Appropriate use of etanercept and infliximab for the treatment of adults with psoriatic arthritis

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

The efficacy data used in the clinical evaluation, evidence synthesis and the economic models are very limited, being derived from a total of three trials and a total of 369 patients, with only 134 patients treated with etanercept and 52 treated with infliximab. Furthermore, these trial populations were not precisely representative of those for whom etanercept and infliximab are licenced: neither population was made up exclusively of patients who had failed to respond to at least two disease-modifying anti-rheumatic drugs (DMARDs). A number of other parameters within the economic models are also based on very limited evidence.

Living with Illness

Effectiveness
Patient-centeredness

• National Institute for Health and Clinical Excellence (NICE). Etanercept and infliximab for the treatment of adults with psoriatic arthritis. London (UK): National Institute for Health and Clinical Excellence (NICE); 2006 Jul. 33 p. (Technology appraisal guidance; no. 104).

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.