The Department of Health has asked the National Institute for Health and Clinical Excellence (NICE) to produce guidance on using etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis in the NHS in England and Wales. The Appraisal Committee has considered the evidence submitted and the views of non-manufacturer consultees and commentators, and clinical specialists and patient experts.

This document has been prepared for consultation with the consultees. It summarises the evidence and views that have been considered, and sets out the draft recommendations made by the Committee. NICE invites comments from the consultees and commentators for this appraisal (see appendix B) and the public. This document should be read along with the evidence base (the evaluation report), which is available from www.nice.org.uk

The Appraisal Committee is interested in receiving comments on the following:

• Has all of the relevant evidence been taken into account?
• Are the summaries of clinical and cost effectiveness reasonable interpretations of the evidence?
• Are the provisional recommendations sound and a suitable basis for guidance to the NHS?
• Are there any aspects of the recommendations that need particular consideration to ensure we avoid unlawful discrimination against any group of people on the grounds of gender, race, disability, age, sexual orientation, religion or belief?

Note that this document is not NICE's final guidance on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis. The recommendations in section 1 may change after consultation.

After consultation:

• The Appraisal Committee will meet again to consider the evidence, this appraisal consultation document and comments from the consultees.
• At that meeting, the Committee will also consider comments made by people who are not consultees.
• After considering these comments, the Committee will prepare the final appraisal determination (FAD).
• Subject to any appeal by consultees, the FAD may be used as the basis for NICE’s guidance on using etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis in the NHS in England and Wales.

For further details, see the ‘Guide to the technology appraisal process’ (available at www.nice.org.uk).

The key dates for this appraisal are:

Closing date for comments: 8^th April 2010

Second Appraisal Committee meeting: 20^th April 2010

Details of membership of the Appraisal Committee are given in appendix A, and a list of the sources of evidence used in the preparation of this document is given in appendix B.

Note that this document is not NICE's final guidance on these technologies. The recommendations in section 1 may change after consultation.

1 Appraisal Committee’s preliminary recommendations

1.1 Etanercept and adalimumab are recommended for the treatment of adults with active and progressive psoriatic arthritis 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 antirheumatic drugs (DMARDs), administered either individually or in combination.

1.2 Infliximab is recommended for the treatment of adults with active and progressive psoriatic arthritis only if:

• the criteria in 1.1 are met and
• the person is intolerant of, or has contraindications to, etanercept and adalimumab, or subcutaneous administration is unsuitable for them.

1.3 Etanercept, adalimumab or infliximab treatment should be stopped in people whose psoriatic arthritis has not shown an adequate response 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, (one of which has to be joint tenderness or swelling score) with no worsening in any of the four criteria.

2 Clinical need and practice

2.1 Psoriatic arthritis is an inflammatory arthritis affecting the joints and connective tissue and associated with psoriasis of the skin or nails. The prevalence of psoriasis in the general population is estimated at 2–3%. The prevalence of inflammatory arthritis in people with psoriasis is estimated at up to 30%. At least 20% of people with psoriasis have severe psoriatic arthritis with progressive joint lesions. Psoriatic arthritis is a progressive disorder ranging from mild synovitis to severe progressive erosive arthropathy. People with psoriatic arthritis presenting with oligoarticular disease progress to polyarticular disease and a large percentage develop joint lesions and deformities, which progress over time. Despite clinical improvement with current DMARD treatment, radiological joint damage has been shown in up to 47% of people with psoriatic arthritis at a median interval of 2 years.

2.2 Psoriatic arthritis can affect people’s ability to work and carry out daily activities, which can have a substantial impact on quality of life. The impact of severe psoriasis on health-related quality of life is considered to be similar to that of other major medical conditions including diabetes, heart disease and cancer. People with psoriatic arthritis have a higher self-rated disease severity than those with psoriasis only. People with psoriatic arthritis have a 60% higher risk of mortality than the general population and their life expectancy is estimated to be approximately 3 years shorter.

2.3 Most people with psoriatic arthritis develop skin symptoms before joint symptoms, although joint symptoms may appear first or simultaneously. Psoriatic arthritis usually develops within 10 years of a diagnosis of psoriasis. The rheumatic characteristics of psoriatic arthritis include joint stiffness, pain and swelling, and tenderness of the joints and surrounding ligaments and tendons. Symptoms can range from mild to very severe.

2.4 Assessing the effectiveness of treatments for psoriatic arthritis relies on outcome measures that accurately and sensitively measure disease activity. Outcomes of effectiveness are based on measures of the anti-inflammatory response (such as the PsARC, and the American College of Rheumatology response criteria [ACR 20/50/70]), measures of psoriatic skin lesions (psoriasis area and severity index [PASI]), functional measures (health assessment questionnaire [HAQ]) and radiological assessments (Total Sharp Score, van der Heijde-Sharp score) of disease progression, quality of life and overall global assessments. Overall response criteria have not yet been clearly defined.

2.5 The aim of psoriatic arthritis treatment is to relieve symptoms, slow disease progression and maintain quality of life. To effectively manage psoriatic arthritis, any associated skin disease also needs to be effectively treated. Non-steroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections are widely used. Disease that is unresponsive to NSAIDs, in particular polyarticular disease, should be treated with DMARDs (currently, methotrexate and sulphasalazine are considered the DMARDs of choice) to reduce joint damage and prevent disability. Aggressive treatment of early stage progressive psoriatic arthritis can help to improve prognosis.

3 The technologies

Etanercept

3.1 Etanercept (Enbrel, Wyeth Pharmaceuticals) is a human tumour necrosis factor (TNF) receptor fusion protein that inhibits TNF-α binding to cell surface TNF receptors. Etanercept is licensed for the treatment of active and progressive psoriatic arthritis in adults whose disease has not responded adequately to previous DMARD therapy.

3.2 The most common adverse events reported in the trials were infections (including upper respiratory tract infections, bronchitis, cystitis and skin infections), injection site reactions (including bleeding, bruising, erythema, itching, pain and swelling), and allergic reactions, such as pruritus. For full details of undesirable effects and contraindications, see the summary of product characteristics.

3.3 The acquisition cost of etanercept is £89.38 per 25 mg prefilled syringe or 25 mg vial with powder for reconstitution (with solvent), and £178.75 per 50 mg prefilled syringe (excluding VAT; British national formulary [BNF] edition 58). The annual cost of etanercept using either 50mg once-weekly doses (52 doses per year) or 25mg twice-weekly doses (104 doses per year) is £9295. Costs may vary in different settings because of negotiated procurement discounts.

Infliximab

3.4 Infliximab (Remicade, Wyeth Pharmaceuticals) is a chimeric human-murine monoclonal antibody that inhibits the functional activity of TNF-α. Infliximab is licensed for the treatment of active and progressive psoriatic arthritis in adults when the disease has not responded adequately to previous DMARD therapy. Infliximab should be administered:

• in combination with methotrexate, or
• alone in people who show intolerance to methotrexate or for whom methotrexate is contraindicated.

3.5 The most common reported adverse events in the trials were infusion reactions and hypersensitivity, infections (tuberculosis, bacterial infections – including sepsis and pneumonia – invasive fungal infections, and other opportunistic infections), hepatitis B reactivation and heart failure. For full details of undesirable effects and contraindications, see the summary of product characteristics.

3.6 The acquisition cost of infliximab is £419.62 per 100 mg vial with powder for reconstitution (excluding VAT; BNF edition 58). For a 75-kg adult, each dose of 5 mg/kg requires four 100-mg vials at a cost of £1678. The three initial doses are given at weeks 0, 2 and 6, at a cost of £5035. The subsequent annual cost following the loading doses is £10,910 per year based on infusions repeated every 8 weeks (average 6.5 doses per year). Costs may vary in different settings because of negotiated procurement discounts.

Adalimumab

3.7 Adalimumab (Humira, Abbott Laboratories) is a recombinant human monoclonal antibody that binds specifically to TNF and neutralises its function. Adalimumab is licensed for the treatment of active and progressive psoriatic arthritis in adults when the disease has not responded adequately to previous DMARD therapy.

3.8 The most common reported adverse events in the trials were infections (including sepsis due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or other opportunistic infections such as listeriosis and pneumocystis), tuberculosis, hepatitis B reactivation, formation of autoimmune antibodies and congestive heart failure. For full details of undesirable effects and contraindications, see the summary of product characteristics.

3.9 The acquisition cost of adalimumab is £357.50 per 40 mg prefilled pen or prefilled syringe (excluding VAT; BNF edition 58). An initial dose of 80 mg is given followed by a 40 mg dose one week later. The subsequent annual cost of adalimumab based on 40 mg doses given every 2 weeks is £9295 (26 doses per year). Costs may vary in different settings because of negotiated procurement discounts.

4 Evidence and interpretation

The Appraisal Committee (appendix A) considered evidence from a number of sources (appendix B).

4.1 Clinical effectiveness

4.1.1 The Assessment Group identified six double-blind, placebo-controlled, randomised controlled trials (RCTs) in people with psoriatic arthritis in total for the technologies: two for etanercept, two for infliximab and two for adalimumab.

Etanercept

4.1.2 The two double-blind, placebo-controlled RCTs of etanercept in adults with active psoriatic arthritis were: Mease 2000 (n = 60; follow-up 12 weeks) and Mease 2004 (n = 205; follow-up 24 weeks). In both trials etanercept was administered by subcutaneous injection twice a week at a dose of 25 mg. The inclusion criteria for both trials were active psoriatic arthritis (defined as more than three swollen joints and more than three tender or painful joints, although only the more recent trial specified stable plaque psoriasis), and psoriatic arthritis that had not responded adequately to NSAIDs. The primary outcome variable in the Mease 2000 trial was PsARC and in Mease 2004 it was ACR 20. Data on PASI at week 12 were available from Mease 2000 only.

4.1.3 The Assessment Group conducted a meta-analysis of the outcomes for etanercept at 12 weeks and the pooled estimates from both trials showed that etanercept was statistically significantly more effective than placebo for all outcomes (PsARC, ACR 20, ACR 50, ACR 70, and HAQ percentage change from baseline). For PsARC the pooled relative risk (RR) estimate was 2.60 (95% confidence interval [CI] 1.96 to 3.45), with some evidence of statistical heterogeneity (I² = 34%) between the two study estimates. For PASI 50, the results from the Mease 2000 trial at 12 weeks showed that etanercept was more effective than placebo (RR = 2.00 [95% CI 0.72 to 5.53]) although this was not statistically significant. For PASI 75 the results showed that etanercept was statistically significantly more effective than placebo (RR = 11.00 [95% CI 0.65 to 186.02]; p = 0.0154).

4.1.4 At 24 weeks the treatment effect for all joint disease outcome measures was statistically significantly greater for etanercept than for placebo, though this data was only available for one trial, Mease 2004. At 24 weeks, the annualised rate of progression as measured radiologically using the Total Sharp Score was statistically significantly lower in people treated with etanercept than people treated with placebo (Total Sharp Score –0.56; 95% CI –0.86 to –0.26).

4.1.5 At 24 weeks the treatment effect on psoriasis favoured etanercept with RRs for PASI 75 of 7.05 (95% CI 1.68 to 29.56), PASI 50 of 2.65 (95% CI 1.46 to 4.80) and PASI 90 of 1.88 (95% CI 0.36 to 9.90). At 1 year the mean annualised rate of progression on the Total Sharp Score for all people was –0.03 (standard deviation [SD] 0.87), indicating that on average there was no clinically significant progression of joint erosion based on uncontrolled follow-up data.

Infliximab

4.1.6 The two double-blind, placebo-controlled RCTs of infliximab for the treatment of psoriatic arthritis were: IMPACT (n = 104) in which participants were randomised to receive infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6 and 14 with follow-up at week 16; and IMPACT 2 (n = 200) in which people were randomised to receive infusions of placebo or infliximab 5 mg/kg at weeks 0, 2, 6, 14 and 22, with assessments at weeks 14 and 24. In both RCTs the inclusion criteria required that participants’ psoriatic arthritis should have five or more swollen/tender joints and to have had an inadequate response to at least one DMARD. IMPACT 2 also required people to have active plaque psoriasis with at least one qualifying target lesion (2 cm or more in diameter).

4.1.7 The Assessment Group conducted a meta-analysis of the outcomes for infliximab at 14 weeks and the results for both trials reported a statistically significant improvement in PsARC for people receiving infliximab, relative to those receiving placebo (pooled RR 3.44, 95% CI 2.53 to 4.69). There was some evidence of statistical heterogeneity (I² = 68%) between the two study estimates. Infliximab was statistically significantly more effective than placebo for all pooled estimates for outcomes of joint response (ACR 20, ACR 50 and ACR 70) as well as the pooled percentage change from baseline in HAQ score with infliximab compared with placebo (mean difference –60.37 [95% CI –75.28 to –45.46]).

4.1.8 The Assessment Group also presented pooled estimates for the outcomes of the skin component of psoriatic arthritis over 14-16 weeks and the results showed that infliximab was statistically significantly more effective than placebo.

4.1.9 The IMPACT 2 trial was randomised for 24 weeks followed by an open-label period. The data for all measures of joint disease, psoriasis and HAQ were similar to those at 14-week follow-up, suggesting that infliximab’s benefits were maintained for up to 24 weeks of treatment and for longer-term follow-up (50 weeks for IMPACT and 54 weeks for IMPACT 2) although the data for the latter were uncontrolled.

4.1.10 In terms of radiographic assessment, there was no statistically significant change from baseline in the total modified van der Heijde-Sharp score for infliximab-treated people followed up at 50 weeks in the IMPACT trial (n = 70: –1.72 [5.82]) or 54 weeks in the IMPACT 2 trial (infliximab/infliximab –0.94 [3.4]; placebo/infliximab 0.53 [2.6]), suggesting infliximab may inhibit progression of joint damage. However, as with other post-24-week outcomes, there was no placebo group for comparison.

Adalimumab

4.1.11 The two double-blind, placebo-controlled RCTs of adalimumab in adults with active psoriatic arthritis were: ADEPT (n = 313, follow-up of 24 weeks) and Genovese 2007 (n = 100, follow-up of 12 weeks). In both trials adults were randomised to adalimumab (administered every other week at a dose of 40 mg) or placebo. The inclusion criteria for both RCTs required people to have active psoriatic arthritis (defined in both trials as more than three swollen joints and more than three tender or painful joints, with active psoriatic skin lesions or a documented history of psoriasis). Overall, the baseline characteristics demonstrated that the trial populations were indistinguishable and represented people who required DMARD or therapy with TNF inhibitors.

4.1.12 The Assessment Group conducted a meta-analysis of the outcomes for adalimumab at 12 weeks and the results from both trials showed a statistically significant improvement for adalimumab compared with placebo for all outcome measures. The pooled RR for PsARC was 2.24 (95% CI 1.74 to 2.88) and the pooled RR for ACR 20 was 3.65 (95% CI 2.57 to 5.17). The pooled RRs for ACR 50 and ACR 70 also favoured adalimumab, although their related CIs were wide. Regarding the associated skin disease, 12‑week PASI response measures were reported by only one trial (ADEPT), and the response was statistically significantly greater for adalimumab than placebo at all three PASI thresholds (RR = 6.50 [95% CI 3.34 to 12.64] for PASI 50, RR = 41.00 [95% CI 5.80 to 289.75] for PASI 75 and RR = 59.00 [95% CI 3.68 to 946.75] for PASI 90). The CIs, especially for PASI 75 and PASI 90, were wide.

4.1.13 The ADEPT trial was randomised for 24 weeks. The data for all measures of joint disease, psoriasis and HAQ were all similar to those at 12-week follow-up. In addition, this trial also reported a statistically significant difference in mean change in Total Sharp Score from baseline (–0.2 versus 0.1, p < 0.001) favouring adalimumab over placebo in terms of delayed progression of joint disease, although this duration of follow-up is short.

Indirect comparison performed by the Assessment Group

4.1.14 In the absence of head-to-head RCTs on the relative efficacy of the three TNF inhibitors an indirect comparison was undertaken by the Assessment Group using placebo as the common comparator. The results were expressed as the probability of each of the TNF inhibitors achieving a response for the outcome measures PsARC, HAQ, PASI and ACR. Infliximab was associated with the highest probability of achieving a response for all of the outcomes measured. The response in joint disease (PsARC and ACR) was higher with etanercept than adalimumab, and the response in skin disease (PASI) was higher with adalimumab than etanercept.

Adverse events

4.1.15 There were no RCTs that directly compared the three drugs. To evaluate the adverse events of the three TNF inhibitors the Assessment Group reviewed a range of study types including RCTs, trial open-label extensions and observational studies.

4.1.16 The Assessment Group provided a range of estimates for serious adverse event and withdrawal rates across non-randomised studies and large RCTs. These comprised serious infections, cancer, activation of latent tuberculosis, mortality and withdrawals from treatment because of adverse events.

4.1.17 The Assessment Group acknowledged that the adverse event data were primarily from people with rheumatoid arthritis or other indications, so it is unclear to what extent these can be generalised to psoriatic arthritis. Overall, the limited evidence prevented them from being able to draw firm conclusions from the systematic review about the comparative adverse event profile of the three TNF inhibitors.

4.2 Cost effectiveness

Published economic evaluations

4.2.1 The Assessment Group performed a systematic review of published literature and identified three studies (Olivieri et al. 2008, Bansback et al. 2007 and Bravo Vergel 2006) that met the inclusion criteria for the cost-effectiveness review.

4.2.2 The study by Olivieri et al. was difficult to compare with the other studies because in this study all TNF inhibitors were considered as a group compared with DMARDs. There were no model results. The economic evaluation was made using before-and-after studies and the effectiveness evidence based on a single trial. This produced an incremental cost-effectiveness ratio (ICER) of around €40,000 (£34,700) per quality-adjusted life year (QALY) gained for TNF inhibitors.

4.2.3 The study by Bansback et al. compared etanercept with ciclosporin and leflunomide. The economic model focused on response according to PsARC and associated HAQ score, with changes in HAQ and further withdrawals modelled over 10 years. Mease 2004 was the source of evidence for response rates and HAQ. The base-case results showed an ICER of around £28,000 per QALY gained for etanercept compared with ciclosporin and £38,000 per QALY gained for etanercept compared with leflunomide.

4.2.4 The study by Bravo Vergel compared etanercept with infliximab and palliative care. The model included response according to PsARC and associated HAQ score. Changes in HAQ and further withdrawals were modelled over 40 and 10 years. Evidence from Mease 2000, Mease 2004 and IMPACT was used to model the PsARC response. The ICER for etanercept was between £26,361 and £30,628 per QALY gained depending on the rebound (deterioration experienced in HAQ at treatment withdrawal) scenario used, compared with palliative care. Infliximab was the most effective strategy which generated the higher number of QALYs.

Manufacturer submission on the cost effectiveness of etanercept

4.2.5 A published cost-effectiveness model originally used to support a submission to NICE in 2004 was adapted to incorporate additional effectiveness evidence and new comparators. The adjusted model compared the costs and benefits associated with etanercept, infliximab, adalimumab and best supportive care over a lifetime horizon. Best supportive care was assumed to be ciclosporin because the population considered in the model were assumed to have already tried other DMARDs (leflunomide, sulphasalazine and methotrexate).

4.2.6 The base-case results showed that the costs for best supportive care were £53,860 and QALYs of 5.96 while for etanercept the costs were £65,650 and QALYs of 6.90. This resulted in an ICER of £12,480 per QALY gained for etanercept when compared with best supportive care. Adalimumab was extendedly dominated by etanercept, that is, additional QALYs could be generated with etanercept relative to adalimumab at a lower cost per QALY gained than is generated by adalimumab relative to palliative care. Infliximab was dominated by adalimumab (that is, infliximab was more costly and less effective).

Manufacturer submission on the cost effectiveness of infliximab

4.2.7 In the economic analysis submitted by the manufacturer of infliximab four treatment alternatives were compared over a lifetime horizon. These included maintenance treatment with a TNF inhibitor (infliximab, adalimumab or etanercept) followed by a sequence of DMARDs. The comparator was palliative care comprising DMARDs. For the health-economic model, the incremental treatment effects for the comparative treatments were estimated for infliximab, etanercept and adalimumab. The direct drug costs for the TNF inhibitors were obtained from BNF edition 56.

4.2.8 The manufacturer presented base-case results for three different scenarios: people weighing 60 kg, 70 kg (with vial optimisation) and 80 kg. For people weighing 60 kg the base-case results showed that infliximab produced an ICER of £16,942 per QALY gained when compared with palliative care. For people weighing 70 kg, and accounting for vial optimisation, infliximab produced an ICER of £19,982 per QALY gained versus palliative care. For people weighing 80 kg infliximab produced an ICER of £23,022 per QALY gained when compared with palliative care.

Manufacturer submission on the cost effectiveness of adalimumab

4.2.9 The manufacturer of adalimumab used an individual sampling model to simulate the disease progression of a cohort of people with psoriatic arthritis over a lifetime horizon under different treatment sequences. A 3-month cycle was used. Baseline characteristics from the ADEPT trial for people for whom two previous DMARDs had failed were used in the base-case analysis. The cost of all drugs used in the analysis was calculated based on the recommended dosages and vial prices given in the Monthly Index of Medical Specialties. The model assumed that four 100 mg vials of infliximab were required per infusion, based on an average person weighing 80 kg.

4.2.10 The base-case results showed that adalimumab, with a mean cost of £73,072 and QALYs of 8.33, was the most cost-effective treatment strategy when compared with a DMARD (mean costs of £47,537 and QALYs of 7.47), resulting in an ICER of £29,827 per QALY gained. Etanercept was more costly and had the same mean QALYs produced as adalimumab (8.33). Infliximab was more costly and more effective than adalimumab, which resulted in an ICER of £199,596 per QALY gained compared with adalimumab.

Assessment Group economic assessment

4.2.11 The Assessment Group updated the economic model developed for ‘Etanercept and infliximab for the treatment of adults with psoriatic arthritis’ (NICE technology appraisal 104). This model allowed the three TNF inhibitors to be compared with each other. A probabilistic decision analytic model was developed to estimate the incremental costs and incremental QALYs of the three TNF inhibitors compared with palliative care over a lifetime horizon (40 years), only. The price year was 2008/2009 and costs and benefits were discounted at a rate of 3.5%.

4.2.12 The decision analytical model followed a cohort of people, which represented the average characteristics of participants in the RCTs and had a Markov structure. People in the cohort were assumed to be 47 years old, had been diagnosed with psoriatic arthritis 7 years previously, were assumed to weigh 70 kg and had psoriatic arthritis that had inadequately responded to at least two DMARDS. The treatment arm received etanercept, infliximab or adalimumab and the control arm received palliative care. The disease’s response to treatment was assessed between 12 and 16 weeks. It was assumed that people whose disease had responded to treatment stayed in the treatment arm, while treatment was discontinued in people whose psoriatic arthritis failed to adequately respond to treatment – these people were assumed to go on to receive palliative care.

4.2.13 The following assumptions were included in the Assessment Group’s model: people in the initial 3-month trial period had some improvement in HAQ (even if they did not reach the PsARC threshold); people who had a PASI 75 response would gain at least a 75% improvement in psoriasis compared with baseline PASI; people continuing on TNF inhibitors maintained their initial improvement in HAQ; and the same ongoing risk of withdrawal from treatment was used for all TNF inhibitors (withdrawal because of reduction in efficacy, adverse events or other reasons).

4.2.14 The base-case analysis in the Assessment Group’s model assumed a lifetime (40-year) time horizon for costs and QALYs, a baseline HAQ of 1.05, a baseline PASI of 7.5, rebound equal to gain and incorporates the correlation between PsARC and PASI 75 outcomes. Health utility was measured as a function of HAQ and PASI based on linear regressions of EQ5D utility versus HAQ and PASI provided by the manufacturers based on RCT evidence. The total lifetime discounted health associated with palliative care was about 5.24 QALYs because the base-case scenario assumed that utility declined fairly rapidly in people with uncontrolled arthritis, and may have been less than 0 (representing a health state worse than death) in later years.

4.2.15 The base-case model assumed that people’s psoriatic arthritis had failed to respond to treatment with at least two DMARDS but they had not received previous treatment with TNF inhibitors. The Assessment Group also modelled the cost effectiveness of sequencing TNF inhibitor therapies after people’s psoriatic arthritis failed to respond to a first-line TNF inhibitor. The base‑case analysis reported the lifetime costs and QALYs of the three TNF inhibitors in people with mild-to-moderate psoriatic arthritis, which was presented as an incremental analysis ranking the alternative strategies by mean cost.

4.2.16 The results for the base case showed that infliximab was the most effective treatment taking into account both joint and skin effects (QALYs of 7.43), followed by etanercept (QALYs of 7.11), then adalimumab (QALYs of 6.64). Infliximab was also the most costly treatment (£89,107), followed by etanercept (£72,172), then adalimumab (£66,408). The ICER of etanercept compared with palliative care was £15,986 per QALY gained. The ICER for infliximab compared with etanercept was £53,750 per QALY gained. Adalimumab was extendedly dominated by a combination of etanercept and palliative care (that is, additional QALYs could be generated with etanercept relative to adalimumab at a lower cost per QALY gained than the ICER of adalimumab relative to palliative care, adalimumab is therefore excluded from the incremental analysis). Etanercept had the highest probability of being cost effective with a 52% and 57% probability of being cost effective at willingness-to-pay thresholds of £20,000 and £30,000 per QALY gained, respectively.

4.2.17 The Assessment Group conducted a number of univariate sensitivity analyses assuming different scenarios. The Assessment Group presented the results according to whether the ICER was less than £20,000 per QALY gained, between £20,000 to £30,000 per QALY gained or greater than £30,000 per QALY gained.

4.2.18 The results of these analyses suggested that in the following scenarios the ICER of etanercept increased to above £20,000 per QALY or was dominated by other strategies, assuming all other variables take mean values as in the base case:

• A patient who does not achieve a PASI 75 response is offered one course of therapy as a hospital inpatient per year to treat psoriasis. The base case assumed these patients are offered UV therapy.
• The HAQ rebounds after withdrawal from TNF inhibitors to natural history rather than to initial gain.
• Treatment with TNF inhibitors becomes ineffective (relative to no treatment) after 10 years.

4.2.19 In the following scenarios the ICER of infliximab fell below £30,000 per QALY, assuming all other variables take mean values as in the base case:

• A patient who does not achieve a PASI 75 response is offered one course of therapy as a hospital inpatient per year to treat psoriasis. The base case assumed these patients are offered UV therapy.
• Infliximab requires three vials rather than four vials per administration.
• If the manufacturer of infliximab’s estimates of the cost of treating psoriasis with phototherapy are used in the Assessment Group’s model.

4.2.20 In the following scenarios the ICER of adalimumab fell below £20,000 per QALY and was no longer dominated by other strategies, assuming all other variables take mean values as in the base case:

• All responders to PsARC have the same change in HAQ at 3 months, regardless of the TNF inhibitor used.
• A patient who does not achieve a PASI 75 response is offered one course of therapy as a hospital inpatient per year to treat psoriasis. The base case assumed these patients are offered UV therapy.
• If the manufacturer of infliximab’s estimates of the cost of treating psoriasis with phototherapy are used in the Assessment Group’s model.

4.2.21 The Assessment Group performed a sensitivity analysis assuming all TNF inhibitors had the same change in HAQ benefit at 3 months for a PsARC responder. The Assessment Group calculated that the ICERs for adalimumab and etanercept fall below £20,000 per QALY while for infliximab the ICER is above £61,000 per QALY.

4.2.22 The Assessment Group also provided a subgroup analysis for a cohort with a worse baseline health-related quality of life (HAQ score of 1.8 based on the British Society for Rheumatology Biologics Register) and a baseline PASI of 12.5, corresponding to moderate-to-severe psoriasis rather than mild-to-moderate as in the model, and a cohort without skin involvement (PASI of 0). The results suggested that in people with negligible baseline psoriasis etanercept was the most cost-effective strategy with an ICER of £16,603 compared with palliative care and the incremental cost effectiveness of infliximab compared with etanercept was £76,132 per QALY. If baseline PASI was moderate-to-severe (12.5 instead of 7.5) the ICER of adalimumab versus palliative care would be less than £14,809 per QALY, the ICER of etanercept versus adalimumab would be around £16,154 per QALY and the ICER of infliximab versus etanercept would be about £36,364 per QALY. If people with uncontrolled psoriasis received annual inpatient treatment instead of annual UV treatment the ICER for infliximab was below £20,000 per QALY and would likely be the most cost-effective strategy.

4.2.23 The Assessment Group presented an analysis that compared the sequencing of the different TNF inhibitors in people with mild-to-moderate skin disease if a first TNF inhibitor has failed. The ICERs depended on which drug was used as first-line therapy, and was therefore ineligible for use as second-line therapy. The Assessment Group noted that the ICERs were broadly similar for people whose psoriatic arthritis failed to respond to first-line therapy because of adverse effects and those whose disease failed first-line therapy because of inefficacy.

4.2.24 An additional sensitivity analysis was performed by the Assessment Group at the Committee meeting and subsequently confirmed by running the model probabilistically. This scenario assumed that adalimumab and etanercept were equally effective while the PsARC responses for infliximab remained the same as in the original analysis (that is, infliximab was assumed to be more effective than adalimumab and etanercept). The ICER for both adalimumab and etanercept compared with palliative care was £18,296 per QALY gained and the ICER for infliximab compared to adalimumab and etanercept was £45,557 per QALY gained. 

4.3 Consideration of the evidence

4.3.1 The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of etanercept, infliximab and adalimumab, having considered evidence on the nature of psoriatic arthritis and the value placed on the benefits of etanercept, infliximab and adalimumab by people with the condition, those who represent them, and clinical specialists. It also took into account the effective use of NHS resources.

4.3.2 The Committee considered the clinical effectiveness evidence for etanercept, infliximab and adalimumab. The Committee noted that there were no head-to-head RCTs comparing the TNF inhibitors and reliance had to be placed on indirect methods of comparison. The Committee also noted that the RCTs were powered primarily to detect statistically significant differences in the effectiveness of TNF inhibitors compared with placebo on joint disease and only secondarily on any associated skin disease. The Committee heard from clinical specialists that placebo, equivalent to palliative care, is considered to be an appropriate comparator for the trials. The Committee also heard from clinical specialists that the inclusion criteria of the RCTs (people whose psoriatic arthritis has inadequately responded to NSAID or DMARD treatment) represented people with less severe psoriatic arthritis than those treated in current clinical practice under the recommendations of NICE technology appraisal guidance 104 and 125 who have had an inadequate response to at least two standard DMARDs. Nevertheless, the Committee concluded that the RCT evidence was sufficient to appraise the clinical effectiveness of TNF inhibitors.

4.3.3 The Committee considered the clinical-effectiveness data presented by the manufacturers and noted that etanercept, infliximab and adalimumab all showed a statistically significant response in the joint disease (PsARC, ACR) and skin disease (PASI) criteria at 12-week and 24-week follow-up compared with placebo. Clinical specialists confirmed that in clinical practice people’s psoriatic arthritis continued to respond to treatment beyond 24 months, and that some people had been maintained on TNF inhibitor treatment for up to 10 years. The Committee heard from a patient expert that TNF inhibitors are effective and a valued option for the treatment of psoriatic arthritis that have an appreciable impact on quality of life. The Committee heard from the clinical rheumatology specialists that etanercept, infliximab and adalimumab were found to be similarly effective in the treatment of psoriatic arthritis in clinical practice, and were used interchangeably. The indirect comparison conducted by the Assessment Group suggested that infliximab could be the most effective treatment overall taking into account skin and joint disease, however the Committee concluded that there was not enough evidence to indicate clinically important differences in the effectiveness of individual TNF inhibitors in the treatment of psoriatic arthritis.

4.3.4 The Committee considered the evidence on the adverse event rates associated with the TNF inhibitors, including the reactivation of tuberculosis and the rate of serious infections reported in RCTs, and noted that these data were mainly for people with rheumatoid arthritis. The Committee heard from clinical specialists that the adverse event profile of TNF inhibitors was comparable to that of conventional DMARDs. It also heard that adverse events could result in a break from treatment, for example, by stopping treatment while an infection is resolved, then restarting. The Committee concluded that the tolerability profile of the three TNF inhibitors was comparable.

4.3.5 The Committee then considered the economic models presented by the manufacturers and the Assessment Group. The Committee noted that the Assessment Group updated the economic model submitted for ‘Etanercept and infliximab for the treatment of psoriatic arthritis’ (NICE technology appraisal 104) by including the effectiveness of the TNF inhibitors treatment on the skin disease as well as the joint disease. The Committee considered the utility estimates incorporated in the Assessment Group model and noted that the utility formula was derived from the PASI and HAQ. The HAQ response had a greater effect on utility than the PASI, indicating that the calculated utility benefit was mainly driven by the response in joint symptoms rather than skin disease. The Committee heard from clinical experts that the HAQ score may not have fully captured health-related quality of life in people with psoriatic arthritis. The Committee was aware of the limitations of using HAQ scores as a basis for determining health-related quality of life in people with psoriatic arthritis. However, the Committee accepted that the Assessment Group’s approach represented the best means of estimating utility for the purposes of the economic analysis given the available data.

4.3.6 The Committee considered the results of the Assessment Group base-case model, which incrementally ranked the costs and QALYs associated with the different TNF inhibitors compared with palliative care. The Committee was aware that the acquisition costs of adalimumab and etanercept were similar, and the acquisition cost of infliximab was dependent on the patient’s weight and the number of vials required, with additional administration costs when compared with etanercept and adalimumab. The results demonstrated that etanercept was the most cost-effective treatment with an ICER of £16,000 per QALY gained compared with palliative care. The Committee noted that adalimumab was extendedly dominated by palliative care and etanercept and was therefore excluded from the incremental analysis. The Committee also noted the high ICER of infliximab compared with etanercept at £54,000 per QALY gained.

4.3.7 The Committee considered the results of the univariate sensitivity analysis performed by the Assessment Group, which showed the impact of changing different model parameters on the ICER. The Committee noted that the model results showed etanercept as having the highest probability of being cost effective at willingness-to-pay thresholds of £20,000 to £30,000 per QALY gained for most modelled scenarios. The Committee noted that the model was most sensitive to assumptions around the cost of treating uncontrolled skin disease associated with psoriatic arthritis, differences in the relative improvements measured by HAQ score and the cost of infliximab (depending on the average number of vials required to treat people with psoriatic arthritis). The Committee noted that if inpatient treatment costs for uncontrolled skin disease associated with psoriatic arthritis were taken into account, both adalimumab and infliximab dominated etanercept (that is, adalimumab and infliximab were more effective and less costly than etanercept) with ICERs under £20,000 per QALY gained. The incremental cost-effectiveness profile of infliximab improved if it was assumed that three vials were used (compared with four vials in the base-case model from the Assessment Group) although the number of vials required to treat people could be five or more.

4.3.8 In a further subgroup analysis the ICER of adalimumab compared with palliative care was lower than that of etanercept in people with severe psoriasis, with a PASI score of 12.5 (PASI of 7.5 in the base case). The Committee agreed that the sensitivity analyses performed by the Assessment Group were comprehensive and robust.

4.3.9 The Committee explored the scenario in which all three drugs had an equivalent beneficial effect on HAQ at 3 months, but which preserved the different rates of initial PsARC response of the drugs and the differential PASI response which was thought to be a plausible assumption based on the clinical specialist evidence. The estimated ICERs were £15,700 per QALY gained for adalimumab compared with palliative care, £19,800 per QALY gained for etanercept compared with adalimumab and £61,400 per QALY gained for infliximab compared with etanercept. The Committee also asked the Assessment Group to run a scenario in which adalimumab and etanercept were assumed to be equally clinically effective and infliximab was assumed to be more efficacious for all outcomes. The results of this scenario generated an ICER of £45,000 per QALY gained for infliximab compared with etanercept and adalimumab. The Committee concluded that even when the assumption of greater effectiveness of infliximab compared with etanercept and adalimumab was accepted, the ICER was too high to represent a cost-effective use of NHS resources.

4.3.10 The Committee considered that the evidence on clinical and cost effectiveness for etanercept and adalimumab was not sufficient to allow a choice to be made between one drug over the other, and was aware that they both represented a cost-effective use of NHS resources, with equivalent acquisition and administration costs. The Committee considered that the criteria for recommending etanercept (in NICE technology appraisal guidance 104) and adalimumab (in NICE technology appraisal guidance 125) remained valid. The Committee therefore concluded that etanercept and adalimumab should be recommended for people with peripheral arthritis who have three or more tender joints and three or more swollen joints and whose 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.

4.3.11 The Committee also recognised the benefits of TNF inhibitors in the treatment of psoriatic arthritis and noted that certain subgroups of people whose disease would not be suitable for treatment with etanercept or adalimumab might benefit from treatment with infliximab. Based on the base-case estimate of cost effectiveness of infliximab compared with palliative care the ICER was £21,000 per QALY gained in these people. The Committee was persuaded that infliximab should be a treatment option in the circumstances where the use of a TNF inhibitor was considered appropriate in a person with psoriatic arthritis (under the criteria outlined for etanercept and adalimumab in section 4.3.10), but only when the person is intolerant of, or has contraindications to, treatment with etanercept or adalimumab, or if subcutaneous administration is unsuitable for them.

4.3.12 The Committee considered the evidence presented by the Assessment Group on the cost effectiveness for the sequencing of TNF inhibitor treatments. The Committee heard from the clinical experts that there were very limited data available on the response rate for second-line treatment with TNF inhibitors. This was derived either from trials for people with rheumatoid arthritis or from registry data, which was uncontrolled and comprised predominantly people with rheumatoid arthritis. The Committee concluded that there was insufficient data to make a recommendation on the sequential use of TNF inhibitors in psoriatic arthritis.

4.3.13 The Committee considered that the recommendations on stopping treatment with etanercept and infliximab (in NICE technology appraisal 104) and with adalimumab (in NICE technology appraisal 125) remained valid. The Committee therefore concluded that etanercept, adalimumab and infliximab treatment should be stopped if a person’s psoriatic arthritis has not shown an adequate response using PsARC 12 weeks after starting treatment. 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.

4.3.14 In summary, the Committee considered the cost effectiveness of etanercept, infliximab and adalimumab in the base-case analysis in the light of clinical specialists’ comments. It considered that there was insufficient evidence of superiority of any one agent. On balance, considering the RCT data, modelling assumptions, modelling results and sensitivity analyses, together with expert opinion, the Committee concluded that etanercept and adalimumab were similarly cost effective at an incremental cost effectiveness of under £20,000 per QALY gained compared with palliative care and the incremental cost effectiveness of infliximab relative to adalimumab and etanercept was too high to be a cost-effective use of NHS resources. The Committee therefore concluded that etanercept and adalimumab should be recommended as a treatment option for people with psoriatic arthritis with three or more affected joints whose disease had inadequately responded to at least two conventional DMARDs. The Committee recommended that infliximab should be a treatment option only for people who were intolerant of, or had contraindications to, treatment with etanercept and adalimumab or if subcutaneous administration was unsuitable for them.

Summary of the Appraisal Committee’s key conclusions

TAXXX (MTA)	Appraisal title: Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis (review)	ACD section
Key conclusion
Etanercept and adalimumab are recommended for the treatment of adults with active and progressive psoriatic arthritis in specific circumstances (see section 1.1) and that infliximab is recommended when the person is intolerant of, or has contraindications to treatment with etanercept and adalimumab, or for if the subcutaneous mode of administration is unsuitable for them.
Current practice
Clinical need	Psoriatic arthritis can affect people’s ability to work and carry out daily activities, which can have a substantial impact on quality of life. People with psoriatic arthritis have a 60% higher risk of mortality than the general population and their life expectancy is estimated to be approximately 3 years shorter.	2.2
Availability of alternative treatments	To effectively manage psoriatic arthritis, any associated skin disease also needs to be effectively treated. Non-steroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections are widely used. Disease that is unresponsive to NSAIDs, in particular polyarticular disease, should be treated with DMARDs (currently, methotrexate and sulphasalazine are considered the DMARDs of choice) to reduce the joint damage and prevent disability.	2.5
What is the position of the treatment in the pathway of care for the condition	The Committee considered that the criteria for recommending etanercept (in NICE technology appraisal guidance 104) andadalimumab (in NICE technology appraisal guidance 125) remained valid. The Committee therefore concluded that etanercept and adalimumab should be recommended for people with peripheral arthritis who have three or more tender joints and three or more swollen joints and whose 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.	4.3.10
The technology
Proposed benefits of the technology from the manufacturer, clinician and patient perspective	The Committee heard from a patient expert that TNF inhibitors are effective and a valued option for the treatment of psoriatic arthritis that have an appreciable impact on quality of life. The Committee heard from the clinical rheumatology specialists that etanercept, infliximab and adalimumab were found to be similarly effective in the treatment of psoriatic arthritis in clinical practice, and were used interchangeably.	4.3.3
Distinguishing features of the technology	The Committee noted that TNF inhibitors are clinically effective alternatives for the treatment of psoriatic arthritis after conventional DMARDS fail.	4.3.2
Adverse effects	The Committee heard from clinical specialists that the adverse event profile of TNF inhibitors was comparable to that of conventional DMARDs. The Committee also heardthat adverse events could result in a break from treatment, for example, by stopping treatment while an infection is resolved, then restarting. The Committee concluded that the tolerability profile of the three TNF inhibitors was comparable.	4.3.4
Evidence for clinical effectiveness
Availability and nature of evidence	The Committee noted that there were no head-to-head RCTs comparing the TNF inhibitors and reliance had to be placed on indirect methods of comparison. The Committee also noted that the RCTs were powered primarily to detect statistically significant differences in the effectiveness of TNF inhibitors compared with placebo on joint disease and only secondarily on any associated skin disease. The Committee heard from clinical specialists that placebo, equivalent to palliative care, is considered to be an appropriate comparator for the trials. The Committee also heard from clinical specialists that the inclusion criteria of the RCTs (people whose psoriatic arthritis has inadequately responded to NSAID or DMARD treatment) represented people with less severe psoriatic arthritis than those treated in current clinical practice under the recommendations of NICE technology appraisal guidance 104 and 125 who have had an inadequate response to at least two standard DMARDs. Nevertheless, the Committee concluded that the RCT evidence was sufficient to appraise the clinical effectiveness of TNF inhibitors.	4.3.2
Quality of the evidence	The Committee noted that there were no head-to-head RCTs comparing the TNF inhibitors and reliance had to be placed on indirect methods of comparison. The Committee also noted that the RCTs were powered primarily to detect statistically significant differences in the effectiveness of TNF inhibitors compared with placebo on joint disease and only secondarily on any associated skin disease.	4.3.2
Relevance to general clinical practice in the NHS	The Committee heard from clinical specialists that the inclusion criteria of the RCTs (people whose psoriatic arthritis has inadequately responded to NSAID or DMARD treatment) represented people with less severe psoriatic arthritis than those treated in current clinical practice under the recommendations of NICE technology appraisal guidance 104 and 125 who have had an inadequate response to at least two standard DMARDs. Nevertheless, the Committee concluded that the RCT evidence was sufficient to appraise the clinical effectiveness of TNF inhibitors.	4.3.2
Uncertainties generated by the evidence	The Committee concluded that there was not enough evidence to indicate clinically important differences in the effectiveness of individual TNF inhibitors in the treatment of psoriatic arthritis.	4.3.3
Are there any clinically relevant subgroups for which there is evidence of differential effectiveness	The Committee also recognised the benefits of TNF inhibitors in the treatment of psoriatic arthritis and noted that certain subgroups of people whose disease would not be suitable for treatment with etanercept or adalimumab might benefit from treatment with infliximab. The Committee was persuaded that infliximab should be a treatment option in the circumstances where the use of a TNF inhibitor was considered appropriate in a person with psoriatic arthritis (under the criteria outlined for etanercept and adalimumab in section 4.3.10), but only when the person is intolerant of, or has contraindications to, treatment with etanercept or adalimumab, or if subcutaneous administration is unsuitable for them.	4.3.11
Evidence for cost effectiveness
Availability and nature of evidence	The Committee noted that the Assessment Group updated the economic modelsubmitted for ‘Etanercept and infliximab for the treatment of psoriatic arthritis’ (NICE technology appraisal 104) by including the effectiveness of the TNF inhibitors treatment on the skin disease as well as the joint disease.	4.3.5
Uncertainties around and plausibility of assumptions and inputs in the economic model	The Committee heard from clinical experts that the HAQ score may not have fully captured health-related quality of life in people with psoriaticarthritis. The Committee was aware of the limitations of using HAQ scores as a basis for determining health-related quality of life in people with psoriatic arthritis. However, the Committee accepted that the Assessment Group’s approach represented the best means of estimating utility for the purposes of the economic analysis given the available data. The Committee noted that the modelwas most sensitive to assumptions around the cost of treating uncontrolled psoriasis, differences in the relative HAQ score and the cost of infliximab (depending on the average number of vials required to treat people with psoriatic arthritis).	4.3.5 4.3.7
Incorporation of health-related quality of life benefits and utility values	The Committee considered the utility estimates incorporated in the Assessment Group model and noted that the utility formula was derived from the PASI and HAQ. The HAQ response had a greater effect on utility than the PASI, indicating that the calculated utility benefit was mainly driven by the response in joint symptoms rather than the skin disease. The Committee accepted that the Assessment Group’s approach represented the best means of estimating utility for the purposes of the economic analysis given the available data.	4.3.5
Are there specific groups of people for whom the technology is particularly cost-effective?	The committee considered the subgroup of people with psoriatic arthritis who are contraindicated to etanercept or adalimumab for example those for whom subcutaneous administration is unsuitable.  Infliximab has been recommended as a treatment option for this subgroup.	1.2
Most likelycost-effectiveness estimate (given as an ICER)	The Committee concluded that etanercept and adalimumab were similarly cost effective at an incremental cost effectiveness of under £20,000 per QALY gained compared with palliative care and the incremental cost effectiveness of infliximab relative to adalimumab and etanercept was too high to be a cost-effective use of NHS resources. The Committee therefore concluded that etanercept and adalimumab should be recommended as a treatment option for people with psoriatic arthritis with three or more affected joints whose disease had inadequately responded to at least two conventionalDMARDs. The Committee recommended that infliximab should be a treatment option only for people who were intolerant of, or had contraindications to, treatment with etanercept and adalimumab or if subcutaneous administration was unsuitable for them.	4.3.14
Additional factors taken into account
Patient access scheme (Pharmaceutical Price Regulation Programme)	No patient access scheme was submitted for any of the technologies being appraised.
End of life considerations (Supplementary advice on End of Life)	The end of life criteria was not applicable for this population.
Equalities considerations, Social Value Judgement	No equalities issues were raised

5 Implementation

5.1 The Secretary of State and the Welsh Assembly Minister for Health and Social Services have issued directions to the NHS on implementing NICE technology appraisal guidance. When a NICE technology appraisal recommends use of a drug or treatment, or other technology, the NHS must provide funding and resources for it within 3 months of the guidance being published. If the Department of Health issues a variation to the 3-month funding direction, details will be available on the NICE website. The NHS is not required to fund treatments that are not recommended by NICE.

5.2 NICE has developed tools to help organisations put this guidance into practice (listed below). These are available on our website (www.nice.org.uk/guidance/TAXXX). [NICE to amend list as needed at time of publication]

• Slides highlighting key messages for local discussion.
• Costing report and costing template to estimate the savings and costs associated with implementation.
• Implementation advice on how to put the guidance into practice and national initiatives that support this locally.
• A costing statement explaining the resource impact of this guidance.
• Audit support for monitoring local practice.

6 Proposed recommendations for further research

6.1 The Committee was aware of the importance of collecting further data within registries including patients receiving biologic treatments for psoriatic arthritis to enable the collection of information on long-term outcomes including adverse events.

7 Related NICE guidance

Published

• Adalimumab for the treatment of psoriatic arthritis. NICE technology appraisal guidance 125 (2007). Available from www.nice.org.uk/guidance/TA125
• Etanercept and infliximab for the treatment of psoriatic arthritis. NICE technology appraisal guidance 104 (2006). Available from www.nice.org.uk/guidance/TA104

Under development

NICE is developing the following guidance (details available from www.nice.org.uk):

• Leflunomide for the treatment of psoriatic arthritis.

8 Proposed date for review of guidance

8.1 NICE proposes that the guidance on this technology is considered for review by the Guidance Executive in March 2013. NICE welcomes comment on this proposed date. The Guidance Executive will decide whether the technology should be reviewed based on information gathered by NICE, and in consultation with consultees and commentators.

Jane Adam
Chair, Appraisal Committee
February 2010

Appendix A: Appraisal Committee members, guideline representatives and NICE project team

A. Appraisal Committee members

The Appraisal Committees are standing advisory committees of NICE. Members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. There are four Appraisal Committees, each with a chair and vice chair. Each Appraisal Committee meets once a month, except in December when there are no meetings. Each Committee considers its own list of technologies, and ongoing topics are not moved between Committees.

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.

The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website.

Dr Jane Adam (Chair)
Department of Diagnostic Radiology, St George’s Hospital

Professor Philip Home (Vice Chair)
Professor of Diabetes Medicine, Newcastle University

Professor A E Ades
Professor of Public Health Science, Department of Community Based Medicine, University of Bristol

Elizabeth Brain
Lay Member

Dr Fiona Duncan
Clinical Nurse Specialist, Anaesthetic Department, Blackpool Victoria Hospital, Blackpool

John Goulston
Chief Executive, Barking, Havering and Redbridge Hospitals NHS Trust

Dr Alec Miners
Lecturer in Health Economics, London School of Hygiene and Tropical Medicine

Dr Ann Richardson
Lay Member

Angela Schofield
Chairman, Bournemouth and Poole Teaching Primary Care Trust (PCT)

David Thomson
Lay Member

William Turner
Consultant Urologist, Addenbrooke's Hospital

Dr Luke Twelves
General Practitioner, Ramsey Health Centre, Cambridgeshire

Mike Spencer
General Manager, Cardiff and Vale University Health Board – Facilities and Clinical Support Services

Professor Iain Squire
Consultant Physician, University Hospitals of Leicester

Dr James Moon
Consultant Cardiologist and Senior Lecturer, University College London Hospital (UCLH) and UCL

Dr Ian Lewin
Consultant Endocrinologist, North Devon District Hospital

Dr Louise Longworth
Reader in Health Economics, Health Economics Research Group, Brunel University

Christopher Earl
Surgical Care Practitioner, Renal Transplant Unit, Manchester Royal Infirmary

Dr Anthony S Wierzbicki
Consultant in Metabolic Medicine/Chemical Pathology, Guy’s and St Thomas’ Hospitals NHS Trust

Dr John Watkins
Clinical Senior Lecturer/Consultant in Public Health Medicine, Cardiff University and National Public Health Service Wales  

Dr Olivia Wu
Reader in Health Economics, University of Glasgow

B. NICE project team

Each technology appraisal is assigned to a team consisting of one or more health technology analysts (who act as technical leads for the appraisal), a technical adviser and a project manager.

João Vieira
Technical Lead

Eleanor Donegan
Technical Adviser

Bijal Joshi
Project Manager

Appendix B: Sources of evidence considered by the Committee

A. The assessment report for this appraisal was prepared by:

CRD/CHE Technology Assessment Group (Centre for Reviews and Dissemination/Centre for Health Economics), University of York

• Rodgers M, Research, Epstein D, et al. Etanercept, Infliximab and adalimumab for the treatment of psoriatic arthritis (November 2009)

B. The following organisations accepted the invitation to participate in this appraisal as consultees and commentators. They were invited to comment on the draft scope, assessment report and the appraisal consultation document (ACD). Organisations listed in I, II and III were also invited to make written submissions and have the opportunity to appeal against the final appraisal determination.

I. Manufacturers/sponsers:

• Abbott Laboratories
• Schering-Plough
• Wyeth Pharmaceuticals

II. Professional/specialist and patient/carer groups:

• Arthritis & Musculoskeletal Alliance
• Arthritis Care
• British Dermatological Nursing Group
• British Association of Dermatologists
• British Society for Rheumatology
• Primary Care Dermatology Society
• Primary Care Rheumatology Society
• Psoriasis and Psoriatic Arthritis Alliance
• Royal College of Physicians
• Skin Care Campaign

III. Other consultees:

• Hull Primary Care Trust

IV. Commentator organisations (without the right of appeal):

• Cochrane Skin Group – Centre of Evidence-based Dermatology
• Department of Health, Social Services and Public Safety for Northern Ireland
• Pfizer
• Sanofi-Aventis
• Schering Plough
• Scottish Intercollegiate Guidelines Network
• Wyeth Pharmaceuticals

C. The following individuals were selected from clinical specialist and patient expert nominations from the non-manufacturer/sponsor consultees and commentators. They participated in the Appraisal Committee discussions and provided evidence to inform the Appraisal Committee’s deliberations. They gave their expert personal view on etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis by attending the initial Committee discussion and/or providing written evidence to the Committee. They are invited to comment on the ACD.

• Dr Philip Helliwell, Senior Lecturer in Rheumatology, nominated by the British Society for Rheumatology – clinical specialist
• Dr Eleanor Korendowych, Consultant Rheumatologist and Honorary Senior Lecturer – clinical specialist
• Professor Alex Anstey, Consultant Dermatologist/Professor, nominated by the British Association for Dermatologists.
• Denise Morris, nominated by the Psoriatic and Psoriatic Arthritis Alliance – patient expert.

D. Representatives from the following manufacturers/sponsors attended Committee meetings. They contributed only when asked by the Committee chair to clarify specific issues and comment on factual accuracy.

• Abbott Laboratories
• Schering Plough
• Wyeth Pharmaceuticals