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NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE
Appraisal Consultation Document
Efalizumab and etanercept for the treatment of plaque psoriasis
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The Department of Health and the Welsh Assembly Government have asked the National Institute for Clinical Excellence (NICE or the Institute) to conduct an appraisal of efalizumab and etanercept for the treatment of psoriasis and provide guidance on its use to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted and the views put forward by the representatives nominated for this appraisal by professional organisations and patient/carer and service user organisations. The Committee has developed preliminary recommendations on the use of efalizumab and etanercept for the treatment of psoriasis. This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website, /). Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation. The process the Institute will follow after the consultation period is summarised below. For further details, see the Guide to the Technology Appraisal Process (this document is available on the Institute's website, /).
The key dates for
this appraisal are: 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. |
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Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation. |
| 1 | Appraisal Committee's preliminary recommendations |
| 1.1 | Etanercept is recommended for the treatment of adults with plaque psoriasis only if all of the following circumstances are met.
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| 1.2 | Efalizumab is recommended for the treatment of adults with plaque psoriasis only if both of the following circumstances are met.
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| 1.3 | It is recommended that the response to etanercept and efalizumab be assessed after 12 weeks of treatment. The drugs should be discontinued unless the disease has clearly responded as defined by a 75% reduction in the PASI score from when treatment started (PASI 75). |
| 1.4 | It is recommended that the use of efalizumab and etanercept for psoriasis should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of psoriasis. If a person has both psoriasis and psoriatic arthritis he or she should be managed by collaboration between rheumatologists and dermatologists. |
<#comment(Section 1, Comment on Section 1: Appraisal Committee's preliminary recommendations)#>
| 2 | Clinical need and practice |
| 2.1 | Psoriasis is an inflammatory skin disease that is characterised by an accelerated rate of turnover of the top layer of the skin (epidermis). Although it is generally considered to be a chronic progressive condition, its course may be erratic, with flare-ups and remissions. |
| 2.2 | The cause of psoriasis is not fully understood but evidence suggests that there is a strong genetic component and that it is mediated by abnormal T lymphocytes. Environmental factors also play a role, and it has been established that in some cases factors such as emotional stress or infection may trigger the first episode of psoriasis and may also cause exacerbations. |
| 2.3 | The most common form (80%) of psoriasis is chronic plaque psoriasis (psoriasis vulgaris), which is characterised by well-demarcated, often symmetrically distributed, thickened, red, scaly plaques. There is considerable variation in both the size and the number of the plaques, which can range from one or two small plaques to 100% body coverage. Although the plaques can affect any part of the skin, they are typically found on the extensor surfaces of the knees and elbows and the scalp. It is estimated that 5-7% of people with psoriasis develop joint inflammation, which is known as psoriatic arthritis. |
| 2.4 | There are few data on the prevalence and incidence of psoriasis in the UK but estimates suggest that it affects approximately 2% of the population. Males and females are affected equally by the condition and there is a higher incidence in caucasians than in other ethnic groups. |
| 2.5 | A UK study of people with severe psoriasis found that 60% had taken time off work in the previous year as a direct result of their condition. People with severe disease may require a number of hospitalisations per year; the average length of a hospital stay is around 20 days. |
| 2.6 | Psoriasis is generally graded as mild, moderate or severe. Several different scales for measuring the severity of psoriasis are also used, which are variably based on the following criteria: the proportion of body surface area affected; the disease activity (degree of plaque redness, thickness and scaling); the response to previous therapies; and the impact of the disease on the person. |
| 2.7 | The Psoriasis Area Severity Index (PASI) is the most widely used measurement tool for psoriasis in clinical trials. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). Trial outcomes are generally reported in terms of the number of people reaching a specified percentage reduction in PASI from their baseline score (for example, PASI 75 is a 75% reduction from baseline score). The European Medicines Evaluation Agency recognises the achievement of a PASI 75 as an indicator in clinical trials that severe psoriasis has responded to treatment. |
| 2.8 | Psoriasis has been shown to affect health-related quality of life (HRQoL) to a similar extent as other chronic diseases such as depression, myocardial infarction, hypertension, congestive heart failure or type 2 diabetes. In general, increased severity of psoriasis is associated with decreased HRQoL. However, the degree of this effect on quality of life is also dependent on the area of the body affected by psoriasis. Thus, even mild psoriasis in the flexures or exposed areas such as the face can be very distressing. The Dermatology Life Quality Index (DLQI) is a validated HRQoL measure that consists of ten questions covering symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Scores range from 0 (best HRQoL) to 30 (worst possible HRQoL). |
| 2.9 | There is no cure for psoriasis but there is a wide range of topical and systemic treatments that can potentially manage the condition. Most treatments, however, only reduce the severity rather than stop the episodes, and the psoriasis therefore has to be treated continually and on a long-term basis. The choice of treatment depends on the severity of the condition, the extent of body surface area affected, and the response before treatment. In general, the evidence base for many of these therapies is not well developed. |
| 2.10 | Mild to moderate psoriasis, particularly when a limited area of skin is involved, can be managed with topical treatments, including emollients and occlusive dressings, keratolytics (salicylic acid), coal tar, dithranol, corticosteroids, retinoids and vitamin D analogues. The burden for the person with psoriasis can be considerable as many of the preparations have a strong smell, are messy and require application two or three times a day. |
| 2.11 | More severe, resistant and/or extensive psoriasis can be treated with photo(chemo)therapy, acitretin (an oral retinoid) and oral drugs that act on the immune system, such as ciclosporin, methotrexate and hydroxycarbamide. Oral treatments can be given alone or in conjunction with topical therapies. All the oral therapies have the potential to cause severe long-term side-effects, and monitoring is required. The toxic effects are cumulative and therefore many people with psoriasis require 'rotational therapy' in order to minimise the cumulative toxicity of any one therapy. |
| 2.12 | There is very little information on current practice in treating psoriasis in the NHS and it is likely that there are widespread variations in service. There are also few data on the current service costs; nearly 1 million prescriptions for psoriasis therapies were dispensed in 2003 at a cost of £27.8 million. This does not include treatments that are also used for other conditions (for example, corticosteroids or methotrexate) or costs associated with treatment in secondary or tertiary care. Excluding drug costs, mean costs per patient have been estimated at £1186 for day care and £2681 for inpatient care. |
<#comment(Section 2, Comment on Section 2: Clinical need and practice)#>
| 3 | The technologies |
| 3.1 | Efalizumab |
| 3.1.1 | Efalizumab (Serono Pharmaceuticals Ltd) is a T-cell modulator that blocks T-cell activation or migration. It is licensed for the treatment of adults with moderate to severe plaque psoriasis who have failed to respond to, or who have a contraindication to, or who are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA. The licence for efalizumab also specifies that the psoriasis should be chronic, and it is contraindicated in patients with specific forms of psoriasis like guttate, erythrodermic or pustular psoriasis as the sole or predominant form. |
| 3.1.2 | The Summary of Product Characteristics (SmPC) states that efalizumab treatment should be initiated by a physician specialised in dermatology. The SmPC states that efalizumab has not been studied in combination with immunosuppressive systemic anti-psoriasis medicinal products and therefore combination therapy with these products is not recommended. The SmPC also states that 'combination therapy with topical corticosteroids is not associated either with any untoward effects or with any observable significant benefit above monotherapy'. |
| 3.1.3 | The most frequent adverse drug reactions reported during efalizumab therapy are mild to moderate dose-related acute flu-like symptoms (associated with the first few doses), leucocytosis and lymphocytosis. Owing to the risk of thrombocytopenia, monthly platelet counts are required on initiation of therapy, but the frequency can be decreased to every 3 months with continued treatment. For full details of side effects and contraindications, see the SmPC. |
| 3.1.4 | Efalizumab is administered at an initial single dose of 0.7 mg/kg body weight followed by weekly subcutaneous injections of 1.0 mg/kg body weight (maximum single dose should not exceed a total of 200 mg). The SmPC states that the duration of therapy is 12 weeks and may only be continued in patients who respond to treatment. The net price for a 125-mg vial is £169.20 (excluding VAT; British National Formulary, 49th edition). Costs may vary in different settings because of negotiated procurement discounts. |
| 3.2 | Etanercept |
| 3.2.1 | Etanercept (Wyeth Pharmaceuticals) is a recombinant human tumour necrosis factor (TNF) receptor fusion protein that inhibits the activity of TNF. TNF is a cytokine that is released from T lymphocytes; it mediates inflammation and modulates the cellular immune response. Etanercept is licensed for the treatment of adults with moderate to severe plaque psoriasis who have failed to respond to, or who have a contraindication to, or who are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA. It is also licensed for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. |
| 3.2.2 | The SmPC specifies that etanercept treatment should be initiated and supervised by specialised physicians with experience in the diagnosis and treatment of psoriasis. The SmPC also states that the use of etanercept in combination with other systemic therapies or phototherapies has not been studied. The net price for a 125-mg vial is £169.20 (excluding VAT; British National Formulary, 49th edition). Costs may vary in different settings because of negotiated procurement discounts. |
| 3.2.3 | The most frequent adverse events reported during etanercept therapy include injection site reactions, infections and allergic reactions. The SmPC specifies a number of uncommon but serious adverse events related to the immunomodulatory activity. There are no monitoring requirements. For full details of side effects and contraindications, see the SmPC. |
| 3.2.4 | 3 Etanercept is administered by subcutaneous injection at a dose of 25 mg twice weekly. Alternatively, 50 mg given twice weekly may be used for up to 12 weeks followed, if necessary, by a dose of 25 mg twice weekly. The SmPC states that treatment with etanercept should continue until remission is achieved, for up to 24 weeks. Treatment should be discontinued in patients who show no response after 12 weeks. If re-treatment with etanercept is indicated, the above guidance on treatment duration should be followed. The net price for a 25-mg vial is £89.38 (excluding VAT; British National Formulary, 49th edition). Costs may vary in different settings because of negotiated procurement discounts. |
| 4 | Evidence and interpretation |
| The Appraisal Committee considered evidence from a number of sources (see Appendix B). | |
| 4.1 | Clinical effectiveness |
| 4.1.1 | Efalizumab |
| 4.1.1.1 | A total of five randomised controlled trials (RCTs) that studied efalizumab at a dose of 1 mg/kg once a week were included in the Assessment Report. Across all doses, a total of 3130 participants were randomised. Each trial was placebo-controlled and of 12 weeks duration. Inadequacies in the reporting of the trials meant that the quality of four of the trials could not be properly assessed by the Assessment Group. Outcomes collected included the proportion of patients achieving PASI 50, PASI 75 and PASI 90; PASI score; DLQI score; global assessments; itching score; psoriatic arthritis frequency and severity. No patient assessments were available. |
| 4.1.1.2 | Not all of the data for each outcome were available. All five trials reported a statistically significant benefit of efalizumab over placebo in the numbers of participants achieving a PASI 50 (pooled relative risk [RR] 3.9; 95% confidence interval [CI], 3.3 to 4.6). Three of the trials reported a PASI 75, and these results were also statistically significant in favour of efalizumab for each trial (pooled RR 6.3; 95% CI, 4.3 to 9.4). The one trial reporting a PASI 90 found no statistically significant differences between efalizumab and placebo (RR 5.3; 95% CI, 0.9 to 31.7). Only one trial reported mean change from baseline in PASI score; it was 52% for efalizumab-treated patients compared with 19% for placebo-treated patients (p < 0.001).="" dlqi="" outcomes="" were="" reported="" in="" four="" trials,="" all="" of="" which="" reported="" a="" statistically="" significant="" greater="" reduction="" in="" patients="" taking="" efalizumab;="" the="" data="" could="" not="" be="" pooled="" due="" to="" lack="" of="" measures="" of=""> |
| 4.1.1.3 | The submission from the manufacturer presented a subgroup analysis of trial IMP24011 (n = 793), which included 526 participants who were resistant to, intolerant of or contraindicated to, at least two currently available systemic agents. These patients therefore potentially more closely matched the marketing authorisation than the overall populations in the five trials. The manufacturer concluded that the efficacy of efalizumab in the high-need group was similar to the efficacy across all treated patients. In all, 103/342 (30%) of participants in the high-need group achieved a PASI 75 compared with 6/184 (3%) who received placebo. The numbers achieving a PASI 75 in the 'non-high need patients' were 61/187 (33%) receiving efalizumab and 5/80 receiving placebo (6.3%). There was, however, sparse information available relating to the trial, and no statistical comparisons were reported. |
| 4.1.1.4 | There was no RCT evidence beyond 12 weeks. The submission presented extension data from one ongoing study and one completed trial in which patients were re-randomised according to their previous response to treatment. The Assessment Group concluded that long-term follow-up data related to a range of doses and were poorly reported and so could not be used to draw even tentative conclusions regarding the long-term efficacy of efalizumab. |
| 4.1.1.5 | The Assessment Group identified data on relapse after treatment from only one trial. Across all doses, mean time to relapse (defined as loss of more than 50% of improvement achieved in PASI score at 24 weeks) in those who had achieved a score of = 50 was 84 days. The submission reported follow-up data from two RCTs; the median time to relapse was reported to be 59 days. The Assessment Group concluded that uncontrolled data from trial follow-up suggests that time to relapse may be around 60 days, but this may not be reliable. No data indicating the existence or absence of any rebound in psoriasis after discontinuation of efalizumab were identified. There was no evidence relating to the efficacy of efalizumab upon re-treatment. |
| 4.1.1.6 | Pooled data from the five RCTs indicated that there were no statistically significant differences between the efalizumab 1 mg/kg and placebo groups in the number of patients experiencing one or more adverse events, those that had a serious event and those that withdrew due to adverse events. Efalizumab was only licensed in late 2004 and therefore limited data were available relating to long-term adverse events. The SmPC states that the safety of efalizumab has not been tested beyond 12 weeks, but the Assessment Group identified data from two 24-week periods and in one study 339 participants were entered into a 3 year open-label follow-up. |
| 4.1.2 | Etanercept |
| 4.1.2.1 | The Assessment Report included three double-blind RCTs that evaluated etanercept at a dose of 25 mg or 50 mg twice a week. In total, 1347 patients were enrolled in the RCTs. The Assessment Group deemed all three of the RCTs to be of 'good' quality. At the end of each trial there was an open-label and/or non-randomised extension period. |
| 4.1.2.2 | All three trials reported statistically significant differences in favour of etanercept 25 mg over placebo as measured by PASI 50, PASI 75 and PASI 90 at 12 weeks. There was no statistically significant heterogeneity in these results and therefore the results of the trials were pooled. The pooled relative risks were PASI 50 RR 5.41 (95% CI, 4.10 to 7.14); PASI 75 RR 10.69 (95% CI, 6.15 to 18.57) and PASI 90 RR 18.55 (95% CI, 5.24 to 65.69). The trial that continued to 24 weeks also showed a statistically significant difference in favour of etanercept for PASI outcomes. Etanercept 50 mg twice a week also showed statistically significant benefits over placebo in both of the RCTs. The pooled relative risks were PASI 50 RR 6.48 (95% CI 4.84 to 8.66); PASI 75 RR 14.80 (95% CI, 8.40 to 26.06) and PASI 90 RR 38.12 (95% CI, 9.43 to 154.06). The number of participants who were rated by the physician as being 'clear or almost clear' of psoriasis showed a statistically significant superiority of etanercept at both doses and time-points. The percentage change in PASI and DLQI echoed this but data were highly skewed and therefore not pooled. At the end of treatment in all three trials there were statistically significant differences in favour of etanercept in the patient measures of disease status. |
| 4.1.2.3 | In one of the RCTs, patients on etanercept continued taking the drug after the 12-week placebo-controlled period for a further 24 weeks (total treatment period = 36 weeks). The Assessment Group concluded that the results at 36 weeks did not indicate any lessening of response over time. However, those who had their 50 mg twice weekly dose halved to 25 mg twice weekly for the remaining 24 weeks had a statistically significant deterioration in their mean PASI score (treatment difference 2.10 [95% CI, 1.12 to 3.08]). |
| 4.1.2.4 | The manufacturer also provided the results of the follow-up after discontinuation for two of the RCTs. Although insufficient data were presented for the smaller trial (only 18% of patients were followed), 3 month post-treatment follow-up data were presented for 409 patients who had responded to etanercept treatment in the larger study. Only one of these 409 participants experienced a rebound of their psoriasis to more than 125% of their baseline PASI score. The larger RCT also provided data on patients who were re-treated. Across all doses, the mean difference in PASI score after 12 weeks re-treatment compared with the initial 12-week treatment was -0.5 (95% CI, -1.09 to 0.09), indicating that there was no statistically significant difference. |
| 4.1.2.5 | The Assessment Group concluded that, in general, etanercept appeared to be well tolerated during short-term and long-term use. Injection site reaction was the most common adverse event. Across the three trials, a total of 232/415 (56%) people on etanercept 25 mg experienced one or more adverse events compared with 211/414 (51%) people taking placebo (RR 1.10; 95% CI, 0.97 to 1.25). The numbers of participants classed as having a serious adverse event were 6/415 (1%) and 4/414(1%) for the etanercept and placebo groups, respectively (RR 1.50; 95%CI, 0.43 to 5.26). In the two groups, a total of 9/415 (2%) and 10/414 (2%) withdrew because of adverse events (RR 0.90; 95% CI, 0.97 to 2.19). There were no statistically significant differences in adverse event rates between the patients taking etanercept 50 mg and those taking placebo. |
| 4.1.2.6 | The Assessment Group undertook a formal evidence synthesis with the aim of bringing together the clinical evidence regarding the efficacy of etanercept, efalizumab and other treatments. This evidence synthesis generated parameter estimates (response rates) used in the economic modelling. The evidence synthesis found that efalizumab was less effective than etanercept 25 mg, and both were less effective than infliximab, methotrexate and ciclosporin. The 50 mg dose of etanercept was found to be more effective than the lower dose. Importantly, the evidence synthesis assumed that trial populations were comparable. |
| 4.2 | Cost effectiveness |
| 4.2.1 | Published economic evaluations |
| 4.2.1.1 | 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 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 US-based and the results were not expressed as incremental costs per quality-adjusted life year (QALYs). |
| 4.2.2 | Efalizumab - manufacturer's model |
| 4.2.2.1 | The manufacturer developed a decision tree based model, which compared the cost effectiveness of efalizumab treatment with that of topical therapies (based on calcipotriol and bethamethasone) over a 10 year timeframe. Utilities (based on a time trade-off approach) were obtained from a study of 87 people with psoriasis. In order to estimate QALYs, the number of successfully treated years was multiplied by the difference in utility between a PASI-50 responder and a non-responder. There were no published PASI-50 response rates for topical therapies in people with moderate to severe psoriasis; therefore the rates associated with the placebo arms of the efalizumab RCTs (which permitted concomitant topical therapy use) were used. Resource use due to adverse events was included in the model. |
| 4.2.2.2 | In the base-case scenario, costs were discounted by 6% and outcomes were discounted by 1.5%. Over the 10-year time horizon, expected 'quality-adjusted response years' with efalizumab were estimated to be 1.39 versus 0.36 for a treatment strategy beginning with topical therapy. The incremental cost/QALY results from the deterministic and probabilistic analyses were around £25,600 and £25,800, respectively. The data were subject to a number of deterministic sensitivity analyses; the incremental cost-effectiveness ratio (ICER) remained below £30,000 under most scenarios. |
| 4.2.3 | Etanercept - manufacturer's model |
| 4.2.3.1 | The manufacturer of etanercept developed a Markov model using pooled data from the three registration RCTs. It aimed to assess the cost effectiveness of etanercept 25 mg (twice per week), etanercept 50 mg (twice per week) and an option of topical therapy only. A mapping exercise was used to estimate the relationship between DLQI (measured in the trials) and utility. Average improvement in utility was multiplied by the time between visits to estimate QALY gain between the visits. The manufacturer modelled a 12-week time horizon and longer-term outcomes (comprising eight 12-week treatment periods) by means of extrapolation. No discounting on costs and effects appears to have been applied and adverse events were not explicitly included. |
| 4.2.3.2 | The short-term (12-week) analysis estimated that the ICER for etanercept 25 mg over no systemic therapy was almost £125,000; the ICER for etanercept 50 mg was substantially higher. In the longer-term (96-week) analysis, the ICER for 25 mg etanercept over no systemic therapy was found to be £53,100 (all patients; continuous therapy). The model also found that the ICER for 50 mg etanercept compared with no systemic therapy was £64,600, and £127,500 when compared with 25 mg etanercept. In the intermittent treatment scenario, the incremental cost per QALY gained for 25 mg etanercept versus placebo was estimated to be £37,200. When people with relatively severe psoriasis (PASI >10) and a poor quality of life (DLQI greater than 15) at baseline were considered in the 96-week analysis, the ICERs for etanercept versus systemic therapy declined markedly. For intermittent and continuous 25 mg etanercept therapy, the ICERs in this subgroup were found to be between £24,000 and £26,000 per QALY, respectively. |
| 4.2.4 | The Assessment Group model |
| 4.2.4.1 | The Assessment Group developed its own model. The main analysis compared efalizumab (continuous), etanercept (intermittent 25 mg and 50 mg, and continuous 25 mg) and supportive care. Utilities were estimated by mapping the mean change in DLQI score (conditional on PASI response) to changes in EQ-5D (a non-disease specific instrument for describing and valuing HRQoL). 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. |
| 4.2.4.2 | The base-case analysis showed that supportive care was the only cost-effective strategy until the threshold reaches £70,000 per QALY. The ICER for intermittent with low dose (25 mg) etanercept was found to be £65,320. The ICER for intermittent high-dose (50 mg) etanercept treatment was substantially higher. Efalizumab and continuous etanercept 25 mg were 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 and continuous etanercept 25 mg were still dominated by 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. |
| 4.3 | Consideration of the evidence |
| 4.3.1 | The Committee reviewed the data available on the clinical and cost effectiveness of etanercept and efalizumab, having considered evidence on the nature of the condition and the value placed on the benefits of etanercept and efalizumab by people with psoriasis, those who represent them, and clinical experts. It was also mindful of the need take account of the effective use of NHS resources. |
| 4.3.2 | The Committee accepted that the RCTs demonstrated the effectiveness of etanercept and efalizumab in people with moderate to severe psoriasis. The Committee noted, however, that participants in those trials were not representative of the population for which these technologies are currently licensed because their psoriasis had not necessarily failed to respond to all other treatment options. However, it heard from the clinical experts that, in clinical practice, these drugs were used as per the licensed indications and were as effective for people who had not responded to all other available treatments as for those who were treatment naive. |
| 4.3.3 | The Committee considered the economic modelling. It recognised that there was considerable uncertainty in the estimates of cost effectiveness that had been produced. This uncertainty related principally to estimates of the efficacy of alternative interventions and long-term outcomes. However, despite this uncertainty, the Committee concluded that it was likely that etanercept 50 mg was not cost effective and 25 mg intermittent etanercept was cost effective in the subgroup of people who had very poor quality of life and who would be likely to require hospital admission for treatment. Testimony from the clinical experts suggested that these people would be those with severe disease who had not responded to all other treatment options. |
| 4.3.4 | The Committee noted that according to the SmPC the maximum duration of etanercept therapy is 24 weeks but there are no stipulations as to the period that needed to be allowed between successive treatment episodes. The experts testified that people who had responded to etanercept sometimes relapsed within weeks of therapy cessation and therefore in practice, intermittent and continuous therapy frequently converged. The Committee therefore concluded that the two etanercept treatment strategies in the Assessment Group model were likely to be the extremes and that actual clinical practice for most people would lie somewhere in between. For this reason the Committee concluded that in practice the cost utility of etanercept 25 mg was likely to lie between the estimates for intermittent and continuous etanercept treatment, which would still be cost effective. |
| 4.3.5 | The Committee noted that in all cost-effectiveness scenarios of the Assessment Group model efalizumab was |