4 Consideration of the evidence

The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of secukinumab, having considered evidence on the nature of psoriasis and the value placed on the benefits of secukinumab by people with the condition, those who represent them, and clinical experts. It also took into account the effective use of NHS resources.

4.1 The Committee heard from the patient and clinical experts about the experience of people with psoriasis. It heard that the disease results in itchy, dry, scaly and thickened skin, which can be physically and psychologically debilitating, particularly if located on the hands, feet and genitals. The Committee heard that, because psoriasis is visible, it can make people feel isolated and lonely, which could lead to them losing self‑confidence and avoiding social situations, and could also affect career opportunities and influence intimate relationships. The Committee agreed that severe psoriasis substantially decreases quality of life.

4.2 The Committee considered the treatment pathway for people with psoriasis. The Committee heard that complete clearance of disease is the goal of treatment. It heard from the clinical experts that, in practice, as first‑line treatment people receive topical treatments, systemic non‑biological therapies (such as methotrexate), and phototherapy. The Committee was aware that these treatments may be associated with adverse effects and patients need monitoring for such effects; generate hospitalisation costs; have a limited lifetime exposure (for example, phototherapy because of the risk of developing skin cancer); and can be inconvenient for patients (for example, because of frequent hospital visits for monitoring or treatment administration). The Committee heard that clinicians may limit the use of tumour necrosis factor (TNF) inhibitors because of their ability to reactivate latent tuberculosis and particularly infliximab because of the development of drug antibodies. If psoriasis is not adequately controlled by these treatments, people may receive second‑line biological treatments, which they continue to receive as long as the drugs continue to work. In addition, the Committee heard that treatment with etanercept (which may be given continuously or intermittently) is offered continuously, rather than intermittently. The clinical experts informed the Committee that, if the disease no longer responds to 1 biological treatment, they offer patients another. This pattern is likely to be repeated over a patient's lifetime; clinical experts noted therefore that it is valuable to have a range of biological treatment options with different mechanisms of action available. The clinical experts noted the large positive impact that biological treatments have had on patients over recent years because patients no longer need to be hospitalised for long periods to receive treatment or monitoring. The clinical experts stated that, because of this, fewer dedicated hospital beds for psoriasis now exist. With respect to secukinumab, the clinical experts stated that they were unlikely to choose it first from among the biological treatments because its long‑term adverse‑effects profile and real‑world effectiveness were not yet well established. The Committee agreed that patients and clinicians value biological treatments such as secukinumab, and that biological treatments administered continuously would be given in clinical practice to the population defined in the scope for this appraisal. It therefore agreed that biological treatments were the most appropriate comparators for secukinumab.

4.3 The Committee heard from the clinical experts that clinicians use both the Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) when monitoring disease and choosing who to offer biological therapies to. This is because of the requirements outlined in existing NICE guidance for biological treatments, and that 'severe' disease is defined as a PASI of 10 or more, and a DLQI of more than 10. However, the Committee also heard that these measures do not identify everyone who might benefit from treatment, for example, people with limited disease but in high impact areas (such as the hands, feet and genitals), or people with anxiety and depression because of their condition. The Committee concluded that PASI and DLQI, which reflect the outcomes used in the trials, are relevant measures used in clinical practice in the NHS.

Clinical effectiveness

4.4 The Committee considered the clinical trials identified in the company submission, agreeing that the company had included relevant, high‑quality trials which contained comparisons with both placebo and an active comparator. It concluded that the clinical trial evidence was appropriate for decision‑making.

4.5 The Committee considered the baseline characteristics of the patients in the trials and heard from clinical experts that they broadly reflected the UK population with severe psoriasis. The Committee noted that the population in the trials and the marketing authorisation for secukinumab included people who are candidates for 'systemic therapy', which is defined as including both non‑biological and biological treatments. Therefore, both the trials and marketing authorisation included some patients who had never received systemic or biological treatments, whereas the scope for this appraisal was narrower ('people for whom systemic treatments are not tolerated, not effective or contraindicated'). The clinical experts agreed with the company that, in clinical practice, secukinumab would be offered at the same time as the existing biological treatments rather than before. Because the results of the trials reflected the effectiveness of secukinumab in a population including people who had not previously received systemic treatments, the Committee was concerned about the extent to which prior systemic treatment could impact the clinical‑effectiveness results of secukinumab. It heard from clinical experts that they did not expect prior systemic treatments to modify the effectiveness of secukinumab. With respect to prior biological treatments, most of which are TNF‑alpha inhibitors, the clinical experts noted that, because secukinumab has a different mechanism of action, they did not expect a change in effectiveness; in general, they were not aware of any evidence that prior treatment impacts the clinical effectiveness of current treatment. However, the Committee concluded that that it would have been more appropriate to present the results of an analysis excluding patients who had never received systemic therapies in line with the population in for which it was proposed to be used. Overall, the Committee concluded that, although the populations in the scope and trial differed, the results of the clinical trials were likely to be generalisable to patients with severe psoriasis and were appropriate for decision‑making on the clinical effectiveness of secukinumab.

4.6 The Committee considered the relevance of the main outcomes used in the trials (that is, percentage reduction in PASI score), to clinical practice. The Committee debated whether measuring an improvement in PASI was objective; it heard from the clinical experts that, once experienced, clinicians can do a PASI assessment quickly with little variability between clinicians. For PASI 75, the primary outcome in the trials, the Committee agreed that this demonstrated whether treatments for psoriasis had a high level of effectiveness. However, even with outcomes such as PASI 75, the psoriasis that remains could still have a significant impact on quality of life, and therefore patients value any treatment that could completely clear the disease (that is, PASI 100). The Committee concluded that PASI 75 was a clinically relevant definition of response to treatment and that, in addition, complete clearance was important; therefore the evidence for PASI 100 should be taken into account when deciding the value of secukinumab to the NHS.

4.7 The Committee discussed the results of the clinical trials. It noted that the clinical trial evidence for secukinumab had generated statistically significant differences in the co‑primary outcomes when compared with both placebo and etanercept (an active comparator that is already recommended by NICE for the population covered by this appraisal). It further noted that a PASI 100 response (that is, complete clearance of disease), occurred more often with secukinumab than with either placebo or etanercept, and that complete clearance of disease was the most important outcome for patients (see sections 4.2 and 4.6). The Committee heard from the clinical experts that the effectiveness of secukinumab and other biologicals is likely to be lower in clinical practice than in the trials, in part, because trials may not include patients with refractory disease. The clinical experts considered treatment with secukinumab to represent a step‑change in the management of psoriasis because it appears to clear disease in some patients, offers a different mechanism of action compared with the TNF‑alpha inhibitors and ustekinumab, and is associated with a low risk of adverse events. The Committee concluded that the evidence had shown that secukinumab was clinically superior to both placebo and etanercept for all primary and secondary outcomes.

4.8 The Committee considered the network meta‑analysis presented by the company to compare secukinumab with the other biological agents specified in the scope. The Committee considered potential limitations of the network meta‑analysis which did not address possible heterogeneity of the patients involved in the trials (for example, prior treatments received). However, it noted that the secukinumab trial populations were likely to be similar with respect to heterogeneity to the trials to which they were being compared, and which formed the basis for previous NICE guidance. The Committee noted that the difference in effectiveness between secukinumab and etanercept was smaller in the direct trial evidence than it was in the network meta‑analysis, which the company used for its modelling (see section 3.6 and table 3). The Committee further noted that, although the results of the network meta‑analysis suggested that secukinumab appears to be more clinically effective than etanercept and adalimumab, and to have similar clinical effectiveness to ustekinumab and infliximab, the only direct trial evidence was for secukinumab compared with etanercept. Therefore the Committee considered that the relative clinical effectiveness of biological treatments for all outcomes was unknown. The Committee was also concerned about the effectiveness of best supportive care generated by the network meta‑analysis reflected, which appeared very low with only 3.6% of people randomised to best supportive care having a PASI 75 response. It heard from clinicians that, in clinical practice, the proportion of people with a PASI 75 response following treatment with best supportive care was likely to be substantially higher (possibly up to 60%) because best supportive care involves active treatments such as topical therapies, ciclosporin and phototherapy. However, the clinical experts stated that a response with best supportive care would be accompanied by disutility because of the intensive, time‑consuming, inconvenient and unpleasant treatments, and with patients relapsing sooner than with biologicals. Overall, the Committee agreed that there were a number of scenarios it would like to have seen presented in the company submission, including a network meta‑analysis for additional outcomes such as utility values, and the impact of prior treatment, to help provide additional assurances about the robustness of the efficacy assumptions. However, it concluded that, despite the limitations of the network meta‑analysis, it was sufficient for the purposes of decision‑making.

4.9 The Committee discussed whether there were any relevant subgroups in which secukinumab might be more effective than in the overall population included in the trials, or which have more to gain. The Committee reflected that it would have liked to have seen more analyses using patient‑level data for people who have previously received either systemic non‑biological or biological treatments, to help reduce any uncertainty about the extent to which prior treatment affects clinical effectiveness. The Committee further heard from the clinical experts that people with concomitant psoriatic arthritis were an important subgroup, particularly those with psoriatic arthritis affecting joints of the hand which could cause difficulty with self‑injecting. The Committee was aware that the monthly administration of secukinumab would be easier to manage for these patients than of other biological agents that need to be injected more frequently. The Committee noted that the company was applying for a marketing authorisation for secukinumab for psoriatic arthritis, that this was being considered for appraisal by NICE, and that ideally 1 treatment would be given for both conditions. In addition, the Committee was aware that there may be small subgroups of patients with comorbidities in whom TNF‑alpha inhibitors would be contraindicated or used with caution (such as people with demyelinating diseases or heart failure) and for whom treatment with secukinumab would be preferred. The Committee discussed whether observational data exists, and learned of a UK registry for biologicals; the company informed the Committee that it did not have access to this registry. The Committee concluded that future appraisals would benefit from UK observational data, but at present there were not sufficient data to identify differential efficacy between people who had received different prior treatments.

4.10 The Committee discussed the adverse events associated with secukinumab, noting that it was generally tolerated, and that the events were consistent between the placebo, etanercept, and secukinumab 300 mg and 150 mg arms of the trials. The Committee was aware that, over time, real‑world data on adverse events will accumulate. Given the evidence to date, the Committee concluded that secukinumab did not appear to be associated with adverse events not already known for biological treatments in general.

Cost effectiveness

4.11 The Committee considered the company's health economic model and noted that the structure of the model was similar to previous appraisals for psoriasis, but did not represent established clinical practice for managing severe psoriasis in several ways including:

  • patients with psoriasis would likely be treated with a series of biologicals, rather than with a single biological drug before moving on to best supportive care (see section 4.2)

  • the 10‑year time horizon was too short because psoriasis is a lifelong condition.

    The Committee further considered that best supportive care is only a relevant comparator for people in whom all other biological treatments were either contraindicated or whose disease had not adequately responded to treatment. The Committee agreed that the short time horizon probably led to overestimated incremental cost effectiveness ratios (ICERs) because secukinumab delayed progression to more expensive, less effective best supportive care treatments. Overall, the Committee concluded that the structure of the model did not reflect UK clinical practice, which led to uncertainty about the cost‑effectiveness estimates generated.

4.12 The Committee considered the sources used by the company to estimate resource use and costs associated with best supportive care, noting that the model was highly sensitive to these inputs, and specifically whether assumptions were taken from Fonia et al. (2010; the Evidence Review Group [(ERG] base case) or NICE's psoriasis guideline and hospital episode statistics (HES) data (the company base case). The Committee noted that, in both instances, the resource use estimates of best supportive care were likely to overestimate actual current best supportive care. This is in part because the populations described in Fonia et al. and the costing template for NICE's psoriasis guideline differed from the population in this appraisal; the costing template for NICE's psoriasis guideline was for a specific, high‑need subpopulation with very severe psoriasis, and Fonia et al. describes care in a tertiary care centre known for treating the most severely affected patients. The Committee further noted that HES data (used to inform length of stay in the base case) were not specifically only for people receiving treatment for psoriasis nor did they necessarily show the number of individual patients who were admitted. The Committee also heard from the clinical experts that, in recent years, the number of patients hospitalised for severe psoriasis has fallen (see section 4.2) because of the availability of a wider range of biological treatment options; therefore, overall hospitalisation costs associated with psoriasis have fallen. The Committee considered that neither the resource use from Fonia et al. nor from NICE's psoriasis guideline and HES data were plausible for the population with severe psoriasis. However, it concluded that resource use for best supportive care is closer to Fonia et al. than to the company's estimates, and that future appraisals for psoriasis should take into account the changes in relevant costs that have occurred over time. The Committee further concluded that defining costs associated with psoriasis was an area of high priority for research.

4.13 The Committee considered the assumption in the company's model that people who receive subcutaneous biological treatments are able to self‑administer treatments after 1 hour of training. It noted that the ERG considered this unrealistic because a proportion of people would not be able to self‑administer treatment (for example, because of physical disability or needle‑phobia), and that a more realistic training time estimate would be closer to 3 hours. It heard from clinical experts that most people would be competent at self‑administration after 2 hours of training. However, most training sessions would take place during normal clinical visits, and so self‑administration training was a cost that did not necessarily need to be separately modelled. Further, the clinical experts stated that the proportion unable to self‑administer treatments subcutaneously would be small. The Committee noted that the ERG base cases included 3 hours of training rather than 1 hour, and the company was happy with this change, which did not have a large impact on cost‑effectiveness estimates. The Committee concluded that it was clinically plausible to assume that most people could self‑administer subcutaneous biological treatments, and that it was appropriate to model training costs using a time of 1–3 hours.

4.14 The Committee considered the company's assumption that modelled patients after treatment during the induction period remain in the same health state for the duration of treatment. It noted clinical data from the FIXTURE trial that showed that some people who were in the PASI 50–74 health state at 12 weeks got better, while others got worse over the remaining 52‑week time period of the model. However the Committee heard from clinical experts that, in clinical practice, with some exceptions, the health state of most people with psoriasis generally remained stable after the induction period. This reassured the Committee that it was reasonable to assume in the model that people remain in the same heath state.

4.15 The Committee discussed the validity of the clinical‑effectiveness data from the network meta‑analysis used by the company in its model. It was aware that registry data exist in the UK, but were not provided in the company's submission because the company stated it did not have access to the data. The Committee agreed that these registry data were a rich source of information about the treatment of people with psoriasis and was disappointed that the company did not have access to these data. The Committee was concerned about the implausibly low value of 3.6% for the proportion of patients whose disease responds to best supportive care treatment (see section 4.8). The Committee noted that the population generating the clinical data underpinning the model had an average PASI higher than 20, which it understood reflected very severe psoriasis, therefore the response rates from the trials may be more relevant for people with very severe disease. The Committee concluded that, in the absence of 'real life' data on the response rates for secukinumab compared with other treatments, the network meta‑analysis assumptions were appropriate to use. However, it concluded that the issues with the network meta‑analysis added to the uncertainty in the cost‑effectiveness estimates generated by the model.

4.16 The Committee considered the company's modelling assumption that 20% of all patients stop biological treatments each year, an assumption the company based on previous appraisals. The Committee heard from clinical experts that this rate was likely to be an overestimate because clinicians had an increasing number of treatments from which to choose. The Committee concluded that fewer patients stopped biologicals than had been assumed by the company but that, because this affected all biological treatments equally, this was likely to have a minimal effect on the cost effectiveness of secukinumab.

4.17 The Committee considered the quality of life and utility values used by the company in its model. It welcomed the use of utility values from trial data (in accordance with the guide to the methods of technology appraisals). However, it noted that the company had used a regression analysis (taking into account PASI and DLQI scores) to predict the utility values in the model. The Committee agreed it that would have preferred to have seen the unadjusted EQ‑5D utility values used in the model. The Committee discussed the plausibility of the absolute values used by the company, agreeing that the baseline utility value (0.642) seemed plausible, although the quality‑adjusted life year (QALY) gain with biological treatments appeared to be low. The Committee noted this may have been because the model did not assume a survival benefit associated with treatment. The Committee noted that the model did not take into account the disutility values associated with best supportive care, and the added benefit of obtaining a complete remission with secukinumab (PASI 100), an important outcome for patients. The Committee concluded that the utility gains estimated from the model were likely to be underestimated.

4.18 The Committee discussed whether secukinumab could be considered innovative. It noted that secukinumab offers a different mechanism of action to the other biological treatments recommended by NICE, and some patients experience complete clearance of disease. The Committee also heard from clinical and patient experts that severe psoriasis can be associated with a stigma apart from its effect on health‑related quality of life, and that NICE methods acknowledge giving extra weight to such conditions. Further, the Committee noted that the disutility of best supportive care was not included in the model. The Committee agreed that these benefits had not been captured when calculating the QALY, that secukinumab reflected a step change in treatment and that the drug could be considered innovative.

4.19 The Committee discussed the estimate of cost effectiveness based on the incremental analyses presented by the company. It noted that the ICERs were sensitive to the costs of best supportive care and the cost of secukinumab, and less sensitive to utility values or assumed rates of stopping biological treatment. However, the Committee considered there to be significant structural and parameter uncertainties in the way that the treatment of psoriasis had been modelled, including: the short time horizon; the assumption that people receive only 1 treatment before best supportive care; and the low effectiveness of best supportive care. It further noted that, because the changes in incremental health benefits between different biological treatments were small, the ICERs could vary dramatically with small QALY changes. The Committee concluded that these structural and parameter uncertainties and the labile nature of the ICERs made it difficult to determine a precise cost‑effectiveness estimate.

4.20 The Committee discussed whether it could determine a most plausible ICER, but agreed this was difficult because of the previously mentioned structural and parameter uncertainties in the model. The Committee and the company both agreed with the ERG's corrections to the model. The Committee also agreed that the most plausible assumptions on resource use were closer to Fonia et al. (2010; ERG base case) than to NICE's psoriasis guideline (company base case). Furthermore, the Committee considered that the ICERs compared with the biological treatments rather than with best supportive care were most appropriate. It agreed that the ICERs ranging from approximately £17,700 per QALY gained (compared with ustekinumab 90 mg) to £42,400 per QALY gained (compared with etanercept) were probably overestimated because the model had not accounted for PASI 100 responses (see section 4.17) nor the disutility values associated with best supportive care. In addition, the Committee pragmatically considered the cost effectiveness of secukinumab in the light of previous appraisals in this disease area. The Committee noted that, even when using direct trial data, secukinumab was more effective than at least one of the already recommended biologicals, etanercept, and was associated with a higher probability of complete remission. Considering the patient access scheme price of secukinumab, the clinical data (compared with etanercept in the FIXTURE trial and with the results of the network meta‑analysis), and the testimony of the experts, the Committee concluded that the most plausible ICER was likely to be in line with the other biologicals already recommended in previous NICE guidance. The Committee therefore concluded that secukinumab could be recommended as a cost‑effective use of NHS resources.

4.21 The Committee discussed the inclusion of a stopping rule in the recommendation. When discussing the appropriate time point at which to measure response, it noted that the trials and the model assessed the effectiveness of secukinumab for the primary outcome at week 12. The Committee was aware that because the clinical effectiveness of secukinumab continued beyond 12 weeks (with a peak effect at week 16), the summary of product characteristics notes that consideration should be given to stopping treatment in people who have not shown a response up to week 16. However, the Committee noted that there is no appropriate placebo data with which to compare the clinical effectiveness of secukinumab at 16 weeks because patients in the placebo arm of the trials were able to crossover to active treatment if they did not have a response at week 12. Also, the company base case used a 12‑week stopping rule. The Committee considered the relevance of stopping rules in existing NICE guidance for biologicals for treating severe psoriasis that, in addition to the PASI 75 response, also refers to a PASI 50 response with a 5‑point reduction in DLQI from the start of treatment. The Committee considered that, because secukinumab was likely to be given at the same point in the pathway as the other biologicals already recommended by NICE for treating psoriasis, any stopping rules should be consistent with previous appraisals. The Committee concluded that the most appropriate time point to assess response was week 12, and that the outcomes used to assess response should be consistent with previous appraisals for psoriasis.

4.22 The Committee was aware that there might be some situations when the DLQI may not be a clinically appropriate tool to inform a clinician's conclusion about the severity of psoriasis; for example, if a person has physical, sensory or learning disabilities, or communication difficulties that could affect their responses to the questionnaire. The Committee heard from the clinical specialists that the DLQI is now available in more than 50 languages and that this has improved assessment for those people whose first language is not English. The Committee concluded that healthcare professionals should take any physical, sensory or learning disabilities and communication difficulties into account when using the DLQI and make any adjustments they consider appropriate.

4.23 The Committee considered a potential equality issue raised by a patient organisation that people with psoriatic arthritis affecting their fingers could find using the pre‑filled syringe difficult, as could those with a needle phobia. The Committee had already concluded that the monthly administration of secukinumab would be easier to manage for these patients than of other biological agents that need to be injected more frequently (see section 4.9). Bearing in mind that the Committee had recommended secukinumab (see section 4.20), it concluded that there was no need to alter or add to its recommendations. It also noted that a separate appraisal was being considered for secukinumab for people with psoriatic arthritis.

4.24 The Appraisal Committee considered whether it should take into account the consequences of the Pharmaceutical Price Regulation Scheme (PPRS) 2014, and in particular the PPRS Payment Mechanism, when appraising secukinumab. The Appraisal Committee noted NICE's position statement in this regard, and accepted the conclusion "that the 2014 PPRS Payment Mechanism should not, as a matter of course, be regarded as a relevant consideration in its assessment of the cost effectiveness of branded medicines". The Committee heard nothing to suggest that there is any basis for taking a different view with regard to the relevance of the PPRS to this appraisal of secukinumab. It therefore concluded that the PPRS Payment Mechanism was irrelevant for the consideration of cost effectiveness of secukinumab.

Summary of Appraisal Committee's key conclusions

TA350

Appraisal title: Secukinumab for treating moderate to severe plaque psoriasis

Section

Key conclusion

Secukinumab is recommended, within its marketing authorisation, as an option for treating adults with plaque psoriasis only when:

  • the disease is severe, as defined by a total Psoriasis Area Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10

  • the disease has failed to respond to standard systemic therapies, for example, ciclosporin, methotrexate and PUVA (psoralen and long‑wave ultraviolet radiation), or these treatments are contraindicated or the person cannot tolerate them

  • the company provides secukinumab with the discount agreed in the patient access scheme.

The Committee concluded that the clinical evidence had shown that secukinumab was clinically superior to both placebo and etanercept for all primary and secondary outcomes.

The Committee agreed that it was difficult determine a most plausible incremental cost‑effectiveness ratio (ICER) because of the structural and parameter uncertainties in the model. It agreed that the ICERs ranging from approximately £17,700 per QALY gained (compared with ustekinumab 90 mg) to £42,400 per QALY gained (compared with etanercept) were probably overestimated because the model had not accounted for PASI 100 responses nor the disutility values associated with best supportive care. Considering the patient access scheme price of secukinumab, the clinical data, and the testimony of the experts, the Committee concluded that the most plausible ICER was likely to be in line with the other biologicals already recommended in previous NICE guidance.

1.1

4.7

4.11

4.15

4.19

4.20

Current practice

Clinical need of patients, including the availability of alternative treatments

The Committee heard from the patient and clinical experts that psoriasis can be physically and psychologically debilitating, particularly if located on the hands, feet and genitals. The Committee heard that, because psoriasis is visible, it can make people feel isolated and lonely, which could lead to them losing self‑confidence and avoiding social situations, and could affect career opportunities and influence intimate relationships. The clinical experts informed the Committee that, if the disease no longer responds to treatment with 1 biological, they offer patients another biological. This pattern is likely to be repeated over a patient's lifetime; clinical experts noted that it is therefore valuable to have a range of biological treatment options with different mechanisms of action available.

4.1

4.2

The technology

Proposed benefits of the technology

How innovative is the technology in its potential to make a significant and substantial impact on health‑related benefits?

The Committee noted that secukinumab offers a different mechanism of action to the other NICE‑recommended biological treatments, and some patients experience complete clearance of disease. The Committee also heard from clinical and patient experts that severe psoriasis can be associated with a stigma, apart from its effect on health‑related quality of life, and that NICE methods acknowledge giving extra weight to such conditions. The Committee agreed that these benefits had not been captured when calculating the quality‑adjusted life years (QALYs), that secukinumab reflected a step change in treatment and that the drug could be considered innovative.

4.18

What is the position of the treatment in the pathway of care for the condition?

The Committee heard from the clinical experts that, if psoriasis is not adequately controlled by first‑line treatments including topical treatments, systemic non‑biological therapies (such as methotrexate) and phototherapy, people may receive second‑line biological treatments, which they continue to receive as long as the drugs continue to work. If the disease no longer responds to treatment with 1 biological, clinicians offer patients another biological. The Committee agreed that biological treatments were the most appropriate comparators for secukinumab.

4.2

Adverse reactions

The Committee concluded that secukinumab did not appear to be associated with adverse events not already known for biological treatments in general.

4.9

Evidence for clinical effectiveness

Availability, nature and quality of evidence

The company included 5 relevant international, multicentre, phase 3, double‑blind, randomised, controlled trials. The Committee agreed that the company had included relevant, high‑quality trials.

The Committee considered that the network meta‑analysis excluded outcomes other than effectiveness, such as utility values, and did not address possible heterogeneity of the patients involved in the trials (for example, prior treatments received). However, it noted that the secukinumab trial populations were likely to be similar with respect to heterogeneity to the trials to which they were being compared, and which formed the basis for previous NICE guidance. The network meta‑analysis also generated a low value of people who achieved PASI 75 (3.6%). Overall, the Committee agreed that, despite the limitations of the network meta‑analysis, it was sufficient for the purposes of decision‑making.

3.1

4.4

4.8

Relevance to general clinical practice in the NHS

The Committee noted that, although both the trials and marketing authorisation included some patients who had never received systemic or biological treatments compared with the scope ('people for whom systemic treatments are not tolerated, not effective or contraindicated'), in clinical practice, secukinumab would be offered at the same time as the existing biological treatments. The Committee considered that the baseline characteristics of the patients in the trials broadly reflected the UK population with severe psoriasis. The Committee concluded that, although the populations in the scope and trials differed, the results of the clinical trials were likely to be generalisable to patients with severe psoriasis and were appropriate for decision‑making on the clinical effectiveness of secukinumab.

4.5

Uncertainties generated by the evidence

The people enrolled in the clinical trials included some patients who had never received systemic or biological treatments. The Committee reflected that it would have liked to have seen more analyses using patient‑level data for people who have previously received either systemic non‑biological or biological treatments, to help reduce any uncertainty about the extent to which prior treatment affects clinical effectiveness.

The Committee agreed that there were a number of scenarios it would like to have seen presented in the main submission (including a network meta‑analysis for additional outcomes such as utility values and the impact of prior treatment) to help provide additional assurances about the robustness of the efficacy assumptions of the network meta‑analysis.

4.5

4.9

Are there any clinically relevant subgroups for which there is evidence of differential effectiveness?

The Committee heard from the clinical experts that people with concomitant psoriatic arthritis were an important subgroup, and that ideally 1 treatment would be given for both conditions; the Committee noted that the company was applying for a licence for secukinumab for psoriatic arthritis, and this was being considered for appraisal by NICE.

It also further noted that there may be small subgroups of patients with co‑morbidities in whom TNF‑alpha inhibitors would be contraindicated (such as people with demyelination or heart failure) and for whom treatment with secukinumab would be preferred.

4.9

Estimate of the size of the clinical effectiveness including strength of supporting evidence

The Committee agreed that secukinumab was clinically superior to both placebo and etanercept for all primary and secondary outcomes.

4.7

Evidence for cost effectiveness

Availability and nature of evidence

The company constructed a new economic model with a 10‑year time horizon (1‑year decision tree and 9‑year Markov cohort model) to compare secukinumab 300 mg with etanercept, ustekinumab (45 mg and 90 mg), adalimumab, infliximab and best supportive care.

3.18

Uncertainties around and plausibility of assumptions and inputs in the economic model

The Committee concluded that the structure of the model did not reflect UK clinical practice (because patients did not receive subsequent biological treatments and the time horizon of 10 years was too short), which led to uncertainty about the robustness of the cost‑effectiveness estimates generated.

The Committee concluded that the issues with the network meta‑analysis added to the uncertainty in the cost‑effectiveness estimates generated by the model.

4.11

4.15

Incorporation of health‑related quality‑of‑life benefits and utility values

Have any potential significant and substantial health‑related benefits been identified that were not included in the economic model, and how have they been considered?

The Committee agreed that the baseline utility value of 0.642 seemed plausible, although the QALY gain with biological treatments appeared to be low. The Committee noted that the model did not take into account the disutility values associated with best supportive care, and the added benefit of obtaining a complete remission with secukinumab (PASI 100). The Committee concluded that the utility gains estimated from the model were likely to be underestimated.

The Committee also heard from clinical and patient experts that severe psoriasis can be associated with a stigma apart from its effect on health‑related quality of life, and that NICE methods acknowledge giving extra weight to such conditions.

4.17

4.18

Are there specific groups of people for whom the technology is particularly cost effective?

The Committee concluded that, at present, there were not sufficient data to identify differential efficacy between people who had received different prior treatments.

4.9

What are the key drivers of cost effectiveness?

The Committee noted that the model was highly sensitive to the costs assumed for best supportive care, and specifically whether assumptions were taken from Fonia et al. (2010; the ERG base case) or NICE's psoriasis guideline and hospital episode statistics (HES) data (the company base case). It further noted that, because the changes in incremental health benefits between different biological treatments were small, the ICERs could vary dramatically with small QALY changes.

4.12

4.19

Most likely cost‑effectiveness estimate (given as an ICER)

The Committee considered there to be significant structural and parameter uncertainties in all of the incremental analyses, including: the short time horizon; the assumption that people receive only 1 treatment before best supportive care; and the low effectiveness of best supportive care.

The Committee considered that the ICERs compared with the biological treatments ranged from approximately £17,700 per QALY gained (compared with ustekinumab 90 mg) to £42,400 per QALY gained (compared with etanercept). The Committee concluded that these ICERs were probably overestimated because of the short time horizon, and because the model had not accounted for PASI 100 responses nor the disutility values associated with best supportive care. Considering the patient access scheme price of secukinumab, the clinical data, and the testimony of the experts, the Committee concluded that the most plausible ICER was likely to be in line with the other biologicals already recommended in previous NICE guidance.

4.20

Additional factors taken into account

Patient access schemes (PPRS)

The company has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the list price of secukinumab, with the discount applied at the point of purchase or invoice. The level of the discount is commercial‑in‑confidence.

2.3

End‑of‑life considerations

Not applicable.

Equalities considerations and social value judgements

A patient organisation expressed the view that people with psoriatic arthritis affecting their fingers could find using the pre‑filled syringe difficult, as could those with a needle phobia. The Committee concluded that the monthly administration of secukinumab would be easier to manage for these patients than of other biological agents that need to be injected more frequently. Bearing in mind that the Committee had recommended secukinumab, it concluded that there was no need to alter or add to its recommendations.

4.9

4.22

  • National Institute for Health and Care Excellence (NICE)