3 Committee discussion

The appraisal committee considered evidence submitted by Janssen, a review of this submission by the evidence review group (ERG), NICE's technical report, and responses from stakeholders. See the committee papers for full details of the evidence.

The appraisal committee was aware that several issues were resolved during the technical engagement stage, and agreed that:

the cost of an hour of nurse time is included in the economic model as a one-off cost when a person begins treatment
all monitoring costs should be the same regardless of how the drug is administered, and should be consistent with costs used in NICE's technology appraisal guidance on etanercept, infliximab and adalimumab
Kobelt et al. (2002) is the preferred source for arthritis-related costs
adverse events should be excluded from the cost-effectiveness model
the placebo response-unadjusted network meta-analysis results, in addition to the placebo-adjusted results, should be considered.

It recognised that there were remaining areas of uncertainty associated with the analyses presented and took these into account in its decision making. It discussed issues 3.1 to 3.4, 3.6, 4.1 and 4.2 which were outstanding after the technical engagement stage. The committee also discussed 2 new issues, identified after technical engagement:
whether it is reasonable to exclude etanercept from the economic analysis
including a more frequent dose (every 4 weeks) for people identified as being at high risk of joint damage.

Clinical need

Psoriatic arthritis substantially affects health-related quality of life

3.1 The patient and clinical experts explained that psoriatic arthritis is a lifelong condition that seriously affects people's quality of life. It can develop at a young age, and affects all aspects of a person's life including education, career, relationships and family life. The patient experts explained that symptoms such as fatigue, pain and associated comorbidities such as inflammatory bowel disorders, cardiovascular disease and diabetes, can have a substantial physical and psychological effect. The clinical and patient experts explained that people with psoriatic arthritis have symptoms ranging from mild, non-destructive disease to erosive and deforming arthritis with substantial effects on physical functioning. Symptoms can include swollen fingers and toes through to inflammation of larger joints such as elbows and knees, joints in the back, and tendonitis. Skin and nail psoriasis also affect quality of life. The committee concluded that psoriatic arthritis substantially affects health-related quality of life.

Clinical management

Clinicians and people with psoriatic arthritis would welcome additional biological treatments that target different inflammation pathways

3.2 The clinical experts explained that the main aim of treatment for active psoriatic arthritis is to control joint and connective tissue inflammation. This prevents joint damage progressing and the associated pain and disability. People will usually have treatment with non-steroidal anti-inflammatory drugs, corticosteroids and conventional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. In NICE's technology appraisal guidance on etanercept, infliximab and adalimumab, people are eligible for biological or small molecule treatments if their disease is poorly controlled after 2 conventional DMARDs. Biological or small molecule treatments include:

tumour necrosis factor inhibitor (TNFi) treatments such as etanercept and adalimumab
interleukin (IL) inhibitor treatments such as secukinumab and ixekizumab (IL‑17A inhibitors) and ustekinumab (IL‑12/IL‑23 inhibitor)
tofacitinib
apremilast.

The clinical experts explained that psoriatic arthritis is an unpredictable disease that can flare and change over time. Sometimes it responds to the first conventional DMARD, or to a second or third, or it may not respond at all. The clinical experts highlighted that because flares and periods of disease remission are common, the treatment pathway is not always the same. After conventional DMARDs, people will often switch among the different TNFi treatments, or to different interleukin modulators (ustekinumab, secukinumab and ixekizumab) or to tofacitinib. People with psoriatic arthritis would benefit from an additional class of treatment targeting a different inflammatory mediator if:
their disease has not responded (or has stopped responding) to DMARDs and other biologicals or small molecules or
they need to stop their previous treatment because of side effects.

Guselkumab is the first monoclonal antibody specifically targeting IL‑23 to be considered by NICE for use in psoriatic arthritis. The committee concluded that people with psoriatic arthritis and clinicians would welcome a further treatment option.

Clinical evidence

Guselkumab is clinically effective compared with placebo

3.3 The efficacy and safety evidence for guselkumab in psoriatic arthritis was based on the results of 2 pivotal trials, DISCOVER‑1 and DISCOVER‑2. These randomised people to have 100 mg guselkumab every 8 weeks or every 4 weeks, or to placebo. The guselkumab trial arms both showed statistically significant and clinically important benefits compared with placebo on disease activity, joint and skin symptoms, functional capacity and health-related quality of life. Guselkumab met the primary endpoint; a higher proportion of people had an American College of Rheumatology (ACR) 20 response compared with placebo at 24 weeks in both trials. The committee noted that the 4-weekly dose of guselkumab was potentially relevant for a subpopulation considered to be at high risk of joint damage (see section 3.14), but both doses were assessed in the full trial populations. The committee concluded that both doses of guselkumab were clinically effective compared with placebo across a range of clinically important outcomes.

The populations in the clinical trials are broadly generalisable to NHS clinical practice and are appropriate for decision making

3.4 The ERG explained that the DISCOVER trials did not include people from the UK. The trials recruited mainly from eastern Europe, where local health systems may have different treatment provision for psoriatic arthritis. In its submission, the company assumed that the baseline characteristics of people in the DISCOVER trials reflected those of people seen in NHS clinical practice. The ERG had concerns about the generalisability of the results of the trials because of key differences in the populations compared with populations in the NHS. The company submission identified 4 subpopulations and presented analyses for:

people whose disease is not adequately controlled by 2 conventional DMARDs but who have not previously had a biological DMARD (subpopulation 2)
people whose disease is not adequately controlled by 2 conventional DMARDs or by at least 1 previous biological DMARD (subpopulation 3)
people whose disease is not adequately controlled by 2 previous conventional DMARDs and the TNFi class of biological DMARD is contraindicated (subpopulation 4).

The clinical experts confirmed the ERG's view that guselkumab was unlikely to be used as the first-line biological treatment in the NHS. Therefore, in clinical practice a high proportion of people would have had another biological treatment before starting guselkumab. The proportion of people in the trials who had previously had a biological treatment (31% in DISCOVER‑1, 0% in DISCOVER‑2) did not therefore reflect NHS clinical practice. The ERG further explained that in the trials less than a third of people had 2 or more conventional DMARDs before. Also, just under 10% of people had no conventional DMARD before. Because NICE recommends that biological DMARDs are offered after 2 conventional DMARDs have been tried (see section 3.2), this further limits the applicability of the trials to the NHS. Another generalisability concern was the baseline Psoriasis Area and Severity Index (PASI) scores of people in the trials. The clinical experts agreed with the ERG that these were high and that it was rare to see people with psoriatic arthritis with PASI scores above 5 in the NHS. Because less than a third of people had 2 conventional DMARDs before starting the DISCOVER trials it was reasonable to expect that the level of disease at baseline was higher. The committee recalled that in previous NICE technology appraisals for psoriatic arthritis, clinical experts considered that trial PASI scores were higher than would be seen in routine clinical practice. The clinical experts confirmed that the populations were different in terms of prior treatments and disease severity at baseline. But they advised that because psoriatic arthritis is unpredictable and the available treatments do not cure it, the populations in the trials and in the NHS both represented people with active disease. The committee agreed that there were significant differences between the trial populations and people with psoriatic arthritis seen in NHS clinical practice. It also agreed that the trial populations were broadly similar to those in comparator trials in the network meta-analyses (NMAs), and those in previous NICE psoriatic arthritis technology appraisals. The committee concluded that although there were marked differences between the populations in the trials and in the NHS, the evidence from the DISCOVER trials was broadly appropriate for decision making.

The low discontinuation rates in DISCOVER-1 and DISCOVER-2 are not likely to be seen in the NHS

3.5 Discontinuation rates for the 100 mg every 4 weeks dose in the pivotal trials were between 2.3% (DISCOVER-1) and 3.7% (DISCOVER-2). In its submission, the company said these low rates were evidence of guselkumab's sustained efficacy, safety and tolerability. The committee recalled the opinion of the ERG and clinical experts about the differences between the trial populations and the people who would have treatment in NHS clinical practice (see section 3.4). The baseline characteristics suggested that people in the countries participating in the trials, mostly eastern Europe, had limited access to the range of treatments available in the NHS. The clinical experts explained that the low discontinuation rates in the trials might reflect this overall lack of access to other treatments. This was supported by the fact that the discontinuation rates in the placebo groups were also extremely low. The clinical experts added that trial discontinuation rates often do not translate into the actual rates seen in clinical practice. In the UK, people whose disease is not controlled would be expected to move quickly to another active treatment. The ERG further explained that it did not consider the company's justification for guselkumab's very low discontinuation rates to be robust. The ERG felt that the company had not shown an underlying biological mechanism for these low rates. The ERG rejected the company's claim that the low discontinuation rates for guselkumab (and ustekinumab) may partly be because of better skin response with these biological treatments. This was because people with psoriatic arthritis mainly have biological DMARDs to control joint disease rather than psoriasis, which tends to be less severe. Also, most studies used to inform the treatment-specific discontinuation rates for guselkumab and the comparators did not report treatment stopping rules in the maintenance period. So it was possible that people in these trials continued treatment beyond the loss of sustained response. This would therefore not reflect the rate seen in clinical practice, where stopping rules would ensure that people did not remain on treatments that were not adequately controlling their disease. The committee agreed with the clinical experts and ERG that the trial populations and the NHS population were not similar. It also agreed about the uncertainties in the evidence base supporting the use of treatment-specific discontinuation rates. The committee concluded that the low discontinuation rates for guselkumab in DISCOVER‑1 and DISCOVER‑2 were not likely to be the same in the NHS.

Early escape in the guselkumab trials results in bias

3.6 'Early escape' to another treatment is common in clinical trials and prevents people staying on a treatment if they have uncontrolled disease. The clinical experts explained that it is important for ensuring people remain in trials, rather than opting out, which improves the generalisability of the data. The committee noted that the company had opted to treat early escape as non-response in the final analysis at 24 weeks (that is, no change from baseline). The ERG explained that early escape, as with treatment switching, always results in the potential for bias. Treating early escape as non-response potentially overestimates the benefit of active treatments because most early escape is expected to be in the placebo arm of trials. The ERG explained that investigators in the DISCOVER trials did not have to tell people that they had qualified for early escape. Of those who were eligible, most were in the placebo arms, and less than 50% escaped to another treatment, but the reasons for this were unclear. The ERG explained that it did not agree with the company's method of dealing with early escape in the trials. Instead, the ERG suggested an assessment time of 16 weeks. This would mean that the data would be free of bias caused by early escape, which was only allowed after 16 weeks in the trials. The company provided re-analyses of the NMAs using guselkumab outcomes assessed at 16 weeks in response to the ERG's request. Also, the ERG did an exploratory analysis to assess the effect on treatment cost at first line of treatment for a 16-week stopping rule. The ERG preferred an alternative approach, to include the full observed response of people who escaped early to another treatment. This would also introduce bias by assigning the benefits of an active treatment to placebo. In contrast to the company's preferred approach, this approach would potentially underestimate guselkumab's benefit and would therefore be a more conservative analysis. The company did not consider that either of the ERG's approaches were appropriate. The company claimed that guselkumab's mechanism of action meant that it continued to be effective, particularly in measures of skin response such as PASI scores, between 16 and 24 weeks. To limit analysis to 16 weeks would therefore not represent guselkumab's full benefits. Also, it claimed that assigning guselkumab's benefits to people in the placebo arm by using the full observed response data from people who escaped early would be clinically implausible. The committee agreed with the ERG that the arguments supporting guselkumab's unique mechanism of action were not convincing and more robust evidence would be needed. The committee agreed that early escape would introduce bias for the 24-week analysis whether it was treated as non-response or the full observed response was used. The committee noted that analysing the DISCOVER trials at 16 weeks only and including the outcome data for early escape at 24 weeks reduced guselkumab's effectiveness relative to placebo. However, the company's preferred approach may have overestimated guselkumab's benefit. The committee concluded that early escape resulted in bias and it would consider all approaches in its decision making.

The assessment time of 24 weeks is appropriate, but clinicians would value the option of assessing response at 16 weeks

3.7 The committee was aware that guselkumab's summary of product characteristics states that consideration should be given to stopping treatment when disease has not responded after 24 weeks of treatment. The patient experts explained that they welcomed the prospect of a new biological treatment that works on an additional inflammation pathway. But they also explained that people with psoriatic arthritis are frequently frustrated by having ineffective treatments, and that irreversible joint damage can occur very quickly. Many people would therefore find it difficult to accept waiting for up to 6 months to have clinical benefit. The clinical experts commented that a 24-week assessment time for guselkumab was much longer than the 12 to 16-week assessment times for other biological DMARDs. They noted that a continuing response beyond 12 to 16 weeks had also been seen for other biological DMARDs and small molecules. The clinical experts would welcome the option to assess response at 16 weeks, to help decide whether to switch treatment or intervene with salvage treatment. The ERG explained that it was not convinced that the evidence for guselkumab's unique mechanism of action would justify waiting until 24 weeks to assess response. It noted that the maximum Psoriatic Arthritis Response Criteria (PsARC), Health Assessment Questionnaire-Disability Index (HAQ-DI) and ACR 50 response was recorded at week 20 in the DISCOVER trials. The ERG further explained that the company's economic model did not capture the potential continued improvement in PASI response between 16 and 24 weeks for people who had guselkumab. Therefore, the model was not suitable to explore the full effect on outcomes of using a 16-week stopping rule for guselkumab. This was because it could misrepresent the quality-adjusted life-year (QALY) gains associated with an improvement in PASI response from 16 to 24 weeks. Also, the ERG explained that it was uncertain whether the improvement in PASI response from 16 to 24 weeks on guselkumab was confounded by the bias potentially introduced by allowing early escape in the DISCOVER trials. The committee noted that the assessment time for skin response was 16 weeks, in line with guselkumab's marketing authorisation for moderate to severe psoriasis. The committee agreed with the ERG that the evidence for further improvement in joint disease between 16 and 24 weeks was limited. But it noted that 24 weeks was the assessment time in the summary of product characteristics. The committee concluded, however, that clinicians would value the option of assessing response at 16 weeks.

Clinicians would value the option to continue treatment based on a PASI 75 response

3.8 Continuing guselkumab treatment depends on whether a person has a PsARC response. The ERG explored the possibility of continuing treatment when the PsARC response does not justify continuing but there is a PASI 75 response. The ERG explained that this was particularly relevant for guselkumab, which is likely to produce a comparable PsARC response to other biological DMARDs, but has the highest PASI 75 response. The clinical experts explained that if a person with psoriatic arthritis and mild psoriasis did not have an adequate PsARC response, it would not be appropriate to continue guselkumab just because of a 75% reduction in their mild psoriasis. But the decision could be different for people with moderate to severe psoriasis, which can severely affect quality of life. The committee recalled the patient expert statement that for some people with psoriatic arthritis, psoriasis symptoms in skin and nails can be hugely debilitating. This not only affects physical discomfort but also psychological health, education, career choices and relationships (see section 3.1). The patient experts also explained that the person's needs must be considered. For some people skin and nail psoriasis symptoms can have a greater effect on quality of life than joint symptoms. The clinical experts explained that if there is only a partial PsARC response, but the person has a PASI 75 response for psoriasis that has affected their quality of life, then it may be appropriate to continue treatment while that clinical benefit lasts. Some people in this situation will continue to have slow incremental improvement in their joints over time. Clinical judgement is therefore important in deciding when to continue treatment without a full PsARC response. The clinical experts explained that about 10% to 15% of the psoriatic arthritis population present with moderate to severe psoriasis so this only affects a minority of people who would have guselkumab. The committee concluded that, when people have an improvement in psoriasis symptoms that benefits their quality of life, but only a partial PsARC response, clinicians would value the option to continue treatment based on a PASI 75 response.

Network meta-analyses

The results of the network meta-analyses are uncertain

3.9 To evaluate the effectiveness of guselkumab compared with comparator treatments the company did network meta-analyses (NMAs) for all main outcomes, for:

people who had not had biologicals (subpopulation 2)
people who had had biologicals (subpopulation 3).

The analysis for people for whom TNFi were contraindicated (subpopulation 4) was handled by removing TNFi treatments from the analyses for people who had not had biologicals before. The committee noted that all included trials were mainly comparisons with placebo, with few head-to-head comparisons of active treatments. Also, most treatments were examined either in a single trial, or a set of closely related trials from the company making the drug. For the population who had not had biologicals before, guselkumab was likely the best treatment for skin symptoms, based on PASI score. But it had more modest results for other outcomes and was generally ranked inferior to TNFi treatments, and similar to secukinumab or ixekizumab. For the population who had had biologicals before, guselkumab generally ranked better in these analyses, because the TNFi treatments were excluded. But the limited data meant that few comparisons (except with placebo) were conclusive. For the people for whom TNFi were contraindicated, guselkumab was the best treatment for PASI outcomes, but not clearly better than secukinumab or ixekizumab. The ERG explained that its main concern with the NMAs reported in the company submission was that they combined outcomes measured at different times. Comparing outcomes assessed at 24 weeks for guselkumab with outcomes assessed at 16 weeks (or earlier) for other treatments may unfairly bias results in favour of guselkumab. The ERG explained that because of the limited data, most differences in effectiveness across treatments were not conclusive. Also, the results of the NMAs should be taken as evidence for how guselkumab might broadly compare with other treatments, rather than for a robust ranking of treatments. The committee agreed with the ERG that guselkumab appeared to be very similar in effectiveness to other interleukin inhibitors (secukinumab and ixekizumab) for all outcomes. All 3 interleukin inhibitors were ranked higher than TNFi treatments for PASI outcomes, but lower on ACR and PsARC outcomes. The committee concluded that the results of the NMAs showed treatment class effects, but the specific treatment rankings were uncertain.

Economic model

The model does not reflect NHS clinical practice but is appropriate for decision making

3.10 The committee noted that the company's model was based on that used in NICE's technology appraisal guidance on certolizumab pegol and secukinumab for the treatment of psoriatic arthritis. Using a Markov structure to capture all costs and outcomes associated with guselkumab and the comparators, the model included up to 3 lines of active treatment before best supportive care. The company submission stated that this structure was intended to reflect current treatment, where multiple lines of targeted treatment are common. The ERG confirmed that this structure was consistent with previous models used in NICE technology appraisals for psoriatic arthritis. But, using a limited number of active treatment lines does not represent NHS clinical practice. The clinical experts agreed with the ERG that because of the range of treatments and because the disease is varied and unpredictable there is no standard treatment sequence in the NHS. People will almost always start treatment with conventional DMARDs such as methotrexate, and then move onto biological DMARDs if their disease is not adequately controlled. But the exact sequence of treatments is determined by the course of the disease for each person. The committee recalled that people often switch between different biological treatments (see section 3.2). The clinical experts explained that the sequencing of biological treatments is often a mix of clinical and economic considerations. Also, there is no pathway of treatments that would suit everyone. The committee concluded that the model was limited in how much it represents clinical practice. But the committee agreed that it was consistent with previous NICE technology appraisals for psoriatic arthritis and was therefore suitable for decision making.

A 16.5% discontinuation rate should be used for all biological treatments in the economic model

3.11 The committee recalled the low discontinuation rates in DISCOVER‑1 and DISCOVER‑2, and the ERG and clinical experts' reasons why these may not be seen in NHS clinical practice (see section 3.5). The ERG explained that the treatment-specific discontinuation rates used in the company's base case were the largest driver of cost-effectiveness. The committee noted that in psoriatic arthritis appraisals since NICE's technology appraisal guidance on etanercept, infliximab and adalimumab, a 16.5% treatment discontinuation rate had been used for all biological treatments. The ERG reiterated that the evidence supporting these different treatment-specific discontinuation rates was not robust. But it noted that even if it were, it was not appropriate to use these rates in the economic model. The ERG explained that the company's economic model allowed up to 3 lines of active treatment before people moved to best supportive care (see section 3.10). It noted that this had implications for the use of treatment-specific discontinuation rates. The clinical experts agreed with the ERG that people often switched between different TNFi treatments, and to different interleukin modulators (ustekinumab, secukinumab and ixekizumab) or to tofacitinib. They also agreed that 16.5% was an appropriate discontinuation rate to use in the model to ensure consistency with other psoriatic arthritis technology appraisals. The ERG explained that in the company's model, people remained on treatment with best supportive care for an implausibly long time. Therefore considerable costs accrue and people's health-related quality of life declines, as their condition deteriorates. Treatment-specific discontinuation rates should only be used when the appropriate range of treatment sequences reflecting the full duration of disease are modelled. Because this was not possible in the company's model, using treatment-specific discontinuation rates introduced bias by inaccurately characterising total costs and QALYs for treatments associated with further lines of active treatment. In its response to technical engagement, the company disagreed with the ERG that treatment-specific discontinuation rates in the model could potentially bias in favour of longer-acting treatments like guselkumab. The company maintained that the additional time spent on guselkumab relative to other treatments before moving to best supportive care represented a real clinical benefit of guselkumab. The ERG further explained that by restricting the number of lines of treatment, the company's model was overly optimistic in quantifying the benefits of 'displacing' best supportive care. This was because it assumed that this occurred earlier than expected in clinical practice. It also assumed that the displaced strategy would be best supportive care rather than another more cost-effective active treatment. The committee agreed that because the model could not accurately portray the range of treatment sequences used in clinical practice, using a 16.5% discontinuation rate for all treatments would offset the risk of bias in the economic model. It would also ensure consistency with other psoriatic arthritis technology appraisals. The committee therefore concluded that a 16.5% discontinuation rate should be used for all treatments in the economic model.

The cost-effectiveness results are sensitive to psoriasis severity

3.12 The baseline PASI scores for people in the DISCOVER trials were high compared with those in people having NHS treatment (see section 3.4). The clinical experts explained that only a small proportion of people (10% to 15% of the psoriatic arthritis population; see section 3.8) present with moderate to severe psoriasis symptoms. The committee was aware that in previous psoriatic arthritis appraisals results were presented by psoriasis subgroup. The ERG considered that this approach was appropriate. It did cost-effectiveness analyses by psoriasis severity using data from the DISCOVER trials. Because guselkumab and the comparators have commercial arrangements, the exact incremental cost-effectiveness ratios (ICERs) are confidential and cannot be reported. However, the committee concluded that the cost-effectiveness results were sensitive to psoriasis severity.

Results of the comparison with etanercept should be included in the fully incremental analysis

3.13 Etanercept was included as a comparator in the scope because NICE recommends it for psoriatic arthritis, and it is commonly used in UK clinical practice (see section 3.2). After technical engagement, the company asked whether etanercept should be excluded as a comparator in the cost-effectiveness analysis. This was because, the company claimed, etanercept's market share was small. Also, in NICE's technology appraisal guidance on tofacitinib for treating active psoriatic arthritis, the committee decided that comparisons with best supportive care were more reliable than the fully incremental analysis. The ERG explained that both pairwise and fully incremental analyses were included in that appraisal, but pairwise comparisons with best supportive care were considered appropriate. This was because the fully incremental analyses were very sensitive to small differences in the estimates of costs and QALYs, given that total costs and QALYs were similar across all active treatments. The ERG explained that the company also raised several concerns about the clinical data supporting etanercept's effectiveness, but did not provide clear evidence of bias in favour of etanercept. The committee noted that etanercept was a comparator in previous psoriatic arthritis appraisals and agreed that there was no case to support excluding it from the comparison. The committee concluded that the results of the comparison with etanercept should be included in the fully incremental analysis.

It is not possible to evaluate the cost effectiveness of a 4-weekly dose for people at high risk of joint damage based on current evidence

3.14 The committee recalled that guselkumab's 2 pivotal trials in psoriatic arthritis, DISCOVER‑1 and DISCOVER‑2, randomised people to 100 mg guselkumab every 8 weeks or every 4 weeks or to placebo (see section 3.3). The company's submission considered the clinical effectiveness of both the 4-weekly and 8-weekly dose but focused on the 8-weekly dose, which reflected the anticipated marketing authorisation. After technical engagement, the company told NICE that the marketing authorisation would also include a 4-weekly dose for people at high risk of joint damage. The ERG explained that this was difficult to evaluate for several reasons. Firstly, as the company had explained, there was no standard definition among clinicians of 'high risk of joint damage'. Clinical experts had advised the company that any definition was likely to focus on diagnostic criteria such as c-reactive protein level and the number of joint erosions at baseline. But they noted that there was currently no agreed definition. The company cited a publication in which the cut-off for a population considered at high risk of joint damage was a c-reactive protein level of 2.87 mg/dL or more. The ERG considered that this seemed reasonable but agreed with the company that a precise definition was probably not possible, given the accepted variation in clinical judgement. It was not possible to evaluate the cost effectiveness of guselkumab in this high-risk population without knowing its clinical effectiveness in the same group. But the clinical effectiveness of the 4-weekly dose provided by the company was based on its effectiveness in the full trial population, and not a subpopulation assessed to be at high risk of joint damage. The ERG explained that in the company submission, there was no evidence that effectiveness was different between the 8-weekly and 4-weekly doses after 16 weeks. The ERG therefore considered it reasonable to assume that both doses would also have the same effectiveness for people at high risk of joint damage. The company provided estimates of the proportion of the population at high risk of joint damage who would be expected to be seen in NHS clinical practice. These estimates are commercial in confidence and cannot be reported. The committee agreed with the ERG that this estimated proportion was highly uncertain. Also, there were insufficient data on whether guselkumab would work better or worse than estimated for people at high risk of joint damage. The committee concluded, based on the evidence provided, that it could not reliably evaluate guselkumab's cost effectiveness for people at high risk of joint damage because of the uncertainty.

Cost-effectiveness estimates

Because of the uncertain evidence, the ICER needs to be at the lower end of the acceptable range

3.15 NICE's guide to the methods of technology appraisal notes that above a most plausible ICER of £20,000 per QALY gained, judgements about the acceptability of a technology as an effective use of NHS resources will take into account the degree of certainty around the ICER. The committee will be more cautious about recommending a technology if it is less certain about the ICERs presented. Because of the high level of uncertainty in the clinical and economic evidence, the committee agreed that an acceptable ICER would be at the lower end of the acceptable range (that is, around £20,000 per QALY gained).

The most plausible cost-effectiveness estimates for guselkumab are too high

3.16 Because guselkumab and the comparators have commercial arrangements, the exact ICERs are confidential and cannot be reported. The committee's preferred assumptions produced a range of ICERs for guselkumab that were more than £20,000 per QALY gained for:

people whose disease is not adequately controlled by 2 conventional DMARDs but who have not previously had a biological DMARD (subpopulation 2)
people whose disease is not adequately controlled by 2 conventional DMARDs or by at least 1 previous biological DMARD (subpopulation 3)
people whose disease is not adequately controlled by 2 previous conventional DMARDs and the TNFi class of biological DMARD is contraindicated (subpopulation 4).

Conclusion

Guselkumab is not recommended

3.17 The committee acknowledged the need for biological treatment options for people with psoriatic arthritis. It agreed that the ERG's preferred base case by psoriasis severity was suitable for decision making. It took into account all commercial discounts for guselkumab and for other treatments in the pathway. But it concluded that the most plausible ICERs were higher than what NICE normally considers a cost-effective use of NHS resources. Therefore, guselkumab was not recommended as an option for treating psoriatic arthritis.

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Guselkumab for treating active psoriatic arthritis after inadequate response to DMARDs