Golimumab for the treatment of ankylosing spondylitis
This is an extract from the guidance. The complete guidance is available at guidance.nice.org.uk/ta233
4 Consideration of the evidence
4.1 The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of golimumab, having considered evidence on the nature of ankylosing spondylitis and the value placed on the benefits of golimumab by people with the condition, those who represent them, and clinical specialists. It also took into account the effective use of NHS resources.
4.2 The Committee noted that currently, adalimumab and etanercept are recommended by NICE as treatment options for people with severe, active ankylosing spondylitis whose condition has responded inadequately to conventional therapy (NICE technology appraisal guidance 143). The Committee heard from the clinical specialists and patient experts that another TNF-α inhibitor would increase the therapeutic options available and allow patients greater choice. The clinical specialists indicated that for patients receiving their first TNF-α inhibitor, approximately 20% may have adverse effects or their condition will not respond adequately to treatment. However, they believed that most of these patients are likely to benefit from trying another TNF-α inhibitor because of differences in the mechanism of action between the agents. The Committee noted that switching between TNF-α inhibitors is not currently recommended in NICE technology appraisal guidance 143, except when intolerance to the first agent occurs in the first 3 months of treatment.
4.3 The Committee heard from the clinical specialists and patient experts that ankylosing spondylitis may have a debilitating effect on quality of life because of pain, decreased mobility and sleep disturbance. Ankylosing spondylitis is a multisystem disease which can have non-skeletal manifestations (including iritis and inflammatory bowel disease) that can be severe. Patients may be unable to work because of their condition. The Committee also heard from the clinical specialists and patient experts that golimumab would allow greater flexibility and decreased discomfort because it is administered only once a month compared with the other subcutaneously administered TNF-α inhibitors which are given more frequently.
4.4 The Committee discussed the results of the GO-RAISE trial, which compared subcutaneous injections of golimumab 50 mg and golimumab 100 mg with placebo, administered every 4 weeks for up to 24 weeks. The Committee noted that, in this trial, patients whose condition had not responded to golimumab 50 mg by week 14 could receive golimumab 100 mg from week 16. The Committee therefore agreed that although the trial had adequately demonstrated the efficacy of the licensed dose (50 mg) of golimumab at 14 weeks, there was uncertainty about the magnitude of the therapeutic effect of the 50 mg dose beyond 16 weeks. However the Committee acknowledged that in clinical practice, treatment with TNF-α inhibitors would be discontinued in the event of inadequate clinical response at 12 weeks, in accordance with NICE technology appraisal guidance 143.
4.5 The Committee discussed the duration of the therapeutic effect of golimumab and heard from the manufacturer that the open-label extension period of the GO-RAISE trial had shown that efficacy was maintained over a 104-week period. The clinical specialists confirmed that when golimumab is used for extended periods in other medical conditions, its efficacy is maintained. The Committee therefore agreed that, despite the lack of data on the long-term efficacy of golimumab from the GO-RAISE trial, there was sufficient evidence to conclude that golimumab was a clinically effective treatment for people with severe, active ankylosing spondylitis.
4.6 The Committee discussed the clinical effectiveness of golimumab in relation to the other currently available TNF-α inhibitors. The Committee noted the result of the manufacturer's mixed-treatment comparison that identified small but non-statistically significant differences between golimumab and the TNF-α inhibitors for most outcomes, including severe adverse events. The Committee also noted that the ERG's analyses indicated that golimumab was more efficacious than etanercept and adalimumab in terms of improvement in BASDAI scores, but that there was a greater risk of treatment discontinuation with golimumab compared with these other treatments. However, the Committee noted that the 95% credible intervals around these estimates were wide and therefore subject to a high degree of uncertainty. The Committee acknowledged that the trials included in the mixed-treatment comparison showed differences between discontinuation rates in patients treated with placebo or TNF-α inhibitors, and that only a small number of discontinuations were observed in patients receiving placebo in the GO-RAISE trial. However the Committee noted that overall there were only a small number of treatment discontinuations in the trials and therefore comparisons between discontinuation rates for each TNF-α inhibitor should be interpreted with caution as there are insufficient data available to show conclusive comparative rates. The Committee also heard from clinical specialists that in clinical practice a similar efficacy and adverse-events profile to other TNF-α inhibitors has been observed when golimumab is used in its other licensed indications. The Committee concluded that golimumab was comparable to the other TNF-α inhibitors in terms of efficacy, adverse-event profile and risk of treatment discontinuation.
4.7 The Committee then discussed the manufacturer's economic model and the critique by the ERG. The Committee noted the ERG's criticism that the model had not been designed to enable evaluation of the cost effectiveness of the sequential use of TNF-α inhibitors. The Committee heard from the manufacturer that there was no evidence on the efficacy of golimumab when used in sequence with the other TNF-α inhibitors. The Committee also heard from the clinical specialists that there was only limited experience with the sequential use of TNF-α inhibitors in clinical practice, although a patient registry was being established by The British Society for Rheumatology to collect long-term data on the treatment of ankylosing spondylitis. The Committee acknowledged that cost-effectiveness estimates for golimumab would be likely to be different if calculated as primary therapy compared with use after another TNF-α inhibitor. The Committee concluded that the manufacturer's approach to structuring its economic model was appropriate and there was insufficient evidence to consider the clinical and cost effectiveness of sequential use of golimumab after another TNF-α inhibitor.
4.8 The Committee discussed the manufacturer's cost-effectiveness estimates and the exploratory analyses by the ERG. The Committee noted the ERG's criticism of the manufacturer's economic model. The Committee agreed that the ICERs presented were all uncertain to a degree because of the lack of available data on which to estimate the long-term efficacy of golimumab and the other TNF-α inhibitors. In addition, the Committee noted that in all the analyses the difference in costs and effectiveness estimates between the TNF-α inhibitors was very small and that the drugs were essentially similar in terms of their clinical and cost effectiveness. The Committee noted that the patient access scheme proposed by the manufacturer allowed dose escalation to 100 mg but did not incur additional costs. The Committee heard from the manufacturer that the cost of golimumab had recently been reduced by 1.5%, although this had only a marginal impact on the ICERs. The Committee was persuaded that golimumab had been shown to have comparable efficacy and cost to adalimumab and etanercept. Consequently, the Committee concluded that, despite its reservations about some aspects of the cost-effectiveness evaluation, golimumab could be considered a cost-effective use of NHS resources when it is used as described for adalimumab and etanercept in 'Adalimumab, etanercept and infliximab for ankylosing spondylitis' (NICE technology appraisal guidance 143).
Summary of Appraisal Committee's key conclusions
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TA 233 |
Appraisal title: Golimumab for the treatment of ankylosing spondylitis |
Section |
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Key conclusion |
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Golimumab is recommended as an option for the treatment of severe, active ankylosing spondylitis in adults only if:
The Committee concluded that, despite its reservations about some aspects of the cost-effectiveness evaluation, golimumab could be considered a cost-effective use of NHS resources when it is used as described for adalimumab and etanercept in 'Adalimumab, etanercept and infliximab for ankylosing spondylitis' (NICE technology appraisal guidance 143). |
1.1 4.8 |
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Current practice |
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Clinical need of patients, including the availability of alternative treatments |
Currently, adalimumab and etanercept are recommended by NICE as treatment options for people with severe, active ankylosing spondylitis whose condition has responded inadequately to conventional therapy (NICE technology appraisal guidance 143). The Committee heard from the clinical specialists and patient experts that another TNF-α inhibitor would increase the therapeutic options available and allow patients greater choice. The clinical specialists indicated that for patients receiving their first TNF-α inhibitor, approximately 20% may have adverse effects or their condition will not respond adequately to treatment. However, they believed that most of these patients are likely to benefit from trying another TNF-α inhibitor because of differences in the mechanism of action between the agents. The Committee noted that switching between TNF-α inhibitors is not currently recommended in NICE technology appraisal guidance 143, except when intolerance to the first agent occurs in the first 3 months of treatment. The main aim of treatment is to reduce the impact of the condition on patients. This includes pain, decreased mobility, disturbed sleep, and decreased opportunities to work. |
4.2 4.3 |
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The technology |
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Proposed benefits of the technology How innovative is the technology in its potential to make a significant and substantial impact on health-related benefits? |
Golimumab (Simponi, MSD) is a tumour necrosis factor alpha (TNF-α) inhibitor. The Committee heard from the clinical specialists and patient experts that golimumab would allow greater flexibility and decreased discomfort because it is administered subcutaneously only once a month compared with the other TNF-α inhibitors which are administered more frequently. |
4.3 |
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What is the position of the treatment in the pathway of care for the condition? |
Golimumab may be offered to patients with severe active ankylosing spondylitis whose condition has responded inadequately to conventional therapy. |
4.2 |
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Adverse effects |
The Committee concluded that golimumab was comparable to the other TNF-α inhibitors in terms of efficacy, adverse-event profile and risk of treatment discontinuation. |
4.6 |
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Evidence for clinical effectiveness |
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Availability, nature and quality of evidence |
The Committee discussed the results of the GO-RAISE trial, which compared subcutaneous injections of golimumab 50 mg and golimumab 100 mg with placebo, administered every 4 weeks for up to 24 weeks. The manufacturer presented a network meta-analysis to compare golimumab with adalimumab and etanercept. |
4.4 4.6 |
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Relevance to general clinical practice in the NHS |
The Committee concluded that golimumab was comparable to the other TNF-α inhibitors in terms of efficacy, adverse-event profile and risk of treatment discontinuation. |
4.6 |
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Uncertainties generated by the evidence |
The Committee agreed that although the GO-RAISE trial had adequately demonstrated the efficacy of the licensed dose (50 mg) of golimumab at 14 weeks, there was uncertainty about the magnitude of the therapeutic effect of the 50 mg dose beyond 16 weeks. |
4.4 |
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Are there any clinically relevant subgroups for which there is evidence of differential effectiveness? |
N/A |
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Estimate of the size of the clinical effectiveness including strength of supporting evidence |
The Committee concluded that there was sufficient evidence to conclude that golimumab was a clinically effective treatment for people with severe, active ankylosing spondylitis. The Committee agreed that although the GO-RAISE trial had adequately demonstrated the efficacy of the licensed dose (50 mg) of golimumab at 14 weeks, there was uncertainty about the magnitude of the therapeutic effect of the 50 mg dose beyond 16 weeks. |
4.5 4.4 |
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Evidence for cost effectiveness |
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Availability and nature of evidence |
The manufacturer submitted a de novo economic model that consisted of a short-term decision tree and a long-term Markov model comparing golimumab with adalimumab, etanercept and conventional treatment (including NSAIDs and DMARDs). |
3.8 |
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Uncertainties around and plausibility of assumptions and inputs in the economic model |
The Committee noted the ERG's criticism of the manufacturer's economic model. The Committee agreed that the ICERs presented were all uncertain to a degree because of the lack of available data on which to estimate the long-term efficacy of golimumab and the other TNF-α inhibitors. In addition, the Committee noted that in all the analyses the difference in costs and effectiveness estimates between the TNF-α inhibitors was very small and that the drugs were essentially similar in terms of their clinical and cost effectiveness. |
4.8 |
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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? |
Although data on general health were collected using the SF-36 survey in the GO-RAISE trial, the manufacturer did not use these to estimate SF-6D utilities on the basis that SF-6D is not in line with the NICE reference case. The manufacturer then attempted to produce an algorithm based on the data recorded in the GO-RAISE trial. However, the manufacturer felt that this algorithm lacked face validity because a number of key variables (age, sex and treatment effect) did not have the anticipated effects on health-related utility. This was inconsistent with published studies, which demonstrated a measurable relationship between these variables and an individual's health-related quality of life. In the end, the manufacturer decided it was more appropriate to use an algorithm from the assessment report for a previous NICE technology appraisal ('Adalimumab, etanercept and infliximab for ankylosing spondylitis' NICE technology appraisal guidance 143). No potential health-related benefits were identified that were not included in the economic model. |
3.10 |
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Are there specific groups of people for whom the technology is particularly cost effective? |
N/A |
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What are the key drivers of cost effectiveness? |
The Committee noted that in all the analyses the difference in costs and effectiveness estimates between the TNF-α inhibitors was very small and that the drugs were essentially similar in terms of their clinical and cost effectiveness. |
4.8 |
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Most likely cost-effectiveness estimate (given as an ICER) |
The revised base-case incremental cost-effectiveness analyses indicated that golimumab was slightly less effective and less costly than the other TNF-α inhibitors (golimumab and adalimumab were extendedly dominated by etanercept). These analyses produced an ICER for golimumab of £26,954 per QALY gained (incremental costs £4134; incremental QALYs 0.1534) compared with conventional treatment. |
3.17 |
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Additional factors taken into account |
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Patient access schemes (PPRS) |
The manufacturer of golimumab has agreed a patient access scheme with the Department of Health in which the 100 mg dose of golimumab will be available to the NHS at the same cost as the 50 mg dose. |
2.5 |
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End-of-life considerations |
N/A |
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Equalities considerations and social value judgements |
No equality issues were identified during the scoping process or during the course of the appraisal. |
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