4.1 The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of natalizumab for highly active relapsing–remitting multiple sclerosis, having considered evidence on the nature of the condition and the value placed on the benefits of natalizumab by people with multiple sclerosis, those who represent them, and clinical specialists. It was also mindful of the need to take account of the effective use of NHS resources.
4.2 The Committee considered the data on the clinical effectiveness of natalizumab in the subgroup of people whose multiple sclerosis has failed to respond to treatment with beta interferon, that is, the suboptimal therapy group. It noted that the ITT population from the AFFIRM study, which showed that natalizumab significantly reduces relapse rate and delays disability progression compared with placebo, was used in the manufacturer's submission as a proxy for this group. The Committee was aware that the Sentinel study was used to inform the licence for the suboptimal therapy group but that the study considered the use of natalizumab in combination with beta interferon; this combination is not licensed because of safety concerns. The Committee noted that there is no direct evidence about the clinical effectiveness of natalizumab monotherapy in the suboptimal therapy group. In addition, the clinical experts confirmed that, although natalizumab may be used in this situation, there are no clinical study data to indicate how clinically effective it is in this group. The Committee therefore concluded that the clinical effectiveness of natalizumab in the suboptimal therapy group has not been fully established.
4.3 The Committee considered the data on the clinical effectiveness of natalizumab in the RES group. The Committee was aware that a post hoc analysis of the AFFIRM study population indicated that natalizumab significantly reduces relapse rate and delays disability progression compared with placebo in the RES group. It noted the results of an indirect analysis performed by the manufacturer showing that natalizumab reduces relapse rate more effectively than beta interferon or glatiramer acetate. The Committee also heard the views of the clinical and patient experts that natalizumab has a clinically important effect on disability progression in people with highly active forms of multiple sclerosis that has not been seen with other disease-modifying therapies. The Committee agreed that natalizumab is clinically effective in the RES group compared with placebo, beta interferon and glatiramer acetate.
4.4 Although the Committee had reservations about the data on the clinical effectiveness of natalizumab in the suboptimal therapy group (as indicated in section 4.2), it reviewed the manufacturer's cost-effectiveness analysis for this group and the ERG's comments. The Committee noted that the base case ICERs estimated by the manufacturer for the suboptimal therapy group were £43,400 per QALY gained or higher. It therefore concluded that natalizumab would not be a cost-effective use of NHS resources in this group of people.
4.5 The Committee noted that the base case ICERs estimated for the RES group by the manufacturer ranged from £32,000 per QALY gained (natalizumab compared with beta interferon) to £44,600 per QALY gained (natalizumab compared with best supportive care).
4.6 The Committee considered which of the comparators used in the manufacturer's cost-effectiveness analysis for the RES group best reflected current clinical practice. The Committee noted that, as described in NICE technology appraisal guidance 32, beta interferon and glatiramer acetate were not recommended by NICE for the treatment of multiple sclerosis on the basis of their cost effectiveness. However, it was aware that, following the Institute's assessment of beta interferon and glatiramer acetate, a risk sharing scheme had been set up by the Department of Health. This allowed the continued use of these technologies with the financial risk being shared between the NHS and the participating pharmaceutical companies. The Committee also noted the information from consultees that treatment with beta interferon is the current standard of practice in the RES group. It was persuaded, therefore, that the most appropriate comparator for determining cost effectiveness in the RES group is beta interferon.
4.7 The Committee noted the views of the ERG that the results of the manufacturer's economic model were associated with considerable uncertainty and that alternative assumptions would substantially increase or decrease the ICERs (see sections 3.9 and 3.12). However, the Committee concluded that the ICER of £32,000 per QALY for natalizumab compared with beta interferon presented by the manufacturer was more likely to be an overestimate. The Committee considered that, for a disease which presents in early life and has limited effect on life expectancy, a time horizon longer than 20 years would be appropriate, which would lower the ICER. In addition it was persuaded that the disutility of relapses may have been underestimated in the model. In addition, the Committee took into account the high degree of clinical need among people in the RES group and the innovative nature of the technology. The Committee therefore concluded that the use of natalizumab for people with RES would be a cost-effective use of NHS resources and that it should be recommended for use within the NHS for the treatment of people with RES.