NICE and new drugs for rheumatoid arthritis by cot14472



NICE and new drugs for rheumatoid arthritis
The Lancet has been a longstanding supporter of the            there are no good long-term data and no direct head-to-
National Institute for Health and Clinical Excellence          head trials comparing other strategies with rituximab,
(NICE) in the UK. Its procedures are rigorous, scientifically   yet rituximab was approved in August last year. The
driven, and publicly accountable. NICE is widely               simple difference is that rituximab is cheaper. Patients
admired by many other western European nations. But            only need two infusions every 6 months compared
consternation and disappointment characterised the             with 14 infusions of abatacept in the first year and
reaction by patient groups and the British Society for         13 thereafter. The incremental cost-effectiveness ratio of

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Rheumatology to NICE’s latest judgment. On April 23,           rituximab is estimated as somewhere between £12 000
NICE rejected an appeal on abatacept for patients with         and £30 000 per QALY gained.
severe rheumatoid arthritis brought by the drug’s                 Rheumatoid arthritis is common and debilitating.
manufacturer Bristol-Myers Squibb, the British Society         About 1% of the adult population in developed coun-
for Rheumatology, the Royal College of Physicians, the         tries is affected, increasing to 5% for women older
National Rheumatoid Arthritis Society, and the Royal           than 55 years. About 60% of people are unable to work
College of Nursing. The appeal committee upheld NICE’s         and are severely restricted in daily activities 10 years
decision of October last year, and the only next possible      after diagnosis. Although progress has been made in
step is an application to the High Court.                      understanding the underlying pathogenic mechanisms,
   Abatacept is, with rituximab and tocilizumab, one           the cause of rheumatoid arthritis remains unknown. The
of three new drug classes that have shown clinically           new treatment approach is to treat early and aggressively
significant improvement for the treatment of severe             to achieve minimum disease progression and ideally
refractory rheumatoid arthritis. Abatacept acts as a           remission, a strategy that achieves the best long-term
selective T-cell co-stimulation modulator, designed            results. However, there is currently no gold standard to
to block a key co-stimulatory signal required for              define remission. Progression and response to treatment
T-cell activation, a new approach to halt or reverse the       are extremely variable between patients. A substantial
inflammatory process. However, with an incremental              proportion of patients (up to 30%) is not adequately
cost-effectiveness ratio of about £37 000–£43 000,              controlled with currently available treatment strategies
possibly even higher if different estimates are included        of non-biological disease-modifying antirheumatic
in the model, abatacept did not provide cost-effective          drugs and TNF α inhibitors.
treatment according to NICE’s threshold of £30 000 per            Any new and effective treatment for such a
quality-adjusted life-year (QALY) gained. Many of these        debilitating condition as rheumatoid arthritis should be
estimates are no more than best guesses based on               welcomed with enthusiasm. But NICE is at the sharp end
insufficient or incomplete evidence. The committee               of husbanding NHS resources. It has to balance evidence
stated that “while recognising the innovative nature of        with cost. And here there is a perilous conflict between
the drug, the severity of the disease and the limitations      its dual clinical and political purpose. There will be
around the use of the HAQ [health assessment                   occasions when exceptions to strict cost-effectiveness
questionnaire] in the economic modelling, ...abatacept         guidelines must be made on clinical grounds. Abatacept
would not be a cost-effective use of NHS [National              is a strong candidate to be such an exception. Worse still,
Health Service] resources for patients in whom rituximab       NICE’s decision may unwittingly act as a disincentive to
failed or in whom rituximab is contraindicated”.               industry to develop new medicines in this neglected and
   How does abatacept differ from rituximab? Rituximab,         poorly understood area. Although NICE will rightly say
a chimeric human-mouse monoclonal antibody directed            that it has followed the letter of its cost-effectiveness
at the CD20 antigen expressed on mature B cells and            law, patients and the public may, with justification,
pre-B cells, acts on a different pathway. Like abatacept,       feel that it has forgotten the spirit of those same
rituximab was shown to be effective in patients treated         laws—namely, that cost-effectiveness evidence needs            For the Review on new therapies
                                                                                                                             for treatment of rheumatoid
with methotrexate who had not responded adequately             to be interpreted with compassion as well as impartial        arthritis see Lancet 2007;
to an additional TNF α inhibitor. Again like abatacept,        science. ■ The Lancet                                         370: 1861–74 Vol 371 May 3, 2008                                                                                                                1477

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