Most notable is the following excerpt -- the importance of individual differences -- which the comparative effectiveness crowd in the US blindly and blithely ignores:
"The new treatment approach is to treat early and aggressively to achieve minimum disease progression and ideally remission, a strategy that achieves the best long-term results. However, there is currently no gold standard to define remission. Progression and response to treatment are extremely variable between patients. A substantial proportion of patients (up to 30%) is not adequately controlled with currently available treatment strategies of non-biological disease-modifying antirheumatic drugs and TNF a inhibitors."
UK, 5/5/2008 - The Lancet has been a longstanding supporter of the National Institute for Health and Clinical Excellence (NICE) in the UK. Its procedures are rigorous, scientifically driven, and publicly accountable. NICE is widely admired by many other western European nations. But consternation and disappointment characterised the reaction by patient groups and the British Society for Rheumatology to NICE's latest judgment. On April 23, NICE rejected an appeal on abatacept for patients with severe rheumatoid arthritis brought by the drug's manufacturer Bristol-Myers Squibb, the British Society for Rheumatology, the Royal College of Physicians, the National Rheumatoid Arthritis Society, and the Royal College of Nursing. The appeal committee upheld NICE's decision of October last year, and the only next possible step is an application to the High Court.
Abatacept is, with rituximab and tocilizumab, one of three new drug classes that have shown clinically significant improvement for the treatment of severe refractory rheumatoid arthritis. Abatacept acts as a selective T-cell co-stimulation modulator, designed to block a key co-stimulatory signal required for T-cell activation, a new approach to halt or reverse the inflammatory process. However, with an incremental cost-effectiveness ratio of about £37?000–£43?000, possibly even higher if different estimates are included in the model, abatacept did not provide cost-effective treatment according to NICE's threshold of £30?000 per quality-adjusted life-year (QALY) gained. Many of these estimates are no more than best guesses based on insufficient or incomplete evidence. The committee stated that “while recognising the innovative nature of the drug, the severity of the disease and the limitations around the use of the HAQ [health assessment questionnaire] in the economic modelling, …abatacept would not be a cost-effective use of NHS [National Health Service] resources for patients in whom rituximab failed or in whom rituximab is contraindicated”.
How does abatacept differ from rituximab? Rituximab, a chimeric human-mouse monoclonal antibody directed at the CD20 antigen expressed on mature B cells and pre-B cells, acts on a different pathway. Like abatacept, rituximab was shown to be effective in patients treated with methotrexate who had not responded adequately to an additional TNF a inhibitor. Again like abatacept, there are no good long-term data and no direct head-to-head trials comparing other strategies with rituximab, yet rituximab was approved in August last year. The simple difference is that rituximab is cheaper. Patients only need two infusions every 6 months compared with 14 infusions of abatacept in the first year and 13 thereafter. The incremental cost-effectiveness ratio of rituximab is estimated as somewhere between £12?000 and £30?000 per QALY gained.
Rheumatoid arthritis is common and debilitating. About 1% of the adult population in developed countries is affected, increasing to 5% for women older than 55 years. About 60% of people are unable to work and are severely restricted in daily activities 10 years after diagnosis. Although progress has been made in understanding the underlying pathogenic mechanisms, the cause of rheumatoid arthritis remains unknown. The new treatment approach is to treat early and aggressively to achieve minimum disease progression and ideally remission, a strategy that achieves the best long-term results. However, there is currently no gold standard to define remission. Progression and response to treatment are extremely variable between patients. A substantial proportion of patients (up to 30%) is not adequately controlled with currently available treatment strategies of non-biological disease-modifying antirheumatic drugs and TNF a inhibitors.
Any new and effective treatment for such a debilitating condition as rheumatoid arthritis should be welcomed with enthusiasm. But NICE is at the sharp end of husbanding NHS resources. It has to balance evidence with cost. And here there is a perilous conflict between its dual clinical and political purpose. There will be occasions when exceptions to strict cost-effectiveness guidelines must be made on clinical grounds. Abatacept is a strong candidate to be such an exception. Worse still, NICE's decision may unwittingly act as a disincentive to industry to develop new medicines in this neglected and poorly understood area. Although NICE will rightly say that it has followed the letter of its cost-effectiveness law, patients and the public may, with justification, feel that it has forgotten the spirit of those same laws—namely, that cost-effectiveness evidence needs to be interpreted with compassion as well as impartial science.