The National Institute for Health and Clinical Excellence has published its preliminary recommendations on the use of biologic therapies to treat rheumatoid arthritis after a TNF inhibitor has failed, and things are not looking good for Orencia.

Bristol-Myers Squibb’s Orencia (abatacept) has been left out in the cold again after the cost watchdog’s appraisal committee ruled that, while clinically effective, with an annual of around £9,444 for a patient weighing between 60kg and 100kg the drug is too expensive for use on the National Health Service when compared with other options currently available.

Things are however, looking much brighter for Roche’s MabThera (rituximab), which has been recommended by the Institute as an option for patients in whom therapy with a TNF inhibitor has failed, as its calculations suggest this treatment pathway is more cost effective than the sequential use of other anti-TNFs or Orencia.

According to NICE, most of the economic models showed that, in comparison with MabThera, the ICERs (incremental cost effectiveness ratio) for the TNF inhibitors were either very high - above £80,000 per QALY gained - or that MabThera was both more effective and less costly.

Similarly, the Committee concluded that while both MabThera and Orencia were proven to be clinically effective in comparison with placebo, one had not been shown to be more effective than the other, but it calculations do suggest that, in comparison with MabThera, costs associated with Orencia are higher, coming in at above £100,000 per QALY gained in the base case scenario.

However, B-MS argues that MabThera does not achieve an effective response in up to 50% of patients, who would them require alternative treatments. The company said it is “very disappointed” with NICE’s rejection of Orencia, which, according to Dr Valerie Campello-Iddison, Executive Medical Director of B-MS, is “proven to be clinically effective in patients who do not respond to an anti-TNF and we believe that it represents good value for money for the NHS”.

“RA is a complex disease where clinicians require options for treatment rather than restricted choices, to enable them to meet the varying needs of patients over their lifetime, as such other therapeutic options should be considered rather than continuing with potentially sub-optimal treatment,” she added.

The decision, says NRAS chief executive Ailsa Bosworth, “is as confusing as it is frustrating”. Patients respond very differently to different therapies and only some patients will benefit from treatment with MabThera after disease-modifying anti-rheumatic drugs and anti-TNF therapies have failed, she explained, and added that Orencia “would be another good option in their care pathway which has again been denied”.

Further restricting treatment options, and much to the disappointment of the National Rheumatoid Arthritis Society, the cost watchdog also said that, based on the current body of evidence available and its own cost effectiveness analyses, it could not recommend “as an appropriate use of NHS resources” Abbott Laboratories’ Humira (adalimumab), Wyeth’s Enbrel (etanercept) and Schering-Plough’s Remicade (infliximab) as alternatives to MabThera following the failure of a first course of TNF inhibition, unless these drugs are being used in the context of research.

Complex disease
According to Bosworth, NICE is failing to understand that RA is a complex disease with different clinical sub-sets, “and therefore we need access to biologic therapies with different mechanisms of action as people’s disease can be driven by different parts of the immune system and access to one TNF, or two under certain circumstances, followed by MabThera is just not adequate, when there are other effective treatments available”.

Chris Deighton, consultant rheumatologist at Derbyshire Royal Infirmary and clinical advisor to NRAS, agrees. “Patients who fail on their first anti-TNF already have very bad rheumatoid arthritis and deserve more choice than just MabThera,” he said, and stressed “we will be doing our best to ensure that the final appraisal offers more treatment options for patients”.