Four disease-modifying therapies (DMTs) for multiple sclerosis — Avonex, Rebif, Betaferon, and Copaxone — are cost-effective and reduce disease progression in MS patients, especially those with relapsing-remitting disease, according to 10-year, real-world results from U.K.’s MS Risk Sharing Scheme (RSS).
But the long-term benefits observed wane over time, and suggest that better outcomes are achieved in patients who are treated earlier and have less disability.
The research, “Assessing the long-term effectiveness of interferon-beta and glatiramer acetate in multiple sclerosis: final 10-year results from the UK multiple sclerosis risk-sharing scheme,” was published in the Journal of Neurology, Neurosurgery & Psychiatry.
The first partnership of its kind in the U.K., the RSS enabled patients to access four DMTs through the country’s National Health Service (NHS) – three formulations of interferon beta, Avonex (by Biogen), Rebif (by EMD Serono), and Betaferon (known as Betaseron in the U.S., by Bayer), and one glatiramer acetate, Copaxone (by Teva Pharmaceuticals).
With help from the MS Trust and other professional and patient groups, the scheme was established in 2002 after the National Institute for Health and Care Excellence (NICE) concluded that, despite evidence of fewer relapses over two-to-three years, it could not recommend these four therapies due to insufficient evidence of cost effectiveness over a 20-year timeframe.
Rather, the treatments became available through the NHS after health officials reached an agreement with the therapies’ manufacturers. The scheme’s “risk” meant a shared financial risk between the NHS and the pharmaceutical companies.
A long-term monitoring study then assessed the medications’ cost-effectiveness over time. The study recruited about 5,000 patients in the U.K., who were given one of the four DMTs between 2002 and 2005, and then were followed for 10 years to compare the long-term benefits of treatment to an untreated “natural history” group of 978 patients in British Columbia, serving as controls.
“By establishing a novel RSS between the manufacturers and payers, we were able to collect high-quality long-term data on disease progression on a treated cohort and use historical data on untreated patients to construct a comparison control group,” the researchers state.
At six years, all four medications effectively reduced the rate of disability in patients with relapsing-remitting MS (RRMS), and were meeting the pre-specified cost-effectiveness target of £36,000 per quality-adjusted life-year projected out for 20 years.
Final results in 4,862 patients, followed for a median of 10 years, showed that in addition to being cost-effective, these four DMTs provided a stable and clinically significant reduction in disability progression, as assessed using the Expanded Disability Status Scale (EDSS), including a meaningful delay to sustained loss of unaided ambulation (EDSS of 6) of around four years in people with walking difficulties at treatment start.
“This study supports a beneficial effect on long-term disability with first-line MS disease-modifying treatments, which is clinically meaningful. The treatment effects appeared larger for patients with RRMS, those who start treatment earlier in their disease course and for women,” the researchers wrote.
However, the findings also indicated a gradual waning of therapeutic benefit over time, which may not justify the DMTs’ prices in some healthcare systems — particularly where costs are higher, the scientists observed. This may have implications in clinical care of MS and other patients with MS, and may warrant a new clinical study to evaluate whether discontinuing treatment — “after a given period on treatment, or after reaching a given level of disability’ — carries “any disadvantage.”
“On the basis of our findings, it might be more cost-effective — and ultimately in the interests both of patients with MS and of patients with other conditions — to intervene earlier in the disease course, rather than to persist with treatment for long periods,” the team wrote.
Of the 4,862 patients in the analysis, 17 percent switched to “non-scheme” treatments during follow-up, particularly Tysabri (natalizumab, by Biogen) and Gilenya (fingolimod, by Novartis), and 18 percent stopped using their DMTs during the study, the study noted.
David Martin, MS Trust’s chief executive, in a press release called the RSS “a truly innovative scheme” that “continues to deliver real benefits” for MS patients.
“Not only has the scheme enabled over 18,000 people with MS to access disease modifying treatments (DMTs), but it has also been the catalyst for the development of MS services, completely transforming the landscape for the 110,000 people living with MS” across the U.K., Martin added.
These benefits include a marked increase in MS nurses, physiotherapists, occupational therapists and neurologists, as well the opening of 70 specialist MS centers, and better education for health professionals specializing in treating MS patients.