The MS off-label vs. licensed-innovator drug wars are about to get nasty. #ClinicSpeak #MSBlog #OffLabel
The study below summarises the off-label experience of using rituximab to treat both relapsing and progressive forms of MS in Sweden. An updated data set was presented at ECTRIMS to gasps from the audience. It is clear that anti-CD20 therapies are very effective DMTs, in both relapsing and progressive MS. These results are no surprise and back-up an enlarging data set on the efficacy of anti-CD20 therapies in MS.
Rituximab is about to come off-patent and there are several rituximab biosimilars waiting in the wings , with one already available in India. Off-label rituximab may therefore disrupt the MS market, particularly markets that are price sensitive. We tried to get NHS England to let us use rituximab in the NHS and they said no. The reason was that rituximab was not licensed for treating MS. It is clear that the NHS don't mind promoting and supporting the use of off-label drugs provided they are low cost and don't involve specialist commissioning, i.e. payment from central, rather than local, budgets. This is the NHS version of Catch-22! With the NHS on its knees you would expect them to embrace off-label drugs. I suspect they want to avoid any more high profile legal disputes with Pharma.
As you are aware we have included rituximab on our essential off-label DMT list and we continue to encourage neurologists in resource-poor settings to consider using rituximab in patients with highly-active MS. In wealthier, developed markets, the debate about high-cost innovator drugs is getting very heated. We are fortunate in the NHS to have NICE that assesses the cost-effectiveness of drugs and negotiates a very good deal of the NHS. In other countries, particularly the USA, this does not occur and drug price inflation has become a political issue. The USA is now subsidising international drug development and this position is unsustainable in the long-term.
For people with MS the good news is that the ocrelizumab, a follow-on from rituximab, should be licensed in the major markets within the next 12-24 months. Ocrelizumab has several advantages over rituximab, the main one being that it is less immunogenic than rituximab with a very low anti-drug antibody rate. An interesting question will arise is whether or not these advantages will change prescribing habits in countries such as Sweden and the USA.
OBJECTIVE: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS).
METHODS: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded.
RESULTS: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS). At baseline, 26.2% had contrast-enhancing lesions (CELs). Patients were treated with 500 or 1,000 mg rituximab IV every 6-12 months, during a mean 21.8 (SD 14.3) months. During treatment, the annualized relapse rates were 0.044 (RRMS), 0.038 (SPMS), and 0.015 (PPMS), and 4.6% of patients displayed CELs. Median Expanded Disability Status Scale remained unchanged in RRMS (p = 0.42) and increased by 0.5 and 1.0 in SPMS and PPMS, respectively (p = 0.10 and 0.25). Infusion-related AEs occurred during 7.8% of infusions and most were mild. A total of 89 AEs grades ≥2 (of which 76 infections) were recorded in 72 patients. No case of progressive multifocal leukoencephalopathy was detected.
CONCLUSIONS: This is the largest cohort of patients with MS treated with rituximab reported so far. The safety, clinical, and MRI findings in this heterogeneous real-world cohort treated with different doses of rituximab were similar to those reported in previous randomized controlled trials on B-cell depletion therapy in MS.