A B-cell targeted therapy repurposed from treatment of leukaemia and rheumatoid arthritis is showing promise in treating patients with relapsing multiple sclerosis.
The anti CD-20 monoclonal antibody ofatumumab significantly reduced new inflammation and resulted in fewer clinical relapses and progressive events, say researchers who compared the safety and efficacy of the immune modulating drug with teriflunomide.
The findings, published in the NEJM, are based on two double-blind phase III trials ASCLEPIOS I and ASCLEPIOS II collectively randomising 946 patients to receive subcutaneous ofatumumab and 936 patients to receive oral teriflunomide for up to 30 months.
The studies, conducted in over 350 sites in 37 countries, enrolled patients between the ages of 18 and 55 years, with an Expanded Disability Status Scale (EDSS) score between 0 and 5.51.
According to investigators 20mg ofatumumab injected every four weeks significantly reduced the annualised relapse rate (ARR) by 51% (0.11 vs 0.22) and 58% (0.10 vs 0.25) in ASCLEPIOS I and II, respectively (P<.001 in both studies) compared to 14mg daily oral teriflunomide – a drug commonly taken for MS.
The trials are the latest to demonstrate the effectiveness of treatments that specifically target B cells to treat MS, say the investigators.
Where teriflunomide, an inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation, ofatumumab selectively depletes B cells. It is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion.
Investigators say ofatumumab lowered B-cell numbers during the loading regimen with the initial B-cell depletion maintained with monthly injections.
The regimen was also associated with a 34% relative risk reduction in three-month confirmed disability worsening (CDW), and 32% in six-month CDW.
Significant reduction of gadolinium enhancing (Gd+) T1 lesions (97% and 94% respectively) and a 92% and 85% relative reduction in new or enlarging T2 lesions on MRI was also demonstrated.
In the second year of treatment, nearly nine out of 10 patients on ofatumumab showed no sign of disease activity, said Professor Stephen Hauser lead author and co-chair of the steering committee for the ASCLEPIOS studies in a press release.
The most common adverse events treated with ofatumumab were injection-related reactions, nasopharyngitis, headache, injection-site reaction, upper respiratory tract infection, and urinary tract infection. Patients in the teriflunomide group noted similar events in addition to alopecia and diarrhoea.