The field of the disease neuromyelitis optica, and especially of its therapy, may have in 2019 the most significant year since the disease was first described 200 years ago, or since it was named neuromyelitis 100 years ago. Neuromyelitis optica spectrum disorder occurs in approximately 1 case per 100000 person-years. That is the prevalence calculated for Denmark and its various regions.
Papp et al. Neurology 2018, 91:e2265-e2275
The investigators used the 2006 Wingerchuk and the 2015 International Panel for NMO Diagnosis, IPND, which includes the aquaporin 4 antibody.
Three drugs have gone through phase 3 clinical trials, with different mechanisms of action, and are on the fast track to gain FDA approval soon. Eculizumab, inebilizumab and satralizumab have come onto a field of zero, no drugs are approved by the FDA for therapy of neuromyelitis optica spectrum disorder. Rituximab, azathioprine and cyclophosphamide are the drugs most commonly used on an off-label basis, but between 25% and 60% of patients continue to suffer of the very severe bouts of the disease, which frequently lead to permanente nervous system damage and physical and mental disability.
Susan Fizgerald. Neurology Today June 06, 2019, vol 19, issue 11
AQP4, the immunoglubulin present in the blood of patients with neuromyelitis optica spectrum disorder, triggers the so-called complemente cascade, the formation of the membrane attack complex and severe inflammation. The eculizumab trial involved 143 patients who received it as an add-on theray to the previous imune suppressant treatments. The active group of 96 people received 4 weekly intravenous doses, followed by biweekly maintainance. At 48 weeks, 98% of those on eculizumab and 63% of those on placebo were relapse free. Unfortunately, there was no difference in disability progression between the groups.
In another study of 231 patients with neuromyelitis optica spectrum disorder with intravenous inebilizumab, the same numbers were respectively 86% and 57% at 28 weeks, with some effect of disability progression, but there were 2 deaths in an open label phase that followed after the study was terminated prematurely due to regard for the safety of the patients on placebo, because patients were not allowed to maintain their previous imune suppresants. Satralizumab was deleveloped and tested in Japan, as a subcutaneous add-on therapy. 91% and 53% of the patients remained relapse-free at 96 weeks of follow-up.
The effect of the scientific progress in the field of neuromyelitis optica spectrum disorder associated with these clinical trials may offer new hope for patients who have dramatic attacks, leading 60% to blindness in one or both eyes, and 50% to severe ambulatory déficits in 5-10 years, in case they are not treated with powerful drugs. The caveat is that these drugs may be very costly, up to US$ 500000 per year for one of them.
Dr Paulo Bittencourt