The general use of monoclonal antibodies in multiple sclerosis and other imune diseases is ever more apparent. One may be reminded that it was some 20 years ago that the present revolution was ignited, when the imune and rejuvenating effect of the drugs used in bone marrow transplantation were grasped by the clinical research community. Immune suppressors were developed, anda the same time monoclonal antibodies began to be developed, to replace the horse and rabbit derived policlonal antibodies. Many monoclonal antibodies are now available in immunology and oncology, and a few are FDA approved for multiple sclerosis. A few others are used off-label.
One concept that has been evaluated is that more intense treatment early on is indicated in multiple sclerosis, because it leads to less neurological deficit later, when the disease becomes progressive. For that purpose, a short one-dose course of rituximab was compared to placebo in 54 patients, given before patients went on standard therapy with glatiramer acetate.
Honce et al Neurology. 2019, 92:e723-e732
With this form of induction therapy, 70% of patients given rituximab entered a state called no evident disease activity, at 6-12 months, compared to 25% on placebo. But the effect was not sustained, and by 36 months 25% of patients in both groups had inactive disease.
Ocrelizumab is another of these monoclonal antibodies, directed at CD20, a B-lymphocyte target. It is similar to rituximab, given by IV infusions every 6 months.
Bruce A Cohen, Neurology 2019, 92:435-436
Over 60000 people have received ocrelizumab for a variety of rheumatic diseases, and one of its toxicities is late low neutrophile counts, below 1500, with signs of mucositis, occurring more than 4 weeks after infusion in more than 10% of patients. In the case described in this report, the patient was treated with methyl-prednisolone and filgrastim. This complcation has been described in 6,5% of patients on rituximab, and boné marrow biopsies have shown maturation arrest at the promyelocyte stage. Most reported cases have been benign and resolved in 20 days.
Dr Paulo Bittencourt
