Disease reactivation is a problem with migration inhibition drugs.
Fingolimod is a migration inhibitor to prevent the disease-causing cells from entering the brain.
It has been suggested that fingolimod traps immune cells in the lymph glands. This stops them getting in the blood and so they are not going to get brain.
However what happens when you have to switch to another drug..In some people catastrophy because their disease comes back, We have heard this story for alemtuzumab where fingolimod traps the cells in the lymph glands so that they can't be depleted by alemtuzumab. The alemtuzumab is cleared from the system quite quickly and then the lymphocytes exit the lymphoid tissue and disease returns.
Unexpected high multiple sclerosis activity after switching from fingolimod to alemtuzumab. Bernard-Valnet R, Pignolet B, Biotti D, Ciron J, Lafontan JF, Dumas H, Bonneville F, Brassat D.
Mult Scler Relat Disord. 2018 ;25:216-218. doi: 10.1016/j.msard.2018.08.006. [Epub ahead of print].
However this is not just a problem for alemtuzumab. It also has been noted with rituximab. Rituximab gets into the lymphoid tissue and also but it is not as efficient there as clearing the blood. However, I suspect the problem is not really in the lymph nodes as spun by the manufacturer, but in the bone marrow. However rituximab is again less active at reducing B cells in the bone marrow and so the problem encountered with alemtuzumab can also occur with rituximab.
Holmøy T, Torkildsen Ø, Zarnovicky S.Extensive Multiple Sclerosis Reactivation after Switching from Fingolimod to Rituximab.Case Rep Neurol Med. 2018 Jul 19;2018:5190794.
During treatment with fingolimod, B cells are redistributed from blood to secondary lymphoid organs, where they are protected from the effect of anti-CD20 and other cell-depleting therapies. We describe a multiple sclerosis patient who had almost complete depletion of B cells in blood during and shortly after treatment with fingolimod. He developed severe disease activity resembling immune reconstitution syndrome after switching from fingolimod to rituximab, with first dose being six weeks after fingolimod cessation. Following recommendations from the Swedish MS Association, rituximab treatment was started as one single dose of 1000 mg. In patients treated with fingolimod, pathogenic B cells may still be sequestered in secondary lymph nodes if this dose is given early. To deplete such B cells as they egress from the lymph nodes, we propose that a second dose of rituximab a few weeks after the first dose should be considered.
Rituximab and ocrelizumab are often given as does a couple of weeks apart (every 6 months) so the second dose can Zap the B cells exiting the bone marrow/lymph glands and maybe stop disease reactivation. However it says considerations needs to be given how you may transition to another treatment before you start fingolimod treatment
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