There are different protocols, but the typical maintenance protocol for RA is: two infusions, two weeks apart and then repeat every 6 months. (range is 6-12 months, minimum of 16 weeks)
http://www.nmouk.nhs.uk/downloads/Rituximab-protocol.pdf
Obviously for CFS we don't know the optimum protocol until more study is done.
As a comparison, use in blood cancers has typically been every week for 4 weeks, with maybe 8 weeks given in the first round. You have to wait a week in order for the patient to build back their supply of
complement. Once the RTX antibodies bind to a B cell, they can attract complement molecules which are part of the innate immune system. These complement molecules of various kinds can then form a
Membrane Attack Complex which makes a hole in the target cell's membrane. It's not too different from slowly letting the air out of a balloon, and the target cell dies.That's one of the three ways of cell killing thought to occur.
The contents of the B cells are being spilled into the circulatory system, including inflammatory chemicals which stimulate even more inflammatory chemicals. That's why people are typically given antihistamines, tylenol and corticosteriods beforehand.
The first infusion of RTX is used up the fastest, since all the original target cells are still there. Then the second infusion is given not long after, to build the levels of RTX back up - but since the number of target cells is already greatly reduced, the RTX isn't used up so fast the second time around and replenishing isn't needed so soon after the second infusion.
The timing of the third dose for CFS then probably involves more than a little guesswork, aimed at when any docs running a trial think the RTX has been depleted. Antibodies can last for months, they're not alive and they're just floating around. I'd guess that they eventually get damaged by oxidation or nitration, and/or damaged and possibly crosslinked by glycation from blood sugars.
IIRC, there are ~25,000 CD20 molecules on a typical B cell, which are the molecules that the RTX binds to. It's said that a B cell can get fairly well
coated or
opsonized with the antibodies - it's not just one antibody resulting in the killing of a B cell.