B cell depleting Milk

B

Pregnacy is an important issue. At present few MS treatments are available for use in pregnacy. If you are taking ocrelizumab you have to wait for 6 months in the USA and 12months in the EU before you try to concieve. Why?. This is because the antibody hangs around for a long time. An

So if you get an infusion of 600mg of ocrelizumab, which equates to about 600mg in 5 litres of blood so 600mg/1000ml maximum concentration = 0.6mg/ml = 600microgramme/ml. About a month later that will be 300ug/ml as the half-life is about a month and a month later 150ug/ml and a month later 75.5ug/ml, a month later and 37.75 ug/ml a month later and 18.875 ug/ml a month later and 9.4375 ug/ml a month later. Now we know that 20mg is fully depleting (20ug/ml so the drug is depletion maximally for at least 4 months.

This is one reason why the dose is about every 6 months. This will cause depletion of CD19 B cells and based on unpublished phase II trial data this from about 27-175weeks. And memory B cells are probably depleted for double that. How do I know that because I can read and know where to look, But that means CD19 B cells are depleted from about 7 months to 44months so for some people about 3.5 years. Now you are taking the drug every 6 months but it you were one of the lucky this information suggests the dose lasts 3.5 years before B cells come back. Now if that occurred maybe you could have your dose,wait 12 months, try to get pregnant say for 6 months, have a baby for 9 months and maybe still have 1.5 years of protection. So if this is true, wouldn’t this be an interesting approach…..a drug free pregnancy but protected from MS.

Wouldn’t it be worth knowing this and wouldn’t this be a study worth doing?

Now that is the best case scenario but you could still have the baby within 24 months of stopping treatment and then go back on ocrelizumab to stop disease reactivation after the baby is born. Would the drug get into the milk?. When pregnant the antibody will cross the placenta and so can deplete the babies B cells. It takes about 2 months for B cells to form and there are instances of babies being born to rituximab treated mothers with depleted B cells.

Rituximab is a lower efficacy CD20 depleting antibody. We know more about this antibody because neuros are doing the studies not the company, so the data more freely flows.

Now it seems that whilst babies can be born without B cells in a few months without exposure to antibody the B cells reach normal levels. But there is a question of if you are breat feeding would enough antibody cross in the milk. In this study this suggests not alot.

This study doesnt say you can safely have a baby on anti-CD20 therapy but it looks promising

Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions. Krysko KM, LaHue SC, Anderson A, Rutatangwa A, Rowles W, Schubert RD, Marcus J, Riley CS, Bevan C, Hale TW, Bove R. Neurol Neuroimmunol Neuroinflamm. 2019 Nov 12;7(1). pii: e637.

OBJECTIVE:To determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.

METHODS:Breast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion.

RESULTS:The median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.

CONCLUSIONS: We determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding.

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