Effect of Plasmapheresis on Ustekinumab Levels

Background:
Plasmapheresis is a way to remove toxic substances from the body. However, it can also result in removal of necessary substances such as medications. Here we present a patient who received a dose of ustekinumab while undergoing plasmapheresis and the effect it had on her serum ustekinumab levels.
Methods:
The patient is a 36-year-old female with pancolonic ulcerative colitis (UC) with cirrhosis due to primary sclerosing cholangitis with autoimmune hepatitis overlap. Her UC was well-controlled on ustekinumab (UST) 90 mg subcutaneous (SC) every 4 weeks. She presented to the emergency department for hematochezia, jaundice, and pruritusHer hematochezia was attributed to hemorrhoidal bleeding based on presentation and prior endoscopies. However, her hospitalization was prolonged due to ongoing pruritus refractory to multiple agents including ursodiol, sertraline, hydroxyzine, diphenhydramine, and cholestyramine ointment. Her ustekinumab dosing was delayed due to her admission and initial concern for infection in the setting of hypotension and pancytopenia. Once infection was ruled out, we arranged for the patient to get her subcutaneous ustekinumab dose while inpatient. During this time, the patient was also started on plasmapheresis due to refractory pruritus. Ustekinumab levels were checked regularly to coincide with her plasmapheresis sessions to monitor drug levels. Just prior to discharge, the patient was called for liver transplant and no longer required plasmapheresis. June 14th – last UST dose 90 mg SC given; Next due: July 12 (not given due to hospitalization) July 16th – 2:00 pm plasmapheresis session 1 July 17th – 10:30 am UST level 0.6 mcg/mL, 2:00 pm UST 90 mg SC dose given July 18th – 8:30 am UST level 0.9 mcg/mL, 2:00 pm plasmapheresis session 2 July 19th – 9:10 am UST level 1.2 mcg/mL July 22nd – 2:00 pm plasmapheresis session 3 July 24th – 6:40 am UST level 2.0 mcg/mL, 2:00 pm plasmapheresis session 4 July 26th – 6:45 am UST level 1.7 mcg/mL, 2:00 pm plasmapheresis session 5, 5:00 pm Patient was called for liver transplant and no longer required plasmapheresis.
Conclusions:
Therapeutic plasma exchange is an efficient way to remove harmful substances from the body via extracorporeal filtration. However, non-selective plasma exchange can result in concomitant removal of beneficial substances. The effect of plasmapheresis on monoclonal antibody levels has been assessed in limited studies following levels of rituximab and natalizumab. These patients, predictably, experienced lower peak and trough levels of these drugs following plasmapheresis. However, these medications are given IV and, thus, have 100% bioavailability and may be filtered more effectively by plasmapheresis. Additionally, drug binding to targets within cells or cell membranes may decrease removal through plasma exchange and allow for continued therapeutic effect despite filtering circulating medication from the bloodstream. Little is known about drug levels directly following administration of a monoclonal antibody subcutaneously. This route may be preferable for a patient requiring plasmapheresis due to slower dissemination from the subcutaneous tissues into the intravascular space. Our patient did continue to have increasing ustekinumab levels until her fifth plasmapheresis session when it first started to decline, suggesting that subcutaneous dosing might have decreased the amount removed by plasmapheresis or possibly that subcutaneous dosing may take longer to reach plasma concentrations.