Rituximab and live virus vaccines
Question:
4/10/2020
Rheumatology service referred a 48 year-old female with Wegner's granulomatosis. The patient has been on two cycles of rituximab (first cycle in September 2018 and second cycle in May 2019). Next cycle will depend on COVID-19 repopulation. The last lymphocyte enumeration was done just last month and revealed a COVID-19 count of 43 (normal 87-507). (level has increased from zero following last cycle). T cell numbers were all within normal limits. Serum IgG was 693 in December 2019. Last serum IgM and IgA was done in November 2018 and levels were 49 and 22 respectively. Serum antibody titers were performed last fall for tetanus (5.1), diphtheria (0.60), and baseline titers to pneumococcus revealed 11 out of 14 titers within protective limits.
Patient had protective antibody titers to mumps and rubella, however antibody testing for measles both quantitative and qualitative was negative. The rheumatologist is wondering when this patient may receive a measles vaccine. My understanding is that rituximab may suppress response to vaccination for at least six months, possibly longer and that the interval following therapy into a live virus vaccines can be administered safely has not been established.
Any thoughts on when we might consider administering the measles vaccine?
Answer:
While it has been 11 months since your patient’s most recent rituximab dose, B cells continue to remain low. Tanrıöver, et al. (1) recommends that vaccines could be administered 6 to 12 months after last dose of rituximab, however live vaccines should be withheld until the B cell count returns to normal levels.
Bühlera, et al. (2) recommends waiting at least 12 months since last dose of Rituximab to administer, though goes on to state that currently no data are available, so this recommendation is based on expert opinion, relying on the half-life of rituximab and on immunogenicity studies of inactivated vaccines. The reasoning for this recommendation is that if an inactivated vaccine is capable of inducing a humoral immune response after a certain time period after rituximab administration, the immune competence will also be sufficiently restored to be able to deal with a live vaccine. They go on to state that CD19+ B cells should be measured at the best proxy available for B cells in the periphery.
Based on these recommendations, avoidance of live virus vaccine would seem prudent until recommended time has elapsed, and B cells return to normal levels. Certain circumstances should be taken into account, such as high community risk of measles.
Clearly more data are needed on the potential risk of vaccination with live vaccines for patients on rituximab.
1) Tanrıöver MD, Akar S, Türkçapar N, Karadağ Ö, Ertenli İ, Kiraz S. Vaccination recommendations for adult patients with rheumatic diseases. Eur J Rheumatol. 2016;3(1):29–35
2) Silja Bühlera , Gilles Eperonb , Camillo Ribic , Diego Kyburzd, Fons van Gompele , Leo G. Visserf, Claire-Anne Siegristg, Christoph Hatza,h. Vaccination recommendations for adult patients with autoimmune inflammatory rheumatic diseases. Swiss Med Wkly. 2015;145:w14159
I hope you find this helpful.
Respectfully submitted,
Jeffrey G Demain, MD, FAAAAI