Rituximab:
Rituximab is a chimeric monoclonal antibody against CD20. Rituximab has been
used successfully to treat autoimmune conditions such as rheumatoid arthritis
(approved use) and SLE (off label). Preliminary it appears quite effective in treating
relapsing remitting multiple sclerosis and neuromyelitis optica as well. Clinical trials
using anti-CD20 molecules are ongoing.
There have also been recent theories that African american may have a b-cell
predominant disease pathophysiology and that a therapy such as Rituximab that
targets B cells may prove more effective in treating this population.
Routine protocol os 2 doses separated by two weeks. CD 20 and CD19 cells can be
checked to monitor efficacy of the drug.
Common side effects are infusion reaction including headache, flushing, low blood
pressure and fatigue. Allergic reactions including anaphylaxis has been reported.
Rittuximab can increase teh risk of infection including bladder infection, sinusitis,
upper respiratory tract infection as well as pneumonia and serious infections. It can
also decrease the effectiveness of immunizations. Immunization should be
administered prior to initiating this therapy. Although not in MS patient but there has
been case report of PML associated with Rituxam used in other disease (1 in 25,000
cases).
Baseline CBC, electrolyte, LFT, hepatitis B panel, beta-hCG and CD 19 should be
checked. Because of risk of hypotension during infusion one can consider holding
antihypertensive medication on the morning of infusion.
In summary:
Rituximab is an intravascular infusion which completely depletes one particular type of
white blood cell called B-cells, which has downstream effects on the rest of the immune
system. Though protocols are slightly different, in general, it is given two times twice a
year (4 infusions total), and is given in an outpatient infusion center. This is because of a
30% risk of an infusion reaction without pre-medication with some cocktail of
methylprednisolone, diphenhydramine and perhaps acetaminophen. The medication is
quite well-tolerated. There are generally no side effects to the medication. There is no
lymphoma risk with this medication. There is a baseline and 6 months blood test to
monitor the B-cell CD20 expression. Rituximab is Category C in pregnancy so may be
toxic in animals or no human data, there are no official FDA reports of birth defects in
cases of pregnancy with rituximab but babies are born with no CD20 cells. It does not
appear to increase risk of infection in babies as the cells re-populate within 6-18 months.
In monkey studies performed by the manufacturer, there was no toxicity on the fetus and
monkey babies were born with no CD20 cells, again with no infection risks. In the largest
case series published in February 2011, out of 153 women who became pregnant on
rituximab, there were 4 post-natal infections and two congenital abnormalities (1 club
foot, 1 heart defect) but these women were also on other immunosuppressant
medications during the pregnancy, including azathioprine and mycophenolate. They
concluded that rituximab does not increase the risk of congenital malformations above
the natural rate of 1-2%. Planned pregnancy is still recommended.
References:
1.http://myelitis.org/symptoms-conditions/neuromyelitis-optica/prognosis-management-nmo/
2. A retrospective study evaluated the efficacy of rituximab in 25 patients with
neuromyelitis optica (Devic’s disease). At a median follow-up of 19 months, the median
annualized posttreatment relapse rate was lower than the pretreatment rate (0 vs. 1.7,
p<0.001), and disability improved or stabilized in 20 of the 25 patients.
Jacob A, Weinshenker BG, Ivo V, McLinskey N, Krupp L, Fox R, Wingerchuk D, Boggild
M, Constantinescu C, Miller A, De Angelis T, Matiello M, Genain C, and Cree B.
Treatment of neuromyelitis optic with rituximab: retrospective analysis of 25 patients.
Archives of Neurology, 2008; 65:1443-1448. PMID 18779415
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