Rituximab in vasculitis

1. Rituximab in Vasculities
Prof. Ahmed M Badheeb, MD.
Professor Of Oncology/Internal Med.

2. • Rituximab — Rituximab has been compared
with cyclophosphamide as initial immunosuppressive
therapy in two randomized trials. Rituximab has been
established for induction therapy but not maintenance
of remission.
• Rituximab as initial therapy — Two randomized trials
that compared rituximab with either oral or
intravenous cyclophosphamide found equivalent
efficacy and tolerability, although rituximab was
superior in inducing remission in patients with relapsed
disease. The data are presented elsewhere. (See "Initial
immunosuppressive therapy in granulomatosis with
polyangiitis and microscopic polyangiitis".)

3. Rituximab as maintenance therapy
• Data are limited on the role of rituximab for maintenance therapy
• A retrospective study reported the results
of rituximab administration to 39 patients who already had
induction of complete or partial remission; approximately 90
percent were still being treated
with cyclophosphamide and prednisone [4]. The rituximab regimen
consisted of two 1 g doses given two weeks apart or four weekly
doses of 375 mg/m2, followed by 1 g every four months. Rituximab
therapy was associated with control of disease activity and allowed
reduction or withdrawal of other immunosuppressive agents. Only
3 of 39 patients had non-organ-threatening flares; no patient had
organ-threatening disease and there were no recurrences of renal
disease, and at two years, the proportion of patients treated with
cyclophosphamide had fallen to 30 percent.

4. Rituximab
• Rituximab was generally well tolerated; two
patients developed late-onset neutropenia and
one patient developed cytomegalovirus colitis.
• ●In another study, rituximab was administered in
variable doses as maintenance therapy to 28
patients, most of whom had also received
rituximab for induction [5]. Organ-threatening
relapses occurred in two patients (7 percent), and
the drug was generally well tolerated.
• ".)

5. The safety of repeated dosing
of rituximab
• in patients with GPA and MPA is being
evaluated in the MAINtenance of remission
using RITuximab in Systemic ANca-associated
vasculitis (MAINRITSAN) trial.

6. Safety
• When used as initial therapy for GPA or MPA,
the frequency of adverse events associated
with rituximab and cyclophosphamide appear
to be equivalent.
• The safety of rituximab as compared with oral
(not intravenous) cyclophosphamide has been
evaluated through 18 months of follow-up;
this is discussed elsewhere

7. The long-term safety of rituximab
• The long-term safety of rituximab in patients
with GPA or MPA has yet to be defined.
Limited observational data suggest that
rituximab may be associated with a high rate
of late-onset neutropenia and severe
infections when used to treat GPA, MPA, or
other rheumatic diseases. As examples:

8. Late-onset neutropenia
• Late-onset neutropenia was noted in 3 of 13
patients (23 percent) with GPA who were
treated with rituximab and followed for at
least 12 months .
• Neutropenia developed a median of 102 days
after the final dose of rituximab. The rate of
late-onset neutropenia was less in the series
mentioned above (5 percent).

9. combination therapy
with rituximab and glucocorticoids
• In a large series of patients with cryoglobulinemic
vasculitis (not GPA or MPA), combination therapy
with rituximab and glucocorticoids was
associated with a higher rate of severe infections
than cyclophosphamide combined with
glucocorticoids (29 versus 7 percent) .
• Other adverse effects associated
with rituximab therapy, such as infusion
reactions, impairment of vaccination responses,
and allergic reactions are reviewed elsewhere.

10. long-term adverse consequences
of cyclophosphamide
• On the other hand, the long-term adverse
consequences of cyclophosphamide therapy
are well established and include bone marrow
suppression, infertility, and malignancy
(bladder cancer, myelodysplasia and acute
leukemia)

11. Vasculitis
• Granulomatosis with polyangiitis: Treatment of
granulomatosis with polyangiitis (GPA; Wegener
granulomatosis) (in combination with glucocorticoids).
• Microscopic polyangiitis: Treatment of microscopic
polyangiitis (MPA) (in combination with
glucocorticoids).
• Rheumatoid arthritis: Treatment of moderately to
severely active rheumatoid arthritis (in combination
with methotrexate) in adult patients with inadequate
response to one or more TNF antagonist therapies.

12. Rituximab + steroids as a first-line
immunosuppressant.
• BMJ Case Rep. 2017 Jan 10;2017. pii: bcr2016217313. doi: 10.1136/bcr-
2016-217313.
• Successful treatment of Takayasu arteritis with rituximab as a first-line
immunosuppressant.
• O'Connor MB1,2, O'Donovan N3, Bond U2, Phelan MJ1,2.
• Author information
• Abstract
• Takayasu arteritis is a rare large vessel vasculitis which has traditionally
been treated with high-dose steroids. There have been a small number of
publications where biological agents have been used to manage refractory
cases. To the authors knowledge, there are no publications using biological
agents in combination with steroids as a first-line treatment in Takayasu
arteritis. In this publication, we document the case of Takayasu arteritis, in
a 39-year-old woman, where rituximab was used in combination with
steroids as a first-line agent in the setting of poorly controlled bipolar
affective disorder.