Comprehensive Coverage of Rituximab in TAO

1. RITUXIMAB IN TAO
DR LAVANYA BONNY
SR, DEPT OF ENDOCRINOLOGY
ST JOHNS MEDICAL COLLEGE
BANGALORE

2. INTRODUCTION
◦ chimeric mouse-human monoclonal antibody
◦ composed of an antigen binding region of murine origin and a constant region of human Ig G1
◦ target - CD20, a B-cell surface marker that is found on pre-B and B cells, but not stem cells or
plasma cells.

3. MECHANISM OF ACTION
◦ depletes more than 95% of CD 20-expressing B cells from the stages of immature to mature B
cells, but not antibody-producing plasma cells
◦ within days of administration and lasts approximately 4–6 months
◦ replenished by new CD20 + B cells from differentiation of progenitor cells after 4-6 months

4. MECHANISM OF ACTION
◦ interfere with the production of inflammatory cytokines and with B cell-driven antigen
presentation
◦ RTX might cause depletion of autoreactive T cells also.

5. IN TAO
◦ 49 patients treated with RTX have been reported in uncontrolled studies.
◦ Overall, significant GO inactivation was observed in about 90% of patients
◦ infusion-related side effects (both minor and major) were reported in about 30% of the patient
◦ disease relapse has not been observed in any of the reported patients, even after a long follow-
up period (52–76 weeks)

6. IN TAO
◦ Total peripheral B cell depletion was reported even after a very low dose of RTX (100mg) by
Salvi et al. in two patients in whom RTX infusion had to be discontinued due to the occurrence
of cytokine release reaction.
◦ GO inactivation occurred within a few weeks, though dose was about 20 times less than the
standard dose

7. IN TAO
◦ Factors favoring better response
◦ younger patients
◦ lower TRAb
◦ shorter duration of disease
◦ RTX might be considered as second-line intervention in patients with moderate-to-severe, early
and active disease that has failed initial therapy

8. DOSING REGIMEN
◦ four consecutive weekly intravenous infusions of 375 mg/m2 of body surface area (typically
used for haematologic disorders)
◦ two intravenous infusions of 1000 mg given 2 weeks apart (typically used in autoimmune
disease)
◦ other dosing regimens -100 mg once
◦ Infusion times range from 3 to 4 hours

10. ADVERSE EFFECTS
◦ MC - mild infusion-related reactions
◦ transient fever (30% of patients), chills (23%), asthenia (23%), and pruritis (20%).
◦ Infusion-related events (on the infusion day) - fever, chills, pain, and throat irritation
◦ usually resolve in less than 1 week without treatment or without interrupting the infusion
◦ May include hypotension

11. ADVERSE EFFECTS
◦ incidence of high-sensitivity reactions decreased with subsequent infusions
◦ premedication recommended
◦ may cause or aggravate inflammatory bowel disease such as ulcerative colitis
◦ arthralgias due to circulating immune complexes

12. ADVERSE EFFECTS
◦ severe infections - associated to concurrent therapy with steroids or other immunosuppressants
◦ progressive multifocal leukoencephalopathy (PML) has rarely been reported in patients
previously treated with other immunosuppressive drugs

13. RITUXIMAB AND DON
◦ Failure of RTX was reported in one patient whose GO progressed to acute DON and in one who
already had DON and failed to improve on RTX despite achieving peripheral B cell depletion.
◦ another ten patients with DON reviewed by Salvi et al. have responded to RTX with
improvement of their visual sight.
◦ No formal trial has addressed the use of RTX in DON

14. RITUXIMAB AND DON
◦ transient increase in proptosis in 3 RTX treated patients in US trial - noticeable at 24 weeks and
it regressed thereafter.
◦ no such case was noted in placebo group
◦ one RTX-treated patient in Italian trial had transient increase of proptosis, with return to baseline
at 52 weeks.

15. RITUXIMAB AND DON
◦ This suggests that in some patients, RTX may induce an increase in the intra-orbital tissue
volume that can lead to anterior displacement of the eye globe with increase in proptosis.
◦ In cases where the orbit cannot accommodate this ‘natural decompression’, the likelihood of
DON increases
◦ Esp if DON is present at a subclinical stage and cannot be recognized easily

16. RITUXIMAB AND DON
◦ 2 patients in the Italian trial, both affected with unilateral GO, developed transient visual loss
right after the infusion
◦ RTX can cause rapid edema of orbital tissue with consequent volume shift due to massive lysis
of B cells mostly occurring in patients with a large intra-orbital lymphocytic infiltration

17. THANK YOU