Use of Rituximab as novel treatment for sjogren

1. Effectiveness of Rituximab Treatment in
Primary Sjogren’s Syndrome
A Randomized, Double-Blind, Placebo-
Controlled Trial
AARRTTHHRRIITTIISS && RRHHEEUUMMAATTIISSMM
VVooll.. 6622,, NNoo.. 44,, AApprriill 22001100

2. Study Eligibility
• Inclusion criteria:
– >18yr
– American-European consensus group criteria for primary
sjogren syndrome
– Rate of secretion of stimulated whole saliva >0.15ml/min
– Positive Anti –SSA and or Anti SSB
– Positive IgM RF
– Positive salivary gland biopsy within last 12 months
– Contraception through entire duration
– No DMARDS 1-6 months prior to study
– Baseline echo and cxr
• Exclusion criteria
– Prior failure to Rituximab
– Chronic systemic illness, malignancy, immune dysfunction,
chronic or latent infection

3. DDrruugg AAddmmiinniissttrraattiioonn
• 20 patients in study group and 10 patients in placebo
arm
• 1,000mg Rituximab infusion on day 1 and day 15
• Pretreatment
– Methylprednisolone 100mg IV, acetaminophen
1000mg orally and clemastine (non selective H1
blocker) 2mg IV
– Prednisone 60mg on days 1,2,3
– 30mg on days 3 and 4
– 15mg on days 5
• Artificial eye drop and saliva on same dose

4. Outcome Meaures
• Primary end point
– Significant improvement in the secretion of
stimulated whole saliva flow rate (ml/min)
• Secondary end point
– Assessment of salivary gland function
– Immunologic parameters
– Subjective response parameters
• Assessment scheduled at baseline, 5, 12, 24, 28
weeks

5. Determination of Salivary and
Lacrimal Function
• Quantitative measurement of whole saliva, parotid,
submandibular/sublingual saliva
• Tested at same time (1-4pm), unstimulated saliva
collected in cups and syringes for 5 minutes
• 10 minutes stimulation with 2% citric solution
• Flow rate and composition by standardized method( not
discussed)
• Schrimer’s test I, Lissamine green test and 1%
Fluorescien Breakup time( BUT)

6. Lissamine green test
• Instillation of 1% lissamine
green in both eyes
• After 1 or 2 full blinks, the
intensity of staining of both
medial and lateral bulbar
conjunctiva and the cornea
was scored
• maximum score of 9 points (up
to 3 points for each section)
• 1 sparsely scattered, 2 densely
scattered, 3 confluent

7. Fluorescien Breakup time
(BUT)
• Interval between a complete
blink and the appearance of
the first randomly
distributed dry spots
• Assessed by instilling a 1%
fluorescein solution in the
fornix of both eyes
• The patient was asked to
blink a few times, after
which the interval in
• seconds between the last
blink and the first break in
the tear film was measured
Patients with a tear-film
breakup time of less than five
seconds can be diagnosed with
dry eye

8. Laboratory and subjective
assessment
• CBC, Immunoglobulins, IgM-RF
• Circulating CD19, CD4, CD8 B cells
• Multifunctional Fatigue inventory
• Oral and ocular sicca VAS 100mm
• Extra glandular manifestations reported as present or absent
• Serum sickness: low complements, Dec PLTS and arthritis
after infusions
• Termination if Serum sickness in 2/9 after 1St and 3/29 after
2nd infusion
• Compared form baseline from the same cohort and from
other arm

9. Randomization of patients with primary sjogren syndrome

10. † P <0.05 versus placebo.

11. Results: Salivary Gland function
• Primary end point: compared to baseline had statistially significant
improvement @5 weeks (P=0.01) and @ 12 weeks (P=0.004)
• These values decreased in placebo arm (progression of disease)
• Mean change from baseline in the group was significant (P=0.038)
• Submandibular/sublingual flow rate significantly increased ( data not
shown)

12. Lacrimal Gland function

13. Changes in Laboratory variables
•Mean change in RF ; P< 0.05)
•Same patterns of change for Immunoglobulins
•Significant change in the MFI score, and improvement in SF 36 scores

14. Changes in Subjective measurement

15. Changes in sicca symptoms

16. SF36 score for vitality and MFI for fatigue

17. Extra glandular manifestations
Significant decrease several extra glandular
manifestations
• Vasculitis @ 24 week (P=0.03)
• Reynaud's (P= 0.057)
• Tendomyalgia (P=0.074)
• Arthralgia (P = 0.058)
• Neuropathy and arthritis improved

18. Adverse events

19. Discussion