Sjogren’s Syndrome: Recognizing and Treating an Autoimmune ...
Effectiveness of rituximab treatment in primary sjogren’s syndrome
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Transcript of Effectiveness of rituximab treatment in primary sjogren’s syndrome
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Effectiveness of Rituximab Treatment in Primary Sjogren’s
Syndrome
A Randomized, Double-Blind, Placebo-Controlled Trial
ARTHRITIS & RHEUMATISMARTHRITIS & RHEUMATISM
Vol. 62, No. 4, April 2010Vol. 62, No. 4, April 2010
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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
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Drug AdministrationDrug Administration
• 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
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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
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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)
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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
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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
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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
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Randomization of patients with primary sjogren syndrome
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† P <0.05 versus placebo.
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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)
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Lacrimal Gland function
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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
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Changes in Subjective measurement
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Changes in sicca symptoms
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SF36 score for vitality and MFI for fatigue
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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
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Adverse events
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Discussion