KOCHI-2016:Sjogren’s Syndrome- Is disease modification possible?

DR SUNDEEP UPADHYAYA-MD,DMASSOCIATE PROF-AHERF

INDRAPRASTHA HOSPITAL-NEW DELHI

WHAT IS THE CENTRAL IDEA OF THIS TALK?

• Restoration of GLANDULAR dysfunction is the principal goal of SS management

• Effective therapies- available with FDA approval are oral cholinergic muscarinic agonists (Pilocarpine, Cevimeline)

• But Secretagogue therapies DO NOT reduce inflammation in SS!!!

• Do c-DMARDs or b-DMARDs have immunomodulatory effect in SS?

AND THAT IS THE DIFFERENCE !!!

• SYMPTOM MODIFYING EFFECT

VS•DISEASE MODIFYING

EFFECT

Question 1

• One of these is the latest classification criteria for primary Sjogren’s syndrome:

1) AECG or the American-European consensus group criteria-

2) SICCAC-Sjogren’s International Collaborative Clinical Alliance Cohort-

3) ACR/EULAR consensus criteria for Sjogren’s syndrome

Primary Sjogren’s : Major Problems related to conduct of drug trials

• Rarer than RA : majority of studies 40 to 50 pts and ~100 is max

• Definition of early and late disease• Inclusion Criteria-AECG now modified –

ACR/EULAR 2016- 4 point system with salivary flow0.1mlper mt/schirmer test 5mm ; Ocular Staining 5(one point each) + Biopsy salivary gland/ Anti-Ro/SSA (3 points each)

Primary Sjogren’s : Major Problems related to conduct of drug trials

• Study-Trial Design:Uncontrolled vs DBCT same agent, different results• Outcome measures: tear production and

saliva production measurements not standardized

Question 2

• Which of the following is true regarding “disease modification” of primary Sjogren’s syndrome(SS)?

1)Biologic agents (eg Rituximab)have disease modifying effects on the SICCA symptoms of SS2)Biologic agents (eg Rituximab)have disease modifying effects on the systemic features of SS3)None of the above

c-DMARDs in management of Sjogren’s Syndrome

HCQ- (JAMA-2014)JOQUER-(120patients)3yrs, DB parallel2008-2011, 24 weeks>30% improvement in 2/3 –PAIN, FATIGUE and DRYNESS but not for systemic fs, SSA and IgG.“NOT MORE EFFECTIVE THAN PLACEBO!!”

c-DMARDs in management of Sjogren’s Syndrome

• METHOTREXATE- used for SS > 35 yrsOpen label one year-18 ptsSubjective improvement+ but no objective as measured by Schirmer’s, Rose Bengal and BUT

Efficacy in primary SS unknown/suspect-but deserves a shot in SS DBCT-trial.

BIOLOGICS in Primary Sjogren’s Syndrome-ANTI-TNF

• INFLIXIMAB• ETANERCEPT

Results dismal: given up for good!

What excited interest in Rituximab for Sjogrens Syndrome ?

–Rituximab in SS (systemic disease)

Efficacy chart

RITUXIMAB in Sjogren’s Syndrome-2014 (2011-2013, UK)

RITUXIMAB-SS-”TRACTISS”

“TRACTISS”-Rituximab in SS

TRACTISS-FINAL RESULTS-2015 end

• “BRITISH SOCIETY RHEUMATOLOGY 2016- GLASGOW”

• SICCA Features and fatigue no different than placebo

• ESSDAI also no significant change

Other Biologics-Potential phase III

• BIOLOGICS-ABATACEPT-RA associated Sjogren’s Syndrome (ROSE)

• Promising results from phase II• Multi-Centre 42 –Phase III clinical trial, 88

patients- ONGOING: (NA, SA, Europe, Asia-Pacific)

• 2020-BMS

BELIMUMAB-BLyS or BAFF inhibitor

• Phase II-BELISS• 30 patients• Both ESSPRI and ESSDAI • Justifies onward march to phase III

Ann Rheum Dis.2015;74(3):526-31

Newer Agents-BMS-986142(kinase Inhibitor) and Peptides

• BMS-986142 is a Btk inhibitor-(targeted synthetic DMARD)

• 34 locations Mexico, Chile, Russia, Poland, Australia etc

• PEPTIDES-”LupozorTM” phase II for lupus but also SS phase II

• Stimulation of T-Regs

SUMMARY of SS management

• 1) FATIGUE-exercise and self care. HCQ may be considered

• 2) MSK- First line HCQ later add MTX, corticosteroids etc

• 3) SICCA symptoms-Rituximab may be considered where conventional therapies fail. Systemic manifestions, rituximab role +

• 4) ANTI-TNF –should not be used to treat Sicca

BATTLE BORN-Five finger Death Punch

• Been to a thousand places, Shook a million hands

• Don’t know where I am going, but I know where I have been

• Everyday a castaway, a vagabond; I am BATTLE BORN