1. Vancomycin in PSC: the counter/con perspective
James H. Tabibian, MD, PhD
Director of Endoscopy
Resident Research Director
Department of Medicine
Olive View-UCLA Medical Center
Health Sciences Clinical Associate Professor
David Geffen School of Medicine at UCLA

2. Objectives
Review cons and areas of uncertainty regarding vancomycin (vanco) on three main levels:
Drug
Patient
Public health/other.
Recognize that many of these areas crossover.
Identify potential future directions in vancomycin research.

3. Uncertainties regarding vanco in PSC: Drug-level concerns
What dose?
How many mg?
How many times per day? Every day, every other day?
Can it eventually be stopped?
After how long?
Once feeling better?
Once labs normalize?
What is the treatment endpoint/biomarker to follow?
ALP change?
Patient-reported outcomes (PROs)?
MRCP findings?

4. Uncertainties regarding vanco in PSC: Patient-level concerns
Which patients should be treated with vancomycin?
All patients?
Those with symptoms?
Those with biochemical abnormalities?
Pre-cirrhosis only?
How about if on vanco but not seeing benefit after 3 months…stop the medication? Keep going?
How to be sure it’s working?
False sense of wellbeing based on biochemistries
Even if labs improve, does this really protect against adverse outcomes/complications? (Longest vanco clinical trial 3 months)

5. Uncertainties regarding vanco in PSC: Other concerns
Selecting for a resistant bacterial organisms
Can impact patient, society.
Cost/insurance coverage
Should/will insurance cover for an off-label indication?
Provider issues
Finding a provider willing to prescribe and follow.
What does biochemical improvement (if achieved) really mean long-term? Lower risks of complications?
Providers: don’t let your guard down.
Medico-legal perspective.
Is vanco really ready for primetime?
Minocycline and metronidazole also shown biochemical improvement (ALP, bilirubin, and/or Mayo Risk score, among others) in PSC.

6. Areas for future research
Mechanistic insights into the impact of vancomycin on (the microbiome in) PSC.
Model systems
Cell culture (i.e. in vitro)
Animal models
More randomized clinical trial data
Larger studies
Longer-term studies (currently longest trial data 3 months)

7. Summary
Promising experience and data thus far with vancomycin; however, many outstanding unknowns.
Unknowns on a variety of levels; potential consequences, particularly long-term, uncertain and understudied.
Further research needed to determine if vancomycin is an safe and effective (life-prolonging) treatment, and if so, what optimal target population and regimen would be.

8. Questions?