JVD 2013 Flashcards
In Lommer’s Efficacy of Cyclosporine for Chronic, Refractory Stomatitis in Cats: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study
MEAN IMPROVEMENT in SDAI (stomatitis disease activity index) scores after 6 weeks was ___% for cats receiving 2.5mg/kg Cyclosporin bid.
Was this significantly more than the cats in the placebo group?
52%
Yes
In Lommer’s Efficacy of Cyclosporine for Chronic, Refractory Stomatitis in Cats: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study
What was the range of trough levels of cats given 2.5mg/kg bid?
32 ng/mL to 1576 ng/mL
In Lommer’s Efficacy of Cyclosporine for Chronic, Refractory Stomatitis in Cats: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study
True of false:
At the end of the 6 week observation period, there was a statistically significant difference among cats with trough whole-blood cyclosporine levels > 300 ng/ml (72.3 % improvement) compared with cats with cyclosporine levels < 300 ng/ml (28.2 % improvement)
True
What are the common inflammatory mediators that have been identified as increased in feline stomatitis cases?
IL-2, IL-4, IL-6, IL-10, IL-12 and IFN-γ
True or false:
Predominant cells infiltrating the caudal oral mucosa in affected cats are primarily CD79a+ IgG isotype plasma cells, along with CD8+ (cytotoxic) T cells, supporting the hypothesis that viral infection may be one initiating factor in the development of this disease
True
What are the predominant cells infiltrating the caudal oral mucosa in affected cats?
rimarily CD79a+ IgG isotype plasma cells, along with CD8+ (cytotoxic) T cells,
What is the percentage of cats that have been reported to have refractory stomatitis after caudal and full mouth extractions?
20-40%
What percentage of cats with chronic stomatitis will significantly improve following extraction of all premolar and molar teeth?
60-80%
True or false:
Cyclosporine is a hydrophilic, cyclic peptide derived from fungi
False
Cyclosporine is a LIPOPHILIC, cyclic peptide derived from fungi
Describe the pharmokinetic effect of cyclosporin to control Stomatitis.
REDUCES IL-2 and IL-4; thereby also reducing T-cell numbers/proliferation.
Cyclosporine inhibits T cell activation by blocking the _transcription of genes codin_g for specific pro-inflammatory cytokines, including IL-2 and IL-4
Its mechanism of action is partially through INHIBITION of calcineurin,
(Calcineurin is a calcium-binding cytoplasmic protein which dephosphorylates nuclear factor of activated T cells (NFAT), allowing NFAT to enter the cell nucleus and initiate cytokine gene expression).
By reducing activated T cell secretion of IL2 - it reduces the positive feedback loop, thereby reducing T cell proliferation.
Calcineurin is also involved in B-cell receptor induced proliferation. So Cyclosporin has been shown to inhibit B cell production in vitro.
In Lommer’s Efficacy of Cyclosporine for Chronic, Refractory Stomatitis in Cats: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study
How many cats in the treatment group required rescue pain meds?
How many in the placebo group?
Was this a statistically significant difference?
None of the cats in the treatment group
4/7 (57%) of cats in the placebo group required rescue medication
Yes, this difference is statistically significant.
In Lommer’s Efficacy of Cyclosporine for Chronic, Refractory Stomatitis in Cats: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study
There was a large variability in cyclosporin levels at 2.5mg/kg bid. Was there a statistically significant difference in mean improvement in cats with levels >300ng/ml vs those with levels <300ng/ml?
Yes! There was a statistically significant difference.
Mean improvement for 5/9 cats with >300ng/ml was 72%
Those (4.9) <300ng/ml mean improvement was only 28%
In In Lommer’s Efficacy of Cyclosporine for Chronic, Refractory Stomatitis in Cats: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study
There was a large variability in cyclosporin levels at 2.5mg/kg bid. in cats that had poor improvement and had low trough levels of cyclosporin IN THE TREATMENT GROUP – did these cats acheive trough levels of >300ng/ml and improve after dose was increased to 5mg/kg bid?
Yes – trough levels increased to >300ng/ml after the dose increase and after another 6 weeks of treatment, the mean improvement in these cats was 53.5%
In In Lommer’s Efficacy of Cyclosporine for Chronic, Refractory Stomatitis in Cats: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study
Cats in the placebo group were put on cyclosporin at 2.5mg/kg bid for 6 weeks. Did these cats show improvement?
Yes.
Although one cat did not show improvement and failed to acheive trough levels of >300ng/ml even after increasing dose to 5mg/kg bid.
In In Lommer’s Efficacy of Cyclosporine for Chronic, Refractory Stomatitis in Cats: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study
What percentage of the treated cats acheived a trough level of >300ng/mL of cyclosporin at 2.5mg/kg bid dosing?
5/9 cats acheived trough levels of >300ng/mL = 56%
