Contributions
Abstract: P1268
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Plasma cytokines concentrations provide markers of inflammatory response in relapsing-remitting multiple sclerosis (RR-MS) patients.
Objective: Here we explore pharmacodynamic effects of dimethylfumarate (DMF) on plasma cytokines. We have tested specifically for decreases in Th1- and Th17- associated cytokines and increases in those associated with the Th2- response.
Methods: Whole blood was taken at baseline and 6 weeks post treatment with dimethyl fumarate from 31 relapsing-remitting MS patients (RR-MS). Blood also was taken from 10 age- and sex-matched volunteers at the same times. Plasma was extracted and cytokine and inflammatory markers were measured using the Meso Scale Discovery (MSD) V-PLEX Human Biomarker 40-Plex Kit. Paired analyses were performed using nonparametric Wilcoxon 2-sample test. Comparisons between groups were performed using Student"s t-test with a significance threshold of p-value < 0.05.
Results: At baseline, patients had higher plasma concentrations of IL-2 than did the healthy volunteers ([0.56 pg/ml vs 0.29 pg/ml], 1.9-fold difference, p < 0.05).
An increase in cytokine expression of IL-4 (36%) [0.05 pg/ml (pre), 0.07 pg/ml (post)] and IL-13 (21%) [1.5 pg/ml (pre), 1.8 pg/ml (post)] were found after treatment with dimethyl fumarate (p < 0.05). Significant decreases in IFNγ (a marker of Th1 activity) or IL-17, GM-CSF or IL-22 (markers of Th17 response) were not found.
Conclusion: Increases in the Th2 associated plasma cytokines IL-4 and IL-13 were found with short-term dimethyl fumarate treatment. We did not find evidence for concomitant decreases in Th1 and Th17 inflammatory markers. Further work is needed to assess whether the peripheral Th2 cytokine changes are sustained or associated directly with clinical responses.
Disclosure:
Arie Gafson: Nothing to disclose.
Richard Nicholas: RN acknowledges research support from Biogen and Teva and has received honoraria or speakers fees from Bayer, Biogen, Merck, Genzyme and Novartis
Gavin Giovannoni: Gavin Giovannoni has received compensation for serving as a consultant from AbbVie, Bayer Schering Healthcare, Biogen, Canbex, Eisai, Elan, Five Prime Therapeutics, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Ironwood Pharmaceuticals, Merck-Serono, Novartis, Pfizer, Roche, Synthon BV, Teva Pharmaceutical Industries, UCB and Vertex Pharmaceuticals.
Paul Matthews: PMM acknowledges research support from Biogen and GlaxoSmithKline and has received honoraria or speakers fees from Novartis, Biogen, IXICO, Adelphi Communications and Transparency Life Sciences.
Abstract: P1268
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: Plasma cytokines concentrations provide markers of inflammatory response in relapsing-remitting multiple sclerosis (RR-MS) patients.
Objective: Here we explore pharmacodynamic effects of dimethylfumarate (DMF) on plasma cytokines. We have tested specifically for decreases in Th1- and Th17- associated cytokines and increases in those associated with the Th2- response.
Methods: Whole blood was taken at baseline and 6 weeks post treatment with dimethyl fumarate from 31 relapsing-remitting MS patients (RR-MS). Blood also was taken from 10 age- and sex-matched volunteers at the same times. Plasma was extracted and cytokine and inflammatory markers were measured using the Meso Scale Discovery (MSD) V-PLEX Human Biomarker 40-Plex Kit. Paired analyses were performed using nonparametric Wilcoxon 2-sample test. Comparisons between groups were performed using Student"s t-test with a significance threshold of p-value < 0.05.
Results: At baseline, patients had higher plasma concentrations of IL-2 than did the healthy volunteers ([0.56 pg/ml vs 0.29 pg/ml], 1.9-fold difference, p < 0.05).
An increase in cytokine expression of IL-4 (36%) [0.05 pg/ml (pre), 0.07 pg/ml (post)] and IL-13 (21%) [1.5 pg/ml (pre), 1.8 pg/ml (post)] were found after treatment with dimethyl fumarate (p < 0.05). Significant decreases in IFNγ (a marker of Th1 activity) or IL-17, GM-CSF or IL-22 (markers of Th17 response) were not found.
Conclusion: Increases in the Th2 associated plasma cytokines IL-4 and IL-13 were found with short-term dimethyl fumarate treatment. We did not find evidence for concomitant decreases in Th1 and Th17 inflammatory markers. Further work is needed to assess whether the peripheral Th2 cytokine changes are sustained or associated directly with clinical responses.
Disclosure:
Arie Gafson: Nothing to disclose.
Richard Nicholas: RN acknowledges research support from Biogen and Teva and has received honoraria or speakers fees from Bayer, Biogen, Merck, Genzyme and Novartis
Gavin Giovannoni: Gavin Giovannoni has received compensation for serving as a consultant from AbbVie, Bayer Schering Healthcare, Biogen, Canbex, Eisai, Elan, Five Prime Therapeutics, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Ironwood Pharmaceuticals, Merck-Serono, Novartis, Pfizer, Roche, Synthon BV, Teva Pharmaceutical Industries, UCB and Vertex Pharmaceuticals.
Paul Matthews: PMM acknowledges research support from Biogen and GlaxoSmithKline and has received honoraria or speakers fees from Novartis, Biogen, IXICO, Adelphi Communications and Transparency Life Sciences.