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The pharmacodynamic impact of apremilast, an oral phosphodiesterase 4 inhibitor, on circulating levels of inflammatory biomarkers in patients with psoriatic arthritis: substudy results from a phase III, randomized, placebo-controlled trial (PALACE 1).

Schafer PH, Chen P, Fang L, Wang A, Chopra R - J Immunol Res (2015)

Bottom Line: At Week 24, IL-8, TNF-α, IL-6, MIP-1β, MCP-1, and ferritin were significantly reduced from baseline with apremilast 20 mg BID or 30 mg BID versus placebo.ACR20 response correlated with change in TNF-α level with both apremilast doses.At Week 40, IL-17, IL-23, IL-6, and ferritin were significantly decreased and IL-10 and IL-1 receptor antagonists significantly increased with apremilast 30 mg BID versus placebo.

View Article: PubMed Central - PubMed

Affiliation: Translational Development, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA.

ABSTRACT
Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo) for treatment of active psoriatic arthritis in the psoriatic arthritis long-term assessment of clinical efficacy (PALACE) phase III clinical trial program. Pharmacodynamic effects of apremilast on plasma biomarkers associated with inflammation were evaluated in a PALACE 1 substudy. Of 504 patients randomized in PALACE 1, 150 (placebo: n = 51; apremilast 20 mg BID: n = 51; apremilast 30 mg BID: n = 48) provided peripheral blood plasma samples for analysis in a multiplexed cytometric bead array assay measuring 47 proteins associated with systemic inflammatory immune responses. Association between biomarker levels and achievement of 20% improvement from baseline in modified American College of Rheumatology (ACR20) response criteria was assessed by logistic regression. At Week 24, IL-8, TNF-α, IL-6, MIP-1β, MCP-1, and ferritin were significantly reduced from baseline with apremilast 20 mg BID or 30 mg BID versus placebo. ACR20 response correlated with change in TNF-α level with both apremilast doses. At Week 40, IL-17, IL-23, IL-6, and ferritin were significantly decreased and IL-10 and IL-1 receptor antagonists significantly increased with apremilast 30 mg BID versus placebo. In patients with active psoriatic arthritis, apremilast reduced circulating levels of Th1 and Th17 proinflammatory mediators and increased anti-inflammatory mediators.

No MeSH data available.


Related in: MedlinePlus

Mean percent change in biomarkers with apremilast 20 mg BID and apremilast 30 mg BID at Week 40; no patients were receiving placebo at this time point. *P < 0.05 Wilcoxon signed rank test (two-sided P value for testing the median of zero).
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fig3: Mean percent change in biomarkers with apremilast 20 mg BID and apremilast 30 mg BID at Week 40; no patients were receiving placebo at this time point. *P < 0.05 Wilcoxon signed rank test (two-sided P value for testing the median of zero).

Mentions: Six biomarkers (IL-6, IL-17, IL-23, ferritin, IL-10, and IL-1RA) exhibited significant changes (versus baseline) at Week 40 among patients who received apremilast 20 mg BID or 30 mg BID (Figure 3). At this time point, there was no longer any placebo-treated group for comparison, because all placebo-treated subjects were rerandomized to receive apremilast 20 mg BID or 30 mg BID at Week 16 (early escape) or Week 24 (the final visit for the placebo-controlled portion of the study). With apremilast treatment, the biomarker change from baseline varied over time. For some analytes, differential effects of apremilast 20 mg BID and 30 mg BID doses were observed (Figures 4(a)–4(f)). Changes in biomarkers that were maintained over time to Week 40 with apremilast 20 mg BID and/or 30 mg BID included, but were not limited to, decreases in IL-17, IL-6, and ferritin, and increases in IL-10 and IL-1RA (Figure 4).


The pharmacodynamic impact of apremilast, an oral phosphodiesterase 4 inhibitor, on circulating levels of inflammatory biomarkers in patients with psoriatic arthritis: substudy results from a phase III, randomized, placebo-controlled trial (PALACE 1).

Schafer PH, Chen P, Fang L, Wang A, Chopra R - J Immunol Res (2015)

Mean percent change in biomarkers with apremilast 20 mg BID and apremilast 30 mg BID at Week 40; no patients were receiving placebo at this time point. *P < 0.05 Wilcoxon signed rank test (two-sided P value for testing the median of zero).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4417944&req=5

fig3: Mean percent change in biomarkers with apremilast 20 mg BID and apremilast 30 mg BID at Week 40; no patients were receiving placebo at this time point. *P < 0.05 Wilcoxon signed rank test (two-sided P value for testing the median of zero).
Mentions: Six biomarkers (IL-6, IL-17, IL-23, ferritin, IL-10, and IL-1RA) exhibited significant changes (versus baseline) at Week 40 among patients who received apremilast 20 mg BID or 30 mg BID (Figure 3). At this time point, there was no longer any placebo-treated group for comparison, because all placebo-treated subjects were rerandomized to receive apremilast 20 mg BID or 30 mg BID at Week 16 (early escape) or Week 24 (the final visit for the placebo-controlled portion of the study). With apremilast treatment, the biomarker change from baseline varied over time. For some analytes, differential effects of apremilast 20 mg BID and 30 mg BID doses were observed (Figures 4(a)–4(f)). Changes in biomarkers that were maintained over time to Week 40 with apremilast 20 mg BID and/or 30 mg BID included, but were not limited to, decreases in IL-17, IL-6, and ferritin, and increases in IL-10 and IL-1RA (Figure 4).

Bottom Line: At Week 24, IL-8, TNF-α, IL-6, MIP-1β, MCP-1, and ferritin were significantly reduced from baseline with apremilast 20 mg BID or 30 mg BID versus placebo.ACR20 response correlated with change in TNF-α level with both apremilast doses.At Week 40, IL-17, IL-23, IL-6, and ferritin were significantly decreased and IL-10 and IL-1 receptor antagonists significantly increased with apremilast 30 mg BID versus placebo.

View Article: PubMed Central - PubMed

Affiliation: Translational Development, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA.

ABSTRACT
Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo) for treatment of active psoriatic arthritis in the psoriatic arthritis long-term assessment of clinical efficacy (PALACE) phase III clinical trial program. Pharmacodynamic effects of apremilast on plasma biomarkers associated with inflammation were evaluated in a PALACE 1 substudy. Of 504 patients randomized in PALACE 1, 150 (placebo: n = 51; apremilast 20 mg BID: n = 51; apremilast 30 mg BID: n = 48) provided peripheral blood plasma samples for analysis in a multiplexed cytometric bead array assay measuring 47 proteins associated with systemic inflammatory immune responses. Association between biomarker levels and achievement of 20% improvement from baseline in modified American College of Rheumatology (ACR20) response criteria was assessed by logistic regression. At Week 24, IL-8, TNF-α, IL-6, MIP-1β, MCP-1, and ferritin were significantly reduced from baseline with apremilast 20 mg BID or 30 mg BID versus placebo. ACR20 response correlated with change in TNF-α level with both apremilast doses. At Week 40, IL-17, IL-23, IL-6, and ferritin were significantly decreased and IL-10 and IL-1 receptor antagonists significantly increased with apremilast 30 mg BID versus placebo. In patients with active psoriatic arthritis, apremilast reduced circulating levels of Th1 and Th17 proinflammatory mediators and increased anti-inflammatory mediators.

No MeSH data available.


Related in: MedlinePlus