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Year in Review - Part 1 - PDE4 for Psoriatic Arthritis

Dr. Andy Thompson  Featured
November 16 2014 1:40 PM ET via RheumReports RheumReports

Rheumatologists have traditionally used DMARDs to treat patients with PsA. In 2002 the biologic era started with the approval of Etanercept for PsA. In 2014, the latest addition, Apremilast, was approved by the FDA.

Cyclic-AMP (cAMP) causes a downregulatory signal in immune cells, thus suppressing the production of proinflammatory mediators, including tumor necrosis factor (TNF)-α, interleukin (IL)-17, and interferon (IFN)-γ. It is also believed that cAMP promotes the production of anti-inflammatory mediators such as IL-10. Therefore cAMP is good to have around to downregulate inflammation.

cAMP is degraded to 5-AMP by PDE4 (phosphodiesterase-4). Apremilast is an inhibitor of PDE4 which ultimately keeps more cAMP around which is good.

The FDA approval for Apremilast was based on 3 Randomized Double Blind Placebo Controlled Trials including 1493 active PsA patients refractory to DMARDs.

The main trial reviewed in this talk was the PALACE 1 Trial (Kavanaugh A et al, Ann Rheum Dis 2014;73:1020-1026).

The primary outcome for this trial was the ACR20 at week 16. Overall, Apremilast 30 mg BID achieved an ACR 20 of 40% vs 19% for PBO (p<0.001). There were also significant improvements in secondary measures such as physical function and psoriasis. 

GI events were the most commonly reported adverse events and were early and self-limiting.

There were no differences in serious adverse events including malignancy & serious infection.


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About the Author

Dr. Andy Thompson
Dr. Andy Thompson

Dr. Andy Thompson is an Associate Professor at Western University and founder of Rheuminfo.com, Rheumtalks.com, and RheumReports.com.

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