Home Forums General Discussion Apremilast for Psoriatic Arthritis

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    MLTelfer
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    Hello to those dealing with psoriatic arthritis.

    According to what I have been able to determine, a new drug named Apremilast will be coming to market on March 21st. Let me say a couple words about this. I learned of this drug through researching PsA and coming across rheumatologists at the Cleveland Clinic that were excited by it’s efficacy and safety profile, so I investigated. Dafna Gladman, a rheumatologist from the University of Toronto Psoriatic Arthritis Clinic (the only one of its kind in the world) is also a proponent. This drug is labeled specifically for psoriasis and psoriatic arthritis. It is intracellular, meaning it it works INSIDE the cell rather than outside the cell like biologics. It is a pill, not an injection.

    Briefly, in secondary chemical signaling that occurs inside the cell, there is a second messenger called cyclic AMP (cAMP). cAMP helps to regulate inflammatory and anti-inflammatory protein production. In psoriatic arthritis a naturally occurring enzyme inside the cell called phosphodiesterase 4 (PDE-4) breaks down the cAMP too quickly and thus deregulates it, releasing too many inflammatory proteins and too few anti-inflammatory proteins. Apremilast suppresses the production of PDE 4 and allows the cAMP to remain active longer, thus allowing the balance of inflammatory/anti-inflammatory proteins to come back into order. In addition to internet searches of Apremilast, may I suggest two other resources for PsA sufferers. Google Celgene PDE 4 for a brief drug company presentation. Then go to youtube and watch Professor Kevin Ahearn from the University of Oregon’s biochemistry class on cell signaling 1. You will then come away with an understanding of the mechanism involved here. It also functions similarly to biologics in that it regulates TNFa but without suppressing the immune system.

    Apremilast has been effective against dactylitis too. Dactylitis is a bit of a mystery because the entire finger/toe swells up like a sausage. How is that possible? If the joints are infected, shouldn’t the fingers be swollen specifically at the locations of the distal, proximal, and metacarpophalangeal joints individually? Shouldn’t there be three swollen finger joints instead of a sausage? Well, nobody knows why exactly, but they have found the flexor tendon to be swollen and tenosynovitis has set into these fingers. Let’s talk psoriatic arthritis here. There is a theory that the infection is occurring at the entheseal insertions of the tendons into the distal (fingertip) bone and inflammatory cytokines are being released. These inflammatory cytokines migrate down the finger and swell the flexor tendon and this tendon inflammation makes the sausage instead of the individual joints. Apremilast has had great success with dactylitis, thus supporting the proposition of intracellular inflammatory mediator imbalances.

    I recommend you do your own research of course. As I have said, I too spend countless hours studying this problem. I am going to stay with AP for perhaps another year even though I have not seen a benefit yet. I am still hopeful it will bring the relief my son deserves.

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