A novel CPLA2 Inhibitor (inhibits the production of arachidonic acid) at the EULAR Meeting 2013

K. Yamanishi and colleagues presented a study [THU0223]: “The novel CPLA2 inhibitor AK106-001616 is a new category of anti-inflammatory/analgesic drug demonstrating efficacy and favorable tolerability in the treatment of rheumatoid arthritis”. “AK106-001616 (AK106) is a selective cytosolic phospholipase A2 (cPLA2) inhibitor with a novel mechanism of action as an anti-inflammatory/analgesic drug”, which inhibits production of arachidonic acid. The drug would reduce the substrate for cyclooxygenase. It would therefore act like a dietary reduction of arachidonic acid. In results we see a reduction of pain at day 28 in AK106 as in naproxen. A ACR20 response has been calculated, but not different to naproxen; perhaps I have to add, that patients had to be on background MTX. The authors concluded: “AK106 was efficacious and well tolerated by patients with RA.” There an adverse events issue concerning the GI tract in the 600 mg group, which is comparable to naproxen 500 mg bid. According to the authors, “AK106 may have a role in the treatment of RA patients”.

I wonder what this role might be. The study tells us about a pain reduction at day 28 and nothing about day 1. My guess is that it takes some time to reduce the arachidonic acid pool. It doesn’t act on the intake of arachidonic acid, so the usual diet may interfere with this novel drug. Moreover the adverse events are comparable to naproxen.

To sum it up, I don’t see an important role of AK 106 in the treatment of RA patients.