In the 3 years of Secukinumab’s trial data in Psoriatic Arthritis, it is reassuring to note that there is no increased signal of infections (including Tuberculosis), major cardiovascular events or malignancies when compared to placebo. Even Candida infections and colitis were very rare.
Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1
Targeting IL23 may have theoretical advantages over targeting IL17A:
1) downstream inhibition of IL22, which is believed to play a role in new bone formation and ankylosis in AS;
2) dampening of excessive and pathological IL17A production, sparing low level housekeeping IL17A maintenence of mucosal defence, thus avoiding the triggering of Inflammatory Bowel Disease which the Spondyloarthritis group of diseases are prone to. In fact, in a proof-of-concept study involving another anti-IL23, Risankizumab, it looked promising as a treatment for Crohn’s Disease.
Psoriatic Arthritis is a T-cell driven disease. It is therefore not surprising that Abatacept, a T-cell co-stimulation blocker, should work.
Finally, a highly effective oral agent for Psoriatic Arthritis, and I’m not talking about Apremilast. Efficacy evident by the second week sounds good too!
Tofacitinib blocks JAK2/TYK2 signaling, through which IL12 & IL23 activate pro-inflammatory cells. Perhaps this is how it exerts its effect against Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis.
For the more “stubborn” enthesitis, and perhaps more widespread psoriasis, the higher 10mg twice daily dose may work better.
Herpes Zoster is the infection to look out for.