IL12/IL23 Inhibition in the Treatment of Psoriatic Arthritis

Abstract

Psoriatic arthritis (PsA) is a potentially crippling systemic inflammatory joint disease with a heterogeneous clinical presentation that may include articular inflammation, enthesitis, dactylitis, abnormal bone turnover, and plaque psoriasis. Until very recently, patients with PsA had very few treatment options available to them and suffered immense physical and social burden from this disease. The use of anti-TNF agents offered some hope to these patients as a percentage of them found improvement of their psoriasis and psoriatic arthritis. However, over time, the biggest issue with anti-TNF drugs for PsA has been the findings that up to 50 % of patients do not respond to or do not tolerate these agents. Ustekinumab (UST) was one of the first agents to offer an alternative mechanism for the treatment of psoriasis and PsA, by blocking the IL12 and IL23 cytokines. The use of this medication relates directly to our improved understanding of the pathophysiology of psoriasis and PsA as being driven by Th1 and Th17 cells. In the PSUMMIT II study, patients naive to anti-TNF agents responded better to UST than patients who were previously treated with those medications. These data indicate that a subset of PsA patients manifest persistently active disease refractory to agents that target alternative immune inflammatory pathways not directly related to TNF. These findings have also been observed in RA. Thus, targeting more than one molecule with an antibody that recognizes two different targets or combination biologics may be required to drive higher treatment responses or even remission. Of course, a major obstacle aside from safety is cost; on average UST, the 90-mg dose can be significantly more expensive compared to anti-TNF agent. However, as new safe and efficacious agents become available for the treatment of psoriasis and PsA, our treatment algorithm for the treatment of PsA will need to be re-evaluated.