At Dermatology Update in Toronto on Sept. 25, 2015, Dr. Kim Papp outlined his predictions about the future of psoriasis research and treatment.
As part of a larger presentation on the history of psoriasis, Dr. Papp, director of Probity Medical Research in Waterloo, Ont., listed a number of topics that are experiencing a lot of mention in the psoriasis literature, and then extrapolated from there to speculate on what the future might hold.
Anti-IL-17 drugs. Many anti-interleukin(IL)-17 molecules already exist, and there is extensive mention of them in the current literature, said Dr. Papp. “We see pretty rapid response, pretty good depth of response, and for the most part reasonable maintenance of response.”
Anti-IL-23 drugs. Attention had fallen away from the IL-23 cytokine for a while, Dr. Papp said, but with new molecules under investigation that target it, new data will soon be available.
PASI-75 vs. PASI-90. There is currently vigorous ongoing discussion about whether, in light of improving treatment efficacy, 90% or greater improvement in Psoriasis Area and Severity Index scores should be adopted as a target for psoriasis clearance over the 75% which has been the common benchmark.
LL-37. The T-cell auto-antigen LL-37 has been discovered to play a role in psoriasis and may represent a new therapeutic target, if not more. “What is the real inciting event that is causing psoriasis? What is initiating it? Maybe this little antimicrobial peptide,” said Dr. Papp.
What differentiates psoriasis and psoriatic arthritis. The two psoriatic conditions “respond differently to our treatments,” said Dr. Papp. “I think there has got to be some key difference, whatever it is.” He speculates that some as yet unidentified interleukin or immune cell may turn out to be the source of the difference in behaviour between the two conditions.
PDE4 inhibitors. Dr. Papp says he expects to see more research into phosphodiesterase type 4 [PDE4] inhibitors, such as apremilast which just received approval in Canada late last year. He is personally interested into dosing research, he said. “We increase the dose, we’re going to see better response,” he predicted. “PDE4 is everywhere. It is a key player in inflammation, so I think it is an obvious target to pursue.”
JAK/STAT inhibitors. Dr. Papp says he expects to see more research into Janus kinase [JAK] inhibitors and signal transducer and activator of transcription [STAT] inhibitors because both JAK and STATs have widespread involvement in inflammation.
NF-kappaB and other transcription elements. “This is a little bit out there, maybe,” Dr. Papp said of research into a potential role of nuclear factor kappa-B [NF-kappaB] in psoriasis. However, he thinks it is a target worth investigating “because it is everywhere. Anywhere you have inflammation, you’re going to see NF-kappaB [activity increased]. Other small transcription elements may also be good targets for investigation, he said.
RORgamma. The nuclear receptor RORgamma controls transcription of IL-17, said Dr. Papp. “So instead of using a biologic, you could get a small molecule that can do the same. It remains to be seen, but there is hope.” Four candidate drugs will be entering clinical trials soon, he said.
Psoriatic disease and cardiovascular risk. “I think there is hope that we can actually demonstrate that [the suspected link between psoriatic disease and cardiovascular risk] is true,” said Dr. Papp. “Right now, I’m not convinced we have the data. I think it is true, but I don’t think we have the data to support it yet. Once that puzzle gets put together, I think it will give us a lot more incentive—possibly—to treat our patients a little more aggressively.”