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Andrew Blauvelt, MD, MBA, began to study psoriasis in depth in Portland, Oregon, over 20 years ago, after spending several years at the National Institutes of Health training in cellular immunology and working as a senior investigator on HIV. In Portland, he was a professor at Oregon Health & Science University, where he conducted basic science research on the immunology of psoriasis, with a focus on how interleukin (IL)-23 and Th17 cells contribute to psoriasis pathogenesis. 

From 2013 to 2022, he was owner and president of the Oregon Medical Research Center, which conducted clinical studies on psoriasis and other conditions. He is now the owner of Blauvelt Consulting, which advises pharmaceutical and biotech companies on research, drug development, trial design, and data analysis, in Annapolis, Maryland, and is adjunct professor of dermatology at the University of Maryland School of Medicine, Baltimore. He has been the senior investigator in numerous psoriasis trials. 

In an interview with Medscape Dermatology, Blauvelt spoke about how psoriasis research and treatment have evolved to a point he didn't think possible years ago. The conversation was edited for clarity and length. 

You often speak at medical meetings about how your father suffered from severe psoriasis. How has your father's experience inspired and driven you as you've focused much of your research on psoriasis?

My father having severe psoriasis was a big part of my childhood. He had complicated severe disease at a time when we didn't have good treatments. The best treatment for him for many years was hospitalization for Goeckerman phototherapy — often twice a year for weeks at a time. It was a big thing. 

He passed away in 1998, before the biologic era. We have such amazing medicines now, but there's still so much untreated and undertreated psoriasis, either because of patient choice or physician choice or insurance barriers, where patients are getting topicals or methotrexate or being put in a lightbox when they really need a biologic. This is 20^th century medicine, not 21^stcentury medicine, and it's incredible and sad to me because I know exactly what those patients are going through. It's miserable. 

And it's especially disheartening in the era of modern biologic therapy. Because of my father, I've been driven to always push for efforts to increase access and decrease insurance barriers — to try to get patients the best therapies first, not last. 

My dad also had pretty bad heart disease at a time we didn't know severe psoriasis was linked to heart attacks and strokes. So when the story of that link broke in 2006, I took a particular interest, and it became a big part of my practice and teaching to tell patients during the first visit that they were at higher risk of heart attack and stroke. 

Will a cure for psoriasis be possible one day?

I've been working with the National Psoriasis Foundation for many years. They've always said that cure is the goal. For many years, I thought to myself, 'no way.' Christopher Griffiths, MD (emeritus professor of dermatology, University of Manchester, and adjunct professor, King's College London, UK), and I are now both talking about how, in the next 10 years of psoriasis research, we're moving towards a cure. It's in our sight, and it's very exciting. I'm 64 years old now, and I think the research has evolved to the point that, within my lifetime, we may see a cure.

Were there defining moments for you, when you started seeing cure as a realistic possibility?

What we've seen in the therapeutic landscape is that drugs can work, including the older drugs, until they're stopped. When we stop, the disease comes back. We've seen a pattern develop over the last 25 years where the shortest-acting drugs — those that you have to take frequently — lead to the quickest recurrences when you stop. 

And with the drugs that last longer — that require less frequent dosing — disease comes back much later. This is particularly true with the IL-23 blockers.

With the IL-23 blockers, for the first time ever, we've also seen a disconnect between drug levels in the blood and the ability to stay in remission. With all the other 

drugs, there is a correlation between drug levels in the blood and disease activity. Disease comes back once there's a zero drug level in the blood. But with IL-23 blockers, people stay clear for a period of time after the drug is gone.

This is a new phenomenon, and it has made me believe that a cure is possible. And we've found in recent years that only IL-23 blockers are capable of decreasing resident memory T cells — the cells that are responsible for psoriasis recurrences. The continued remission seen with IL-23 blockers even when there's no drug on board is an effect of this class of drug on these cells. The cells take longer to recover when they've seen an IL-23 blocker. It has opened up a whole new area of research.

You are the lead investigator of the recently published  phase 2 KNOCKOUT study, which documented the impact of higher-than-approved doses of the IL-23 inhibitor risankizumab on resident memory T cells in patients with moderate to severe psoriasis. What were your main takeaways?

With the KNOCKOUT study, the hypothesis was that if we can knock down resident memory T cells with IL-23 blockers, maybe we could push the hit on the cells even further and get even longer remission if we treated with higher doses at double and quadruple the approved dose. 

We found two important things. For one, the short-term efficacy was much greater than what we see with the lower, standard doses. We saw 83% of patients achieving PASI 100 at week 28. Normally, with approved doses of risankizumab, about 50%-60% become completely clear.

Secondly, the hypothesis proved true. Four of 18 patients maintained PASI-90 at 2 years, and another two patients remained completely clear. So, in 11%, the disease didn't come back, and about a quarter of the patients didn't require any treatment 2 years after their last dose. (Doses were given at weeks 0, 4, and 16.) It is pretty remarkable. 

Are there signs that resident memory T cells could be cleared for the long term? And what other cell types and tissue findings are of interest for remission and possible cure? 

We studied this in detail in the KNOCKOUT study. My colleague and one of the study co-authors — Johann Gudjonsson, MD, PhD, from the University of Michigan, Ann Arbor — collected and analyzed the tissue data, and we will have another paper published in the next several months. There were dramatic changes going on with just about every cell type: keratinocytes, fibroblasts, endothelial cells, macrophages, T cells. The whole inflammatory network and the whole inflammatory architecture of psoriasis is being dramatically altered with high-dose IL-23 inhibition.

How are remission and cure currently being defined?

In a paper I wrote with April Armstrong, MD (professor and chief of dermatology, University of California, Los Angeles), and others in 2020, we defined remission as no treatment, no disease for at least 1 year. This is how I think of it. We haven't defined cure. It will involve a bit of semantics, but the point is, cure starts with long-term remission. We're in the long-term remission era right now — the pre-cure era.

You've long been a proponent of a 'hit hard, hit early' approach. Your KNOCKOUT study, as you've described, has addressed the first part of this strategy. Talk about the 'hit early' part. Has research nailed down an ideal window of opportunity for initiation of biologics?

Two major studies in recent years focused on early intervention, or on patients we now call short-disease-duration (SDD) patients vs long-disease-duration (LDD) patients. The STEPIn study of secukinumab defined SDD as 1 year or less. The GUIDE study using guselkumab defined SDD as having psoriasis for less than 2 years. Both found high efficacy of the drugs in patients with SDD. 

The GUIDE study directly compared treatment in patients with SDD and LDD and found a much greater likelihood of complete clearance if the patients had short disease duration. It was dramatic. SDD patients also had much longer remissions when the drug was stopped. 

I lean toward 1 year as the best cutoff for SDD in research, because a deep dive into the GUIDE data suggests that 15 months is a critical time point. Patients treated above 15 months from symptom onset actually behaved more like LDD (> 2 years), whereas those with 12-15 months of disease duration behaved like those with less than a year's disease duration.

Certainly, if you treat earlier, you have a better chance of clearing your patients and a better chance of them staying in drug-free remission.

What research do you now have your eyes on? 

What's most exciting for me right now is a new IL-23 inhibitor with an extended half-life. It is made by a small biotech company called Oruka Therapeutics (I'm head of the scientific advisory board) and it was reported at the 2025 EADV Congress to have approximately a 100-day half-life. It's the longest-acting monoclonal antibody ever made. And they're dosing it at KNOCKOUT doses in their current phase 2 program. 

The company recently announced positive interim results from a phase 2a trial, replicating what I showed in KNOCKOUT. In the future, using the drug in SDD patients so we get that combination of 'hit hard, hit early' would be particularly exciting.

We also learned through ClinicalTrials.gov that AbbVie has developed a new long-acting IL-23 inhibitor that they're planning on dosing at high levels as well. So again, we're now in this era of long-term remission.

What needs to happen on the ground in every practice, and with health care policy, to make early diagnosis and disease remission a routine occurrence in patients with psoriasis?

I think about it all the time. Through the last 25 years, we've had incredible advances, and I've seen these advances dramatically change lives for the 'haves.' People with insurance, people who have money, people who know how to work the system, have benefited greatly, not just in the US but throughout the world.

But others have not experienced the benefits of these advances. And I'm doubtful anything will change in the foreseeable future. There are so many uninsured and underinsured patients with psoriasis who will never get a biologic. In an ideal world, we'd have a once-a-year treatment that would be affordable. Oruka is planning on having two high-induction doses at the beginning and then once-a-year dosing after that. Maybe with once-a-year dosing, we'll see more patients getting access through special programs. 

Blauvelt has served as a speaker (received honoraria) for Eli Lilly and UCB, has served as a scientific adviser (received honoraria) for AbbVie, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Bausch Health, Eli Lilly, Incyte, Janssen, Khanda Therapeutics, Leo, Novartis, Oruka, Pfizer, Re-AIM, Recludix, Regeneron, Sanofi, Sun Pharma, Takeda, UCB, and Zai Lab, and owns stock in Lipidio and Oruka.