Psoriatic Arthritis: Where We Are and Where We’re Going

Related Conditions

Generally speaking, psoriasis manifests on the skin and PsA shows up in the joints. But the inflammation underlying each can also affect other tissues and organs. That means people with psoriatic disease are at a higher risk for developing related health conditions, or comorbidities.

In 2019, NPF and the American Academy of Dermatology released new treatment guidelines for psoriasis. People with PsA are at risk for the same comorbidities as psoriasis, including cardiovascular disease (diseases of the heart and arteries), metabolic syndrome (including high blood pressure, high cholesterol and type 2 diabetes) and mental health issues (depression and anxiety).

M. Elaine Husni, M.D., MPH, is a rheumatologist at the Cleveland Clinic in Ohio and a member of the NPF board of directors. She’s a former member of our medical board, a participant in our live educational programming, and a past recipient of an NPF-funded research grant. She is also vice chair of rheumatology and director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic.

“Unfortunately, we still have a certain percentage of patients who don’t respond to our current therapies, so that’s why we’re trying to develop new therapies,” she says. “But at the same time, our understanding of comorbidities is so much better that we’re able to not only take care of the skin and joints, but really address all the other issues in a more timely manner, which gives the patient a fuller life.”

How PsA Is Currently Treated

At the end of 2018, NPF, in partnership with the American College of Rheumatology, released a pioneering treatment guideline for PsA. For the first time, doctors who care for people with PsA have a guide to all current treatments and the evidence-based recommendation to use biologics as a front-line treatment, before oral systemics.

The guideline adopted a “treat to target” approach for PsA: The doctor and patient set targets for improvement and change how they manage the patient’s disease if targets aren’t met. The guideline also includes evidence that patients can benefit from “self-management”: diet, exercise, lifestyle (including avoiding or stopping smoking) and physical therapy.

“For us, at least in psoriatic arthritis, we have so many more treatments than when I was in medical school in the ’90s. All we had then was methotrexate [an oral systemic],” Husni says. “It’s been really great to be able to have all these tools in my toolkit to use more individualized treatments. We have so many more treatments that are really working well, and allowing people to go back to their jobs, allowing people to go back to being active with their families.”

The most common treatments for PsA are biologics, oral treatments and, at times, off-label use of systemic therapies indicated for other inflammatory conditions. Biologics are made from living sources, such as human, animal or bacteria cells. They are given as injections or intravenous infusions.

Biologics target specific parts of the immune system. (Traditional oral systemic drugs may impact the entire system.) The biologics used to treat psoriatic disease block the action of a specific type of immune cell called a T cell, or they block proteins in the immune system, such as tumor necrosis factor-alpha (TNF-alpha), interleukin 17-A, or interleukins 12 and 23.These cells and proteins all play a major role in the inflammation behind PsA.

Oral treatments are medications taken by mouth. Some oral treatments target specific cells of the immune system to lower the part of the immune system that is not functioning properly. Other oral treatments may act on the whole immune system.

An off-label systemic treatment is a medication used for a health condition other than the one it was approved for by the U.S. Food and Drug Administration. Some off-label treatments that you may use for PsA include antimalarial treatments, non-steroidal anti-inflammatory drugs (commonly called NSAIDs and including over-the-counter medications such as aspirin and ibuprofen as well as prescription products) and systemic steroids.

Where NPF-Funded Research Is Taking Us

In 1976, NPF, with the help of U.S. Rep. Wendell Wyatt, R-Oregon, secured the first line item in a federal budget for what was then called “skin disease research.” In plain English, this was the first time the U.S. government had ever funded research into diseases that involve the skin.

Times have changed. In 2019, NPF funded $2.8 million in psoriatic disease research all by itself.

Here’s a look at some of the research we’re funding.

Diagnosing PsA: The Missing Link

Although our knowledge of PsA has exploded in the past half-century, there’s still a lot we don’t know. But here’s one thing we do know: The more time it takes to reach a diagnosis, the more time PsA has to run unchecked through your body. If we can reduce the average time to diagnosis, we can reduce the damage that untreated PsA can do to your joints.

A Selection of Active NPF-Funded Research Projects

“We are very fortunate to have such phenomenal researchers and clinicians working with us. They’re the best and the brightest,” says NPF chief science and medical officer Stacie Bell, Ph.D. “They’re all working together and with NPF to benefit our patient community, whether it is implementing new cutting-edge methods or discovering new treatment options or novel screening techniques.”

We’ve spotlighted the work of three of our currently funded researchers. Go to our research portfolio to learn more, because this selection is just the tip of the iceberg.

Why do so many people report lengthy delays in getting a diagnosis of PsA? The problem is not necessarily the health care provider. The problem is more likely the health care provider’s lack of tools. If your doctor can order a blood test to check your cholesterol or blood sugar, why not a similar test to check for markers of PsA? Waiting years to be diagnosed is not an effective treatment strategy.

This is why, beginning in 2019, NPF is committed to funding research that will bring us closer to developing a diagnostic test. We call this funding mechanism the PsA Diagnostic Test Grants.

“The goal of developing a psoriatic arthritis diagnostic test is particularly appealing due to the massive delay of diagnosis of many patients,” says Wilson Liao, M.D., director of the UCSF Psoriasis Center at the University of California, San Francisco, and chair of NPF’s scientific advisory committee. “The ability to diagnose psoriatic arthritis earlier would have a huge impact on our ability to prevent long-term joint damage.”

We are currently funding six PsA Diagnostic Test Grants. We’ll provide more funding to these projects if they demonstrate progress during the proof-of-concept phase (when a researcher demonstrates that the funded project has practical potential). Watch this video about the challenges of diagnosing PsA.

Stopping Psoriatic Disease Before It Starts

NPF’s latest research grant is the Psoriasis Prevention Initiative. The PPI aims to invest $6.5 million over five years to prevent the onset of psoriatic disease, disease relapse and/or related comorbidities.

NPF hopes to accomplish these goals by establishing a multi-institution, multi-disciplinary, team-based research network. The collaborative approach to unraveling the complex questions surrounding disease prevention takes inspiration from similar efforts by those studying HIV and cancer. The PPI is closely modeled on the National Institutes of Health’s Accelerating Medicines Partnership venture, which pairs public and private entities to work on new treatments and cures for diseases such as Alzheimer’s disease, lupus and type 2 diabetes.

This team-based approach is relatively new and has a lot of merit in the field of medical research, says rheumatologist Christopher Ritchlin, M.D., MPH, who is a member of the PPI steering committee. “It has to do with the evolution of research over the last 20 or so years. Because of the complexity of the science, you need teams with different expertise to come together to use different technologies and approaches to answer important medical questions.

“The success of PPI means we have prevented some of the adverse outcomes associated with psoriatic disease,” adds Ritchlin. “The ability to decrease the burden on the patient community would be a major win.”

NPF has also launched the Milestones to a Cure Grant, which aims to support psoriatic disease research focused on treatment durability, remission/relapse, prevention and personalized medicine. Grants will be for one-year terms, and up to $100,000 per grant will be awarded.

What Does the Future Hold in the Field of PsA?

Predicting the future is a risky business, but three of our experts were willing to take that risk. We asked them to look ahead two or three years and report back. Their comments follow.

Jose Scher: Moving the Field in Multiple Directions

“The challenge with PsA is very different from psoriasis. The new psoriasis treatments have shown dramatic improvements in patient outcomes. We know that. People get clear or almost clear. It’s amazing,” says Jose U. Scher, M.D. Scher is an associate professor and director of NYU Langone’s Psoriatic Arthritis Center and the Microbiome Center for Rheumatology and Autoimmunity. He was the recipient of a 2019 PsA Diagnostic Test Grant. “But if you’re using the same medications in PsA, the outcomes have not changed much over the last 15 or so years.”

Scher sees the field moving toward two approaches. “The first is preventive – trying to understand the question of whether initiating therapy before anyone has actual synovio-entheseal inflammation will prevent, delay or mitigate PsA. Once someone gets PsA, at times it’s very difficult to treat,” he explains.

“The second is the fact that we may be at a time in psoriatic arthritis therapeutics when we have to think about combining biologic therapies and/or small molecules,” Scher says. “Blocking one mechanism or molecular pathway may not be good enough for some patients. We could combine sequentially, concurrently, with different dosing regimens. Those are details that need to be ironed out.”

Iannis Adamopoulos: A Race Against Time

Iannis Adamopoulos, D.Phil, is an associate professor of rheumatology at the University of California, Davis. In the layman’s statement for his two current NPF-funded grants, Adamopoulos wrote, “Our study will determine the pathogenic mechanisms relevant to human PsA and open new avenues of treatment for PsA patients.”

What will those new avenues look like?

“We have learned a lot over the years on a molecular and cellular level we did not appreciate before,” he says. “As an example, although we designed inhibitors to block the interaction between IL-23 and the IL-23 receptor, we really did not know very much about the structure of those proteins and their interactions. Now we have a much better understanding of these interactions, and we can predict the signaling pathways and the pathological determinants of the disease. It’s a race against time to collect and analyze the data we need, gain better understanding of the pathology that occurs in PsA patients and provide personalized treatment options.”

He is optimistic about “the steady increase of interdisciplinary research,” and what it means for our own field.

“This increase will continue to reward us with new opportunities. And with the new emerging technologies in translational and clinical science, combined with computational systems biology, I anticipate an explosion of new data and a reshaping of the scientific landscape,” Adamopoulos says. “It really is a very interesting time to be a scientist. We are entering a phase not only of discovery as it was 50 years ago, but of detailed understanding of regulatory mechanisms that we may be soon able to modulate for the benefit of patients worldwide.”

M. Elaine Husni: Raising the Bar on Treatments – and Awareness

“I think with our increased understanding of the pathogenesis of the disease, we are now able to personalize treatment,” says Husni. “We used to have one-size-fits-all. We said, 'Oh, you have PsA? OK, use this particular biologic. Or that one.’ But now we’re asking for more from our treatments. We’re not just going to treat this disease, PsA. We’re going to treat your disease and how PsA affects you. We’re going to choose a treatment that not only treats PsA but also the specific signs and symptoms that bother you.”

PsA is a heterogeneous disease, Husni points out. “Some people have more skin involvement than joints, some people have more joints than skin, some people have enthesitis with a little bit of skin, some people have dactylitis with a lot of skin, and so on,” she says. “This is why we have to raise the bar and personalize our treatments.”

Though Husni says she’s more tempered in her enthusiasm for what the next few years will bring, she’s excited about social media and how NPF is using it to increase awareness.

“People are talking about it, opening up that conversation, which I think is so important because this is a disease that hasn’t been talked about. The more people who talk about it and tell us how they feel with it, then we learn more, and we can do more for them,” says Husni. She cites celebrities such as singer Cindy Lauper and pro golfer Phil Mickelson, who both have psoriatic disease and who have both spoken in public about it.

“NPF has done so much in this arena. I’m so proud to be attached to an organization that in such a short period of time has made such a big difference,” Husni says. “I think NPF has really done amazing work, elevating PsA, bringing it out from the shadow of other diseases like rheumatoid arthritis. I feel like the organization has an appropriate focus and energy and sustainability for this disease. It’s the reason why I’m still with them.”

The Stats of PsA

As many as 2.4 million Americans have PsA, which can develop at any age. [1]

About 1 in 3 people with psoriasis develop PsA. [1]

More than 15 percent of people with psoriasis may be living with undiagnosed PsA. [2]

In 85 percent of individuals, psoriasis develops before PsA. [3]

1 Journal of the American Academy of Dermatology, 2013
2 Journal of the American Academy of Dermatology, 2015
3 New England Journal of Medicine, 2017

Research assistance by Jessica N. Smith, NPF Research Programs Coordinator.