Search Is On for Genomic Clues in Psoriatic Arthritis
Here’s why psoriatic arthritis is among the first clinical areas Cleveland Clinic’s collaborative Center for Clinical Genomics has chosen to focus on.
To unleash more of the power of genetic research, Cleveland Clinic’s Center for Clinical Genomics is working with select research teams from across all of Cleveland Clinic to conduct pilot studies to uncover genomic information that clinicians can incorporate directly into patient care.
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One of the first researchers they’ve chosen to collaborate with is M. Elaine Husni, MD, MPH, to gain insights into psoriatic arthritis through the resources built up in the Psoriatic Disease Biobank she directs out of the Department of Rheumatic and Immunologic Diseases.
Consult QD caught up with Dr. Husni, who is a rheumatologist, and cardiologist W.H. Wilson Tang, MD, Director of the Center for Clinical Genomics, to discuss their distinctive collaboration.
Dr. Tang: Psoriatic arthritis is a condition where the clinical presentation is well understood but the molecular underpinnings remain unknown. The ability to unearth genetic clues will allow us to work with specialists to explore therapeutic options.
Also, psoriatic arthritis appears to involve a mechanism that may be applicable, from therapeutic and pathophysiologic standpoints, to other inflammatory diseases. There may be common mutations, genetic determinants and responses to therapeutics relevant to other areas that use similar medicines or have similar physiologic characteristics. Psoriatic arthritis also has cross-disciplinary appeal. It’s of interest to dermatology, rheumatology and immunology and can involve significant comorbidities managed by specialties like mine, cardiology.
Additionally, Cleveland Clinic has a well-established clinical and research infrastructure for psoriatic arthritis. Over the past few years, Dr. Husni has created extensive biobank capabilities around psoriatic disease, and she continues to excel in collaborative activities across disciplines. We want to leverage that expertise.
Dr. Husni: Psoriatic disease is a ripe model for further exploration because several genetic risk loci for psoriatic arthritis have been identified in patients with psoriasis. One-third of patients with psoriasis develop psoriatic arthritis, while two-thirds do not. We want to understand why that latter group of patients is not at risk.
And there are many unmet clinical needs. A significant portion of psoriasis patients are nonresponsive to current treatments. My passion for this program stems from our current state, which doesn’t help us identify who will respond to treatment or who may need aggressive treatment. It’s distressing when a patient comes to our clinic and already has irreversible joint damage. No one associated their aches and pains with their skin disease. We have disease-modifying agents that can slow or prevent joint deterioration, so it’s more important than ever to identify the disease early, when it’s easier to treat. It would be even better to identify those psoriasis patients who will go on to develop arthritis before it manifests. Given the explosion of genomic capabilities, we want to be able to better characterize the specific gene loci and apply this information to patients.
“One-third of patients with psoriasis develop psoriatic arthritis, while two-thirds do not. We want to understand why that latter group of patients is not at risk.” — M. Elaine Husni, MD, MPH
Dr. Husni: Anyone intimately involved with biorepositories knows it’s far more complicated than collecting a blood sample and performing some investigational test. I wish it were that easy!
To develop a targeted screening program to identify people at high risk for psoriatic arthritis or its cardiovascular comorbidities, for instance, you need to carefully define targets and capture them before, during or after treatment. We are probably in a very good position with psoriatic diseases to do this work; we are primed to get to the next level, having the experience of managing biorepositories for years.
Dr. Tang: Dr. Husni has done an excellent job of beginning to characterize those with psoriasis who may ultimately develop psoriatic arthritis and those who will not. So now we are going upstream with family members with this condition to see if they can give us clues about vulnerabilities and downstream problems. This now becomes a much more focused effort. The beauty of genomics and genomic technology is that they help identify molecular processes prior to development of the disease. That’s the real potential of this approach.
Dr. Tang: Cleveland Clinic has a large volume of patients and expertise, which translates to having an abundance of patients participating in blood sample collection.
Dr. Husni: We also have a robust cardiovascular program. Cardiovascular disease is one of the leading comorbidities of psoriasis and psoriatic arthritis. With our large clinical volume and expertise, coupled with our Psoriatic Disease Biobank — which includes highly annotated histories on more than 250 people and over 5,000 specimens and samples — we can drill down to better understand cardiovascular disease in these individuals.
Dr. Tang: We want to increase biorepository accrual through comprehensive outreach and patient recruitment processes, and we need to improve clinical annotation. One key for biorepositories is to characterize the phenotype, not just presence or absence of disease. Treatment responses and physiologic characteristics are often poorly described in standard database annotations. Once we get those, the downstream yield of analyzing the genetic data will be far more robust.
We also will need national and international cooperation. We need large numbers of subjects, and the techniques are complicated; no single center can complete this task.
Although early discoveries have emerged, few are currently used at the bedside because translation is slow and tedious. We want to help practicing physicians like us understand how current and future discoveries can be incorporated into everyday care.
Dr. Husni: Combining our biorepository work and research with the genomics team will push us forward in answering some of the questions discussed earlier. That’s what I love about this effort — the prospect of developing more effective therapies and improving outcomes.
For more on the Psoriatic Disease Biobank and these research efforts, contact Dr. Husni at firstname.lastname@example.org or 216.445.1853.