Psoriatic Arthritis Notes and Notable: Dr. M. Elaine Husni on PsA vs RA – Why More Clinical Trials Are Needed

Drug Market Info presents Psoriatic Arthritis Notes & Notable, an interview series with leading voices in the struggle against Psoriatic Arthritis, or PsA. (For more data on Psoriatic Arthritis, see the Drug Market Info Psoriatic Arthritis Fact Sheet)

Today we present our interview with M. Elaine Husni, MD, MPH. Dr. Husni is the Department Vice Chair of Rheumatology and Director, Arthritis and Musculoskeletal Treatment Center at the Cleveland Clinic. The Department of Rheumatic and Immunologic Diseases at Cleveland Clinic is ranked second in the nation by U.S. News & World Report. Dr. Husni is also Assistant Professor at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and current Director of Musculoskeletal Outcomes research and the fellow’s research committee for the Rheumatology Department.

Dr. Husni is a member of the medical and scientific committee for the Arthritis Foundation and a recipient of the Clinical Investigator Award and Physician Scientist Development Award from the American College of Rheumatology for her research on health outcomes among patients with rheumatoid arthritis and psoriatic arthritis. She is involved in a number of rheumatology clinical trials at Cleveland Clinic and serves on the Executive Committee of the PRECISION trial.

Here is what Dr. Husni has to say about Psoriatic Arthritis:

In your opinion, why are there fewer clinical trials for psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA)?

The pathogenesis of RA has been more extensively studied than PsA leading to more specific therapeutic targets. In addition, there is a perception that RA tends to carry a greater personal and societal disease burden than psoriatic arthritis. I believe that PsA research is growing and we will see more clinical trials in the near future as the mechanism of this disease is better elucidated.

How do clinical trial endpoints differ for psoriatic arthritis and rheumatoid arthritis?

The main difference is that RA trials measure predominant joint involvement, function, serum markers of inflammation, and quality of life. PsA has all the above, but also includes a skin measurement score. Therefore, PsA endpoints generally incorporate both the skin and joints, whereas RA is the joint only.

Is it more difficult to prove efficacy and safety for PsA than RA?

No, probably not. Proving safety and efficacy is the hallmark of scientific research and disease investigation. Similar methods can and should be used for PsA and RA. In patients with PsA, efficacy trials may be a bit more challenging due to the incorporation of multi-system outcomes for both skin and joints.

What do you feel is needed for more companies to undertake trials for PSA?

This is a great question. From a basic science perspective, we need to increase our understanding of the pathophysiology of PsA and improve animal models of PsA disease. As we continue to investigate the etiology of PsA at the molecular and cellular level we must also expand investigation of the role of genetics and gene-environmental interactions. Understanding the biological, genetic and environmental relationships which exist can lead to targeted therapeutics which treat or maybe even cure the disease.

How is first line therapy for PsA patients generally determined?

In general, overall disease activity is assessed. I always consider the severity of the patient’s disease (number of joints involved, inflammatory markers, and function) and how it globally impacts their life. Furthermore, their level of joint involvement and their skin disease activity will determine the treatment plan, with the goal being to impact both with the fewest side effects.

Are most of your PsA patients on combined therapy with methotrexate and the biologics?

The majority of PsA patients may be on combination therapy, but many are on monotherapy as well. Combination therapy is a more common treatment path for patients with RA. In psoriasis and PsA, many patients start with one agent and remain on one agent as the literature does not support combination therapy as strongly as in RA.

What are the similarities and differences regarding how patients with rheumatoid arthritis versus psoriatic arthritis respond to methotrexate and biologics?

There are probably more similarities than differences. DMARDs (disease modifying anti-rheumatologic drugs) such as methotrexate and biologics, are widely used to treat both RA and PsA. The American College of Rheumatology (ACR) has published recommendations and guidelines for use of these agents. Treatment response is generally efficacious with some patients experiencing months or years of stable disease or remission without disease progression. This is the goal of therapy: to halt disease progression, lengthen periods of remission and prevent joint destruction. There are many more DMARDs that are FDA approved for RA compared to DMARDs for PsA.

What are the most troublesome side effects for PsA patients with both of these therapies?

The most troublesome side effects of drugs like methotrexate and biologics are the increased risk of serious infection as these drugs reset the immune system. What is also important to understand is that patients with PsA tend to have a “hyperactive” immune system which can be improved with the use of DMARDs. Most anti-TNF therapies are well tolerated. Side effects exist, but are rare and if diagnosed early, good outcomes are still possible.

The use of medications like methotrexate and biologics require close monitoring and regular visits to the rheumatologist in order to minimize these side effects.

Is there one biologic that you feel works better for PsA than the others?

No. Anti-TNF therapies have similar effects on the disease; however, a particular patient may respond better to one over another. There are limited head-to-head trials comparing anti-TNF therapies.

How do PsA patients feel about being on biologic therapy long-term?

Biologics are generally used to treat moderate to severe PsA when other treatments have failed. Biologics have been shown to slow disease progression by targeting specific components of the immune system. As with most immune-targeting treatment, the risk of infection (including tuberculosis) is highest in the first six months of therapy. Careful monitoring for signs of infection, cardiovascular disease, and even malignancy is required to minimize side effects of these drugs.

Are drug holidays ever an option and how long should a holiday last?

There is no good clinical data supporting “drug holidays” in PsA. A drug holiday is not a practice which I encourage my patients to consider, but many patients do stop drugs on their own. I encourage patients to let me know if they are planning a “drug holiday” so they can be monitored more frequently to avoid permanent joint damage.

What, if any, long-term effects have you noted with use of the biologics for PsA?

Recent reports have shown that biologics slow disease progression, especially when all other treatments have failed. Permanent, irreversible joint damage and life altering physical disability can be halted or prevented by the proper use and monitoring of biologic agents. Efficacy may wane with long-term use of biologics, but more studies are needed to understand this. If efficacy of a biologic does wane, there is always the option of adding a topical, utilizing phototherapy or introducing an oral agent like methotrexate.