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10 Articles in Volume 15, Issue #1
Psoriatic Arthritis: Current Strategies for Diagnosis and Treatment
Traumatic Brain Injury: Evaluation, Treatment, and Rehabilitation
Pain Management in the Elderly: Treatment Considerations
9 Best Practices in Evaluating and Treating Pain in Primary Care
Rationale for Medical Management
New York State Enacts New Law to Prevent Drug Diversion
Editor's Memo: Acknowledging the Failure of Standard Pain Treatment
PPM Editorial Board Discusses Epidural Steroid Injections and Blindness
Ask the Expert: False Positive Amphetamine Urine Screens
Letters to the Editor: Pregnenolone, Acute Porphyria, Opioid Calculator, Arachnoiditis

Psoriatic Arthritis: Current Strategies for Diagnosis and Treatment

Although patients with psoriasis have a relatively high risk of psoriatic arthritis, they often go undiagnosed, leaving them at risk for progressive joint damage and disability. To follow is a discussion with Dr. Mease.

Q: How prevalent is PSA, and what are the barriers to accurate and timely diagnosis of this condition?

Dr. Mease: Psoriasis occurs in 3.2% of the US population, according to current findings from the National Health and Nutrition Examination Survey.1 Of these patients with psoriasis, 10% to 30% have PSA, based on findings from recent large-scale surveys. Unfortunately, many patients with PSA are undiagnosed.

This underdiagnosis was documented in the Prevalence of Psoriatic Arthritis in Adults with Psoriasis (PREPARE) trial, during which 949 patients were assessed for plaque psoriasis in dermatology offices in North America and Europe and then were referred to rheumatologists for evaluation, regardless of their musculoskeletal symptoms.2 Of these 949 patients, 30% were diagnosed with PSA based on a careful rheumatologic exam. Of the patients diagnosed with PSA, 41% had not been given this diagnosis previously.

Part of this underdiagnosis of PSA is simply lack of knowledge and awareness among clinicians and patients that patients with psoriasis can have an arthritic condition.

Q: How can clinicians overcome these barriers to diagnosis?

Dr. Mease: The key is to seed in the minds of primary care physicians (PCPs) and dermatologists the need to ask patients with psoriasis the question, “Have you ever had problems with persistent arthritis, morning stiffness, or back pain.”

For the PCP, the first step is to distinguish between inflammatory/immunologic conditions (inflammatory arthritis, enthesitis, or ankylosing spondylitis) versus mechanical/degenerative conditions (mechanical or degenerative arthritis, tendonitis, and back pain). Mechanical/degenerative conditions are ubiquitous issues in the primary care population and PCPs and other health care providers may not necessarily take the extra step to think, “could this possibly be an immunologic inflammatory condition?” Some key factors that would indicate the possibility of PSA include the following:

  • Age of onset—the younger the age, the more likely it is to be an inflammatory condition
  • Persistence of pain
  • Multiple sites of pain
  • Prominent and prolonged morning stiffness
  • Stiffness after being still for a period

In the case of back pain, a key question to ask is, “does the pain awaken you in the middle of the night?” Another key question is, “Does the pain getter better or worse with activity.” If the pain improves with activity, it raises the possibility of it being related to an inflammatory condition.

In addition, it is important for clinicians to be educated about the clinical features that can be seen in patients with PSA. For example, enthesitis is an important clinical part of PSA. Enthesitis is inflammation that occurs wherever tendons and ligaments insert into bone. Common locations include the Achilles tendon insertion at the heel, plantar fascia insertion at the heel, and patellar tendon insertions. Even the ligamentous tissue that binds the rib cage together can be inflamed, causing chest pain. Many PCPs are not aware that immunologic cells can set up inflammation right at that juncture of the ribs in patients with PSA. Enthesitis may be tougher to treat than arthritis in patients with PSA and you may need to go further up the treatment ladder to effectively treat it.

Dactylitis is another clinical condition that occurs fairly frequently in patients with PSA. In this condition, a whole digit becomes swollen and looks like a sausage. Dactylitis is highly predictive of either PSA or another spondyloarthritis condition (Figure 1).

An inflammatory spondylitis also can occur in patients with PSA. All of these conditions—arthritis, enthesitis, dactylitis, and spondylitis—can occur, depending on the individual patient. The heterogeneity of the PSA presentation is somewhat of an obstacle to making the diagnosis; on the other hand, these conditions can help the clinician make the diagnosis through pattern recognition.

Q: Are there any screening questionnaires for PSA?

Dr. Mease:Approximately 6 or 7 different screening questionnaires have been developed and validated for PSA. Examples include the following:

  • Psoriasis Epidemiology Screening Tool (PEST)—This tool involves 5 simple questions. If a patient responds positively to 4 out of the 5 questions, there is a high likelihood that they have PSA (Figure 2).3
  • Psoriatic Arthritis Screening and Evaluation (PASE)—A 15-item questionnaire to screen for PSA in patients with psoriasis.4
  • Toronto Psoriatic Arthritis Screen (ToPAS)—An 11-item self-administered questionnaire to screen for PSA in patients with psoriasis as well as the general population.5

All of the questionnaires show high sensitivity and specificity. The problem is getting clinicians to use them.

Q: What is the typical treatment ladder for patients with PSA?

Dr. Mease: Treatment guidelines are being updated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and will be released in 2015.6 The previous version of these guidelines was published in 2009 and, thus, does not include recently approved agents.7

Patients seen in the primary care setting often self-treat or are prescribed nonsteroidal anti-inflammatory drugs. These agents may be helpful, especially in patients with milder manifestations of PSA.

PCPs also may prescribe a course of prednisone to treat symptoms. A caution is that there have been reports of people with psoriasis who experience a significant flare of their underlying disease once treatment with prednisone is stopped. Thus, there is a bit of an art to using steroids in patients with PSA.

For initiation of immunomodulatory treatment, referral to a rheumatologist typically is required. Methotrexate is the disease-modifying antirheumatic drug (DMARD) most commonly prescribed as first-line for the treatment of PSA. Ironically, there is no controlled trial of methotrexate in the treatment of PSA that has shown it to be an effective medication compared to placebo. The reason for this lack of evidence is mainly because only 2 or 3 trials have been performed, and none were adequately powered with respect to the number of patients studied and/or they had other limitations.

However, the practical point is that we use methotrexate often, and it works in some patients adequately as monotherapy. In other patients, methotrexate is not adequate but is partially helpful and is used in combination with a biologic agent or apremilast (Otezla), an oral agent recently approved for plaque psoriasis and PSA.

Next are the biologic therapies, which have revolutionized and changed the whole treatment landscape for PSA. We now are able to treat to target—meaning treat to a target of either low disease activity or even remission.8 In addition, we now have quantitative measures that can be employed in rheumatology to quantitate disease response (ie, Minimal Disease Activity Criteria).9

Typically, the first biologic agent we will use is one of the anti-tumor necrosis factor (TNF) inhibitors (eg, adalimumab [Humira], etanercept [Enbrel], certolizumab [Cimzia], golimumab [Simponi], or infliximab [Remicade]), which have been a major part of our treatment armamentarium over the last decade.

Q: What newer agents are available?

Dr. Mease: Newer agents that have been approved include the non–anti-TNF biologic ustekinumab (Stelera), which is an interleukin 12 and 23 inhibitor that is very effective in the treatment of psoriasis when given once ever 3 months via subcutaneous injection, and it also has been shown to be effective in PSA.

The oral agent apremilast, which inhibits the enzyme phosphodiesterase 4, is given twice-daily. It, theoretically, is not as potent as some of the biologics, and, thus, ideally would be used earlier in treatment ladder for patients with milder disease.

Emerging treatments that have shown promise in clinical studies but are not yet approved include the IL-17 receptor inhibitor brodalumab, which has shown very effective results in psoriasis and good results in PSA.10

In addition, at the 2014 ACR meeting, my colleagues and I presented two Phase III trials of the anti-IL-17 inhibitor secukinumab.11,12 These were large trials with x-ray outcomes demonstrating that secukinumab was significantly effective for treating the psoriasis, as well as the arthritis, enthesitis, and dactylitis components of PSA. In addition, secukinumab has shown efficacy in the treatment of ankylosing spondylitis.13 In late January, the FDA approved secukinumab (Cosentyx) for the treatment of plaque psoriasis.

Q: What research studies are you currently working on?

Dr. Mease: I am involved in Phase III trials of the IL-17 inhibitors brodalumab and ixekizumab,as well as the JAK inhibitor, tofacitinb.

I also am involved in an initiative called PsA BioDam (Psoriatic Arthritis Biomarkers for Joint Damage), which is being conducted by GRAPPA. The goal of this project is to identify biomarkers for ascertaining disease activity.14

In addition, our institute just received funding for an initiative to develop a simple criteria set (eg, 5 elements of history and physical) that PCPs and other clinicians can use to differentiate inflammatory from mechanical/degenerative conditions in patients presenting with musculoskeletal problems. We are doing qualitative research to see how patients articulate what their daily experience is like. For example, we will ask patients what their pain, stiffness, and fatigue is like on a daily basis. Using this information, we will develop a simple set of highly sensitive and specific criteria that, hopefully, will help clinicians determine when to suspect inflammatory conditions. We hope to publish these criteria in 3 to 4 years.

A number of us who are investigators in the Corrona (Consortium of Rheumatology Investigators of North America) registry are involved in analyzing and publishing the data of patients with psoriatic arthritis and spondyloarthritis in that registry.

—Reported by Kristin Della Volpe

Last updated on: January 20, 2016
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