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Article
Pharmacy Practice in Focus: Health Systems
Psoriatic Arthritis Diagnosis and Treatment
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Psoriatic arthritis (PsA) is an inflammatory seronegative spondyloarthropathy that is related to psoriasis while remaining a distinct clinical entity.1 It is unclear exactly how many patients with psoriasis will develop PsA, but some studies have shown a prevalence as high as 42%.2 In the United States, it is estimated to affect between 0.l% and 0.25% of the general population.2 PsA may develop at any time, but it usually presents between the ages of 30 and 50 years.1,3 It is characterized by pain and stiffness in the affected joints, with stiffness exacerbated by immobility.
Upon physical examination, affected joints may have asymmetric stress pain, joint line tenderness, and effusions, with approximately 50% of cases affecting the distal interphalangeal (DIP) joints.3 Often, nail disease is found in patients with DIP joint involvement.1 PsA ranges from mild and nondestructive to a severe arthropathy with resulting joint destruction. It is estimated that approximately 40% to 60% of patients with PsA progress to debilitating arthritis.2
Classification and Diagnosis
In 2006, a classification system was developed following the Classification of Psoriatic Arthritis (CASPAR) study, which included over 500 patients with PsA.4 These criteria may aid in the clinical diagnosis of PsA but may only be used in the context of patients demonstrating evidence for inflammatory musculoskeletal disease. To meet CASPAR criteria, a patient must have either inflammatory joint, spine, or entheseal articular joint disease along with >3 points from 1 of the 5 CASPAR categories (Table 1).4
Although the diagnosis of PsA is largely based on clinical judgment and there are no specific serologic tests to confirm the presence of PsA, the following factors aid in clinical diagnosis: the presence of joint inflammation, along with nail and skin lesions and the absence of rheumatoid factor.1 Radiographs are useful in revealing the extent and location of joint damage. PsA can be further subdivided into mild, moderate, and severe based on the impact of disease on the patient’s quality of life (QOL) (Table 2).1 Upon diagnosis of PsA, treatment should be initiated to alleviate symptoms of PsA, inhibit further structural damage, and improve a patient’s QOL.1,5
Pharmacologic Treatment
PsA treatment targets both skin and joint disease with the goal to control inflammation while preventing further joint damage and alleviating discomfort.5,6
Mild PsA
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for patients presenting with mild disease. The selection of NSAIDs is largely dependent on both patient coorbidity concerns (eg, use of COX-2 inhibitor in patient with CAD) and patient/prescriber preference. Local intra-articular injection of corticosteroids may be considered when only a few joints are involved. 1,5 Both of these treatment options lead to significant symptom improvements, but neither inhibit the progression of structural joint damage.
Moderate PsA
Disease-modifying antirheumatic drugs (DMARDs) are used in the treatment of moderate PsA, which is marked by an aggressive form of the disease as well as a lack of therapeutic response to NSAIDs. Methotrexate is the preferred DMARD given its low cost and ability to treat both skin and joint disease.1 Other options include sulfasalazine, leflunomide, and cyclosporine. Of note, clinical trial data for all of these agents are limited to small sample sizes and are showing only modest benefit.
A more promising sub-category of DMARDs includes tumor necrosis factor-alpha (TNF-α) inhibitors. These agents inhibit the production of TNF-α, which is believed to be involved in the inflammatory processes seen in PsA. TNF-α inhibitors include etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira). All 3 of these agents have been shown to elicit similar therapeutic responses as measured by ACR20. ACR20 is the American College of Rheumatology 20% improvement criteria which is defined as having at least a 20% improvement in both tender joint count and swollen joint count as well as improvement in 3 of 5 other core measures, which include physician or patient assessment of disease, patient assessment of physical function, pain, and levels of either C-reactive protein or erythrocyte sedimentation rate.8
Severe PsA
In patients with more severe disease impacting QOL to a significant degree, the usual treatment includes both MTX and TNF-α inhibitors.1,5 Despite the short-term expense of TNF-α inhibitors compared with MTX, there may be potential long-term cost savings and benefits, such as a reduction in joint replacement surgery, concomitant medications, and improvement in both QOL and the potential to remain in the workforce.7
Promising New Therapies
Certolizumab, a PEGylated TNF-α inhibitor already approved for use in rheumatoid arthritis and Crohn’s disease, is currently in Phase III studies for use in PsA.9 Alefacept is a fusion protein which blocks the activation of T lymphocytes. It has been FDA approved for use in plaque psoriasis and is currently being studied in a phase 2 clinical trial in conjunction with MTX in the treatment of PsA.10
Apremilast is a novel PDE-4 (type 4 phosphodiesterase) inhibitor taken orally. A previous Phase II study showed a positive suppression of immune and inflammatory responses in patients with PsA. It is currently being studied at higher doses in a Phase III clinical trial.11 Finally, ustekinumab, a human anti-interleukin 12 and anti-interleukin 23 monoclonal antibody, showed promise in relieving tender, swollen joints in a Phase II, placebo-controlled trial. It is currently being studied in a Phase III clinical trial for the treatment of PsA.12
Role of the Pharmacist
Pharmacists can have an active role in the management of patients receiving treatment for PsA. There are potential toxicities which may result in the use of both MTX and TNF-α inhibitors. Pharmacists can play a key role in the promotion of safe use of these medications by ensuring appropriate monitoring and follow-up, as well as patient instruction on proper administration techniques.
Summary
PsA is an inflammatory disease associated with psoriasis. If left untreated, it could result in progressive joint damage leading to severe disability, thereby reducing a patient’s QOL. Therefore, early detection and treatment are paramount in the management of this disease.
Ginny D. Crisp, PharmD, BCACP, received her doctor of pharmacy in 2009 from the Eshelman School of Pharmacy at the University of North Carolina (UNC) at Chapel Hill. She completed her general pharmacy practice residency at Ralph H. Johnson VA Medical Center in Charleston, South Carolina followed by a Geriatrics Specialty Residency at UNC Hospitals and Clinics. She is currently the coordinator of the Carolina Assessment of Medications Program which provides clinical and financial services to the UNC Pharmacy Assistance Program patients. Additionally, she serves as a clinical assistance professor at the UNC Eshelman School of Pharmacy.
References
1. Gottlieb, A, Korman, NJ, Gordon, KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol 2008; 58: 851-64.
2. Gelfand JM, Gladman DD, Mease PJ, et al. Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol 2005; 53:573.
3. Oriente P, Biondi-Oriente C, Scarpa R. Psoriatic Arthritis. Clinical Manifestations. Baillieres Clin Rheumatol 1994;8:277.
4. Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic arthritis: development of new criteria from large international study. Arthritis Rheum 2006; 54:2665-2673.
5. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol 2011; 65:137-74.
6. Bruce, IN, Gladman DD. Psoriatic arthritis: recognition and management. BioDrugs 1998; 9:271.
7. Kimball AB, Jackson JM, Sobell JM, et al. Reductions in healthcare resource utilization in psoriatic arthritis patients receiving etanercept therapy: results from the educate trial. J Drugs Dermatol 2007; 57:581-87.
8. Felson D, Aletaha D, Anderson, J, et al. A proposed revision to the ACR20: The hybrid measure of American College of Rheumatology Response. Arthritis Rheum 2007; 57(2):193-202.
9. Certolizumab and Psoriatic Arthritis. www.clinicaltrials.gov. Accessed on 28 June 2012.
10. Alefacept and Psoriatic Arthritis. www.clinicaltrials.gov. Accessed on 29 June 2012.
11. Apremilast and Psoriatic Arthritis. www.clinicaltrials.gov. Accessed on 29 June 2012.
12. Ustekinumab and Psoriatic Arthritis. www.clincaltrials.gov. Accessed on 30 June 2012.
13. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. J Am Acad Dermatol 2008; 58:826-50.
