Reports

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PHYSICIAN PERSPECTIVE - Based on the following articles: Arthritis Rheum 2006;54:2665-73, Ann Rheum Dis 2008 Oct 24;Epub ahead of print.

November 2008

Editorial review:

Dafna D. Gladman, MD, FRCPC

Senior Scientist, Toronto Western Research Institute, Centre for Prognosis Studies in the Rheumatic Diseases, UHN-Toronto Western Hospital, Professor of Medicine, University of Toronto, Toronto, Ontario

Developments in Disease Classification: The CASPAR Criteria

Though variable in presentation, one widely cited descriptor defines psoriatic arthritis (PsA) as “an inflammatory arthritis associated with psoriasis and usually with a negative serological test for rheumatoid arthritis (RA)” (Semin Arthritis Rheum 1973;3:55-78). Characteristic features include erythema, warmth and swelling of the affected joint. Patients can present with asymmetric joint involvement, then progressing and involving more joints over time and virtually any joint can be involved (Skin Therapy Lett 2008;13:4-8).

Several classification criteria for PsA have been developed and published, but no consensus existed as to which criteria most accurately reflect the condition. Recently, the Classification Criteria for Psoriatic Arthritis (CASPAR) Study Group published diagnostic criteria based on prospectively collected data from a large cohort of patients with PsA and other forms of inflammatory arthritis (Arthritis Rheum 2006;54:2665-73).

To meet the CASPAR criteria for a diagnosis of PsA, a patient must have inflammatory articular disease (joint, spine or entheseal) accompanied by at least three of the following: evidence of current psoriasis; a personal history of psoriasis or a family history of psoriasis; typical psoriatic nail dystrophy, including onycholysis, pitting and hyperkeratosis; a negative test for rheumatoid factor by any method except latex; either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis; or evidence of juxta-articular new bone formation, appearing as ill-defined ossification near joint margins on plain radiographs of the hand or foot.

When applied to their study population, the CASPAR Study Group found that the criteria had a sensitivity of 91.4% and specificity of 98.7% for diagnosis of PsA. The criteria are simple to use and can readily be incorporated into evaluation of patients in clinical practice.

Treatment Recommendations

More recently, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) published the first evidence-based recommendations for treatment of PsA (Ann Rheum Dis 2008 Oct 24;Epub ahead of print). GRAPPA developed recommendations for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the PsA setting. The group drafted a total of 19 recommendations, 16 of which had more than 80% agreement among members of GRAPPA.

As an overarching principle, the GRAPPA recommendations emphasize the need for early and aggressive treatment. A growing body of data show that inflammatory joint disease, such as PsA and RA, may result in damage early in the disease process. To prevent joint damage and associated disability, clinicians must be vigilant in recognizing and diagnosing the disease as soon as possible and then initiate treatment that increasingly includes early use of a combination of conventional disease-modifying antirheumatic drugs (DMARDs) and biologic agents, such as inhibitors of tumour necrosis factor alpha (TNF-a).

The GRAPPA recommendations include criteria for categorizing disease as mild, moderate or severe. Separate severity criteria have been developed for peripheral arthritis, skin disease, nail disease, axial (spinal) disease, enthesitis and dactylitis. Appropriate characterization of disease severity is essential to guide treatment decisions aimed at using the most effective therapy for an individual patient. The most severe component determines the severity of the disease for each patient.

Some patients have multiple manifestations of PsA, which can have a synergistic impact on a patient’s physical condition and quality of life (QOL). The impact can be assessed by patient global assessment, the Health Assessment Questionnaire (HAQ) and certain disease-specific instruments.

Peripheral Arthritis and Dactylitis

GRAPPA recommends use of the CASPAR criteria for diagnosis of PsA. The group suggests confirmation of a psoriasis diagnosis by a dermatologist and inflammatory musculoskeletal disease by a rheumatologist. However, the group also notes that any “appropriately qualified health professional” can diagnose either condition.

GRAPPA cites NSAIDs as appropriate only for patients with mild disease. Moderate or severe disease should be treated with DMARDs or TNF-a inhibitors. The authors of the recommendations note an absence of evidence supporting TNF-a inhibitors ahead of DMARDs, despite a much larger treatment effect of TNF-a inhibitors.

In patients whose disease does not respond to at least one trial of a DMARD, anti-TNF-a therapies should be given. However, patients with poor-prognosis features can be considered candidates for TNF-a inhibitors in the absence of a failed DMARD trial.

Studies reported at the 2008 meetings of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) reflected current interest in the use of anti-TNF therapy in early arthritis. In patients with RA, several studies showed that initiation of therapy with a TNF-a inhibitor plus methotrexate provided better disease control compared with methotrexate alone. For example, data from the Dutch Behandel Strategieën (BeSt) study showed that patients initially treated with methotrexate plus infliximab had a higher rate of drug-free remission compared with other treatment strategies, a higher rate of prolonged (mean duration 22 months) drug-free remission, and better preservation of function, as judged by HAQ scores. However, such information is not available for PsA.

Dactylitis is defined as a uniform swelling of a digit. The swelling is caused by synovitis, tenosynovitis and enthesitis combined with soft-tissue edema. Prevalence varies, as estimates range from 16 to 48% of patients with PsA. However, acute dactylitis may predict more severe forms of the disease. Conversely, chronic, non-tender, diffuse swelling may confer less clinical significance. In some patients, recurrent isolated dactylitis might be the only clinical manifestation of PsA. According to GRAPPA, treatment of dactylitis is largely empirical. The notable exception is infliximab, which has A-level evidence to support its use for treatment. NSAIDs are recommended as initial treatment for mild disease, but rapid progression to use of injected steroids is not uncommon.

Axial Disease and Enthesitis

A patient must exhibit at least two of the following for a positive diagnosis: inflammatory back pain; limitation of motion of the cervical, thoracic or lumbar spine in both saggital and frontal planes; or radiologic criteria (plain X-ray, syndesmophytes, MRI changes in bone marrow edema in sacroiliac joints, erosions, joint space narrowing).

Treatment recommendations were derived from those for ankylosing spondylitis (AS). Traditional nonbiologic DMARDs have not proved to be effective in axial manifestations of AS. By extrapolation, the agents are considered inadequate for axial disease in PsA. For patients with mild-to-moderate disease, GRAPPA recommends NSAIDs, physiotherapy, analgesia, and injection of the sacroiliac joint. In AS, infliximab, adalimumab and etanercept have demonstrated efficacy; the group consensus was that they would be similarly effective in axial PsA. In fact, data supporting that consensus emerged from a study reported at the ACR meeting, demonstrating activity in patients with PsA treated with the investigational TNF-a inhibitor golimumab.

Enthesitis poses a diagnostic challenge, and GRAPPA cites three approaches to diagnosis: clinical examination, power Doppler ultrasound and MRI. Several assessment instruments have been proposed, but none has won widespread support. A visual analogue pain scale offers another option. Mild disease can be managed with NSAIDs, physical therapy and corticosteroids. The group recommends conventional DMARDs for moderately severe enthesitis and TNF-a inhibitors for severe enthesitis. Only the TNF-a recommendation is backed by A-level evidence.

Cutaneous Manifestations and Nail Disease

Patients with mild psoriasis usually are candidates for topical therapy. GRAPPA defines mild disease as generally asymptomatic; minimal impact on QOL; amenable and responsive to localized therapy; <5% for plaque psoriasis; and no incapacity and/or disability. Patients with moderate or severe disease are candidates for additional therapy or a switch to systemic agents.

GRAPPA cited high-level evidence for multiple agents that can be used in patients with moderate or severe skin disease. These include methotrexate, cyclosporine, fumaric acid esters, efalizumab, infliximab and the other approved TNF-a inhibitors. Second- and third-line therapies with A-level support include acitretin, alefacept, sulfasalazine and leflunomide. Hydroxyurea and mycophenolate mofetil have only level C support (extrapolation from other sources of evidence).

The same diagnostic criteria applied to skin disease can be applied to evaluation of patients for evidence of nail involvement. With respect to treatment, several classes of agents have similar support. These include retinoids, oral PUVA, cyclosporine and TNF-a inhibitors. The efficacy of TNF-a inhibitors in management of nail disease is limited to infliximab and alefacept.

Summary

The highly variable disease manifestations, severity and clinical features of PsA makes the condition a formidable challenge for clinicians. Therapeutic decisions should be based on a thorough assessment of all areas of involvement, including skin and nails. Widespread inflammation can lead to profound impairment of function and quality of life. The therapeutic strategies described in the GRAPPA recommendations are the first-ever treatment recommendations for PsA. The recommendations were developed with input from rheumatologists and dermatologists, as both specialties are involved in comprehensive management of the disease and its myriad clinical manifestations. The therapeutic recommendations were derived from a thorough literature review, followed by an exercise in consensus development. Interest in PsA has increased in recent years as a result of improved understanding of underlying mechanisms, better clinical trial design and the emergence of effective biologic agents and the TNF-a inhibitor class. As knowledge of this challenging disease process continues to evolve, the treatment recommendations will be refined and updated as new data become available.

Table 1.