Management of psoriatic arthritis

Rheumatoid arthritis (RA)

Patients with PsA in the form of a polyarthritis can present in a fashion that may be indistinguishable from RA. However, the involvement of the distal interphalangeal (DIP) joints, an asymmetric distribution of joint disease, spondyloarthritis, sausage digits, new bone formation on radiographs, cutaneous findings, and the characteristic nail manifestations of PsA all help to distinguish it from RA.^[5] Only a small number of patients with PsA will test positive for rheumatoid factor or anti-citrullinated peptide antibodies, while these tests are positive in a majority of patients with RA.

Reactive arthritis

Asymmetric oligoarthritis, enthesitis, sausage digits, and back pain can be seen in patients with either reactive arthritis (formerly called Reiter syndrome) or PsA. However, unlike reactive arthritis, a history of an antecedent infectious illness, with either genitourinary symptoms of urethritis or a dysenteric illness, would not be characteristic of PsA. In addition, human leukocyte antigen-B27 positivity occurs more commonly in patients with reactive arthritis.

Arthritis of inflammatory bowel disease

The peripheral and axial arthritis associated with inflammatory bowel disease may occur in a very similar pattern to that seen in PsA; both diseases may manifest as symmetric or asymmetric oligoarthritis or sacroiliitis. Uveitis may be seen in both and the frequency of psoriasis may be increased in patients with Crohn’s disease. However, inflammatory bowel disease can usually be suspected based on clinical findings and confirmed with endoscopic investigation and biopsy.

Ankylosing spondylitis

A spinal disease that occurs in patients with PsA may be difficult to distinguish from ankylosing spondylitis.^[5,6] Peripheral features of PsA such as enthesitis and dactylitis can occur in either condition. However, the presence of psoriasis and some radiographic features may help distinguish the two disorders. PsA is more often associated with the presence of asymmetric sacroiliitis, non-marginal syndesmophytes, asymmetric syndesmophytes, more frequent involvement of the cervical spine, and less frequent involvement of the lumbar spine.

Gout

Both PsA and gout can present as an acute monoarthritis or oligoarthritis, and psoriasis can be associated with hyperuricemia. The diagnosis of gout can be confirmed by finding monosodium urate crystals on examination of the synovial fluid.

Osteoarthritis

Both PsA and osteoarthritis may be characterized by involvement of the DIP joints. PsA as the cause of DIP joint involvement can generally be distinguished from osteoarthritis with Heberden’s nodes by the nodular bony change of osteoarthritis, the more diffuse swelling of the joint in PsA, and the presence of other characteristic findings of PsA.

Mild arthritis

In patients with mild arthritis, defined as disease involving <4 joints, no radiological evidence of damage, and minimal discomfort or functional impairment, initial treatment can be started with NSAIDs (e.g. naproxen 375–500 mg twice daily, celecoxib 200 mg twice daily, or etoricoxib 60–90 mg daily) rather than starting a DMARD.^[7,8] Other NSAIDs that can be used include ibuprofen (up to 2400 mg/day), diclofenac (up to 150 mg/day), or ketoprofen (up to 200 mg/day). Comparative studies did not find any difference in efficacy between different NSAIDs and there was no significant aggravation of skin disease.

Leflunomide

LEF (20 mg daily, taken orally) is used in patients who have persistent joint inflammation despite 3 months of treatment with MTX and in patients who are unable to tolerate MTX due to adverse effects, such as liver toxicity. It also improves skin disease but may be less effective for the skin changes than MTX.^[11]

Apremilast

In patients with PsA and nonerosive inflammatory arthritis, apremilast (30 mg twice daily following an up-titration at a rate of 10 mg daily over 6 days), a novel, orally administered phosphodiesterase-4 inhibitor, is recommended. The drug modifies multiple pro-inflammatory mediators and cytokines involved in the innate and adaptive immunity.^[12]

Apremilast may also be of benefit in patients with enthesitis and dactylitis early in the disease course. It may be particularly appropriate for PsA patients with multiple comorbidities, given the excellent safety profile and documented efficacy in randomized trials for both psoriasis and PsA. It is also useful for patients who wish to avoid DMARD therapy, infusions, or injections. Some patients require up to 4 months of treatment to achieve a maximal response to the drug.

Apremilast should not be used in patients with the erosive disease, as the capacity of apremilast to prevent joint injury has not been established. Routine laboratory monitoring is not required, but baseline serum creatinine is important because the dose should be reduced to 30 mg once daily in patients with creatinine clearance estimated at <30 mL/min.^[13]

Etanercept

About 50 mg as a subcutaneous injection once weekly, etanercept is a dimeric p75 TNF-alpha receptor Fc fragment fusion protein that binds TNF.

Infliximab

Administered as 5mg/kg by intravenous infusion at 0, 2, and 6 weeks, followed by 5 mg/ kg every 8 weeks thereafter. It may be given either with or without MTX. Infliximab is a human/mouse chimeric anti-TNF-alpha antibody.

Adalimumab

About 40 mg subcutaneously once every 2 weeks, adalimumab is a human monoclonal anti-TNF antibody.

Golimumab

About 50 mg subcutaneously once monthly, golimumab is a human monoclonal anti-TNF antibody.

Certolizumab pegol

Initial dose of 400 mg (administered as two 200 mg injections subcutaneously), repeated 2 and 4 weeks after the initial dose; maintenance is with 200 mg once every other week, or 400 mg every 4 weeks. Certolizumab pegol is a pegylated Fab fragment of a humanized anti-TNF monoclonal antibody.

Screening for latent TB before beginning therapy with anti-TNF agents is necessary, and those with evidence of disease usually require prophylactic anti-TB therapy. TNF inhibitors are usually avoided in patients with first-degree relatives with multiple sclerosis.

Sustained benefit from these drugs has been shown among patients with PsA according to the various studies.^[15,16] In addition to improvement in clinical signs and symptoms, these agents also reduce radiographic progression of disease.^[17] The efficacy of these drugs for PsA appears comparable, and the choice of the agent is based on a patient preference for route and frequency of administration and the potential cost to the patient.

Anti-IL-17 therapies

Several drugs that inhibit IL-17 are available for use in PsA and/ or psoriasis

Tofacitinib

An oral inhibitor of JAK has demonstrated efficacy in the treatment of PsA in several randomized trials, including both patients with an inadequate response to a conventional synthetic DMARD^[23] and patients with an inadequate response to TNF inhibitor therapy.^[24] Tofacitinib inhibits cytokine pathways important in PsA and psoriasis through its effects on JAK3 and JAK1. The dosage is 5 mg or 10 mg twice daily.

Other JAK inhibitors, including the selective JAK1 inhibitor and filgotinib, are under investigation. Dosage is 200 mg orally once daily.^[25]

Risk factors for progressive joint damage

The factors predicting a poor prognosis with respect to progression of peripheral joint injury are:^[29]

• Increased numbers of actively inflamed joints

• Elevated erythrocyte sedimentation rate or C-reactive protein

• Failure of previous medication trials

• The presence of joint damage (clinically or radiographically)

• Loss of function (by Health Assessment Questionnaire)

• Diminished quality of life.

Remission

Complete relief of joint tenderness and swelling may occur in a substantial minority of treated patients. In one study involving 391 patients, 69 (18%) achieved remission, and nearly one-half remained free of active joint disease without continued use of medication.^[30]

Clinical monitoring of disease should include joint counts that assess both the upper and lower extremities and the number of areas involved by enthesitis and by dactylitis. In clinical practice, plain film radiography of clinically involved peripheral joints, the sacroiliac joints, and the spine is used to assess the extent and progression of disease at these sites.