Psoriatic Arthritis Treatment & Management

Updated: Oct 25, 2019
  • Author: Anwar Al Hammadi, MD, FRCPC; Chief Editor: Herbert S Diamond, MD  more...
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Treatment

Approach Considerations

The treatment of psoriatic arthritis is directed at controlling the inflammatory process. Although no clear correlation exists between joint inflammation and the skin in every patient, the skin and joint aspects of the disease often must be treated simultaneously.

 Although traditional therapy has consisted of nonsteroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections, with disease-modifying antirheunatic drugs (DMARDs) being reserved for NSAID-resistant cases, the finding that 40% of patients may develop erosive and deforming arthritis has led to recommendations of early treatment with DMARDs in patients with active disease (see Guidelines). In addition to older DMARDs, several biologic agents and targeted synthetic agents have become available for use in psoriatic arthritis. [56]

Physical therapy should be started early in the disease process, with the regimen individualized. Different approaches are appropriate, depending on the disease phase.

Currently, no prospective studies are addressing surgical intervention in patients with psoriatic arthritis. Patients in severe pain or with significant contractures may be referred for possible surgical intervention (eg, synovectomy, joint replacement). Treatment should be aimed at pain relief or increasing the patient's function.

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Pharmacotherapy

Medical treatment regimens include the use of NSAIDs, Janus kinase (JAK) inhibitors, and disease-modifying antirheumatic drugs (DMARDs). DMARDs include methotrexate, sulfasalazine, cyclosporine, and leflunomide, as well as biologic agents (eg, anti–TNF-alpha medications, interleukin-12 [IL-12], IL-17, or IL-23 monoclonal antibodies). [5, 57, 58]

A randomized, 6-month study by Scarpa et al showed that the early use of methotrexate in patients with early psoriatic arthritis markedly improved tender and swollen joints and/or entheses. However, no significant difference was found after 3 months of treatment with NSAIDs or methotrexate. [59] These results suggest that other therapeutic approaches capable of modifying the early course of the disease should be used. [60]

Patients receiving long-term methotrexate therapy with high cumulative doses can be monitored using serial liver function tests (LFTs). Liver biopsy should be considered if LFT values are persistently elevated. Pro-collagen 3 N-terminal peptide (PIIINP) is an alternate test, although Lindsay et al reported that PIIINP frequently showed elevated values despite normal liver biopsy results. [61]

The U.S. Food and Drug Administration (FDA) and the European Union approved ustekinumab, an IL-12/23 inhibitor, for the treatment of active psoriatic arthritis in adults who have not responded adequately to previous treatment with nonbiologic DMARDs. [62] The drug was already approved in Europe and the United States for treatment of moderate to severe psoriatic plaques in adults.

Approval was based on 2 randomized, double-blind, placebo-controlled trials in 927 patients with active psoriatic arthritis who had at least 5 tender and 5 swollen joints and C-reactive protein levels of 0.3 mg/dL or higher despite previous conventional therapy. [62] At week 24, 42% of patients receiving ustekinumab 45 mg and 50% of those receiving 90 mg achieved at least 20% improvement; at 52 weeks, this response was found to have been sustained. Treatment with ustekinumab also improved dactylitis, enthesitis, and skin component. [62]

The TNF inhibitor certolizumab pegol (Cimzia) was also approved by the FDA for the treatment of active psoriatic arthritis in adults. [63] Approval was based on an ongoing, randomized, double-blind, placebo-controlled trial in 409 patients with active and progressive adult-onset psoriatic arthritis (RAPID-PsA) in which certolizumab-treated patients were significantly more likely to meet American College of Rheumatology 20%, 50%, and 70% response criteria by week 12 than placebo-treated patients. Certolizumab reduced radiographic progression and improved skin manifestations. [63]  Further analysis of the RAPID-PsA  showed that improvement occurred with certolizumab pegol used as monotherapy or given with concomitant DMARDs. [64]

Apremilast (Otezla), was approved by the FDA for treatment of active psoriatic arthritis. It is a phosphodiesterase-4 (PDE4) inhibitor that is specific for cyclic adenosine monophosphate (cAMP), resulting in increased intracellular cAMP levels. In studies involving nearly 1500 patients with psoriatic arthritis, improvement was observed in 32-41% of patients at week 6, a statistically significant difference compared with placebo (p < 0.05). Patients received apremilast 30 mg orally twice daily plus concomitant therapy with at least 1 DMARD, methotrexate, leflunomide, oral corticosteroids, or NSAIDs. [65, 66, 59, 60]

Secukinumab (Cosentyx) is a human IgG1 monoclonal antibody that selectively binds to and neutralizes IL-17A, which is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab was approved by the FDA for adults with active psoriatic arthritis in January 2016.

Approval of secukinumab was based on the FUTURE 1 and 2 phase 3 trials. In the FUTURE 1 trial (n=606), the American College of Rheumatology 20 (ACR20) response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P< 0.001 for both comparisons with placebo). [57] In FUTURE 2, a significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab doses of 300 mg (54%; P< 0.0001) and 150 mg (51%; P< 0.0001) compared with placebo (15%). [58]

Like certolizumab, golimumab (Simponi Aria) is a fully human anti-TNF-alpha monoclonal antibody. Golimumab received FDA approval for psoriatic arthritis in October 2017. It was initially approved in 2013 for the treatment of moderately to severely active rheumatoid arthritis. 

The approval was based on data from the GO-VIBRANT trial. In this phase 3, multicenter, randomized, double-blind, placebo-controlled trial, patients were randomized to either IV or golimumab 2 mg/kg at weeks 0, 4, 12, and 20 with crossover to golimumab at week 24. At week 14, 75.1% in the golimumab group achieved ACR criteria (ACR20) vs. 21.8% in the placebo group. Greater proportions of golimumab-treated patients had ACR50 (43.6% vs 6.3%), ACR70 (24.5% vs 2.1%), and PASI75 (59.2% vs 13.6%) at week 14. The golimumab group had greater mean changes at week 14 in Health Assessment Questionnaire-Disability Index (HAQ-DI) compared with placebo (-0.60 vs -0.12;). At week 24, the mean change in van der Heijde-Sharp (vdH-S) score was -0.4 in the golimumab group and 2.0 in the placebo. [67]

Abatacept (Orencia) was approved by the FDA for adults with active psoriatic arthritis in June 2017. Approval was based on a randomized, placebo-controlled phase 3 clinical trial in which abatacept significantly increased ACR20 response compared with placebo at week 24 (39.4% vs 22.3%; p< 0.001). The study was continued with open-labeled SC abatacept and efficacy was maintained or improved up to week 52. [68]

Ixekizumab (Taltz) was approved for active psoriatic arthritis in December 2017. Ixekizumab is a humanized monoclonal IgG4 antibody that targets IL-17A, resulting in neutralization of IL-17A’s proinflammatory effects.

Approval of ixekizumab was based on 2 randomized, double-blind, placebo-controlled phase 3 studies (SPIRIT-P1 and SPIRIT-P2), which included more than 670 adults. Results from both studies demonstrated that patients treated with ixekizumab achieved significant improvement in joint symptoms, as measured by ACR20, compared with placebo.

SPIRIT-P1 evaluated the safety and efficacy of ixekizumab compared with placebo in patients who had never been treated with a biologic DMARD. SPIRIT-P2 evaluated safety and efficacy compared with placebo in patients in whom treatment with 1 or 2 TNF inhibitors had failed. At 24 weeks, patients who received ixekizumab had an ACR20 response superior to placebo (58% vs 30%, respectively, in SPIRIT-P1; 53% vs 20% in SPIRIT-P2) . [69, 70]

In December 2017, tofacitinib was approved by the FDA as the first-in-class Janus kinase (JAK) inhibitor for active psoriatic arthritis in patients who inadequately respond or are intolerant to methotrexate or other DMARDS.  Approval was based on data from the Phase 3 Oral Psoriatic Arthritis Trial (OPAL) clinical development program, OPAL Broaden and OPAL Beyond, and available data from the ongoing long-term extension trial, OPAL Balance.

In the OPAL Broaden study, 50% of patients who received tofacitinib 5 mg PO BID in combination with a nonbiologic DMARD achieved an American College of Rheumatology 20 (ACR20) response at 3 months, compared with 33% of those treated with placebo. [71]

In the OPAL Beyond study, 50% of patients achieved an ACR20 response with tofacitinib 5 mg PO BID at 3 months, when compared with 24% taking placebo. In both studies, significant improvements in ACR20 response was also seen with tofacitinib 5 mg PO BID when compared with placebo at week 2, which was a secondary endpoint and the first post-baseline assessment (OPAL Broaden: 22% vs. 6%; OPAL Beyond: 27% vs. 13%). [72]

In patients with severe skin inflammation, medications such as methotrexate, retinoic acid derivatives, and psoralen plus ultraviolet (UV) light should be considered. These agents have been shown to work on skin and joint manifestations.

Intolerance to methotrexate was observed in 14.3% of patients with psoriatic arthritis in a cross-sectional study (n=291), as measured with the Methotrexate Intolerance Severity Score (MISS). GI symptoms, including nausea, abdominal pain, and vomiting, occurred during methotrexate treatment in 123 patients (42.3%); behavioral symptoms, including restlessness and irritability, were also common. Methotrexate intolerance was more common with parenteral (20.6%) than oral (6.2%) administration. [61, 73]

Intra-articular injection of entheses or single inflamed joints with corticosteroids may be particularly effective in some patients. Use disease-modifying drugs in individuals whose arthritis is persistent. If the skin disease is well controlled with topical medication, the joint disease can be treated with a variety of second-line or cytotoxic drugs. Intramuscular administration of gold has been used in the past but has been supplanted by newer DMARDs.

In a study completed by the Psoriatic Arthritis Study Group, patients with psoriasis and psoriatic arthritis who were receiving stable doses of methotrexate were found to benefit from the addition of 1 or more courses of intramuscular alefacept, a T-cell inhibitor via a human lymphocyte function–associated antigen 3 (LFA-3) Fc fusion protein that blocks the interaction between CD2 on T cells and LFA-3 on antigen-presenting cells. Further benefit in psoriatic arthritis was apparent after a second course of alefacept, and no additional toxicity was observed. [4]

Sulfasalazine and cyclosporine are second-line DMARDs that have received particular attention in the management of psoriatic arthritis. Although these drugs may control the acute inflammation in persons with psoriatic arthritis, they have not been helpful in arresting the progression of clinical and radiologic damage. Thus, the disease must be treated earlier or better drugs are necessary, to prevent the damage that may ensue as a result of psoriatic arthritis.

Cyclosporine appears to be an effective agent for the treatment of psoriasis and psoriatic arthritis. The major concern with this drug is its toxicity, especially its nephrotoxicity, and hypertension.

Combination therapy (eg, methotrexate/sulfasalazine, methotrexate/cyclosporine) may be more efficacious in some patients. [74]

Other agents that have been tried in psoriatic arthritis but whose efficacy remains unproven include the following:

  • Vitamin D-3
  • Bromocriptine
  • Peptide T
  • Fish oils

The Medical Board of the National Psoriasis Foundation weakly recommends vitamin D supplementation in patients with psoriatic arthritis, as well as dietary weight reduction with a hypocaloric diet in overweight and obese patients. The Board recommends that dietary interventions should always be used in conjunction with standard medical therapies. [75]

Antimalarials, particularly hydroxychloroquine, are usually avoided in patients with psoriasis for fear of precipitating exfoliative dermatitis or exacerbating psoriasis. However, 2 studies showed that these reactions did not occur in patients who were treated with hydroxychloroquine; therefore, this drug is occasionally used to treat psoriatic arthritis.

Systemic corticosteroids are usually avoided because of possible rebound of the skin disease upon withdrawal.

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Physical Therapy

The rehabilitation treatment program for patients with psoriatic arthritis should be individualized and should be started early in the disease process. Such a program should consider the use of the following:

  • Rest: Local and systemic

  • Exercise: Passive, active, stretching, strengthening, and endurance

  • Modalities: Heat and cold treatments can temporarily relieve pain and reduce joint swelling; such treatments include soaking in a warm tub or placing a warm compress or cold pack on the painful joint

  • Orthotics: Upper and lower extremities, spinal

  • Assistive devices for gait and adaptive devices for self-care tasks: Including possible modifications to homes and automobiles

  • Education about the disease, energy conservation techniques, and joint protection

  • Possible vocational readjustments

With regard to the first item above, prolonged rest should be avoided to prevent the deleterious effects of immobility. In a very few people, psoriatic arthritis may cause extreme fatigue.

Acute phase

Encourage rest as indicated. Splints may be used for rest and pain relief, especially for the hands, wrists, knees, or ankles. Cold modalities should be used to decrease inflammation and assist with pain relief. Joints should not be moved beyond the limit of pain; passive movements should be limited at this time. Education should be completed during this phase, with topics including the disease itself, the importance of rest, the exercise program, joint protection, energy conservation, and weight loss, if appropriate.

Subacute and long-term phase

Isometric exercises are begun, with progression to active movement. Gradual range-of-motion (ROM) exercises include passive and active exercises; areas with subluxation should not be forced passively. Heating modalities, including moist heat packs, paraffin wax, diathermy, and ultrasound, can be used to decrease pain; heat therapy should be administered just prior to the performance of ROM exercises.

Institute gait activities, with the patient bearing weight as tolerated, with or without an assistive device. Gentle stretching should be gradually introduced. If pain persists beyond 2 hours after therapies, then the intensity should be decreased. If a joint is swollen, then no resistive exercises should be performed through full ROM.

For patients with axial spine involvement, spine extension exercises help with flexibility and strength. ROM exercises should be performed, but not in patients with increased pain.

If the patient has sausage toes, extra-depth shoes with a high toe box should be considered to protect the foot. With pain in the toes, such shoes should have a rocker-bottom modification to alleviate forces during the toe-off phase in the gait cycle. The patient may also benefit from arch supports if plantar fascitis is a problem.

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Synovectomy and Arthroplasty

Arthroscopic synovectomy has been effective in treating severe, chronic, monoarticular synovitis. Because of an enhanced tendency for patients to develop fibrosis in association with this therapy, anti-inflammatory and physical therapy measures aimed at improving ROM are important adjuncts to this intervention.

Joint replacement and forms of reconstructive therapy are occasionally necessary. Hip and knee joint replacements have been successful, for the most part, in patients with psoriatic arthritis. Arthrodesis and arthroplasty have also been used on joints, such as the proximal interphalangeal joint of the thumb. The wrist often spontaneously fuses, and this may relieve the patient's pain without surgical intervention.

Because of the diffuse soft-tissue involvement that is associated with psoriatic arthritis, high rates of recurrence of joint contractures have been noted after surgical release, especially in the hand.

For arthritis mutilans, surgical intervention is usually directed toward salvage of the hand. Combinations of arthrodesis, arthroplasty, and bone grafts to lengthen the digits may be used. The goal is to maintain the pinch mechanism of the thumb and the first 2 fingers.

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Consultations

If the patient's physiatrist feels uncomfortable with prescribing medications for psoriatic arthritis, referral to a rheumatologist with more experience with these agents may be advisable. The physiatrist may then concentrate on functional restoration of the patient. Referral to a surgeon should be considered for appropriate patients.

Patients with juvenile psoriatic arthritis should be examined by an ophthalmologist annually to check for the several forms of eye inflammation usually associated with various forms of juvenile arthritis.

Given the complexity of DMARD therapy, patients with psoriatic arthritis should be followed simultaneously by a rheumatologist and physiatrist. In addition, consultation with an orthopedic surgeon is warranted for individuals who may benefit from joint replacement, arthrodesis, or contracture release.

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Deterrence and Prevention

A number of medications can exacerbate psoriasis; therefore, avoidance of these agents may help to prevent or minimize flare-ups. Lithium and withdrawal from systemic corticosteroids are well known to cause disease flare-ups.

Other drugs that have been implicated include beta-blockers, antimalarials (although, as previously mentioned, evidence suggests that hydroxychloroquine does not exacerbate skin lesions), and NSAIDs. If skin lesions worsen with an NSAID, switch to a different family of NSAID.

Prevention includes rest and exercise. Joint protection, including splints, braces, and other supports, may be helpful. No definitive prevention exists, because this is a chronic disease that can wax and wane.

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Complications

Many patients with psoriatic arthritis have comorbidities, such as the following:

  • Cardiovascular disease
  • Metabolic syndrome
  • Inflammatory bowel disease
  • Osteoporosis
  • Malignancy
  • Ophthalmic disease
  • Liver disease

Kocijan et al reported that psoriatic arthritis is associated with significantly decreased trabecular volumetric bone mineral density (BMD) and deterioration of trabecular bone microstructure. Those effects on bone correlated with the duration of skin disease. [76] A study by Simon et al found that despite longer disease duration, patients with psoriatic arthritis treated with biologic disease-modifying antirheumatic drugs (DMARDs) had higher bone mass and better bone strength than those treated with methotrexate PsA patients receiving MTX or no DMARDs. [77]

A longitudinal cohort study in 1061 Canadian patients with psoriatic arthritis identified liver abnormalities or disease in 32%. In most cases, the liver abnormalities or disease were not present when the patient was first evaluated in clinic, but instead developed after an average of 8.3 years of follow-up and at a mean age of 50.5 years. Drug-induced hepatitis (14%) and fatty liver (13%) were the most common conditions. [78] On multivariable analysis, the following factors were independently associated with liver abnormalities:

  • High body mass index (odds ratio [OR], 1.07)
  • Daily alcohol intake (OR, 4.46)
  • Damaged joint count (OR, 1.04)
  • Elevated C-reactive protein level (OR, 2.00)
  • Treatment with methotrexate or leflunomide (OR, 4.39)
  • Treatment with tumor necrosis factor inhibitors (OR, 10.56)

These authors recommend monitoring of liver function in psoriatic arthritis who are at high risk for liver abnormalities. [78]

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