Psoriatic Arthritis Treatment & Management

Updated: Jul 15, 2020
  • 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 skin involvement in every patient, the skin and joint aspects of the disease often must be treated simultaneously. The finding that 40% of patients may develop erosive and deforming arthritis has led to recommendations of early treatment with disease-modifying antirheumatic drugs (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. [66]

Nonpharmacologic treatment such as physical therapy should be considered early in the disease process, with the regimen individualized to the individual patient's need. Different approaches are appropriate, depending on the disease phase.

Currently, no prospective studies address surgical intervention in patients with psoriatic arthritis. Patients in severe pain or with significant contractures may be referred for consideration of surgical intervention (eg, synovectomy, joint replacement). Treatment should be aimed at symptom relief and functional improvemnet.

Guidelines and recommendations are designed to help physicians work with patients to select the optimum therapy. The following are important considerations that may additionally influence therapy choice:

  • Presence of comorbidities such as infections, inflammatory bowel disease (IBD), diabetes mellitus, and uveitis
  • Previous therapies and reasons for failure
  • Peripheral or axial joint involvement
  • Severity of joint involvement and the patient’s functional status
  • Other active domains of the disease (skin and/or nails)

The severity of the psoriatic arthritis and psoriasis is usually assessed on a case-by-case basis, as there is no widely approved definition. In the case of cutaneous psoriasis, particularly in clinical trials, a Psoriasis Area and Severity Index (PASI) score of ≥12 and body surface area (BSA) score ≥10 is widely considered severe. [67] The 2007 National Psoriasis Foundation (NSF) expert consensus statement defined psoriatic arthritis and psoriasis as moderate to severe if one or more items in the lists below were positive. [68]

Criteria for psoriatic arthritis:

  • Erosive disease
  • Elevated markers of inflammation attributed to psoriatic arthritis (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP])
  • Long-term damage that interferes with function (eg, joint deformity)
  • Highly active disease that causes a major impairment in quality of life
  • Active psoriatic arthritis at many sites, including dactylitis and enthesitis
  • Function-limiting psoriatic arthritis at a few sites
  • Rapidly progressive disease

Criteria for psoriasis:

  • PASI of 12 or more
  • BSA of 5-10% or more
  • Significant involvement in specific areas (face, hands, feet, nails, scalp, intertriginous areas) where the burden of the disease causes significant disability
  • Impairment of physical of mental function

The following indices have been developed for measuring disease activity and response to treatment in psoriatic arthritis [69]

  • Psoriatic Arthritis Disease Activity Score (PASDAS)
  • Arithmetic Mean of the Desirability Function (AMDF)
  • Composite Psoriatic Disease Activity Index (CPDAI)
  • Disease Activity Index for Psoriatic Arthritis (DAPSA)

A study comparing those indices concluded that PASDAS and AMDF were better able to distinguish treatment effect, having larger effect sizes at 24 weeks, while PASDAS, AMDF, and modified CPDAI better reflected domains such as skin, enthesitis, and dactylitis.112 Although the PASDAS can differentiate low, moderate, and high disease activity, its use in routine clinical care has been called into questioned due to its complexity. However, Mulder et al reported successful implementation of PASDAS measurements and skin assessment in routine clinical care for the 1300 psoriatic arthritis patients at their outpatient clinic. [70]

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Pharmacotherapy

Medical treatment regimens include the following:

  • Medication for symptomatic relief, such as nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and glucocorticoid joint injections
  • Oral small molecules (OSMs), such as DMARDs, including methotrexate, sulfasalazine, cyclosporine, leflunomide, and apremilast
  • Biologic therapy

Intra-articular injection of entheses or single inflamed joints with corticosteroids may be particularly effective in some patients. Use DMARDs 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 injection of gold was used in the past but has been supplanted by newer DMARDs.

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 both skin and joint manifestations.

Methotrexate

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. [71]  These results suggested that other therapeutic approaches capable of modifying the early course of the disease should be used.

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 alternative test, although Lindsay et al reported that PIIINP frequently showed elevated values despite normal liver biopsy results. [72]

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. [73, 74]

Biologic therapy

Biologic agents include the following:

  • Tumor necrosis factor (TNF) inhibitors [5] - Etanercept, infliximab, adalimumab, golimumab, certolizumab pegol
  • Interleukin (IL)-12/23 inhibitors - Ustekinumab, guselkumab
  • IL-17 inhibitors - Secukinumab, ixekizumab, brodalumab [75, 76]
  • Janus kinase (JAK) inhibitors - Tofacitinib
  • Phosphodiesterase-4 (PDE4) inhibitor - Apremilast

Certolizumab pegol

The TNF inhibitor certolizumab pegol (Cimzia) is approved by the U.S. Food and Drug Administration (FDA)  for the treatment of active psoriatic arthritis in adults. [77] 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 (ACR20, ACR50, ACR70) by week 12 than placebo-treated patients. Certolizumab reduced radiographic progression and improved skin manifestations. [77]  Further analysis of the RAPID-PsA  showed that improvement occurred with certolizumab pegol used as monotherapy or given with concomitant DMARDs. [78]

Golimumab

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. 

Approval for psoriatic arthritis 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 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 group. [79]

Ustekinumab

The FDA and the European Union have 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. [80]  The drug was previously approved in the US and Europe 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 CRP levels of 0.3 mg/dL or higher despite previous conventional therapy. At week 24, 42% of patients receiving ustekinumab 45 mg and 50% of those receiving 90 mg achieved at least 20% improvement; this response was sustained at 52 weeks. Treatment with ustekinumab also improved dactylitis, enthesitis, and skin lesions. [80, 81]

Guselkumab

Guselkumab (Tremfya) is the first selective interleukin-23 inhibitor approved to treat active psoriatic arthritis in adults. Approval was based on 2 randomized, double-blind. placebo-controlled trials, DISCOVER-1 and DISCOVER-2, which evaluated the efficacy and safety of guselkumab in adults with active psoriatic arthritis. In both trials, the primary endpoint of American College of Rheumatology 20% improvement (ACR20) at week 24 was reached. In Discover-1, 59% (every 4 weeks) and 52% (every 8 weeks) of the guselkumab-treated arms achieved ACR20 at week 24. In Discover-2, 64% (every 4 weeks and every 8 weeks) of the guselkumab-treated arms achieved ACR20 at week 24. Similar responses were seen in both trials regardless of concomitant or previous treatment with classical DMARDs, gender, and body weight. [82]

Secukinumab

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 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). [75] 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%). [76]

Abatacept

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-label abatacept and efficacy was maintained or improved up to week 52. [83]

Ixekizumab

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) . [84, 85]

Tofacitinib

In December 2017, tofacitinib was approved by the FDA as the first-in-class JAK inhibitor for active psoriatic arthritis in patients who experience inadequate response or intolerance to methotrexate or other DMARDS. Approval was based on data from the phase III 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 ACR20 response at 3 months, compared with 33% of those treated with placebo. [86]

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%). [87]

Apremilast

Apremilast (Otezla) is approved by the FDA for treatment of active psoriatic arthritis. It is a 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. [88, 89, 90, 91]

Other agents

In a study 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 may control the acute inflammation in persons with psoriatic arthritis, but they have not been found helpful in arresting the progression of clinical and radiologic damage. Thus, earlier treatment or use of more effective drugs is necessary, to prevent the long-term damage that psoriatic arthritis may cause.

Cyclosporine appears to be an effective agent for the treatment of psoriasis and psoriatic arthritis. [92] 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. [93]

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

  • Vitamin D3
  • 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. [94]

Antimalarials, particularly hydroxychloroquine, are usually avoided in patients with psoriasis for fear of precipitating exfoliative dermatitis or exacerbating psoriasis. However, in 2 studies these reactions did not occur in patients who were treated with hydroxychloroquine; therefore, this drug is occasionally used to treat psoriatic arthritis. [95]

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

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Nonpharmacologic therapy

The 2018 American College of Rheumatology/National Psoriasis Foundation (ACR/NPF) guidelines [96]  recommend that all patients with active psoriatic arthritis consider the following forms of nonpharmacologic therapy:

  • Exercise
  • Physical therapy
  • Massage therapy
  • Occupational therapy
  • Acupuncture

The ACR/NPF guidelines recommend the use of one form or a combination of those therapies, if tolerated. For patients with active joint disease,  low-impact exercise such as tai chi, yoga, and swimming is more suitable than high-impact sports such as running. [97]

Smoking cessation is an important consideration. Clinicians should offer their psoriatic arthritis patients referrals or tools to stop smoking, as multiple randomized controlled trials validate the benefit of smoking cessation in other conditions and in the general population. [98, 99]

Weight loss in individuals with a high body mass index can potentially provide benefit by reducing mechanical stress on joints, improving mobility, and potentially increasing pharmacologic response. 

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

  • Heat and cold: These modalities 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 cases, 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 following:

  • The disease itself (see Overview/Patient Education)
  • The importance of rest
  • An exercise program
  • Joint protection
  • Energy conservation
  • 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. In patients with painful toes, such shoes should have a rocker-bottom modification to alleviate forces during the toe-off phase in the gait cycle. Arch supports may be beneficial 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 physician feels uncomfortable with prescribing medications for psoriatic arthritis, referral to a rheumatologist with more experience with these agents may be advisable. A physiatrist may concentrate on functional restoration of the patient. 

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 pharmacologic therapy, patients with psoriatic arthritis should be cared for by a multidiscplinary team, especially if more than one domain of the disease is active. In addition, those with joint deformities may require consultation with an orthopedic surgeon, as joint replacement, arthrodesis, or contracture release may be needed.

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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 usually 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. [100] A study by Simon et al found that despite longer disease duration, patients with psoriatic arthritis treated with biologic DMARDs had higher bone mass and better bone strength than those treated with methotrexate or no DMARDs. [101]

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. [102] 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. [102]

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