Psoriatic Arthritis Xử trí

Course of the Disease

The course of psoriatic arthritis varies, ranging from mild and non-destructive to a severe, debilitating, erosive arthropathy.  Erosive and deforming arthritis occurs in 40-60% of patients and may be progressive as early as within the first year of diagnosis. This is characterized by flares and remissions and can have persistent inflammation, progressive joint damage, severe physical limitations, disability, and increased mortality if left untreated. Patients are at increased risk of comorbid conditions such as diabetes mellitus (DM), hypertension, coronary heart disease, inflammatory bowel disease (IBD), lymphoma, and depression. Adverse prognostic factors include ≥5 swollen joints, increased C-reactive protein (CRP) of >3 months, history of use of oral corticosteroids, and/or structural joint damage due to disease.

Severity Assessment

ASSESSMENT OF SEVERITY IN PSORIATIC ARTHRITIS
	Mild	Moderate	Severe
Peripheral arthritis	<5 joints No damage on X-ray No loss of physical function Minimal impact on the quality of life Mild on patient evaluation	≥5 swollen or tender joints Damage on X-ray Moderate loss of physical function Moderate impact on the quality of life Moderate on patient evaluation Inadequate response to mild treatment	≥5 swollen or tender joints Severe damage on X-ray Severe loss of physical function Severe impact on the quality of life (eg cannot perform daily tasks of living without pain or dysfunction) Severe on patient evaluation Inadequate response to mild-moderate disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor (TNF) inhibitors as monotherapy
Skin disease	BSA <5, PASI <5, asymptomatic	No response to topicals, DLQI, PASI <10	BSA >10, DLQI >10, PASI >10
Spinal disease	Mild pain No loss of function	Loss of function or BASDAI >4	Failure of response
Enthesitis	1-2 sites No loss of function	>2 sites Loss of function	>2 sites and failure of response Loss of function
Dactylitis	Absence of pain to mild pain Normal function	Erosive disease Loss of function	Failure of response
BSA = body surface area, BASDAI = Bath Ankylosing Spondylitis Disability Activity Index, PASI = Psoriasis Activity Severity Index, DLQI = Dermatology Life Quality Index Reference: Ritchlin CT, Kavanaugh A, Gladman DD, et al. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis. 2009;68:1387-1394.

Treatment of psoriatic arthritis patients should be based on shared decisions between physician and patient and must aim at the best care while taking into consideration the patient's preferences and medical history and drug efficacy, safety, and costs. Treatment is guided at the beginning through disease severity assessment, which includes the degree of disease activity, damage, and impact on the patient, followed by initial attention to the most severely affected region, such as peripheral or axial arthritis. Treatment of axial (involving spine and sacroiliac joints) psoriatic arthritis depends on the severity of the disease and the patient's response to therapy. Treatment should include multidisciplinary care and should be initiated once psoriatic arthritis is diagnosed in order to alleviate the manifestations, prevent structural damage, delay disease progression, avoid or minimize complications from untreated disease or from therapy, normalize function and social participation, and maximize the quality of life. Each musculoskeletal manifestation should be considered and managed accordingly by a rheumatologist.

Non-musculoskeletal or extra-articular manifestations such as uveitis, inflammatory bowel disease (IBD), or skin involvement, as well as comorbidities such as cardiovascular (CV) disease, metabolic syndrome, obesity, chronic kidney disease, osteoporosis, fatty liver disease, or depression, should be considered, monitored, and managed accordingly. The recommended treatment for uveitis includes TNF inhibitors; for IBD, TNF inhibitors, interleukin (IL)-12/23 or IL-23 inhibitors, or a JAK inhibitor; and for skin involvement, IL-17, IL-23 or IL-12/23 inhibitors. If a bDMARD or JAK inhibitor is inappropriate, consider using a phosphodiesterase-4 inhibitor in patients with mild disease.

Treatment is aimed at reaching a target of clinical remission or, alternatively, low or minimal disease activity through regular assessment of disease activity and appropriate therapy adjustment. Treat to target is defined as a 50% reduction in disease activity within 3 months and achievement of the target within 6 months from initiation of treatment. Treatment targets must be individualized based on present clinical manifestations of the disease.

Patients are said to have low or minimal disease activity if five out of the following seven criteria have been achieved. Patients are considered to be in remission if all of the above seven criteria are met.

• ≤1 tender joint count
• ≤1 swollen joint count
• ≤1 enthesitis count
• ≤1 PASI score or ≤3 BSA
• ≤20 mm patient global visual analogue score (VAS)
• ≤15 mm patient pain VAS
• ≤0.5 Health Assessment Questionnaire (HAQ)

The choice of DMARDs is dependent on psoriasis disease activity and severity as well as arthritis. If a patient is unresponsive to therapy, consider switching within the drug class and then to another class; if intolerant, consider switching to another drug class. Consider the drugs’ modes of action for optimization of the benefit-risk profile. Cautious tapering of DMARDs may be considered in patients with sustained remission (ie complete remission for ≥6 consecutive months). This will help prevent treatment-related risks, meet patients’ desires and demands, and reduce the cost of treatment. Disease-modifying anti-rheumatic drug failure is considered if ≥1 DMARD has failed individually or in combination in an adequate therapeutic trial (treatment for ≥3 months, of which ≥2 months is at the standard target dose). 

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drug monotherapy may only be given to patients with very mild peripheral disease or with predominant axial or entheseal disease. NSAIDs provide good short-term symptomatic relief for patients with mild peripheral psoriatic arthritis. These are recommended for patients with mild axial disease, including patients with inflammatory back pain that does not interfere with function, and for patients with enthesitis. These do not inhibit the development of structural joint damage. The lowest effective dose of NSAID or cyclooxygenase-2 (COX-2) selective inhibitor should be given for the shortest duration in controlling symptoms due to the potential cardiotoxicity.

Corticosteroids 







Glucocorticoid injections may be used as an adjunct in the treatment of psoriatic arthritis. Intra-articular corticosteroids are used for persistent synovitis (eg monoarthritis or oligoarthritis) or for bridging therapy while waiting for the systemic treatment to take effect. These can be used when only a few joints are involved. Systemic corticosteroids are not recommended in patients with axial psoriatic arthritis, enthesitis, or dactylitis. Studies showed no evidence to support the use of systemic corticosteroids in patients with peripheral psoriatic arthritis.

Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) or Non-biologic DMARDs

Example drugs: Leflunomide, Methotrexate, Sulfasalazine

Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or non-biologic disease-modifying anti-rheumatic drugs (DMARDs) are recommended for rapid initiation in patients with polyarthritis and for patients with resistance to NSAIDs and glucocorticoid injections. These are used for patients with moderate to severe psoriatic arthritis that is more extensive or aggressive disease requiring more potent treatment. These may be a treatment option for patients with monoarthritis or oligoarthritis with poor prognostic factors such as high erythrocyte sedimentation rate (ESR) or CRP, structural damage, dactylitis, or nail involvement. These may be effective for dactylitis but with limited evidence in axial psoriatic arthritis and enthesitis. The choice of DMARD should be based on patient preference, severity of joint and skin diseases, efficacy, comorbidities, risks of adverse effects, cost of medication, and monitoring. These are not capable of preventing or slowing radiographic damage.

Leflunomide

Leflunomide selectively inhibits pyrimidine synthesis that targets activated T-lymphocytes. This is recommended for the treatment of active peripheral psoriatic arthritis and is effective against dactylitis and Crohn’s disease. This is an alternative for patients not willing to take Methotrexate or unresponsive to Methotrexate. This may be used as a first-line DMARD in patients with a low skin burden of psoriasis and is less effective in treating skin involvement compared to Methotrexate.

Methotrexate

Methotrexate is the primary conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in peripheral psoriatic arthritis and the first-line therapy for patients with moderate to severe active psoriatic arthritis. This is effective in treating clinically relevant skin and joint involvement and is the preferred DMARD for patients with polyarthritis with extensive (>10%) skin involvement. Studies showed reduction in joint swelling, tenderness, and erythrocyte sedimentation rate (ESR). Patients given with Methotrexate also showed superior physician assessment of arthritis activity compared to the placebo group. This is effective also for extra-articular manifestations (eg uveitis and Crohn’s disease). Folate supplementation is recommended to reduce the adverse effects of Methotrexate.

Sulfasalazine

Sulfasalazine has modest efficacy in patients with psoriatic arthritis. This is used as an alternative in treating peripheral psoriatic arthritis. This can be effective against joint and skin symptoms in peripheral psoriatic arthritis, uveitis, and ulcerative colitis. There were statistically significant positive effects on patient and physician global assessment of disease activity.

Other Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)

Ciclosporin is effective against peripheral joint and skin symptoms, refractory ulcerative colitis, and anterior uveitis. This may be considered in patients with active arthritis unresponsive to ≥2 conventional DMARDs. The use is limited because of toxicity issues. Further studies are needed to prove the efficacy of Azathioprine and D-Penicillamine for the treatment of psoriatic arthritis.

Biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) 





Example drugs: TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors

Biologic DMARDs are used when progression of disease occurs and these are capable of limiting joint damage and rapidly restoring function. These are recommended for patients with peripheral arthritis who are unresponsive or intolerant to ≥1 csDMARD and for patients with severe disease at presentation (eg involvement of many joints, erosive disease, functional limitation). These may be a treatment option for patients with predominantly axial active disease and with inadequate response to NSAIDs and for patients with unequivocal enthesitis with inadequate response to NSAIDs or local glucocorticoid injections. These may be used for patients with severe dactylitis (affecting several digits and interfering with function). Switching to another bDMARD or to a targeted synthetic DMARD such as a JAK inhibitor may be an option for patients unresponsive or intolerant to a bDMARD. Switching within a class may be done once.

Tumor Necrosis Factor (TNF) Inhibitors

Example drugs: Adalimumab, Certolizumab pegol, Etanercept, Golimumab, Infliximab

Tumor necrosis factor (TNF) inhibitors inhibit the pro-inflammatory cytokine involved in inflammation of the skin, synovium, and joint fluid. These are recommended by the American College of Rheumatology/National Psoriasis Foundation as the first-line treatment for treatment-naive patients with active psoriatic arthritis. These are the first-line treatments for severe active peripheral psoriatic arthritis and are recommended for the treatment of dactylitis in patients with psoriatic arthritis. These are recommended also for treatment of active psoriatic arthritis in patients who are unresponsive or intolerant to ≥2 DMARDs or 1 DMARD with poor prognostic factors and for patients with resistance or without improvement to non-biologic DMARD after 3 months of treatment.

TNF inhibitors may be used as the preferred treatment option for patients with predominantly axial active disease or moderate to severe axial psoriatic arthritis and with inadequate response to NSAIDs. Patients with axial disease and unresponsive to the first TNF inhibitor may be switched to a second TNF inhibitor, and if still unresponsive, may be switched to other bDMARDs. These were shown in clinical trials to reduce activity of arthritis, reduce radiographic progression, and improve physical function. These are more expensive compared with DMARDs but more cost-effective when used for a long period.

TNF inhibitors provide the following long-term benefits: Decreased need for joint replacement surgery; reduced demands on medical, nursing, and therapy services; reduced need for other medicines; decreased demands on social services and careers; improved quality of life; increased probability of maintaining work; and increased life expectancy. The choice of TNF blocker to use is individualized, taking into account the degree and severity of skin involvement. Other factors to consider are cost, patient preference, and physician preference.

Most clinicians use the combination of TNF inhibitor and Methotrexate as the standard care for the treatment of psoriatic arthritis. Methotrexate combined with Adalimumab, Golimumab or Infliximab may decrease the formation of anti-drug antibodies, thus prolonging retention of the drug and reducing adverse events. The FDA warns of reports on the occurrence of hepatosplenic T-cell lymphoma, a rare malignancy, in patients receiving TNF inhibitors (eg Adalimumab, Etanercept, Golimumab).

Adalimumab

Adalimumab is a human monoclonal anti-TNF antibody and is effective in the treatment of moderate to severe peripheral psoriatic arthritis. Studies showed significant benefits such as better response rates, decreased radiographic progression of hand and foot joint disease, and improvement in disability.

Certolizumab pegol

Certolizumab pegol is a pegylated Fab fragment of a humanized anti-TNF monoclonal antibody.

Etanercept

Etanercept is a dimeric p75 TNF-alpha receptor Fc fragment fusion protein that binds to TNF and is effective in treating moderate to severe peripheral psoriatic arthritis. Studies showed improvement in signs and symptoms such as a decrease in the number of tender joints, swollen joints, and morning stiffness. Noted are decreased C-reactive protein (CRP) levels, inhibition of radiographic disease progression and better physician and patient global ratings.

Golimumab

Golimumab is a human monoclonal anti-TNF antibody and is recommended for the treatment of active and progressive psoriatic arthritis. Studies showed statistically significant improvements in joint disease as compared to placebo.

Infliximab

Infliximab is a human or mouse chimeric anti-TNF-alpha antibody and is effective in moderate to severe peripheral psoriatic arthritis. This may be given with or without Methotrexate. Continuation of treatment with Methotrexate is recommended in patients taking Infliximab in order to reduce the risk of decreased response to Infliximab over time. Studies showed better response rates, decreased dactylitis and enthesitis, and inhibition of radiographic disease progression.

Interleukin (IL)-17 Inhibitors

Example drugs: Bimekizumab, Ixekizumab, Secukinumab

IL-17 inhibitors are the preferred treatment option for patients with peripheral arthritis with extensive skin involvement who are unresponsive or intolerant to ≥1 csDMARD. These are recommended for the treatment of dactylitis in patients with psoriatic arthritis. These may be used as the preferred treatment option for patients with predominantly axial active disease with inadequate response to NSAIDs and with extensive skin involvement.

Bimekizumab

Bimekizumab is a humanized IgG1-kappa monoclonal antibody with two identical antigen-binding regions that selectively bind and neutralize IL-17A and IL-17F cytokines, targeting all three inflammatory-inducing cytokines: IL-17A, IL-17F, and IL-17A/F. Targeting IL-17F in addition to IL-17A is a unique dual mechanism of Bimekizumab noted in the 2023 European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of psoriatic arthritis. Only Bimekizumab was able to inhibit IL-6 production induced by all three cytokines, unlike IL-17A inhibitors in an in vitro neutralization assay. This is indicated for the treatment of active psoriatic arthritis in patients with or without coexisting moderate to severe plaque psoriasis. This may be given alone or in combination with Methotrexate for the treatment of active psoriatic arthritis in adults who have had an inadequate response or are intolerant to ≥1 DMARDs. This is an effective, long-term treatment option for patients with psoriatic arthritis regardless of their prior biologic (TNF inhibitor) use.

Bimekizumab has been shown to improve joint and skin outcomes, significantly reduce radiographic progression, and achieve resolution of enthesitis and dactylitis in trials. There is demonstrated good tolerability with treatment-emergent adverse event (TEAE) exposure-adjusted incidence rates (EAIRs) remaining stable over extended treatment periods in patients with psoriatic arthritis and either remaining consistent or decreasing with longer treatment exposure in patients with psoriasis.

Ixekizumab

Ixekizumab is an anti-IL-17A receptor antibody and is effective in patients with skin involvement and may be used in those with contraindications or resistance to TNF inhibitors. This may be a treatment option for patients unresponsive to two different TNF inhibitors. This has been shown to reduce radiographic progression and improve psoriatic skin disease in trials.

Secukinumab

Secukinumab is a human anti-IL-17A monoclonal antibody and an alternative to TNF inhibitors for the treatment of patients with severe peripheral arthritis. This is effective in patients with skin involvement and may be used in those with contraindications or resistance to TNF inhibitors. Treatment option for patients unresponsive to two different TNF inhibitors. This showed efficacy in patients with axial spondyloarthritis as well as patients with predominantly axial psoriatic arthritis and may be used with or without Methotrexate. This has been shown to significantly reduce radiographic progression and reduce the frequency of enthesitis and dactylitis in trials.

Interleukin (IL)-12/23 Inhibitor

Ustekinumab

Ustekinumab is a human monoclonal antibody that targets IL-12 and IL-23 and is the preferred treatment option for patients with peripheral arthritis with extensive skin involvement who are unresponsive or intolerant to ≥1 csDMARD. This may be considered if the patient has an inadequate response, intolerance, or contraindication to TNF inhibitors or IL-17 inhibitors. This may be an alternative to TNF inhibitors for treatment of patients with severe peripheral arthritis and are also effective in patients with skin involvement. Ustekinumab may be used alone or in combination with Methotrexate and is recommended for the treatment of dactylitis in patients with psoriatic arthritis. This has been shown to significantly reduce radiographic progression of joint injury and improve psoriasis, enthesitis, and dactylitis in trials.

Interleukin (IL)-23 Inhibitors

Example drugs: Guselkumab, Risankizumab

IL-23 inhibitors are anti-IL-23-specific monoclonal antibodies that target the p19-protein subunit of IL-23 and are indicated for the treatment of active psoriatic arthritis. These are recommended for the treatment of dactylitis in patients with psoriatic arthritis and may be given as monotherapy or in combination with non-biologic DMARDs.

Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA4)-Immunoglobulin

Abatacept

Abatacept is a selective T-cell costimulation modulator and a treatment option for patients who are unresponsive or intolerant to a bDMARD (eg TNF inhibitor). This has a relatively low efficacy.

Targeted Synthetic DMARDs (tsDMARDs)

Targeted synthetic DMARDs are used when patients are unresponsive or intolerant to all classes of biologic agents.

Janus Kinase (JAK) Inhibitors

Example drugs: Tofacitinib, Upadacitinib

Janus kinase (JAK) inhibitors are also known as signal transducer and activator of transcription (STAT) inhibitors. These inhibit cytokine pathways, which are important in psoriatic arthritis and psoriasis, through their effect on JAK3 and JAK1. These are indicated for adult patients with active psoriatic arthritis who are intolerant to or responded inadequately to ≥1 DMARDs. These are recommended for patients with predominantly axial disease with inadequate response to NSAIDs and recommended for the treatment of dactylitis in patients with psoriatic arthritis. These are used in combination with Methotrexate though Upadacitinib may also be used as monotherapy. Use with caution in patients ≥65 years old, with a history of long-time smoking, a history of atherosclerotic CV disease or other CV risk factors, or with risk factors for venous thromboembolism or malignancy.

Phosphodiesterase-4 (PDE-4) Inhibitor

Example drug: Apremilast

Phosphodiesterase-4 (PDE-4) inhibitor is a cyclic adenosine monophosphate (cAMP)-specific PDE-4 inhibitor that acts by suppressing pro-inflammatory mediators. This is a treatment option for patients with active psoriatic arthritis. This is for patients with mild to moderate arthritis who want to avoid treatment with DMARD or prefer oral therapy and for treatment-naive patients with active psoriatic arthritis with predominant enthesitis and who have contraindications to TNF inhibitors or recurrent infections or if oral therapy is preferred. This is preferred for patients with mild disease (eg involving ≤4 joints, limited skin involvement) who are intolerant or unresponsive to ≥1 csDMARD and in whom a bDMARD or JAK inhibitor is not appropriate. This is recommended for the treatment of dactylitis in patients with psoriatic arthritis and not recommended for patients with erosive disease. Studies have shown that patients showed less joint tenderness and swelling and better physical function while on Apremilast therapy. 

Patient Education

Educating the patient improves the patient's understanding of the disease, adherence to treatment, and satisfaction with disease management. Explain what psoriatic arthritis is all about, its relation to psoriasis, and its unpredictable, recurring nature. Explain that psoriatic arthritis is a long-term, progressive disease but can be managed with appropriate therapy. Discuss the quality-of-life issues and reassure them that these issues may not be present in every case. These issues include pain and fatigue; employment problems and managing therapy while at work; possible stigma and impact on daily tasks; family life and relationships; and emotional issues (eg depression, anxiety, and stress).

Inform the patient about the increased risk of comorbid conditions (eg CV disease, diabetes) and the need for regular follow-up and screening. Encourage a healthy lifestyle such as regular exercise, weight management (aim for body mass index [BMI] 18.5-22.9 kg/m²), smoking cessation, alcohol restriction and blood pressure control. Emphasize that the goal of therapy is to control joint pain, stiffness and damage in order to improve the quality of life and prevent long-term disability. Consider rehabilitation programs, including low-impact exercise and physical therapy.

Discuss the various treatment options, including surgical procedures, and ensure that the patient is part of the decision-making. Explain the benefits, adverse effects, and risks of therapy to help the patients make an informed consent. Inquire regarding the patient's use of complementary and alternative medicine and explain the inadequate evidence supporting its use, its effect on the efficacy and safety of non-pharmacological and pharmacological therapy, and the risks and poor outcomes associated with delayed evidence-based medical treatment. Explain the importance of compliance to the therapy and discuss how to overcome the potential problems about adherence. Discuss the requirements for monitoring and assessment of the disease and their results. Identify and avoid triggering factors. Develop strategies to cope with flare-ups.