Psoriatic%20arthritis Treatment

Treatment

Principles of Therapy

Treatment of psoriatic arthritis patients should be based on shared decision between physician and patient and must aim at the best care while taking into consideration patient's preference and medical history, and drug efficacy, safety and costs
Treatment is guided at the beginning through disease severity assessment which includes 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 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
Non-musculoskeletal or extra-articular manifestations such as uveitis, IBD, or skin involvement as well as comorbidities such as cardiovascular (CV) disease, metabolic syndrome, chronic kidney disease, osteoporosis, fatty liver disease, or depression should be considered, monitored and managed accordingly
- Recommended treatment for uveitis include tumor necrosis factor (TNF) inhibitors and TNF inhibitors or interleukin (IL)-12/23 inhibitor for IBD
Treatment is aimed at reaching 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 50% reduction in composite measure within 3 months and achievement of the target within 6 months from initiation of treatment
- Treatment target must be individualized based on present clinical manifestations of the disease
- Patients are said to have low or minimal disease activity if 5 out of the following 7 criteria have been achieved:
  - ≤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 HAQ
- Patients are considered to be in remission if all of the above 7 criteria are met
Choice of DMARDs is dependent on psoriasis disease activity and severity as well as arthritis
- If patient is unresponsive to therapy, may consider switching within drug class then to another class; if intolerant, may consider switching to another drug class
Cautious tapering of DMARDs may be done in patients with sustained remission (ie complete remission for ≥6 consecutive months)
- Will help prevent treatment-related risks, meet patients’ desires and demands, and reduce cost of treatment
DMARD 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 standard target dose)

Pharmacotherapy

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Provide good short-term symptomatic relief for patients with mild peripheral psoriatic arthritis
Recommended for patients with mild axial disease including patients with inflammatory back pain which does not interfere with function and for patients with enthesitis
Do not inhibit the development of structural joint damage
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

Provide good symptomatic relief for mild psoriatic arthritis but corticosteroids cannot inhibit joint damage
Glucocorticoid injections may be used as 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
- 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 Nonbiologic DMARDs

Eg Ciclosporin, Leflunomide, Methotrexate, Sulfasalazine
Recommended for rapid initiation in patients with polyarthritis and for patients with resistance to NSAIDs and glucocorticoid injections
Used for patients with moderate to severe psoriatic arthritis that is more extensive or aggressive disease requiring more potent treatment
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
May be effective for dactylitis but with limited evidence in axial psoriatic arthritis and enthesitis
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
Not capable of preventing or slowing radiographic damage

Ciclosporin

Effective against peripheral joint and skin symptoms, refractory ulcerative colitis and anterior uveitis
May be considered in patients with active arthritis unresponsive to ≥2 conventional DMARDs
Use is limited because of toxicity issues

Leflunomide

Selectively inhibits pyrimidine synthesis that targets activated T-lymphocytes
Recommended for treatment of active peripheral psoriatic arthritis; effective against dactylitis and Crohn’s disease
Alternative for patients not willing to take Methotrexate or unresponsive to Methotrexate
May be used as 1st-line DMARD in patients with low skin burden of psoriasis
- Less effective in treating skin involvement compared to Methotrexate

Methotrexate

Primary csDMARD in peripheral psoriatic arthritis
First-line therapy for patients with moderate to severe active psoriatic arthritis
Effective in treating skin and joint involvement
- Preferred DMARD for patients with polyarthritis with extensive (>10%) skin involvement
- Studies showed reduction in joint swelling, tenderness and erythrocyte sedimentation rate
  - Patients given with Methotrexate also showed superior physician assessment of arthritis activity compared to the placebo group
Effective also for extra-articular manifestations, eg uveitis and Crohn’s disease

Sulfasalazine

Has modest efficacy in patients with psoriatic arthritis
Used as an alternative in treating peripheral psoriatic arthritis
- 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 csDMARDs

Further studies are needed to prove efficacy of Azathioprine and D-Penicillamine for the treatment of psoriatic arthritis

Biologic DMARDs (bDMARDs)

Eg TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitor, IL-23 inhibitors
Used when progression of disease occurs; capable of limiting joint damage and rapidly restore function
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)
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
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 to another bDMARD of the same class may be done once

TNF Inhibitors

Eg Adalimumab, Certolizumab pegol, Etanercept, Golimumab, Infliximab
Inhibit the pro-inflammatory cytokine involved in inflammation of the skin, synovium and joint fluid
Recommended by the American College of Rheumatology/National Psoriasis Foundation as 1st-line treatment for treatment-naive patients with active psoriatic arthritis
1st-line treatment of severe active peripheral psoriatic arthritis
Recommended for the treatment of dactylitis in patients with psoriatic arthritis
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 nonbiologic DMARD after 3 months of treatment
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 1st TNF inhibitor may be switched to a 2nd TNF inhibitor and if still unresponsive may be switched to other bDMARDs
Were shown in clinical trials to reduce activity of arthritis, reduce radiographic progression and improve physical function
More expensive compared with DMARDs but more cost-effective when used for a long period
Provide the following long-term benefits:
- Decreased need for joint replacement surgery
- Reduced demands on medical, nursing, and therapy services
- Reduced needs for other medicines
- Decreased demands on social services and careers
- Improved quality of life
- Increased probability of maintaining work
- Increased life expectancy

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 formation of anti-drug antibody thus prolonging retention of the drug and reducing adverse events
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
- A human monoclonal anti-TNF antibody
- 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
- A pegylated Fab fragment of a humanized anti-TNF monoclonal antibody
Etanercept
- Dimeric p75 TNF-alpha receptor Fc fragment fusion protein which binds to TNF
- Effective in treating moderate to severe peripheral psoriatic arthritis
- Studies showed improvement in signs and symptoms such as decrease in number of tender joints, swollen joints, and morning stiffness
  - Also noted are decreased C-reactive protein levels, inhibition of radiographic disease progression and better physician and patient global ratings
Golimumab
- A human monoclonal anti-TNF antibody
- Recommended for the treatment of active and progressive psoriatic arthritis
- Studies showed statistically significant improvements in joint disease as compared to placebo
Infliximab
- A human or mouse chimeric anti-TNF-alpha antibody
- Effective in moderate to severe peripheral psoriatic arthritis
- 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

IL-17 Inhibitors

Eg Brodalumab, Ixekizumab, Secukinumab
Preferred treatment option for patients with peripheral arthritis with extensive skin involvement who are unresponsive or intolerant to ≥1 csDMARD
Recommended for the treatment of dactylitis in patients with psoriatic arthritis
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
Brodalumab
- A human anti-IL-17A monoclonal antibody
Ixekizumab
- An anti-IL-17A receptor antibody
- Is effective in patients with skin involvement and may be used in those with contraindications or resistance to TNF inhibitors
- May be a treatment option for patients unresponsive to 2 different TNF inhibitors
- Has been shown to reduce radiographic progression and improve psoriatic skin disease in trials
Secukinumab
- A human anti-IL-17A monoclonal antibody
- An alternative to TNF inhibitors for treatment of patients with severe peripheral arthritis
  - 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 2 different TNF inhibitors
- Showed efficacy in patients with axial spondyloarthritis as well as patients with predominantly axial psoriatic arthritis
- May be used with or without Methotrexate
- Has been shown to significantly reduce radiographic progression and reduce frequency of enthesitis and dactylitis in trials

IL-12/23 Inhibitor

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

IL-23 Inhibitors

Eg Guselkumab, Risankizumab
Anti-IL-23-specific monoclonal antibodies which target the p19-protein subunit of IL-23
Indicated for the treatment of active psoriatic arthritis
Recommended for the treatment of dactylitis in patients with psoriatic arthritis
May be given as monotherapy or in combination with nonbiologic DMARDs

Targeted Synthetic DMARDs (tsDMARDs)

Used when patients are unresponsive or intolerant to all classes of biologic agents

Janus Kinase (JAK) Inhibitors

Eg Tofacitinib, Upadacitinib
Also known as signal transducer and activator of transcription (STAT) inhibitor
Inhibit cytokine pathways which are important in psoriatic arthritis and psoriasis through its effect on JAK3 and JAK1
Indicated for adult patients with active psoriatic arthritis who are intolerant to or responded inadequately to ≥1 DMARDs
Recommended for patients with predominantly axial disease
Recommended for the treatment of dactylitis in patients with psoriatic arthritis
Used in combination with Methotrexate though Upadacitinib may also be used as monotherapy

Phosphodiesterase-4 (PDE-4) Inhibitor

Eg Apremilast
A cyclic adenoside monophosphate (cAMP)-specific PDE-4 inhibitor that acts by suppressing pro-inflammatory mediators
A treatment option for patients with active psoriatic arthritis
- For patients with mild to moderate arthritis who want to avoid treatment with DMARD or prefer oral therapy
- For treatment-naive patients with active psoriatic arthritis with predominant enthesitis and have contraindications to TNF inhibitors, recurrent infections or if oral therapy is preferred
- Preferred, or 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
Recommended for the treatment of dactylitis in patients with psoriatic arthritis
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

Other DMARD

Abatacept