Treatment of Psoriatic Arthritis
For treatment-naïve patients with active psoriatic arthritis, start with a TNF inhibitor over oral small molecule DMARDs when disease is moderate to severe, or begin with methotrexate (15-25 mg weekly) when significant skin involvement coexists with peripheral arthritis. 1, 2
Initial Disease Severity Assessment
Active PsA is defined as symptoms at an unacceptably bothersome level with at least one of the following: actively inflamed joints, dactylitis, enthesitis, axial disease, active skin/nail involvement, or extraarticular manifestations such as uveitis or inflammatory bowel disease. 1
Poor prognostic factors requiring aggressive early treatment include: 1, 2
- Polyarticular disease (multiple joint involvement)
- Elevated inflammatory markers (ESR)
- Existing structural joint damage on imaging
- Dactylitis or nail involvement
- Diminished quality of life scores
Treatment Algorithm by Disease Severity
Mild Disease (Limited Joint Involvement)
NSAIDs represent first-line therapy for symptom control, but provide only symptomatic relief without preventing structural joint damage. 2, 3
Add intra-articular glucocorticoid injections for persistently inflamed joints, avoiding injection through psoriatic plaques to prevent infection risk. 2, 3
Critical caveat: Systemic corticosteroids are NOT recommended for chronic use due to potential post-steroid psoriasis flare and other adverse effects. 1, 3
Moderate to Severe Disease (First-Line DMARD Selection)
When significant skin involvement coexists with arthritis, methotrexate is the preferred first-line DMARD at 15-25 mg weekly with folic acid supplementation (Level B evidence). 2, 3
Alternative first-line DMARDs with Level A evidence include: 1, 2
- Sulfasalazine for peripheral arthritis
- Leflunomide for peripheral arthritis
Important exception: In patients with concomitant diabetes, use sulfasalazine or leflunomide instead of methotrexate due to higher risk of fatty liver disease and hepatotoxicity. 2
DMARD failure is defined as: treatment for >3 months with >2 months at standard target dose without acceptable clinical improvement, unless significant intolerance or toxicity occurs. 1
Escalation to Biologic Therapy
Progress to a TNF inhibitor after failing at least one adequate DMARD trial, defined as treatment for more than 3 months with more than 2 months at standard target dose. 1, 3
The three TNF inhibitors are equally effective for peripheral arthritis and inhibiting radiographic progression (Level A evidence): 1, 2
- Etanercept: 50 mg subcutaneously weekly 4
- Adalimumab: 40 mg subcutaneously every other week 5
- Infliximab: per standard dosing protocols 1
TNF inhibitors can be used as monotherapy or combined with methotrexate at reduced doses (10-15 mg weekly), with combination therapy providing additional benefit. 2
Consider TNF inhibitors earlier (without requiring DMARD failure) in patients with: 2, 3
- Poor prognostic factors (polyarticular disease, elevated inflammatory markers, existing joint damage)
- Severe disease at presentation
- Rapidly progressive disease
Alternative Biologic Pathways (Per 2018 ACR/NPF Guidelines)
When TNF inhibitors are contraindicated or patient has specific features, consider: 1, 2
- IL-17 inhibitors: If severe psoriasis, contraindications to TNF inhibitors (recurrent infections, congestive heart failure, demyelinating disease), or relevant skin involvement with axial disease
- IL-12/23 inhibitors: If concomitant inflammatory bowel disease, severe psoriasis, or patient desires less frequent drug administration
- Oral small molecules (OSMs): If patient prefers oral therapy, has frequent serious infections, or has contraindications to biologics
Special Clinical Scenarios
Axial Disease (Spinal Involvement)
Traditional oral DMARDs (methotrexate, leflunomide, sulfasalazine) have NOT been shown to be effective for axial manifestations and should not be considered adequate for PsA axial disease. 1, 6
Treatment algorithm for axial disease: 6
- First-line: NSAIDs plus physical therapy
- Second-line: TNF inhibitors for moderate to severe spinal disease with insufficient response to NSAIDs
- Alternative: IL-17 inhibitors if relevant skin involvement coexists with axial disease
Disease activity is measured using BASDAI, with active disease defined as BASDAI score >4, and treatment response defined as BASDAI <3 or reduction by 2 points after 6 weeks. 1, 6
Dactylitis (Sausage Digits)
Dactylitis occurs in 16-48% of PsA cases and represents synovitis, tenosynovitis, and enthesitis with soft-tissue edema. 3
Acute dactylitis is a clinical indicator of disease severity warranting more aggressive treatment, potentially bypassing traditional DMARD trials. 3
Enthesitis
Treatment follows similar algorithm to peripheral arthritis, starting with NSAIDs and local measures, progressing to DMARDs for resistant cases, and considering TNF inhibitors for severe or refractory cases. 2
Critical Safety Monitoring
Prior to initiating TNF inhibitors: 4, 5
- Test for latent tuberculosis and initiate treatment for latent infection prior to TNF inhibitor use
- Complete age-appropriate vaccinations per current immunization guidelines
- Screen for chronic or recurrent infections, congestive heart failure, demyelinating disease
Black box warnings for TNF inhibitors include: 4, 5
- Serious infections (tuberculosis, invasive fungal infections, bacterial/viral/opportunistic infections)
- Malignancies (lymphoma and other malignancies, including hepatosplenic T-cell lymphoma in adolescents/young adults receiving concomitant azathioprine or 6-mercaptopurine)
Monitor patients closely for signs and symptoms of infection during and after treatment, including possible development of tuberculosis in patients who tested negative for latent TB prior to initiating therapy. 4, 5
Concomitant Medications
The following may be continued during biologic therapy: 4, 5
- Methotrexate (at reduced doses when combined with biologics)
- Glucocorticoids (avoid systemic use chronically)
- NSAIDs
- Analgesics
Avoid combining TNF inhibitors with azathioprine or 6-mercaptopurine in adolescents and young adults due to increased risk of hepatosplenic T-cell lymphoma. 5
Treatment Goals and Monitoring
The primary goal is maximizing health-related quality of life through symptom control, prevention of structural damage, normalization of function, and social participation. 3, 6
Aim for remission or low disease activity through regular disease activity assessment (every 3-6 months) and appropriate therapy adjustment. 2, 3
Response may be inadequate if there is evidence of progression of joint damage on radiographs, even with symptomatic improvement. 1