What is the role of Ustekinumab (Stelara) in the treatment of Psoriatic Arthritis?

Ustekinumab in Psoriatic Arthritis Treatment

Ustekinumab is recommended as a monotherapy treatment option for adult patients with plaque psoriasis of any severity when associated with psoriatic arthritis, with a strong recommendation (Grade A) based on high-quality evidence. 1

Mechanism and Indication

Ustekinumab (Stelara®) is a human interleukin-12 and -23 antagonist that works by binding to the shared p40 subunit of IL-12 and IL-23, blocking their signaling pathways 2, 3. It is FDA-approved for:

• Adults and pediatric patients 6 years and older with active psoriatic arthritis
• Adults and pediatric patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
• Adults with moderately to severely active Crohn's disease or ulcerative colitis 2

Dosing Recommendations

For patients with psoriatic arthritis:

• Weight-based dosing:

  • For patients ≤100 kg: 45 mg administered subcutaneously initially and 4 weeks later, followed by 45 mg every 12 weeks
  • For patients >100 kg: 90 mg administered subcutaneously initially and 4 weeks later, followed by 90 mg every 12 weeks 1

• Alternative dosing for inadequate responders:

  • Consider increasing to 90 mg (for patients ≤100 kg) or
  • Increasing frequency to every 8 weeks during maintenance phase 1

Efficacy in Psoriatic Arthritis

Ustekinumab demonstrates significant efficacy in psoriatic arthritis:

• In the PSUMMIT 1 trial, significantly more patients achieved ACR20 at week 24 with ustekinumab compared to placebo (42.4% with 45 mg, 49.5% with 90 mg vs. 22.8% with placebo) 4
• Response is maintained during long-term therapy (up to 100 weeks) 3
• Efficacy is observed with or without concomitant methotrexate 3
• Improvements are seen in multiple domains:
  • Joint symptoms (ACR response)
  • Skin manifestations (PASI scores)
  • Enthesitis and dactylitis scores
  • Radiographic progression
  • Health Assessment Questionnaire-Disability Index scores 3

Combination Therapy Options

Ustekinumab may be combined with other therapies to enhance efficacy:

• Methotrexate: Substantial evidence supports this combination (Grade B recommendation) 1
• Acitretin: May be combined to augment efficacy (Grade B) 1
• Topical therapies: High-potency corticosteroids with/without vitamin D analogs (Grade C) 1
• Apremilast or Cyclosporine: Limited evidence supports these combinations (Grade C) 1
• Narrowband UVB phototherapy: Can be combined with improved response (Grade B) 1

Monitoring and Response Assessment

• Response evaluation: Definitive response should be assessed after 12 weeks of continuous therapy 1
• Laboratory monitoring:
  • Tuberculosis screening before initiation
  • Hepatitis B testing recommended
  • Routine laboratory monitoring not mandatory but consider baseline CBC and liver function tests 1

Safety Considerations

Ustekinumab is generally well-tolerated with a safety profile similar to that observed in plaque psoriasis 3:

• Infections: Risk of serious infections is low, but monitor for signs of infection 2
• Malignancy: No definitive evidence of increased risk when used as monotherapy 1
• Immunogenicity: Antibodies against ustekinumab can develop in some patients, potentially reducing efficacy 1
• Pregnancy/lactation: Safety during pregnancy and lactation is uncertain 1

Important Caveats and Limitations

1. TNF inhibitor comparison: Ustekinumab is considered less effective than TNF-α inhibitors for PsA. Patients switched from TNF inhibitors to ustekinumab might experience worsening of arthritis symptoms 1

2. Case reports of arthritis flares: Despite overall efficacy, there have been reports of ustekinumab unmasking or aggravating joint disease in selected patients with psoriasis 5

3. Contraindications:

   • History of allergic reaction to ustekinumab or vehicle
   • Relative contraindications include untreated hepatitis B, history of lymphoreticular malignancy, and active infections 1

4. Temporary discontinuation: Consider temporary discontinuation during febrile illness, especially those requiring antibiotic treatment 1

In summary, ustekinumab offers an effective alternative treatment mechanism for patients with psoriatic arthritis, particularly valuable for those with inadequate response to non-biological DMARDs or those who have failed anti-TNF therapy 3. However, clinicians should be aware that TNF inhibitors may be more effective for joint manifestations in most patients with psoriatic arthritis.