Recent Advancements in Psoriasis Treatment (2021-2024)
The most significant recent advancement in psoriasis treatment is the development of selective tyrosine kinase 2 (TYK2) inhibitors, particularly deucravacitinib, which has demonstrated superior efficacy compared to older oral treatments while maintaining a favorable safety profile for moderate-to-severe plaque psoriasis.
Novel TYK2 Inhibitors
Deucravacitinib
- Mechanism of action: First-in-class selective allosteric TYK2 inhibitor that binds to the regulatory domain of TYK2, preventing conformational changes needed for activation 1
- Dosage: 6 mg once daily orally 2
- Efficacy: Nearly 60% of patients achieve PASI 75 at 16 weeks, with efficacy improving over 24 weeks and maintained through 4 years of continuous treatment 1, 3
- Advantages:
- Superior to apremilast in head-to-head trials (58.4% vs 35.1% PASI 75 response at week 16) 4
- Effective for difficult-to-treat areas including scalp, palms, and soles 1
- Does not require routine laboratory monitoring except for tuberculosis screening 1
- Lacks the safety concerns associated with JAK inhibitors 5
Brepocitinib
- Mechanism of action: Dual JAK1/TYK2 inhibitor that targets the catalytic domain 6, 5
- Status: In late-stage clinical development for PsA 6
- Note: Orthosteric inhibitor (different from deucravacitinib's allosteric mechanism) 5
IL-23 Inhibitors
Tildrakizumab
- Mechanism of action: Humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of IL-23 7
- Dosage: 100 mg subcutaneous injection at weeks 0,4, and every 12 weeks thereafter 7
- Efficacy: 61-64% of patients achieve PASI 75 at week 12; 84% of responders maintain PASI 75 at week 64 with continued treatment 7
Risankizumab
Guselkumab
IL-17 Pathway Inhibitors
Bimekizumab
- Mechanism of action: Novel IL-17A/F inhibitor that targets both IL-17A and IL-17F cytokines 6, 8
- Status: Recently approved (2024) for plaque psoriasis 8
- Advantage: Dual targeting may provide enhanced efficacy compared to IL-17A inhibitors alone 6
Izokibep
- Mechanism of action: IL-17A inhibitor with a novel structure 6
- Status: In clinical development for PsA 6
JAK Inhibitors
Upadacitinib
- Mechanism of action: Selective JAK1/JAK2 inhibitor 6
- Status: Approved for PsA 6
- Note: JAK inhibitors carry boxed warnings for serious infections, mortality, malignancies, and cardiovascular events based on safety findings in RA studies 6
Treatment Selection Algorithm
For mild psoriasis (<10% BSA):
For moderate-to-severe psoriasis (≥10% BSA or significant QOL impact):
First-line biologics (based on comorbidities):
Oral options:
- TYK2 inhibitors (deucravacitinib): Preferred oral option for moderate-to-severe disease with excellent safety profile 1, 2
- JAK inhibitors: Effective but require monitoring due to safety concerns 6
- PDE4 inhibitors (apremilast): Moderate efficacy but favorable safety profile 9
- Traditional systemics (methotrexate, cyclosporine): For patients unable to access newer therapies 9
Monitoring Recommendations
- Deucravacitinib: Tuberculosis evaluation before initiation; monitoring of triglycerides in high-risk patients 1
- IL-23 inhibitors: No specific laboratory monitoring required; evaluate for infections 7
- JAK inhibitors: Regular monitoring for infections, laboratory abnormalities, and cardiovascular events 6
Key Considerations
- The selection between newer biologics should be influenced by head-to-head studies, presence of comorbidities, and disease activity in specific domains 6
- Long-term safety data continues to accumulate for newer agents, with deucravacitinib showing consistent safety through 4 years 3
- For patients with psoriatic arthritis, early treatment is essential to prevent joint damage 9
These recent advancements provide more targeted treatment options with improved efficacy and safety profiles, allowing for better personalization of therapy based on disease characteristics and comorbidities.