Newer Treatment Options for Psoriasis
Most Recent Biologic Therapies Are First-Line for Moderate-to-Severe Disease
For moderate-to-severe psoriasis (≥5% body surface area or symptomatic disease), biologic agents targeting IL-17 and IL-23 pathways represent the newest and most effective treatments, with IL-17 and IL-23 inhibitors demonstrating superior efficacy compared to older TNF inhibitors. 1, 2
Disease Severity Classification Determines Treatment Selection
- Mild psoriasis (<5% BSA, asymptomatic): Topical combination therapy with calcipotriene/betamethasone dipropionate is the newest and most effective topical option, achieving 69-74% clear or almost clear status versus 27% with vehicle 2
- Moderate-to-severe psoriasis (≥5% BSA or symptomatic): Newer biologics are recommended as first-line systemic therapy 1, 3
- Any severity with pain, bleeding, or itching: Consider systemic or phototherapy regardless of BSA involvement 1, 4
Newest Biologic Agents by Mechanism
IL-23 Inhibitors (Newest Class - Most Selective)
- Guselkumab, tildrakizumab, risankizumab, and mirikizumab target the p19 subunit of IL-23 specifically 3
- These represent the most recent advancement in biologic therapy with high efficacy for skin involvement 1
IL-17 Inhibitors (Newer Than TNF Inhibitors)
- Secukinumab, ixekizumab, bimekizumab, and brodalumab directly inhibit IL-17 3
- Show higher efficacy for skin involvement compared to TNF inhibitors 1
IL-12/23 Inhibitors
- Ustekinumab targets the p40 subunit shared by IL-12 and IL-23 3
- Less selective than the newer IL-23 p19 inhibitors 3
TNF Inhibitors (Older Biologics, Still Effective)
- Adalimumab, infliximab, etanercept, and certolizumab remain options but are generally less effective for skin disease than newer IL-17/IL-23 inhibitors 1, 5, 3
- Adalimumab is FDA-approved for psoriasis and psoriatic arthritis at 40 mg every other week, with some patients benefiting from 40 mg weekly or 80 mg every other week 5
Newest Topical Combination Therapy
The fixed-combination calcipotriene 0.005%/betamethasone dipropionate 0.064% (vitamin D analog plus corticosteroid) represents the most effective topical treatment available, superior to either agent alone with proven safety for up to 52 weeks 2, 6
Optimal Topical Regimen for Mild Disease
- Initial phase (4-8 weeks): Apply calcipotriene/betamethasone dipropionate once daily 1, 2
- Transition phase: High-potency corticosteroid twice daily on weekends only, with vitamin D analog twice daily on weekdays 1, 4
- Maintenance phase: Mometasone furoate once daily or alternate-day application 2
- Maximum vitamin D analog use is 100g per week to avoid hypercalcemia 4, 2
Newer Oral Small Molecule Therapy
Apremilast (phosphodiesterase 4 inhibitor) represents the newest oral non-biologic systemic agent, offering an alternative to traditional agents like methotrexate, cyclosporine, and acitretin 3
Critical Safety Considerations for Newer Biologics
Infection Risk Assessment Before Initiating Biologics
- Test for latent tuberculosis before starting any TNF inhibitor or other biologic - if positive, treat TB before initiating therapy 5
- Monitor all patients for active TB during treatment, even with negative initial testing 5
- Discontinue biologic if serious infection or sepsis develops 5
- For patients with history of recurrent infections or immune-related conditions, consider the increased risk of serious infections including bacterial sepsis, invasive fungal infections (histoplasmosis), and opportunistic pathogens 5
Malignancy Risk
- Lymphoma and other malignancies have been reported with TNF blockers, including rare hepatosplenic T-cell lymphoma in adolescents and young adults with inflammatory bowel disease 5
- This risk must be weighed against disease severity and quality of life impact 5
Site-Specific Newer Treatment Approaches
Scalp Psoriasis
- Calcipotriene foam or calcipotriene plus betamethasone dipropionate gel for 4-12 weeks represents the newest topical approach 1, 2
Facial and Intertriginous Psoriasis
- Tacalcitol ointment or calcipotriene combined with hydrocortisone for 8 weeks 4, 2
- Low-potency corticosteroids or tacrolimus to avoid skin atrophy 1, 2
Nail Psoriasis
- Topical vitamin D analogs combined with betamethasone dipropionate reduce nail thickness and hyperkeratosis 4, 2
- Note: Topical agents have limited efficacy for severe nail disease; systemic biologics are more effective 4
Combination Strategy with Newer Biologics
Adding ultrahigh-potency topical corticosteroids or calcipotriene/betamethasone to biologics accelerates clearance and targets residual plaques - this represents a newer treatment paradigm 2
- Adding class 1 corticosteroid to etanercept for 12 weeks (Level I evidence) 2
- Adding calcipotriene/betamethasone to adalimumab for 16 weeks accelerates plaque clearance 2
- All topical corticosteroids can be combined with any biologic 2
Critical Pitfalls to Avoid
- Never use systemic corticosteroids for psoriasis - they cause disease flare during taper 1
- Avoid interrupted biologic therapy - increases antibody formation, infusion reactions, and reduces efficacy 2
- Never combine salicylic acid with calcipotriene simultaneously - acidic pH inactivates calcipotriene 4
- Do not use high-potency corticosteroids on face or flexures - use low-potency agents instead 4
- Limit continuous high-potency corticosteroid use to 4 weeks maximum to prevent skin atrophy, striae, and HPA axis suppression 4, 2
Treatment Algorithm Based on Past Medical History
For Patients with History of Infections
- Prioritize IL-23 or IL-17 inhibitors over TNF inhibitors if biologics are needed, as they may have different infection risk profiles 3
- Complete latent TB testing and treatment before any biologic 5
- Consider empiric antifungal therapy if systemic illness develops in patients who reside or travel to endemic mycoses regions 5