What is the management of moderate to severe plaque psoriasis with biologics?

Management of Moderate to Severe Plaque Psoriasis with Biologics

For moderate-to-severe plaque psoriasis (≥5% body surface area or PASI ≥10 with DLQI >10), initiate biologic therapy with adalimumab as first-line systemic treatment, dosed at 80 mg initial dose, followed by 40 mg one week later, then 40 mg every 2 weeks thereafter. 1, 2, 3

Patient Selection Criteria for Biologic Therapy

Biologics are indicated when patients meet all of the following criteria:

• PASI ≥10 AND DLQI >10 1
• Failed, have contraindications to, or are intolerant of at least one conventional systemic therapy (methotrexate, cyclosporine, or PUVA) 1, 3
• For psoriatic arthritis of any severity, biologics are indicated regardless of skin disease extent 1, 4

First-Line Biologic Selection Algorithm

TNF-α Inhibitors (Preferred Initial Options)

Adalimumab is the preferred first-line biologic:

• Dosing: 80 mg subcutaneous on Day 1, then 40 mg at Week 1, then 40 mg every 2 weeks 1, 3
• Efficacy: Achieves PASI 75 in 71% of patients at week 16 (vs. 7% placebo) 1, 2
• For enhanced disease control: May increase to 40 mg weekly in patients requiring better response 1
• Strength of recommendation: A 1

Infliximab is an alternative first-line option:

• Dosing: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks 1, 2
• Efficacy: Achieves PASI 75 in 80% of patients 2, 4
• Critical caveat: Must add methotrexate to reduce immunogenicity and prevent antibody formation that causes loss of efficacy 1
• Avoid intervals >8 weeks between infusions as this increases infusion reactions and treatment failure 1
• Strength of recommendation: A 1

Etanercept is a third TNF-α option:

• Dosing: 50 mg subcutaneous twice weekly for 12 weeks, then 50 mg once weekly maintenance 1
• Efficacy: Achieves PASI 75 in 48-66% at week 12 2, 4
• Note: 50 mg twice weekly is more efficacious than once weekly and may be required for better control 1
• Strength of recommendation: A 1

When to Avoid TNF-α Inhibitors

Do not use TNF-α inhibitors in patients with:

• Heart failure 5
• Demyelinating disease 5
• Recurrent infections 5
• Active tuberculosis (must test and treat latent TB before initiating) 3

Site-Specific Biologic Recommendations

Palmoplantar Psoriasis

• Adalimumab is strongly recommended (Strength A) 1

Nail Psoriasis

• Adalimumab is strongly recommended (Strength A) 1
• Etanercept is also recommended (Strength A) 1

Scalp Psoriasis

• Adalimumab can be recommended (Strength B) 1
• Etanercept is recommended (Strength A) 1

Pustular or Erythrodermic Psoriasis

• Adalimumab can be recommended (Strength B) 1
• Etanercept can be recommended (Strength B) 1

Psoriatic Arthritis

• Adalimumab is strongly recommended regardless of skin disease severity, as it treats both skin and joint symptoms and inhibits radiographic joint damage (Strength A) 1, 2, 4
• Infliximab is also strongly recommended for psoriatic arthritis (Strength A) 2, 4

Combination Therapy to Augment Efficacy

With Topical Agents (Recommended)

High-potency corticosteroids ± vitamin D analogues:

• Add to etanercept for 12 weeks (Strength A) 1, 2
• Add to adalimumab for 16 weeks (Strength B) 1, 2
• Can be combined with any biologic (Strength C) 2

With Conventional Systemic Agents

Methotrexate combinations:

• Etanercept + methotrexate (Strength B) 1
• Adalimumab + methotrexate (Strength B) 1
• Infliximab + methotrexate is strongly recommended to reduce immunogenicity 1

Acitretin combinations:

• Etanercept + acitretin (Strength B) 1
• Adalimumab + acitretin (Strength C) 1

Other combinations (lower evidence):

• Adalimumab + apremilast (Strength C) 1
• Adalimumab + cyclosporine (Strength C) 1

With Phototherapy

Narrowband UVB + biologics:

• Etanercept + NB-UVB (Strength B) 1
• Adalimumab + NB-UVB (Strength B) 1

Assessment of Treatment Response

Timing of Response Assessment

• Etanercept: Assess at 12 weeks 1
• Adalimumab: Assess at 16 weeks 1
• Infliximab: Assess at 10-14 weeks 1

Definition of Treatment Success

Continue biologic therapy if patient achieves:

• PASI 75 (75% improvement) OR
• PASI 50 (50% improvement) AND DLQI improvement >5 points 1

Management of Treatment Failure

For primary non-response (failure to achieve PASI 50 at assessment timepoint):

• Switch to a different biologic class 6
• Evidence supports switching from TNF-α inhibitor to IL-12/23 or IL-17 inhibitor 6

For secondary loss of response:

• Consider switching to adalimumab if failing etanercept (achieves PASI 50 in 80% of etanercept non-responders) 7
• Switch to different mechanism of action (IL-12/23 or IL-17 inhibitor) 6

Critical Safety Monitoring

Before Initiating Biologics

• Test for latent tuberculosis and treat if positive before starting 3
• Screen for hepatitis B and C 3
• Ensure no active infections 3

During Treatment

• Monitor for serious infections at every visit; discontinue if serious infection develops 3
• Monitor for malignancy, particularly lymphoma 3
• Continue monitoring for active TB even if initial test was negative 3

Common Pitfalls to Avoid

• Never use systemic corticosteroids (prednisone) for psoriasis due to poor long-term efficacy and rebound flares 4, 5
• Do not delay biologics in patients with >5% BSA involvement; topicals alone are insufficient and biologics have favorable benefit-to-risk ratio 4
• Do not extend infliximab intervals beyond 8 weeks as this increases immunogenicity and treatment failure 1
• Always add methotrexate to infliximab to prevent antibody formation 1
• Avoid salicylic acid with calcipotriene as the acidic pH inactivates calcipotriene 2

Long-Term Safety Profile

Biologics demonstrate good long-term tolerability (≥1 year) in extension studies, with TNF-α inhibitors (etanercept, infliximab, adalimumab) offering a viable alternative to conventional systemic agents with acceptable safety profiles 8, 9