When should biological therapy be started in a patient with moderate to severe psoriasis who has failed topical and systemic therapies?

When to Start Biological Therapy in Psoriasis

Offer biologic therapy to patients with moderate-to-severe psoriasis when methotrexate and ciclosporin have both failed, are not tolerated, or are contraindicated, AND the disease has a large impact on quality of life (DLQI >10) with either extensive disease (BSA >10% or PASI ≥10) or severe localized disease causing significant functional impairment. 1

Disease Severity Criteria Required

Before considering biologics, patients must meet both of the following:

Quality of Life Impact

• DLQI >10 (or Children's DLQI >10 for pediatric patients) 1
• OR clinically relevant depressive or anxiety symptoms 1
• Disease must have been severe for at least 6 months and resistant to treatment 1

Disease Extent (at least one must apply)

• PASI ≥10 (range 0-72) 1
• BSA >10% where PASI is not applicable (e.g., pustular psoriasis) 1
• Severe disease at localized high-impact sites (face, scalp, palms, soles, flexures, genitals, nails) with significant functional impairment and/or high distress levels 1

Mandatory Treatment Failures Before Biologics

Standard pathway requires failure of BOTH:

• Methotrexate (inadequate response, intolerance, or contraindication) 1
• Ciclosporin (inadequate response, intolerance, or contraindication) 1

Additional qualifying scenarios include failure of, intolerance to, or contraindication to PUVA therapy 1

Earlier Biologic Initiation Scenarios

Consider biologics earlier in the treatment pathway (e.g., after only methotrexate failure) when patients meet disease severity criteria AND have: 1

• Active psoriatic arthritis requiring treatment 1
• Rapidly relapsing disease (>50% baseline severity returns within 3 months of stopping any treatment that cannot be continued long-term, such as narrowband UV-B) 1
• Severe, unstable, life-threatening disease (erythrodermic or generalized pustular psoriasis) 1
• Clinically important drug-related toxicity risk from standard systemic agents 1
• Significant unrelated comorbidity precluding use of methotrexate or ciclosporin 1
• Disease controlled only by repeated inpatient management 1

Special Considerations for Infliximab

For very severe disease specifically, infliximab may be considered when: 1

• PASI ≥20 AND
• DLQI ≥18 AND
• Ciclosporin, methotrexate, or PUVA has failed or cannot be used 1

This represents a higher threshold than other biologics and should be reserved for the most severe presentations 2

Critical Prescribing Requirements

• Initiation and supervision must be by specialist physicians experienced in psoriasis diagnosis and treatment 1
• Formalize arrangements for drug administration, monitoring, and follow-up between healthcare providers and patient 1
• Enroll patients in long-term safety registries (BADBIR in UK/Ireland) 1
• Screen for contraindications including active serious infections, latent tuberculosis, hepatitis B/C, and malignancy history 3

Common Pitfalls to Avoid

• Do not use biologics as first-line therapy for uncomplicated moderate-to-severe psoriasis without documented failure of standard systemic agents 1
• Do not start biologics during active infection - if infection develops during treatment, monitor carefully and discontinue if it becomes serious 3
• Do not assume topical therapy alone is adequate for extensive disease (BSA >10% or PASI ≥10) - this delays appropriate systemic treatment 4
• Do not interrupt biologic therapy unnecessarily once started, as this increases antibody formation, infusion reactions, and reduces efficacy 4
• Do not overlook psoriatic arthritis - its presence justifies earlier biologic initiation and influences drug selection (adalimumab is particularly favorable) 2

First-Line Biologic Selection

When criteria are met, recommended first-line biologics include: 2

• Ustekinumab (45 mg for <100 kg or 90 mg for ≥100 kg every 12 weeks) 2
• Adalimumab (40 mg every other week, particularly when psoriatic arthritis present) 2
• Secukinumab (for psoriasis with or without psoriatic arthritis) 2

The most effective agents for achieving PASI 90 based on network meta-analysis are infliximab, bimekizumab, ixekizumab, and risankizumab, all with high-certainty evidence 5