What are the indications, recommended biologic agents, dosing regimens, baseline screening requirements, and monitoring guidelines for patients with moderate-to-severe inflammatory or autoimmune diseases who have not achieved adequate control with conventional non‑biologic therapies?

Biologics for Moderate-to-Severe Inflammatory and Autoimmune Diseases

For patients with moderate-to-severe inflammatory or autoimmune diseases who have failed conventional therapies, initiate biologic therapy with disease-specific first-line agents: ustekinumab or adalimumab for psoriasis, infliximab or adalimumab for Crohn's disease, and TNF inhibitors for rheumatoid arthritis, with mandatory tuberculosis screening before starting any biologic.

Disease-Specific Indications and First-Line Biologic Selection

Psoriasis

Offer ustekinumab as first-line biologic therapy for adults with moderate-to-severe psoriasis (defined as PASI ≥12 or body surface area ≥10%, or lower involvement in critical areas causing significant disability) 1.

Alternative first-line options include:

• Adalimumab: Particularly when psoriatic arthropathy is present 1
• Secukinumab: Consider for psoriasis with or without psoriatic arthritis 1
• Reserve infliximab for very severe disease or after other biologics have failed 1

Crohn's Disease

Use infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib as first-line biologic therapy for moderate-to-severe inflammatory Crohn's disease after corticosteroid failure 2.

The 2025 AGA guidelines prioritize higher efficacy medications (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab) over lower efficacy options (certolizumab pegol, upadacitinib) in biologic-naive patients 2.

For pediatric Crohn's disease, anti-TNF therapy (adalimumab, infliximab) is strongly recommended for moderate-to-severe disease after corticosteroid failure 3.

Rheumatoid Arthritis

After 3 months of inadequate response to methotrexate or DMARD combination therapy, add or switch to an anti-TNF biologic, abatacept, or rituximab 4, 5.

Dosing Regimens

Psoriasis Standard Dosing 1

• Ustekinumab: 45 mg every 12 weeks (<100 kg) or 90 mg every 12 weeks (>100 kg)
• Adalimumab: 40 mg every other week
• Etanercept: 50 mg once weekly
• Infliximab: 5 mg/kg every 8 weeks

Crohn's Disease Considerations 2

• Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs
• Subcutaneous formulations of infliximab and vedolizumab show comparable efficacy to intravenous maintenance doses
• Higher maintenance doses may be preferred in patients with high inflammatory burden or prior TNF antagonist failure

Dose Escalation Strategies

Consider dose escalation when inadequate primary response occurs, particularly in obese patients or those experiencing disease relapse during treatment cycles 1:

Biologic	Escalation Strategy
Ustekinumab 45 mg q12wks (<100 kg)	Increase to 90 mg q12wks
Ustekinumab 90 mg q12wks (>100 kg)	Shorten to 90 mg q8wks
Adalimumab 40 mg q2wks	Increase to 40 mg weekly
Etanercept 50 mg weekly	Increase to 50 mg twice weekly
Infliximab 5 mg/kg q8wks	Shorten to 5 mg/kg q6wks

Baseline Screening Requirements

Mandatory Tuberculosis Screening

Screen all patients for tuberculosis before initiating any biologic therapy 4, 5. This includes:

• Tuberculin skin test
• Interferon-gamma release assay (IGRA)
• Chest radiograph if either test is positive

Latent tuberculosis reactivation occurred in 0.8% of anti-TNF patients in prospective monitoring 6.

Hepatitis B Screening

Test all patients for hepatitis B before biologic initiation 5, 6:

• HBsAg
• Anti-HBc IgG
• Consider HBV DNA if positive

Do not use biologics in patients with untreated chronic hepatitis B or treated chronic hepatitis B with Child-Pugh Class B or higher 5.

For HBsAg-positive patients, provide prophylactic antiviral therapy; for anti-HBc positive/HBsAg-negative patients, consider preemptive monitoring 6.

Hepatitis C

Etanercept can potentially be used in patients with hepatitis C requiring treatment 5.

Vaccination Status

Complete all pending immunizations before starting biologics 7, 8. Vaccination coverage remains suboptimal, with only 23.8% for influenza and 4.7% for pneumococcal vaccines in monitored cohorts 6.

Additional Baseline Assessments

• Complete blood count
• Liver function tests
• Pregnancy test in women of childbearing potential
• Screen for active infections
• Assess for contraindications: congestive heart failure (avoid anti-TNF), demyelinating disease, recent malignancy

Monitoring Guidelines

Regular Laboratory Monitoring

Monitor complete blood counts and liver function tests every 6 months during biologic therapy 1, 2.

Response Assessment Timing

Assess treatment response at defined intervals 1:

• Psoriasis: Evaluate at end of induction phase
• Crohn's disease: After 3 months for TNF antagonists, 6 months for non-TNF biologics 5
• Rheumatoid arthritis: After 3 months of therapy 5

Minimal Response Criteria for Psoriasis 1

Treatment success requires BOTH:

• ≥50% reduction in baseline disease severity (PASI 50 response)
• Clinically relevant improvement in quality of life (≥4-point DLQI improvement or resolution of low mood)

Therapeutic Drug Monitoring

Consider proactive therapeutic drug monitoring for TNF inhibitors (infliximab, adalimumab) during maintenance therapy to optimize dosing and prevent disease flares 9. This involves measuring drug concentrations and anti-drug antibodies at timed intervals regardless of disease activity.

For suboptimal response or loss of response, use therapeutic drug monitoring to guide regimen intensification 3, 2.

Management of Treatment Failure

Primary Failure (No Initial Response)

Switch to an alternative biologic if minimal response criteria are not met 1:

• Psoriasis: Offer any currently licensed biologic therapy 1
• Crohn's disease: Switch to another anti-TNF or non-TNF biologic 5
• Rheumatoid arthritis: Switch to another anti-TNF or non-TNF biologic 5

Secondary Failure (Loss of Response)

Consider switching biologics or dose escalation 1. First address modifiable factors:

• Obesity and poor adherence
• Optimize adjunctive therapy (e.g., switch oral to subcutaneous methotrexate)
• Consider therapeutic drug monitoring to assess for low drug levels or anti-drug antibodies

After Multiple Biologic Failures

Seek advice from a clinician with expertise in biologic therapy 1. For psoriasis after second biologic failure, consider returning to non-biologic approaches (phototherapy, standard systemic therapy) 1.

Combination Therapy Considerations

Crohn's Disease

In biologic-naive patients starting infliximab, consider combination with thiopurines rather than infliximab monotherapy 2. However, in males, avoid combining anti-TNF therapy with thiopurines due to increased risk of hepatosplenic T-cell lymphoma; use methotrexate instead if combination therapy is needed 3.

Rheumatoid Arthritis

In patients achieving corticosteroid-free remission for ≥6 months on combination TNF antagonist plus immunomodulator therapy, withdraw the immunomodulator 2. Continue combination therapy only in patients at higher risk of immunogenicity (prior anti-drug antibody formation, HLA-DQA1*05 carriers, low drug trough levels).

Special Populations

Pediatric Patients

For psoriasis 1:

• Adalimumab (age ≥4 years)
• Etanercept (age ≥6 years)
• Ustekinumab (age ≥12 years)

For Crohn's disease: Anti-TNF therapy (adalimumab, infliximab) is strongly recommended for moderate-to-severe disease 3.

Pregnancy

Methotrexate is contraindicated in women actively considering pregnancy or who are pregnant 2. JAK inhibitors (upadacitinib) have limited safety data in pregnancy and should generally be avoided 2.

Malignancy History

For solid malignancies treated >5 years ago or non-melanoma skin cancer treated >5 years ago, start or resume any biologic 5. For more recent malignancies, melanoma, or lymphoproliferative malignancy, use rituximab only 5.

Congestive Heart Failure

Do not use anti-TNF biologics in patients with congestive heart failure 5.

Common Pitfalls to Avoid

1. Failing to screen for tuberculosis: This is mandatory before any biologic initiation and prevents potentially life-threatening reactivation
2. Using fixed dosing without considering therapeutic drug monitoring: Proactive TDM can prevent loss of response and optimize outcomes
3. Continuing ineffective therapy too long: Assess response at defined timepoints (3-6 months) and switch promptly if minimal response criteria are not met
4. Combining anti-TNF with thiopurines in males: This increases risk of hepatosplenic T-cell lymphoma; use methotrexate instead
5. Inadequate vaccination before therapy: Complete all vaccines before starting biologics, as live vaccines are contraindicated during treatment
6. Ignoring modifiable factors: Address obesity, adherence, and optimize adjunctive therapies before declaring treatment failure