What are the risks of using biologics, such as adalimumab (adalimumab) or etanercept (etanercept), in patients with a history of recurrent infections, malignancy, autoimmune diseases, or hepatitis B?

Risks of Biologics in High-Risk Populations

Biologics carry significant risks in patients with recurrent infections, malignancy history, autoimmune diseases, or hepatitis B, and require mandatory pre-treatment screening with tuberculosis testing, hepatitis panel, complete blood count, and liver function tests before initiation. 1

Pre-Treatment Screening Requirements

All patients must undergo comprehensive baseline testing before starting any biologic therapy:

• Tuberculosis screening: IGRA (interferon-gamma release assay) and chest X-ray are mandatory for all patients 1
• Hepatitis panel: Test for HBsAg, anti-HBc, anti-HBs, and HCV antibodies 1
• Complete blood count with platelet count 1
• Chemistry panel with liver function tests 1
• EBV and VZV serology in patients under 30 years or without clear history 1
• HIV testing should be performed 1

Infection Risks

Tuberculosis Reactivation

TNF inhibitors carry the highest risk of TB reactivation, with infliximab and adalimumab showing incidence rates of 103-171 per 100,000 patient-years compared to 39 per 100,000 for etanercept. 1

• The risk of TB reactivation is 4.68 times higher with biologics compared to control (NNTH = 681) 2
• Monoclonal antibodies (infliximab, adalimumab) pose greater TB risk than fusion proteins (etanercept) 1
• At least 50% of TB cases with infliximab are extrapulmonary, making diagnosis challenging 1
• Median time to TB diagnosis: 3 months with infliximab, 4-6 months with adalimumab, 11.5 months with etanercept 1

Serious Infections

Hold biologic therapy immediately if any infection requiring antibiotics develops; discontinue permanently for serious or opportunistic infections. 1

• Certolizumab pegol shows the highest risk of serious infections (OR 3.51, NNTH = 17) compared to control 2
• Upper respiratory tract infections are most common across all biologics 1
• Opportunistic infections (histoplasmosis, listeriosis, cryptococcosis, aspergillosis) occur more frequently with monoclonal antibodies than etanercept 1
• Patients with chronic, serious, or recurring infections should avoid biologics entirely 1

Hepatitis B Reactivation

All HBsAg-positive patients require antiviral prophylaxis before starting biologics; treatment with biologics is contraindicated in untreated chronic hepatitis B or Child-Pugh Class B and higher. 1, 3

• HBV reactivation occurs in 36% of HBsAg-positive IBD patients on immunosuppression without prophylaxis 1
• TNF inhibitors (infliximab, adalimumab) can reactivate chronic hepatitis B with risk of fatal liver failure 1, 4
• Infliximab causes HBV reactivation in 50-66% of HBsAg-positive patients without prophylaxis 4
• Even HBsAg-negative/anti-HBc-positive patients can experience reactivation, though less frequently 1
• Etanercept may be considered in hepatitis C patients with compensated cirrhosis 3

Malignancy Risks

Lymphoma

The risk of lymphoma is elevated with biologics, particularly in rheumatoid arthritis patients, though baseline disease activity confounds this association. 1

• Adalimumab shows a standardized incidence ratio of 2.98 for lymphomas in RA trials 1
• The observed lymphoma rate may reflect underlying disease severity rather than drug effect alone 1

Skin Cancer

Infliximab increases non-melanoma skin cancer risk (OR 1.7) and melanoma risk (OR 2.6). 1

• Patients with prior non-melanoma skin cancer require dermatology surveillance during biologic therapy 1
• The risk is compounded in psoriasis patients with prior phototherapy or immunosuppressive drug exposure 1

Malignancy History

For patients with solid malignancy treated within 5 years, melanoma, or lymphoproliferative malignancy, rituximab is the preferred biologic. 5

Autoimmune and Neurologic Complications

Demyelinating Disorders

TNF inhibitors are absolutely contraindicated in patients with personal history of demyelinating conditions (multiple sclerosis, optic neuritis, transverse myelitis). 1, 6

• Peripheral neuropathy occurs in 0.4-0.6% of patients on TNF inhibitors 6
• If any neurological symptoms develop during treatment, immediately withhold the TNF inhibitor and obtain urgent neurological evaluation 6

Lupus-Like Reactions

Rare lupus-like syndromes occur at 0.1 per 100 patient-years with adalimumab 1

Inflammatory Bowel Disease Exacerbation

Secukinumab and ixekizumab are associated with new-onset or exacerbation of Crohn's disease and should be avoided in patients with IBD. 1

• For AS patients with coexisting IBD, use TNF monoclonal antibodies (infliximab, adalimumab, certolizumab, golimumab) rather than etanercept 1

Monitoring During Treatment

Re-evaluate patients periodically for new infections, malignancy symptoms, and neurological changes throughout biologic therapy. 1

• Liver function tests every 4 weeks for first 3 months, then every 8-12 weeks if stable 3
• Complete blood count monitoring at intervals per drug-specific guidelines 1
• Maintain high index of suspicion for atypical infections throughout treatment 1

Contraindications Summary

Absolute contraindications to biologics:

• Active serious infections 1
• Untreated latent tuberculosis 1
• Untreated chronic hepatitis B or Child-Pugh Class B/C cirrhosis 1, 3
• Personal history of demyelinating disorders (for TNF inhibitors) 1, 6
• NYHA Class III/IV heart failure with EF ≤50% (for TNF inhibitors) 5

Vaccination Considerations

Administer all indicated vaccinations before starting biologics; live vaccines are contraindicated during biologic therapy. 1

• Pneumococcal and influenza vaccines show adequate but attenuated immune responses during TNF blocker therapy 1
• Patients should participate in national cancer screening programs 1