Immunogenicity and autoimmunity during anti-TNF therapy

Area of Science:

• Immunology
• Rheumatology
• Pharmacology

Background:

• Anti-tumour necrosis factor (TNF) agents have transformed treatment for rheumatoid arthritis (RA), Crohn's disease (CD), and spondyloarthritis (SpA).
• Conventional therapies are often ineffective for patients with active disease.
• TNF inhibitors are a critical therapeutic option for refractory autoimmune conditions.

Purpose of the Study:

• To review the potential development of autoantibodies and anti-drug antibodies in patients treated with TNF inhibitors.
• To highlight the clinical significance of these antibodies in patient management.
• To discuss strategies for mitigating antibody induction during biological therapy.

Main Methods:

• Literature review of studies reporting antibody development in patients receiving TNF inhibitors.
• Analysis of reported cases of autoimmune phenomena and anti-drug antibodies.
• Examination of the impact of anti-drug antibodies on infliximab pharmacokinetics and adverse events.

Main Results:

• A subset of patients on TNF inhibitors develop autoantibodies, including antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies.
• Anti-phospholipid antibodies have been detected in RA patients using TNF blockers.
• Anti-drug antibodies, particularly against infliximab, can affect drug efficacy and cause infusion/injection site reactions.

Conclusions:

• The onset of autoimmune diseases during biological treatment, though rare, requires prompt recognition and management.
• Anti-drug antibodies can compromise the therapeutic benefits of TNF inhibitors.
• Co-administration of immunosuppressive drugs may reduce the induction of anti-TNF antibodies.