TNF Blockade
๐ฅ TNF: A Pivotal Cytokine Mediator
- ๐งฌ Tumour Necrosis Factor (TNF) is a master regulator of inflammation, central to many immune-mediated diseases.
- Exists in both soluble and transmembrane forms.
- Binds to TNFR1 and TNFR2 โ driving inflammation, apoptosis, and cell survival pathways.
๐ TNF Blockade: A Revolutionary Therapy
- First modern biological therapy introduced at the turn of the 21st century.
- Now licensed for both adults and children across several immune-mediated diseases:
- ๐คฒ Rheumatoid arthritis
- ๐ฆด Ankylosing spondylitis
- ๐งฉ Psoriatic arthritis
- ๐ถ Juvenile idiopathic arthritis
- ๐ฉธ Psoriasis
- ๐ฟ Crohnโs disease
- ๐งป Ulcerative colitis
- ๐ Uveitis
- ๐ฅ Hidradenitis suppurativa
๐ Licensed Anti-TNF Agents
- Currently 5 licensed anti-TNF drugs:
- ๐งฌ Fully human monoclonal antibodies (e.g., adalimumab, golimumab)
- ๐งช Chimeric monoclonal antibody (infliximab)
- โ๏ธ Certolizumab โ PEGylated Fab fragment, produced in E. coli
- ๐ Etanercept โ soluble receptor (also blocks lymphotoxin-ฮฑ3)
๐คฒ Impact on Rheumatoid Arthritis
- ๐ Licensed in early 2000s โ transformed management.
- Marked improvements in pain, stiffness, fatigue โ reduced disability and need for surgery.
- Registry data: โ risk of serious infection, but no increase in malignancy overall.
- ๐ก Teaching pearl: Anti-TNFs often combined with methotrexate for durability and to reduce antibody formation against biologics.
โ ๏ธ Unexpected Complications
- ๐งซ Tuberculosis (TB) reactivation:
- Disruption of granulomas โ extrapulmonary/miliary TB.
- Now standard: TB screening (IGRA or Mantoux + CXR) before therapy.
- Etanercept less likely to reactivate TB compared to infliximab/adalimumab.
- โฌ๏ธ Susceptibility to intracellular pathogens: listeria, salmonella, fungi.
๐ฟ Crohnโs Disease & Ulcerative Colitis
- Highly effective in severe Crohnโs (esp. fistulising or perianal disease).
- ~50% achieve remission & mucosal healing within 2 years.
- Etanercept โ ineffective in Crohnโs โ reflects granulomatous nature of disease.
- Effective in ulcerative colitis too.
๐ฉธ Psoriasis & Psoriatic Arthritis
- Clear benefit in moderate-severe psoriasis: infliximab โ >80% achieve PASI 75 improvement.
- Also effective in psoriatic arthritis & ankylosing spondylitis โ โ joint inflammation and improved spinal mobility.
๐ซ Limitations of TNF Blockade
- Not effective in all conditions โ can worsen:
- ๐ง Multiple sclerosis
- โค๏ธ Congestive heart failure
- Trials in these diseases stopped due to adverse outcomes.
๐ฅ Adverse Effects of TNF Blockade
- In addition to infections, rare but important side effects include:
- ๐ฉธ Neutropenia
- ๐ฉป Vasculitis
- ๐ฉบ Paradoxical psoriasis (new onset)
- ๐ Drug-induced lupus (including renal & CNS disease)
๐ก Clinical pearl: Anti-TNF agents have redefined outcomes in chronic inflammatory diseases, but require pre-treatment screening (TB, hepatitis B/C, HIV) and ongoing vigilance for infections and autoimmune complications.
