Anti-TNF Therapy Causes Immune Suppression in Ulcerative Colitis Patients
Yes, anti-TNF therapy does cause immune suppression in ulcerative colitis patients, leading to an increased risk of opportunistic infections and other immune-related complications. 1
Mechanism and Evidence of Immune Suppression
- Anti-TNF therapies (infliximab, adalimumab, golimumab) are associated with a 2-fold increased risk of opportunistic infections compared to placebo in patients with inflammatory bowel disease 1
- The absolute risk of opportunistic infections is approximately 0.9% in patients receiving anti-TNF therapies versus 0.3% in patients receiving placebo 1
- Anti-TNF therapy is associated with increased rates of serious bacterial infections, particularly in the first 6 months of treatment initiation 1
- The TREAT registry showed an increased risk of serious infections with anti-TNF therapy in Crohn's disease (hazard ratio 1.47) 1
Types of Infections Associated with Anti-TNF Therapy
Anti-TNF therapy has been associated with various types of infections:
- Mycobacterium tuberculosis (2.5-fold increased risk) 1
- Herpes simplex infections 1
- Oral or esophageal candidiasis 1
- Herpes zoster infections 1
- Varicella-zoster virus infections 1
- Cytomegalovirus or Epstein-Barr virus infections 1
- Nocardia infections 1
Risk Factors for Increased Immune Suppression
The risk of immune suppression and associated infections increases significantly with:
- Combination therapy with other immunosuppressants 1
- Concomitant use of corticosteroids 1
- Age over 50 years (OR 3.0,95% CI 1.2-7.2 relative to age < 25 years) 1
- Duration of therapy (prolonged use may increase sensitization) 1
Combination Therapy Risks
- Combinations of immunomodulator therapy in IBD are associated with an incremental increase in the relative risk of opportunistic infection 1
- Three-fold increased risk with any one immunomodulator used 1
- Substantially higher risk (OR 14.5,95% CI 4.9-43) if two or more drugs are used concomitantly 1
- When anti-TNF therapy is combined with thiopurines, there is a higher risk of hepatosplenic T-cell lymphoma, particularly in adolescent and young adult males with Crohn's disease or ulcerative colitis 2, 3
Malignancy Risk
- Anti-TNF therapy does not appear to be associated with an increased risk of overall malignancy in trials of up to 1 year (RR 0.77; 95% CI 0.37-1.59) 1
- However, there are specific concerns about:
Clinical Recommendations
- When starting anti-TNF therapy, it is recommended to combine it with a thiopurine or methotrexate rather than using it as monotherapy to induce complete remission 1
- However, patients should be informed of the potential safety issues, particularly when anti-TNF therapies are used in combination with corticosteroids or immunosuppressants 1
- Anti-TNF therapy can be continued in the preoperative period for patients undergoing surgery for ulcerative colitis 1
- Patients with ulcerative colitis treated with a biological therapy who remain corticosteroid-dependent (particularly if on triple immunosuppression) are at significant risk of opportunistic infections 1
Monitoring and Prevention
- Screen for tuberculosis prior to initiating anti-TNF therapy 1
- Evaluate patients at risk for HBV infection before starting therapy, as anti-TNF can reactivate hepatitis B virus 2
- Consider periodic skin examinations, particularly in patients with risk factors for skin cancer 3
- For women, continue periodic screening for cervical cancer 3
- Monitor for signs of infection throughout therapy and for several months following termination of therapy 2
Anti-TNF therapy remains an important treatment option for ulcerative colitis, but clinicians must balance its efficacy against the increased risk of immune suppression and associated complications.