What is the risk of infection in a patient with a history of autoimmune disorders or hemolysis being considered for vedolizumab (vedolizumab) treatment?

Risk of Infection with Vedolizumab in Patients with Autoimmune Disorders or Hemolysis

Vedolizumab has a favorable infection risk profile with serious infections occurring in only 0.6% of patients, and its gut-selective mechanism results in lower systemic infection rates compared to anti-TNF agents, though enteric infections may be slightly more common. 1

Overall Infection Risk Profile

Vedolizumab demonstrates reassuringly low infection rates across multiple large-scale studies:

• Integrated long-term safety data showed serious C. difficile infections, sepsis, or tuberculosis occurred in only 0.6% of patients, with no cases of progressive multifocal leukoencephalopathy (PML) over 4 years of follow-up 1
• The exposure-adjusted incidence rate for opportunistic infections was 0.7 per 100 patient-years in GEMINI trials and 1.0 per 100 patient-years in long-term safety studies 2
• A meta-analysis of 49 biologics studies showed that the risk of opportunistic infections with vedolizumab is no different from anti-TNF agents 1
• Long-term safety data over 9 years remain reassuring with very small numbers of serious infections 1

Gut-Selective Immunosuppression Advantage

The mechanism of vedolizumab provides a distinct safety advantage for systemic infections:

• Vedolizumab does not alter immune responses to parenterally administered antigens, maintaining systemic immunity while targeting gut inflammation 1
• Studies show a trend toward lower rates of non-gastrointestinal infections compared to systemic immunosuppressants 1
• Vedolizumab is classified as causing "gut-selective treatment with no systemic effects, but increased risk for intestinal infections" 1

Specific Infection Considerations

Enteric infections require particular attention:

• Enteric infections such as Clostridioides difficile may occur more frequently with vedolizumab due to its gut-selective mechanism 1
• One comparative study found gut infections occurred at 1.5 per 100 patient-years, more common in the vedolizumab group compared to anti-TNF or ustekinumab (P = 0.0001) 3
• The overall exposure-adjusted infection rate was 11.5 per 100 patient-years, with vedolizumab at 17.5 per 100 patient-years 3

Tuberculosis risk is minimal:

• Tuberculosis was reported at only 0.1 per 100 patient-years in clinical trials, with 7 events total in post-marketing surveillance 2
• No tuberculosis-related deaths were reported in either clinical trials or post-marketing settings 2

No viral reactivation concerns:

• In 29 patients with history of or concurrent hepatitis B/C infection, no viral reactivation was observed 2
• No cases of PML have been reported across all vedolizumab studies 1, 2

Contraindications and Screening Requirements

Vedolizumab is contraindicated in specific active infections:

• Active tuberculosis, sepsis, or opportunistic infections including gut infections such as C. difficile are absolute contraindications 1
• Pretreatment screening should be undertaken as for anti-TNF treatment, including tuberculosis screening 1
• Latent tuberculosis must be treated prior to commencing vedolizumab 1

Vaccination requirements:

• Patients should be up to date with vaccinations prior to starting treatment where possible 1
• Non-live vaccines may be administered during vedolizumab treatment 1
• Live vaccines are contraindicated during treatment 1
• Vedolizumab affects the response to orally administered vaccines but not parenteral vaccines 1

Risk Factors for Serious Infection

Independent predictors of serious infection in ulcerative colitis patients on vedolizumab:

• Prior failure of anti-TNF therapy (HR 1.99,95% CI 1.16-3.42, p=0.0122) 1, 4
• Narcotic analgesic use (HR 2.68,95% CI 1.57-4.58, p=0.0003) 4

Independent predictors in Crohn's disease patients:

• Younger age (HR 0.97,95% CI 0.95-0.98, p<0.0001) 4
• Corticosteroid use (HR 1.88,95% CI 1.35-2.63, p=0.0002) 4
• Narcotic analgesic use (HR 2.72,95% CI 1.90-3.89, p<0.0001) 4

Special Populations

Patients with autoimmune disorders:

• Vedolizumab has been successfully used in a patient with X-linked agammaglobulinemia without side effects over 18 months, demonstrating safety even in severely immunocompromised patients 5
• No specific contraindications exist for patients with autoimmune disorders beyond active infections 1

Patients with hemolysis:

• One case report documented autoimmune hemolytic anemia possibly secondary to vedolizumab, though causality was difficult to establish 6
• This represents an extremely rare occurrence (<1% of patients) and should not preclude vedolizumab use in patients with history of hemolysis 6

Monitoring and Management

Ongoing surveillance requirements:

• Patients should be monitored for and advised to report any neurological symptoms due to rare PML occurrence with other integrin receptor antagonists (though none reported with vedolizumab) 1
• Vedolizumab should be stopped if severe infection develops 1
• Annual review is recommended to assess safety and efficacy of long-term treatment 1

Common pitfalls to avoid:

• Do not confuse vedolizumab's gut-selective mechanism with complete lack of infection risk—enteric infections remain a concern 1, 3
• Do not overlook the need for tuberculosis screening despite lower risk compared to anti-TNF agents 1
• Do not administer live vaccines during treatment 1
• Do not use concomitantly with natalizumab or TNF blockers due to increased infection risk 7