What is the risk of severe infections with ocrelizumab (Ocrevus) use?

Incidence of Severe Infections with Ocrelizumab Use

Ocrelizumab is associated with a serious infection rate of 2.01 per 100 patient-years (95% CI: 1.81-2.23), which remains stable over long-term treatment and is considered manageable with appropriate monitoring. 1

Infection Risk Profile

• The overall infection rate with ocrelizumab is 76.2 per 100 patient-years (95% CI: 74.9-77.4) in clinical trials, with most infections being mild to moderate 1
• Serious infections occur in approximately 1.3% of patients treated with ocrelizumab compared to 2.9% of patients treated with interferon beta-1a in relapsing multiple sclerosis (RMS) trials 2
• The incidence of serious infections remains stable over treatment periods extending up to 14 years, indicating no cumulative risk with continued exposure 3
• Infection rates differ between MS subtypes: 1.50 per 100 patient-years in relapsing MS versus 3.70 per 100 patient-years in progressive MS 3

Types of Infections

• The most common serious infections associated with ocrelizumab are:

  • Lower respiratory tract infections 3
  • Urinary tract infections 3
  • Abdominal and gastrointestinal infections 3
  • Skin infections 4

• Upper respiratory tract infections occur more frequently with ocrelizumab than comparator treatments, but are typically mild to moderate in severity 4

• Herpes-related infections are more common with ocrelizumab, including:

  • Herpes zoster 4
  • Herpes simplex 4
  • Oral herpes 4
  • Genital herpes 4

Risk Factors for Severe Infections

• The presence of comorbidities significantly increases infection risk:

  • One comorbidity increases risk by 1.66 times 3
  • Two or more comorbidities increases risk by 2.73 times in RMS and 1.80 times in progressive MS 3

• Higher disability (EDSS score ≥6.0) is associated with:

  • 2.02 times increased risk of serious infections in RMS 3
  • 4.31 times increased risk in primary progressive MS (the strongest risk factor) 3

• Recent relapse activity increases infection risk by 2.06 times 3

• Abnormal IgM levels increase risk by 1.89 times in progressive MS 3

• Overweight/obesity increases risk by 1.46 times in progressive MS 3

• Importantly, time on ocrelizumab and abnormal IgG levels were not significantly associated with increased serious infection risk 3

Clinical Course and Management of Infections

• Approximately 90% of serious infections resolve with appropriate management 3

• Ocrelizumab treatment can be continued in over 80% of cases following resolution of the infection 3

• Serious herpes virus infections may occur at any time during treatment and require temporary discontinuation until the infection resolves 4

• For life-threatening infections, ocrelizumab should be permanently discontinued 4

Prevention and Monitoring

• Screening for active or latent infections (particularly tuberculosis and hepatitis B) is essential before initiating ocrelizumab 4

• Patients should be monitored for signs and symptoms of infection during and after treatment 4

• Ocrelizumab should be delayed in patients with active infections until resolution 4

• Patients with higher risk factors (multiple comorbidities, higher disability scores) require more vigilant monitoring 3

Long-term Safety Perspective

• Long-term data up to 7 years from clinical trials show a consistent and favorable safety profile without emerging safety concerns 1

• Real-world data with over 3 years of follow-up confirms the manageable safety profile seen in clinical trials 1

• The most recent real-world study with median follow-up of approximately 4 years continues to show a favorable safety profile 5

In conclusion, while ocrelizumab is associated with an increased risk of infections, the incidence of severe infections is relatively low and stable over time. Proper patient selection, pre-treatment screening, and monitoring can help manage this risk effectively. The benefit-risk profile remains favorable for appropriate patients with multiple sclerosis.