What's the longest period you can safely discontinue Entyvio (Natalizumab) without forming antibodies?

Maximum Safe Discontinuation Period for Entyvio Without Antibody Formation

For patients on Entyvio (vedolizumab), there is no established maximum safe discontinuation period that guarantees prevention of antibody formation, but most patients can safely resume treatment after temporary discontinuation with a high success rate of recapturing response.

Understanding Vedolizumab Discontinuation and Antibody Risk

• Vedolizumab is a humanized monoclonal antibody that blocks α4β7 integrin-mediated leukocyte migration, used in treating inflammatory bowel diseases 1
• Unlike some other biologics, vedolizumab has shown favorable immunogenicity profiles with relatively low rates of antibody formation 2
• The risk of antibody formation specifically related to treatment interruption has not been extensively studied in large clinical trials 1

Evidence on Discontinuation and Retreatment

• In a multicentre study of patients who discontinued vedolizumab while in steroid-free clinical remission, approximately 64% experienced disease relapse within a median follow-up period of 11.2 months 2
• When patients who relapsed were retreated with vedolizumab, 71% achieved steroid-free clinical remission by week 14, and 62.5% maintained remission during follow-up 2
• Importantly, no infusion reactions were reported upon retreatment, suggesting absence of clinically significant antibody formation 2

Factors Affecting Successful Retreatment

• Patients with C-reactive protein levels less than 5 mg/L at the time of discontinuation had a significantly lower risk of relapse (HR = 0.56,95% CI [0.33-0.95]) 2
• Patients who discontinued vedolizumab by choice rather than due to adverse events or other reasons had better outcomes upon retreatment (HR = 0.41,95% CI [0.21-0.80]) 2
• The duration of prior vedolizumab treatment may influence successful retreatment, with longer treatment duration potentially associated with better outcomes 1

Dosing Interval Considerations

• In the GEMINI long-term safety study, some patients were successfully transitioned from 4-weekly to 8-weekly dosing with only 15% experiencing relapse 1
• Among those who relapsed after extending the dosing interval, 80% re-entered remission when returned to the original 4-weekly dosing schedule 1
• This suggests that even with planned dosing interval changes, most patients maintain response and can be recaptured if relapse occurs 1

Clinical Recommendations

• There is no definitive maximum "safe" period for discontinuation, but shorter interruptions (weeks rather than months) likely carry lower risk of antibody formation 2
• For patients requiring temporary discontinuation, monitoring C-reactive protein levels before and after discontinuation may help predict successful retreatment 2
• If discontinuation is necessary, documenting the reason for discontinuation is important as it may predict likelihood of successful retreatment 2
• Upon restarting therapy after discontinuation, monitor closely for infusion reactions or loss of response that might indicate antibody formation 2

Practical Approach

• For planned temporary discontinuations (such as for surgery or travel), aim to limit the interruption to less than 8-12 weeks if possible 1, 2
• For longer interruptions, consider that approximately two-thirds of patients may experience disease relapse within a year 2
• When restarting after a prolonged interruption, be prepared to adjust dosing frequency if needed, as some patients may require more frequent dosing to recapture response 1

Caution

• Individual patient factors including disease severity, prior treatment history, and concomitant immunomodulator use may influence antibody formation risk 2
• The evidence specifically addressing antibody formation during treatment interruption is limited, and decisions should consider the patient's overall clinical status and risk of disease flare 2