How does immune tolerance induction work?
With immune tolerance induction (ITI) therapy, factor concentrate is given regularly over a period of time until the body is trained to recognize the treatment product without reacting to it. When immune tolerance induction is successful, the inhibitors disappear and the patient’s response to factor concentrates returns to normal. The majority of people who undergo ITI therapy will see an improvement within 12 months, but more difficult cases can take two years or longer.
Different dosing schedules are currently being used for ITI therapy, and the best one for eliminating inhibitors has not yet been defined. Daily high doses of factor concentrates may induce tolerance faster, but this type of regimen is more expensive and carries different risks than do schedules that involve giving less factor concentrate, less frequently.
An ongoing study called the Immune Tolerance Induction Study (www.itistudy.com) is trying to compare the effectiveness and safety of different dosing regimens. The results of this study will help improve ITI therapy for people with factor VIII inhibitors in both developed and developing countries.
What factors influence the outcome of immune tolerance induction therapy?
It is still unclear why ITI works better in some people than in others. Factors that have been associated with successful ITI therapy include:
- Begininng ITI in people whose inhibitor levels are below 10 BU/mL and ideally below 5 BU/mL.
- Begininng ITI in people whose inhibitor levels have never gone higher than 200 BU/mL and have ideally stayed below 50 BU/mL.
- Begininng ITI within five years of a person being diagnosed with the inhibitor.
Stopping treatment early or taking breaks in the treatment schedule (missed doses) may interfere with the success of ITI and/or increase the time it takes for the person with inhibitors to achieve tolerance.
Researchers are also looking at whether the type or brand of factor concentrate (intermediate or high-purity plasma-derived factor concentrates or recombinant products) used in ITI can influence the success of therapy. So far, similar success rates have been obtained with both recombinant and plasma-derived products.
Content developed by the WFH Inhibitors Working Group
Updated May 2012