Can inhibitors be eliminated?

Immune Tolerance Therapy

Yes. Immune tolerance therapy (ITT; also known as immune tolerance induction or ITI) is a treatment that consists of repeated infusions of factor concentrate over a period of time. The goal of ITT is to train the body to tolerate the factor concentrate and not react to the protein by creating antibodies.

ITT regimens vary in effectiveness and not one treatment has been proven to be more effective than another. Some treatments consist of daily doses of factor while other regimens recommend twice or three times per week.聽 While it is generally agreed that inhibitor patients should begin ITT using the same factor product that resulted in the development of antibodies, some HTCs may use a plasma-derived, von Willebrand-containing factor product for ITT purposes.

Immune Tolerance is highly effective and works in about 80% of people with inhibitors. Predictors of success include how soon the inhibitor was detected and how soon ITT was started, and the peak level of inhibitor titer. Factor VIII patients have a higher rate of success than factor IX patients.

There are differing medical opinions on which ITT regimen or protocol is the most effective.聽 Below is a brief discussion of ITT options; patients should discuss their individual medical treatment with their healthcare provider.

Malmo Regimen

The Malmo Regimen is named for the area in Sweden where it was initiated in 1982.聽 It is traditionally done over a short term (one-two month) in an in-patient hospital setting and is a combination of immune tolerance therapy with factor at high dose, immunosuppressive drugs, and intravenous immunoglobulin (IVIG).聽 Some have suggested that inhibitors are tolerized quickly using this method, but the side effects of the immunosuppressing drugs are a challenge.聽 Few outside Scandinavia use this regimen.

Bonn Protocol

The Bonn Protocol began in Bonn, Germany in the late 1970s.聽 It involves regular administration of factor replacement over a prolonged period of time in conjunction with the use of activated prothrombin complex concentrate (aPCC, brand name: FEIBA).聽 Dosing rates vary and patients using this method traditionally stay on it for several months to several years.

International ITI Study & International Workshop on Inhibitors: Consensus Recommendations

When ITT Doesn鈥檛 Work/Decisions about when to stop ITT

According to the 鈥淚nternational workshop on immune tolerance induction: consensus recommendations鈥 the consensus definition of successful ITT involves three things:

  1. The inhibitor titer can no longer be measured.
  2. Factor recovery is greater than 66% of normal.
  3. The half-life of Factor VIII is greater than 6 hours.

What happens if a patient tries ITT for a prolonged period and hasn鈥檛 met these criteria? The International ITI study states that if success has not come within 33 months of beginning ITT and there is a lack of a 20% decrease in the inhibitor titer over a six-month period, that it鈥檚 considered a failure. However, definitions of 鈥渇ailure鈥 vary from one provider to another.

Some clinicians will begin 鈥渞escue therapy鈥, which may involve changing the dosing regimen of ITT or changing factor product.

Other Inhibitor Eradication 聽Methods

While ITT is normally the first method of trying to eradicate an inhibitor, it does not always work for everyone. Other methods for inhibitor eradication are less studied and are somewhat controversial among medical professionals.

Immunosuppression or Immunomodulation

Immunosuppression is an act that reduces how the immune system activates or the efficacy of the immune system. In general, while this method has been used with limited success, it has not been thoroughly studied in congenital hemophilia inhibitor eradication and the long-term effects of using immune-suppressing drugs are unknown.聽 Suppression can be against the entire immune system or focused specifically on the T or B cells.聽 Various medications (immune suppressants) have been used, such as Rituximab (trade name Rituxan; Mycophenolate mofetil (trade name CellCept); Corticosteroids, i.e. Prednisone).

Treatment regimens vary from HTC to HTC.


Plasmapheresis is the removal, treatment, and return of (components of) blood plasma from blood circulation.聽 This procedure will remove or reduce the antibodies that cause the inhibitor;, however, it does not have a lasting effect and is not a widely used method.

Sign up for E-mails, Dateline Magazine, and other ways to stay connected.