Immune thrombocytopenia (ITP), previously called idiopathic thrombocytopenic purpura, is a rare blood disorder where your body’s immune system attacks and destroys your platelets. Platelets help form blood clots that stop bleeding. Not having enough platelets can make you bruise or bleed easily. If you have ITP and your platelets are too low or you have serious bleeding, you may need to have a platelet transfusion.
There are three different types of ITP, and the types are based on how long the symptoms last.
- Acute ITP: Symptoms last less than three months.
- Persistent ITP: Symptoms last 3-12 months.
- Chronic ITP: Symptoms last longer than 12 months.
Corticosteroids are often used to treat ITP when it is first diagnosed. Tavalisse (fostamatinib) is a newer medicine available to treat adults with chronic ITP who are not able to control their symptoms with other treatments. Continue reading to learn more about taking Tavalisse to treat chronic ITP.
How Does Tavalisse Work for Immune Thrombocytopenia (ITP)?
If you have immune thrombocytopenia (ITP), your immune system attacks and destroys your platelets. Some signals that tell your immune system to destroy platelets are sent through a substance called spleen tyrosine kinase (SYK). Tavalisse is a prodrug. A prodrug is a medicine that does not work on its own. It gets turned into an active form (known as the active metabolite) after it is inside your body. So after you take Tavalisse, your body changes it inside your stomach so it can start working. Once your body converts Tavalisse into its active metabolite, it blocks SYK, which helps stop your immune system from destroying your platelets.
How Was Tavalisse Studied for the Immune Thrombocytopenia (ITP)?
There were two main studies (FIT-1 and FIT-2) used to see how well Tavalisse worked compared to a placebo (no medicine) to increase platelets in people with persistent or chronic ITP. In both of these studies, neither the people in the studies nor the study investigators knew who was getting Tavalisse or a placebo.
There were a total of 151 people in FIT-1 and FIT-2. They ranged in age from 20 to 88 years old, and most were female (61%). The far majority of the people in these trials were White (~93%), with about 3% Asian, 3% Black, and 1% classified as other. Almost half (47%) of the people in these studies were on stable treatment for ITP with medicines such as azathioprine, danazol, or prednisone. Prior ITP treatments included corticosteroids (94%), immunoglobulins (53%), and thrombopoietin receptor agonists, such as avatrombopag, eltrombopag, lusutrombopag, or romiplostim (48%).
Of the people in FIT-1 and FIT-2, 93% had chronic ITP and 7% had persistent ITP. The median (the middle number) time since diagnosis was between eight and nine years ago. About a third (35%) of the people no longer had their spleen. Almost half (45%) of the people had platelets less than 15,000 per microliter (normal platelets are usually about 150,000 to 450,000 per microliter).
Everyone in FIT-1 and FIT-2 started taking Tavalisse 100 mg twice a day or a matching placebo. Over the course of the 24-week studies, 88% of people had their dose increased to Tavalisse 150 mg twice a day or a matching placebo, starting as early as the four-week mark. The primary outcome of the studies was a stable platelet response, defined as a platelet count of at least 50,000 at at least four of the six visits between study weeks 14 and 24.
There was an extension study (FIT-3) for 123 people who either completed FIT-1 or FIT-2 or were nonresponders at the 12-week mark during these studies. In FIT-3, everyone in the study took Tavalisse, so if you received the placebo in FIT-1 or FIT-2, you would definitely get Tavalisse in FIT-3. People who responded to Tavalisse in FIT-1 or FIT-2 continued taking the same dose of Tavalisse. Nonresponders from FIT-1 and FIT-2 started taking Tavalisse 100 mg twice a day in FIT-3.
Of the 123 people in FIT-3, 44 took a placebo, and 79 took Tavalisse in FIT-1 or FIT-2. The primary outcome of FIT-3 was a stable platelet response, but it was defined differently. In FIT-3, a stable platelet response meant that once a person’s platelets reached 50,000 or higher, platelets stayed at or above the goal level over the next 12 weeks. During these 12 weeks, study participants could not have two platelet labs, at least four weeks apart, where their platelets dropped below 50,000, unless there was a later visit showing the count had gone back up to 50,000 or higher on its own (meaning without any emergency treatments).
What Were the Results From These Studies?
The results from FIT-1 and FIT-2 are shown in the table below.
FIT-1 | FIT-2 | |||
|---|---|---|---|---|
Tavalisse (n=51) | Placebo (n=25) | Tavalisse (n=50) | Placebo (n=24) | |
| Stable platelet response | 18% | 0 | 16% | 4% |
| Nonresponder at 12 weeks | 55% | 88% | 66% | 79% |
| Completed 24-week study | 24% | 4% | 26% | 8% |
More people in the Tavalisse groups had a stable platelet response (a platelet count of at least 50,000 during at least four of the six visits between study weeks 14 and 24) than people who took a placebo (no medicine). This shows that Tavalisse seems to do a better job of increasing platelets in adults with chronic ITP than placebo.
There were fewer serious or severe bleeding-related adverse events in people who took Tavalisse compared to people who took a placebo.
| Bleeding Severity | Tavalisse (FIT-1 and FIT-2, N=101) | Placebo (FIT-1 and FIT-2, N=49) |
|---|---|---|
| Moderate | 9 % | 10 % |
| Severe (led to hospital stay) | 1 % | 6 % |
| Serious | 4 % | 10 % |
Ten of the 44 people (23%) in FIT-1 or FIT-2 who took a placebo had a stable platelet response during FIT-3. Also, of the 27 people who achieved stable platelet response in FIT-1, FIT-2, and FIT-3 trials, 18 people were able to maintain their platelet count at or above 50,000 for at least 12 months.
Your results may differ from what was seen in these studies.
How Can I Manage Diarrhea From Tavalisse?
A common side effect of Tavalisse is diarrhea, which can sometimes be severe. Your body loses water each time you have diarrhea. It is important to manage your fluid intake in order to avoid getting dehydrated. You can drink clear liquids, such as water, broth, or juice that is diluted and free of pulp, to stay hydrated. Liquids with electrolytes (such as Gatorade or Pedialyte) can also be helpful when you have diarrhea.
If you have diarrhea, you also may want to avoid certain foods and drinks that can upset your stomach and worsen your diarrhea. Some foods you may want to avoid include spicy foods, fried or fatty foods, milk or other dairy products, coffee or other things with caffeine in them, and citrus fruits.
If you have diarrhea while taking Tavalisse, let your health care provider know. They can give advice to manage your symptoms, may recommend medication to help, or might lower your dose or ask you to stop taking Tavalisse.
Does Tavalisse Have Any Drug Interactions?
Tavalisse may cause problems with other medicines and vice versa. Many of these interactions are caused by the effects of Tavalisse and other medicines on enzymes called cytochrome P450 (CYP). These are enzymes in your liver that metabolize or break down medicines. Some medicines may speed up, slow down, or even completely block these enzymes. When this happens, the amount of medicine in your body may increase (similar to taking too much) or decrease (similar to taking too little). Either way, this may cause problems that can sometimes be serious.
Medicines known as strong CYP3A4 inhibitors can increase your risk of side effects from Tavalisse because they can increase the levels of Tavalisse’s active metabolite. If you need to take a strong CYP3A4 inhibitor while you are taking Tavalisse, your health care provider may need to give you a lower dose of Tavalisse to lower your risk of side effects.
Medicines known as strong CYP3A4 inducers can reduce how well Tavalisse works for you because they can decrease how much Tavalisse is converted to the active metabolite (the form of the medicine that works in your body). It is not recommended to take Tavalisse with strong CYP3A4 inducers.
Always tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using.
How Should I Take Tavalisse?
Tavalisse is a tablet you swallow. It can be taken with or without food. Most people start by taking one tablet twice a day.
Your health care provider will monitor your platelet counts and other labs to see if any dosage changes are needed. Some people may need a higher dose if their platelet counts do not improve enough. Some people may need a lower dose if they have certain side effects. Do not change your dose of Tavalisse unless your health care provider tells you to do so. If your platelets do not increase enough after taking Tavalisse for 12 weeks, your health care provider may stop the medicine and talk with you about other treatment options.