Countermeasures after fostatinib/fotantinib resistance

Fostamatinib is an oral spleen tyrosine kinase (Syk) inhibitor that mainly reduces abnormal immune responses by inhibiting B cell receptor and Fc receptor-mediated signaling. In the treatment of diseases such as chronic immune thrombocytopenia (ITP), some patients may experience weakening of the efficacy or no longer stable response after using it for a period of time. This phenomenon is often understood clinically as functional resistance or secondary insufficient efficacy.

When the efficacy of fostatinib decreases, it is first necessary to determine whether it is true resistance. Overseas clinical practice emphasizes that patients' medication compliance, concomitant medications, and the fluctuating characteristics of the disease itself should be comprehensively evaluated. Changes in platelet levels or symptoms in some patients are not entirely due to drug failure, but may be related to infection, stress, or the concurrent use of drugs that affect immune function. After eliminating these factors, we can more accurately determine whether the treatment strategy needs to be adjusted.

For patients who are confirmed to have insufficient efficacy, a common response is to re-evaluate the dosage or dosage regimen based on individual tolerance. In some people, optimizing the dosing rhythm or short-term combined supportive treatment can sometimes regain a certain disease control effect. If the desired response still cannot be achieved after adjustment, overseas guidelines usually recommend considering changing to a treatment regimen with a different mechanism of action rather than simply prolonging the original medication.

In the field of immune thrombocytopenia, alternatives often include other immunomodulatory drugs or targeted therapies targeting different signaling pathways. The purpose of this is to avoid adaptive changes caused by long-term inhibition of a single pathway, thereby improving the overall treatment success rate. In addition, some patients may reduce their dependence on a single drug through individualized comprehensive management strategies during the stable disease stage.

Reference materials:https://go.drugbank.com/drugs/DB12010