Side Effects of fostamatinib: A Synthesis of Findings from 13 Studies

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Original Abstract of the Article

Major Research Findings

Fostamatinib is an oral drug that inhibits spleen tyrosine kinase (Syk) and is used to treat rheumatoid arthritis. 6 , 5 , 13 . Clinical trials have shown that fostamatinib is effective for patients with rheumatoid arthritis who do not respond to conventional treatments such as methotrexate. 6 , 5 . However, some side effects of fostamatinib have been reported. 6 , 5 .

R406, the active metabolite of fostamatinib, has been shown to have antagonist activity at the adenosine A3 receptor in the range relevant to clinical effects, in addition to the kinase domain. 4 . Furthermore, R406 has been shown to be active against many protein kinases at therapeutically relevant concentrations when tested in multiple in vitro systems. 4 . These results suggest that some of the side effects of fostamatinib may be caused by off-target effects. 4 .

Fostamatinib has also been suggested to act as an autophagy modulator. 11 . Fostamatinib may inhibit autophagy, and its effects may occur through the involvement of core autophagy-related proteins such as mTOR, AKT, and AMPK. 11 .

Reason for Side Effects

The side effects of fostamatinib may be due to its pharmacological profile. 4 . Fostamatinib has been reported to be active against many protein kinases, and these off-target effects may be causing side effects. 4 .

Common Side Effects

Gastrointestinal Symptoms

The most common side effects of fostamatinib are gastrointestinal symptoms. 6 , 5 . These symptoms include abdominal pain, diarrhea, nausea, and vomiting. 6 , 5 .

Neutropenia

Fostamatinib can cause neutropenia. 6 , 5 . Neutropenia can increase the risk of infection. 6 , 5 .

Hypertension

Fostamatinib can cause hypertension. 6 , 5 , 4 . Hypertension can increase the risk of heart disease and stroke. 6 , 5 . One mechanism by which fostamatinib may induce hypertension is inhibition of the vascular endothelial growth factor receptor (KDR). 4 .

Elevated Liver Function Tests

Fostamatinib can cause elevated liver function tests. 6 , 5 . Elevated liver function tests can indicate liver damage. 6 , 5 .

Lipid Abnormalities

Fostamatinib can cause lipid abnormalities. 6 . Lipid abnormalities can increase the risk of heart disease. 6 .

Measures to Address Side Effects

Gastrointestinal Symptoms

Gastrointestinal symptoms caused by fostamatinib can sometimes be alleviated through dietary changes and medication. 6 .

Neutropenia

Neutropenia caused by fostamatinib can be monitored through blood tests and treated as necessary. 6 .

Hypertension

Hypertension caused by fostamatinib can be managed through lifestyle changes and medication. 6 , 5 .

Elevated Liver Function Tests

Elevated liver function tests caused by fostamatinib can be monitored through regular blood tests and treated as necessary. 6 , 5 .

Lipid Abnormalities

Lipid abnormalities caused by fostamatinib can be managed through lifestyle changes and medication. 6 .

Comparison Between Studies

Commonalities in Studies

Multiple studies have shown that fostamatinib is effective for treating rheumatoid arthritis. 6 , 5 , 13 . Studies have also reported that fostamatinib can cause side effects such as gastrointestinal symptoms, neutropenia, hypertension, elevated liver function tests, and lipid abnormalities. 6 , 5 .

Differences in Studies

Evaluations of the effectiveness and safety of fostamatinib have yielded different results across studies. 5 . While fostamatinib has been shown to be effective for patients with rheumatoid arthritis who do not respond to methotrexate, its effectiveness for patients who do not respond to biological agents has not been confirmed. 5 .

Considerations for Real-Life Applications

Fostamatinib is a potentially effective treatment for rheumatoid arthritis, but the risk of side effects should be considered. 6 , 5 . When considering the use of fostamatinib, it is important to consult with your doctor and weigh the benefits and risks. 6 , 5 .

Limitations of Current Research

The long-term safety profile of fostamatinib is still unknown. 6 . Fostamatinib has been used for only short periods in clinical trials, and there is a lack of data on long-term side effects. 6 .

Future Research Directions

Further research is needed to evaluate the long-term safety and effectiveness of fostamatinib. 6 . Research is also needed to elucidate the mechanisms of fostamatinib's side effects. 4 .

Conclusion

Fostamatinib holds promise as a treatment for rheumatoid arthritis, but the risk of side effects must be considered. 6 , 5 . When considering the use of fostamatinib, it is important to consult with your doctor and weigh the benefits and risks. 6 , 5 .

Literature analysis of 13 papers
Positive Content
12
Neutral Content
1
Negative Content
0
Article Type
1
0
0
7
13
1.

[Comparison of therapeutic effect of different doses of ganciclovir for neonatal congenital cytomegalovirus infection].

Author: HeXiao-Ri, ChenPing-Yang, WangTao, XieZong-De, HuJin-Tao, BoTao, GeJian-Fang

CMV infection
Side effects

This study compared the efficacy and side effects of relatively low and high doses of ganciclovir in the treatment of neonatal congenital cytomegalovirus (CMV) infection.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

2.

Immune Thrombocytopenia in Adults: Modern Approaches to Diagnosis and Treatment.

Author: Al-SamkariHanny, KuterDavid J

ITP treatment
Asplenia risk

This comprehensive review explores diagnostic considerations and surveys new and old treatment options for adults with ITP.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

3.

Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond.

Author: MaTerry King-Wing, McAdooStephen P, TamFrederick Wai Keung

Treats Glomerulonephritis
Infective Complications

This review discusses the current unmet medical needs in glomerulonephritis (GN) treatment and research. The authors explore the potential of tyrosine kinase inhibitors (TKIs) for GN treatment, emphasizing the need for accelerated translational research to investigate their safety and efficacy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis.

Author: NijjarJagtar Singh, TindellAlistair, McInnesIain B, SiebertStefan

Oral bioavailability
Rheumatoid arthritis treatment
Gastrointestinal effects
Hypertension
Neutropenia
Transaminitis
Upper respiratory tract infections

Fostamatinib, a spleen tyrosine kinase inhibitor, has been shown to be effective in treating rheumatoid arthritis in patients who have not responded to methotrexate or biologic therapies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

Emerging role of kinase-targeted strategies in chronic lymphocytic leukemia.

Author: WiestnerAdrian

CLL remission
Reduced lymphadenopathy
Reduced splenomegaly
Moderate side effects

Chronic lymphocytic leukemia (CLL) is a type of cancer that affects mature B cells. These cancer cells rely on host factors for survival and growth. Small-molecule inhibitors can target kinases essential for CLL cell signaling and have shown promising results in treating relapsed and refractory CLL patients. These drugs, like fostamatinib, ibrutinib, and GS-1101, have shown impressive responses with manageable side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

Novel small-molecular therapeutics for rheumatoid arthritis.

Author: FleischmannRoy

Oral administration
Treats RA

This article reviews the progress made in the development of oral small molecule immune modulators for rheumatoid arthritis (RA). These compounds aim to offer a safer and more convenient alternative to biologic therapies, with the potential to be less expensive.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

10.

Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization.

Author: Tempest-RoeShenzhen, PrendeckiMaria, McAdooStephen P, ClarkeCandice, TannaAnisha, Turner-StokesTabitha, MasudaEsteban S, WillicombeMichelle, CookH Terence, RoufosseCandice, TaubeDavid, PuseyCharles D, TamFrederick W K

Renal transplant sensitization

This study investigated the role of spleen tyrosine kinase (SYK) in the production of donor-specific antibodies (DSA), a major cause of renal allograft loss. Using a rodent model, the study showed that fostamatinib, a selective SYK inhibitor, strongly blocked DSA production without affecting overall immunoglobulin levels. The findings suggest that fostamatinib could be a potential therapeutic option to prevent sensitization in patients awaiting renal transplant.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Emerging role of kinase-targeted strategies in chronic lymphocytic leukemia.

Author: WiestnerAdrian

Impressive responses
Moderate side effects

This review explores the use of kinase inhibitors as targeted therapy for chronic lymphocytic leukemia (CLL). These inhibitors target key signaling pathways involved in CLL cell survival and proliferation, leading to promising responses in patients with relapsed or refractory disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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