• Skip to primary navigation
  • Skip to main content
  • Skip to primary sidebar
  • Skip to footer

Johns Hopkins Arthritis Center

Show Search
Hide Search
  • Disease Information
    • Rheumatoid Arthritis
    • Psoriatic Arthritis
    • Ankylosing Spondylitis
    • Osteoarthritis
    • Gout
    • Osteoporosis
  • Patient Corner
    • Drug Information Sheets
    • Managing Your Arthritis
    • RheumTV – Patient Education Video Library
  • Our Research
    • Patient-Centered Outcomes Research
    • Current Research Studies
    • The Camille Julia Morgan Arthritis Research and Education Fund
  • About Us
    • Appointment Information
    • Contact Us
    • Our Faculty
    • Our Staff
    • Rheumatology Specialty Centers
  • Donate
Home / Arthritis News / Study Demonstrates Promise for Spleen Tyrosine Kinase (Syk) Inhibitors for the Treatment of Rheumatoid Arthritis

Study Demonstrates Promise for Spleen Tyrosine Kinase (Syk) Inhibitors for the Treatment of Rheumatoid Arthritis

September 24, 2010 By Arthritis Center

RA HandSpleen tyrosine kinase (Syk) is an important mediator of inflammatory signals from extracellular receptors to the nucleus of immune cells.  Inhibiting Syk with the oral, small-molecule inhibitor fostamatinib has shown efficacy compared to placebo in a short term study of RA patients on background methotrexate.  Here, Weinblatt et al (NEJM 2010; published online ahead of print on September 22, 2010) report six month efficacy and safety data of fostamatinib for the treatment of RA.

Methods

RA patients with active disease were randomized to receive treatment with fostmatanib 100 mg twice daily, 150 mg daily, or placebo.  Patients were required to be on stable background methotrexate, but could also be on other stable background sulfasalazine, anti-malarials, NSAIDS, or low dose prednisone.  Prior TNF inhibitor and leflunomide use was permitted, but required washout prior to enrollment.  The primary efficacy outcome was ACR20 response at 6 months.  Safety outcomes were monitored throughout the study.

Results

A total of 457 patients were enrolled; 304 to either of the fostamatanib doses (equally apportioned) and 153 to placebo.  Characteristics of the patients were typical for RA clinical trials.  The average age was around 50 years, most (85%) were female, with an RA duration of around 9 years and an average DAS28 score at enrollment of 6.15 units.  The average number of swollen joints was 12.  Because many of the enrollment sites were in Central and South America, the prevalence of Hispanic ethnicity was nearly 50%.  Baseline characteristics were balanced between the treatment groups.  Dropouts were 21% of the placebo group compared to 16% of the active treatment groups.

Clinical responses are described in the table (below).  Patients receiving the highest dose of study drug had higher responses than those receiving the lower dose or placebo.  Differences in response compared to placebo were observed as early as the first week of the study.

ACR 20 Responses (Percentage of Patients meeting ACR 20 Responses, by Group)
Week 1 Week 24
Placebo 14 35
Fostamatanib 150 mg QD 23 57*
Fostamatanib 100 mg BID 36* 67*
* p<0.05 compared to placebo

There were 21 withdrawals from the study due to adverse events (15 from the active treatment groups).  Adverse events that were increased in the active treatment groups compared to placebo included diarrhea, upper respiratory infection, neutropenia, abdominal pain, and hypertension.

For the open label extension, all patients received active drug and were followed for an additional 6 months (n=297).  Of these, 69 (18%) withdrew—19 for inefficacy and 21 for adverse events (nausea, diarrhea, elevated liver function tests).  There were 3 deaths in the open label extension phase (septicemia, cerebral hemorrhage, and sudden death) and 24 additional serious adverse events (among which were a B-cell lymphoma, cervical carcinoma, and a myocardial infarction).

Conclusions

The oral Syk inhibitor fostamatanib was superior to placebo in reducing the signs and symptoms of active RA, with higher doses demonstrating more robust efficacy.  Some adverse events, such as diarrhea and hypertension, were higher among treated patients.

Editorial Comment

Kinase inhibitors represent an exciting new area of pharmacotherapeutics in RA.  For fostamatinib, oral administration, the magnitude of efficacy, and quick onset of action are compelling aspects.  Side effects, such as nausea, diarrhea, and hypertension are issue to follow in further studies, and it is yet unclear whether these will emerge as nuisance side-effects that can be managed, or whether they will limit the wide application of the drug.  Additional study is required to determine long-term safety of the drug, particularly in terms of serious side-effects, such as cardiovascular events, infection, and malignancy.

Receive the Latest News from Johns Hopkins Rheumatology

Receive the Latest News from Johns Hopkins Rheumatology

Join our mailing list to receive the latest news and updates from Johns Hopkins Rheumatology.

Interested In

You have Successfully Subscribed!

Arthritis Center

Founded in 1998, the Arthritis Center at Johns Hopkins is dedicated to providing quality education to patients and healthcare providers alike.

Use of this Site

All information contained within the Johns Hopkins Arthritis Center website is intended for educational purposes only. Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained within this site. Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website.

Primary Sidebar

Recent News

Exercise Tips for Arthritis Patients

How Does Exercise Affect my Joints? How Frequently Should I Be Exercising? Should I Lose Weight for Exercise to be

Risks and Benefits of Biologic Medications

Victoria Ruffing, RN, BC, Director of Patient Education at the Johns Hopkins Arthritis Center, shares the risks and benefits of biologic for

How to Manage Rheumatoid Arthritis Flares

Through research, doctors have a clearer understanding of how flares can impact a patient on a personal and emotional level. Dr. Uzma Haque

Complementary & Alternative Medicines for Psoriatic Arthritis

There are many complementary & alternative medicines and practices that have been found to be beneficial in curbing arthritis pain,

I can’t be a runner because I have Rheumatoid Arthritis (RA), right?

Dr. Manno discusses running and Rheumatoid Arthritis. Is it an option for the RA patient?

News Categories

  • Ankylosing Spondylitis News
  • Fibromyalgia News
  • Gout News
  • Lupus News
  • Osteoarthritis News
  • Osteoporosis News
  • Psoriatic Arthritis News
  • Rheumatoid Arthritis News
RheumTV Logo

Rheum.TV is an informational platform created to educate patients living with a rheumatic disease. With over 100 disease education videos produced by the team at Johns Hopkins Rheumatology.

Visit Rheum.TV

Footer

Johns Hopkins Rheumatology

  • Johns Hopkins Rheumatology
  • Johns Hopkins Lupus Center
  • Johns Hopkins Lyme Disease Research Center
  • Johns Hopkins Myositis Center
  • Johns Hopkins Scleroderma Center
  • Johns Hopkins Sjögren’s Syndrome Center
  • Johns Hopkins Vasculitis Center

Connect With Us

  • Facebook
  • Twitter
  • YouTube

Johns Hopkins Medicine

© 2023 Johns Hopkins Arthritis Center
Patient Privacy