Navigation Links
Study of anti-CD20 therapy effective B cell depletion
Date:6/2/2008

B cells, precursors of autoantibody-secreting cells, have emerged as promising new therapeutic targets in autoimmune diseases, including rheumatoid arthritis (RA). In particular, B cell depletion with the anti-CD20 antibody rituximab seems to work for RA patients resistant to standard disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor α (TNFα) blockers. In large trials, about half of these hard-to-treat patients respond to rituximab, achieving at least a 20 percent improvement in disease activity based on the American College of Rheumatology criteria. However, in the majority of responders, the disease relapses over time. After a single treatment with rituximab, complete remission of RA symptoms for longer than a year is very rare.

With the goal of identifying reliable predictors of response or relapse to rituximab, a trio of researchers in Germany focused on the recovery response of different B cell subsets to repeated B cell depletion. Their analysis, featured in the June 2008 issue of Arthritis & Rheumatism (www.interscience.wiley.com/journal/arthritis), reveals the critical role of memory B cells in the compromised immune reaction of RA and the short-term gains of rituximab therapy.

Conducted by Petra Roll, M.D., and Hans-Peter Tony, M.D., at the University of Wrzburg and Thomas Drner, M.D., an affiliate of the University of Berlin, the B cell investigation began with an open-label trial of one cycle of rituximab on 17 RA patients. The participants, 14 women and 3 men, had a median age of 51 years, a median disease duration of 14 years, and a history of failure to respond to DMARD and/or anti-TNFα therapy. 16 of the patients received 2 infusions rituximab, 1,000 milligrams each, 2 weeks apart, and one patient received 4 weekly infusions of rituximab at a dose of 375 milligrams. Blood samples from all participants were obtained at baseline, on day 15, and at a 3-month followup, and analyzed for B cell repopulation.

After receiving one cycle of rituximab, 12 of the 17 patients showed a good clinical response, with significant improvement in the Disease Activity Score in 28 joints (DAS28). At the time of B cell recovery, the IgD +, CD27+ memory B cell subset was significantly larger in the nonresponder group. Within the group of 12 responders, 6 patients experienced an early relapse of RA activity, between 24 and 40 weeks after rituximab treatment. The relapsers were characterized by a significantly higher proportion of overall CD27+ memory B cells before therapy. 11 patients were re-treated and again achieved a good clinical response. After the second cycle of rituximab, the pattern of B cell reconstitution was repeated. The number of B cells was still reduced at the time of second depletion but recovered to levels similar to those following the first cycle of therapy. This indicates an unimpaired capacity of B cell regeneration after repeated B cell depletion.

Based on statistical analysis, the researchers found a significant correlation between the size of the IgD +, CD27+ memory B cell subset during the early phase of B cell repletion and the response to anti-CD20 treatment. "Patients with lower numbers of IgD memory cells at the beginning of peripheral B cell repopulation had a much more favorable clinical response," notes Dr. Tony. "Therefore, the extent of memory B cell repletion seems to be a key factor influencing the pathophysiology of RA."

While revealing a potentially important target for rituximab therapy in RA, this study calls for further research into whether patients with a high level of particular memory B cells may benefit from early re-treatment or may even require higher doses of this anti-CD20 antibody.


'/>"/>

Contact: Sean Wagner
swagner@wiley.com
781-388-8550
Wiley-Blackwell
Source:Eurekalert

Related medicine news :

1. Large Study Identifies Most Costly Adverse Events in Childrens Hospitals
2. Large study identifies most costly adverse events in childrens hospitals
3. First study to examine vitamin D insufficiency in pediatric patients with low bone density
4. Study examines cold medication use in young children
5. Look before you leap: New study examines self-control
6. International Diabetes Federation grant supports study to prevent type 2 diabetes in India
7. Study suggests chemotherapy diminishes fertility in breast cancer patients
8. Quality of life predicts cancer survival, U-M study finds
9. USC study finds sex, age and ethnicity assciated with colorectal cancer survival
10. Montana Center for Work Physiology and Exercise Metabolism presents firefighter health study
11. Moonview Sanctuary Releases First Case Study of Client Treated Using Unique Moonview Model
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... , ... October 13, 2017 , ... “America On The ... identity. “America On The Brink” is the creation of published author, William Nowers. ... great-grandchildren. As a WWII veteran, he spent thirty years in the Navy. ...
(Date:10/12/2017)... ... October 12, 2017 , ... The ... demand of today’s consumer and regulatory authorities worldwide. From Children’s to Adults 50+, ... to meet the highest standard. , These products are also: Gluten Free, ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... ... drug delivery system that we intend to develop to enable prevention of a ... lead to severe hearing loss, especially in pediatric patients. For cisplatin, hearing loss ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... On Saturday, ... a treadmill relay – Miles by Moonlight to raise money for the American Heart ... or more. , Teams will work together to keep their treadmills moving for ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... in wound care advancements to physician colleagues, skilled nursing facility medical directors and ... the Treacherous Waters of Wound Care." , "At many of these conferences we ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... Pa. , Oct. 12, 2017 ... leader in innovative solutions for injectable drug administration, today ... before the market opens on Thursday, October 26, 2017, ... the results and business expectations at 9:00 a.m. Eastern ... (U.S.) or 253-336-8738 (International). The conference ID is 94093362. ...
(Date:10/11/2017)... 11, 2017  Hill-Rom Holdings, Inc. ("Hill-Rom") (NYSE: HRC), ... in Las Piedras, Puerto Rico , ... Following a ... sustained minor structural damage, temporary loss of power and ... been completed, manufacturing operations have resumed, and the company ...
(Date:10/5/2017)... Ill. , Oct. 5, 2017  In ... Association of Oral and Maxillofacial Surgeons (AAOMS) released ... opioids – to be used as a first-line ... pain. Recognizing ... the AAOMS White Paper "Opioid Prescribing: Acute and ...
Breaking Medicine Technology: