Hello,
A call to the Medical College of Ohio confirmed that the drug you're
referring to is "Rituxan" (chemical name Rituximab, also marketed as
MabThera). Catherine, a nurse at the Medical College of Ohio
Hospital, notes that the drug's name is often misspelt and that
doctors aren't always clear in their pronounciation.
Approved by the FDA in November of 1997, Rituxan is most commonly used
to treat B-cell non-Hodgkinds lymphoma (cancer of the lymphatic
system). It's "off label" (not approved for marketing) uses include
treatments for chronic lymphocytic leukemia, Waldenstrom's
macroglobulinemia and immune or idiopathic thrombocytopenic purpura.
FDA approves first drug in decade for non-Hodgkin's lymphoma
Athens Banner-Herald, November 2, 1997
http://www.athensnewspapers.com/1997/112797/1127.a3fda.html
ASH MEETING: Over A Quarter Of Rituxan Responders Still In Remission
http://www.pslgroup.com/dg/ca23e.htm
Cancer Drug Helps Rheumatoid Arthritis: Rituxan More Effective than
Methotrexate, Study Shows
http://my.webmd.com/content/article/53/50460.htm
Rituxan for Rheumatoid Arthritis
http://www.biotech-world.de/newsusa.shtml?shownews=57
Rituximab - MedLinePlus
http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203423.html
Recent research indicates that Rituxan may be beneficial to certain
patients with Rheumatoid Arthritis:
"International, multicenter investigators, led by Edwards,
Szczepanski, and Shaw evaluated 122 study subjects of a 161-patient
randomized, double-blind, placebo-controlled trial in which Rituxan
was used in combination with methotrexate. Methotrexate is one of
several standard treatments for RA. The results included:
* 80% of combination therapy recipients, compared with 33% of
methotrexate monotherapy recipients, achieved 20% or greater symptom
improvement (ACR20).
* 50% of combination therapy recipients, compared with 10%
methotrexate monotherapy recipients, achieved 50% or greater symptom
improvement (ACR50).
* 23% of combination therapy recipients, compared with 0% methotrexate
monotherapy recipients, achieved 70% or greater symptom improvement
(ACR70).
* A Rituxan-cyclophosphamide combination provided 84%, 45%, and 16% of
recipients ACR20, ACR50, and ACR70, respectively. Methotrexate is
clinically favorable over cyclophospamide from an adverse effect
profile perspective.
One Rituxan recipient who did not receive continued methotrexate died
from pneumonia five months into the study period, although the local
investigator concluded, "this event was unrelated to trial
medication."
These data add to recent enthusiasm about Rituxan for RA generated by
a manuscript published in the August issue of Arthritis and Rheumatism
(2002; 46:1984-1985 & 2029-2033). In that article, Dr. Gianfranco
Ferraccioli and colleagues at University of Udine (Italy) demonstrated
that Rituxan could selectively block specific B cell action and
appeared to be responsible for a significant magnitude of therapeutic
effect in certain refractory RA cases. The Italian investigation
involved five women with refractory, aggressive RA who received an
NHL-like regimen of Rituxan in four weekly IV infusions of 375 mg/m2."
Rituxan for Rheumatoid Arthritis
October 02, 2002
http://www.pcsresearch.com/bt/NewsDetail.cfm?NewsID=371
Results of a Phase II clinical study, presented at the American
College of Rheumatology (ACR) meeting on October 26, 2003, showed that
65% of study participants showed at least a 20% improvement in their
RA symptoms, and 35% showed at least a 50% improvement in symptoms.
As a result of this study, the makers of Rituxan (Rituximab, MabThera)
are continuing research into possible use of this drug in the
treatment of RA, and are currently enrolling patients in a Phase III
clinical trial. A successful Phase III trial could lead to FDA
approval of the use of Rituxan for the treatment of RA:
"Roche, Genentech and IDEC Pharmaceuticals Inc. today announced
positive results from an extended Phase II study showing that a
single, short course of treatment (two doses) with MabThera
(rituximab) significantly improved symptoms in patients with severe
rheumatoid arthritis (RA) for up to 48 weeks*.
In the study, investigators followed up with patients who had
completed a 24-week clinical trial, in order to assess duration of
response with MabThera beyond the initial endpoint of 24 weeks.
Participants in the 24 week, four arm, placebo controlled trial were
randomized to receive MabThera alone or in combination with
cyclophosphamide or methotrexate (MTX), as compared to patients
receiving MTX alone.
At 48 weeks, patients receiving the combination of MabThera and MTX
had the greatest improvement in symptoms:
• 65% of patients showed at least a 20% improvement in symptoms
• 35% showed at least a 50% improvement
• 15% showed at least a 70% improvement."
Long-term data shows MabThera to be a highly promising treatment for
Rheumatoid Arthritis (RA)
http://www.roche.com/med-corp-detail-2003?id=1068&media-language=e
"We are also beginning the process of expanding Rituxan's potential
use in non-malignant areas. This quarter, Genentech, IDEC and Roche
announced positive preliminary results of a randomized, controlled and
double-blind Phase II study evaluating Rituxan (Rituximab/MabTheraŽ)
alone or in combination with other therapies in rheumatoid arthritis."
Genetech 2002 Second Quarter Letter to Stockholders
http://www.gene.com/gene/ir/financials/quarterly-reports/2002/q2/
"In the study, investigators followed patients who had completed the
24-week clinical trial in order to assess duration of response with
Rituxan beyond the initial endpoint of 24 weeks. Patients in the
four-arm, placebo-controlled trial were randomized to receive Rituxan
alone or in combination with MTX or CTX, as compared to patients
receiving MTX alone. At 48 weeks, patients receiving the combination
of Rituxan and MTX had the greatest improvement in symptoms: 65
percent (26/40 patients) showed at least a 20 percent improvement in
symptoms (ACR20), 35 percent (14/40 patients) showed at least a 50
percent improvement (ACR50) and 15 percent (6/40 patients) showed at
least a 70 percent improvement (ACR70). The study was blinded through
the 48-week period.
"These data indicating a durable response with just two infusions of
Rituxan are encouraging," said Charles Johnson, Genentech senior
director, Specialty Biotherapeutics. "Rituxan represents a potentially
novel approach to treating this disease by selectively targeting
B-cells which appear to be a significant contributing factor in the
development of rheumatoid arthritis."
Global Phase IIb and Phase III Clinical Trials Enrolling Patients to
Investigate the Role of Rituxan in the Treatment of Rheumatoid
Arthritis
http://www.thetsector.com/displayarticle6091.html?POSTNUKESID=a5bdebc43a46c34aeaa2240399788873
"A blockbuster drug for cancer also offers long-term relief to
rheumatoid arthritis sufferers, according to results of an
intermediate Phase II clinical study released on Sunday.
Patients given just two doses of MabThera, also known as Rituxan,
continued to show a substantial improvement in symptoms for up to 48
weeks, data presented to the American College of Rheumatology and
released in London showed.
[...]
If eventually approved for rheumatoid arthritis it would compete
against Amgen Inc's (nasdaq: AMGN - news - people) Enbrel and Johnson
& Johnson's (nyse: AMGN - news - people) Remicade, two popular new
drugs that treat rheumatoid arthritis by blocking an
inflammation-causing protein called tumour necrosis factor."
Roche, Genentech drug helps arthritis long-term
http://www.forbes.com/home_europe/newswire/2003/10/26/rtr1123162.html
"Results from Phase II clinical trials for Rituxan were announced by
Genentech, IDEC Pharmaceuticals, and Roche, at the 2003 American
College of Rheumatology meeting in Orlando, Florida. A single, short
course of treatment with Rituxan (two infusions during the first 15
days of treatment) alone, or in combination with methotrexate (MTX) or
cyclophosphamide (CTX) improved symptoms in patients with moderate to
severe rheumatoid arthritis for up to 48 weeks, compared to
methotrexate alone."
Rituxan Shows Sustained Benefit For RA In Phase II Trials
http://arthritis.about.com/cs/ra/a/rituxan.htm
Rituxan works by depleting B-cells, abnormal antibodies produced by
b-lymphocytes (white blood cells) which cause joints to become
inflamed. It's theorized that by destroying these b-cells, the immune
system can be made to "re-boot", and produce normal antibodies again.
Early investigations in 2000 showed promising results in the small
test group, but more research must be done before definite conclusions
can be drawn:
"News reports were a response to an abstract presented by Edwards et
al.1 regarding the use of rituximab (RituxanŽ in U.S., MabtheraŽ in
Europe) in the treatment of rheumatoid arthritis. Rituximab is an
anti-CD 20 chimeric mouse/human monoclonal antibody approved in 1997
for the treatment of B-cell lymphomas and has since been used in more
than 50,000 patients. The monoclonal antibody has been shown to
selectively deplete mature and malignant CD-20 positive pre B-and
mature B-cells, and is the first monoclonal agent approved for cancer
therapy. Based on their hypothesis that rheumatoid arthritis may be
driven by auto-reactive B-lymphocytes, the authors utilized rituximab
to deplete B-cells in five patients with refractory rheumatoid
arthritis.
[...]
This novel study has resurrected the notion that RA may be a B cell
driven process in some patients and that therapies aimed at curtailing
the humoral response may be efficacious. Nonetheless, this is a very
preliminary and uncontrolled trial in a small number of patients.
Moreover, it is not certain to what extent cyclophosphamide and
corticosteroids contributed to the therapeutic responses observed.
More clinical research with this combination regimen is necessary
before it can be applied in the clinic."
Rituximab in the Treatment of Rheumatoid Arthritis
November 20, 2000
Robert Spiera, MD; John J. Cush, MD
http://www.rheumatology.org/research/hotline/1100rituximab.html
See also:
B-Cell Depletion Triggers RA Remission
http://arthritis.about.com/library/weekly/aa110400a.htm
B-Lymphocyte Depletion Therapy - Wading Through The Hype
http://arthritis.about.com/library/weekly/aa112700a.htm
Arthritis cure: the facts behind the hype
British Medical Journal - 11-11-2000
http://bmj.bmjjournals.com/cgi/content/full/321/7270/1232
Most actual research is buried in subscription only medical journals,
however, some abstracts are available. If you're interested in
reading the in-depth research, your father's physician may be able to
obtain copies of the articles abstracted, or you may obtain a "day
pass" to view the full text of certain studies (such as those in the
Annals of the Rheumatic Diseases Online):
"The most recent trial in rheumatoid arthritis indicates that
rituximab works very well if given with steroid cover. Treatment with
rituximab alone, under steroid cover, produced a 50% or greater
improvement (ACR50 grade) in 50% of patients, which is as good as any
other available therapy. The patients studied were also taking
methotrexate throughout the study, but there is no reason to think
that this contributed to the improvement following rituximab. (Other
information suggests that methotrexate is unlikely to be needed for
the rituximab to work, that is, it is unlikely to be synergistic.)
Patients who had their methotrexate stopped at the same time as being
given rituximab did slightly less well. This means that the effects of
rituximab and methotrexate can probably be additive and that if
patients were to be started on methotrexate and rituximab at the same
time, more than 50% would be likely to achieve the ACR50 improvement
grade.
The trial also indicated that results are likely to be better if
rituximab is combined with another drug which is traditionally used
for B cell depletion, cyclophosphamide (cytoxan). Cyclophosphamide can
make people feel sick and has other potential problems with side
effects, so it is not as attractive as a treatment as methotrexate,
even though cyclophosphamide acts on B cells together with rituximab
whereas methotrexate probably does not.
It is not clear at present which is the best way to use rituximab;
alone, just with steroid cover, or with additional methotrexate or
cyclophosphamide. It is probably worth using alone but the other drugs
probably all increase the potential for improvement. It is likely that
rituximab should be given in full dose in most cases. It seems to be
satisfactory to give the two double doses rather than the four single
doses. So far the two double doses have been given two weeks apart,
but there is no particular reason why they should not be given a week
apart."
Update on B Lymphocyte Depletion Therapy (30.10.2003)
http://www.ucl.ac.uk/~regfjxe/B.htm
Abstracts:
B-lymphocyte depletion therapy in rheumatoid arthritis and other
autoimmune disorders.
Edwards JC, Leandro MJ, Cambridge G.
Centre for Rheumatology, University College London, Arthur Stanley
House, 40-50 Tottenham Street, London W1T 4NJ, UK.
jo.edwards@ucl.ac.uk
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12196207&dopt=Abstract
Clinical outcome in 22 patients with rheumatoid arthritis treated with
B lymphocyte depletion
M J Leandro, J C W Edwards and G Cambridge
Centre for Rheumatology, University College London, UK
Correspondence to:
Professor J C W Edwards, Centre for Rheumatology, Arthur Stanley
House, 40-50 Tottenham Street, London W1T 4NJ, UK;
jo.edwards@ucl.ac.uk
http://ard.bmjjournals.com/cgi/content/abstract/61/10/883
Sustained improvement in rheumatoid arthritis following a protocol
designed to deplete B lymphocytes
J. C. W. Edwards and G. Cambridge
University College London Centre for Rheumatology, London, UK
http://rheumatology.oupjournals.org/cgi/content/full/40/2/205
B cell Depletion In Rheumatoid Arthritis
JCW Edwards (M Leandro and G Cambridge)
Department of Rheumatology, University College London, UK
6th International Symposium on the Immunotherapy of the Rheumatic
Diseases
15-19 May 2002
http://www.kcl.ac.uk/ip/jeremycridland/rsymp/abstracts-10.htm
Articles available only in full text, at a price:
B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20)
experience
Shaw et al. Ann Rheum Dis.2003; 62: 55-59.
http://ard.bmjjournals.com/cgi/content/full/62/suppl_2/ii55?hits=10&FIRSTINDEX=0&SEARCHID=1067823101895_729&gca=annrheumdis%3B62%2Fsuppl_2%2Fii55&gca=annrheumdis%3B61%2F10%2F863&
Treating human autoimmune disease by depleting B cells
Looney Ann Rheum Dis.2002; 61: 863-866.
http://ard.bmjjournals.com/cgi/content/full/61/10/863?hits=10&FIRSTINDEX=0&SEARCHID=1067823101895_729&gca=annrheumdis%3B62%2Fsuppl_2%2Fii55&gca=annrheumdis%3B61%2F10%2F863&
There are certain side effects associated with the use of Rituxan.
Most frequent side effects include:
-- angioedema (swelling of the lips and face)
-- bronchospasm (narrowing of the airway)
-- chills
-- dyspnea (difficulty breathing)
-- facial Flushing
-- fatigue
-- fever
-- headache
-- hypotension (low blood pressure)
-- nausea
-- pruritus (itchiness)
-- rhinitis (runny nose)
-- urticaria (hives)
-- vomiting
RITUXIMAB INTRAVEN.
Adverse Effects List & Discussion
http://www.medscape.com/druginfo/SideEffect?id=A-16848&name=RITUXIMAB+INTRAVEN.&DrugType=1&MenuID=ADE&ClassID=N&GeneralStatement=N
There have been 8 cases of fatal reactions to Rituxan since 1997. (It
should be noted that in the time since this article was written, use
of Rituxan has expanded to more than 50,000 patients worldwide):
"Severe infusion-related effects, sometimes fatal, have been reported
in patients receiving rituximab.In some patients, death has occurred
within 24 hours of rituximab infusion.These fatal reactions occurred
following a complex of severe manifestations and sequelae of an
infusion-related reaction including hypoxia, pulmonary infiltrates,
acute respiratory distress syndrome, myocardial infarction,
ventricular fibrillation, and/or cardiogenic shock.Approximately 80%
of fatal infusion reactions occurred in association with the initial
infusion of rituximab, with a usual time of onset between 30-120
minutes after starting the infusion.Factors associated with an
increased risk of fatal outcome in cases of severe infusion-related
reactions induced by rituximab include female gender, presence of
pulmonary infiltrates, and diagnosis of chronic lymphocytic leukemia
or mantle cell lymphoma.The manufacturer reports that approximately 70
cases of serious infusion-related events, 8 of which were fatal, have
been reported out of an estimated 12,000-14,000 patients worldwide who
received rituximab therapy between November 1997 and December 1998."
Infusion-related Effects
http://www.medscape.com/druginfo/SideEffect?id=A-16848&name=RITUXIMAB+INTRAVEN.&DrugType=1&MenuID=ADE&ClassID=N&GeneralStatement=N#1285042
According to Genentech, the patients who died while undergoing Rituxan
treatment for non-Hodgkins lymphoma had a high tumor burden:
"Review of the reports for these eight patients did not reveal a
common pattern of predisposing factors. However, it appears that
patients with a high tumor burden or with a high number (>50,000/mm3)
of circulating malignant cells may be at higher risk. Therefore, these
patients should be treated with extreme caution and be closely
monitored throughout each infusion."
Important Prescribing Information
http://www.fda.gov/medwatch/safety/1998/rituxa.htm
Although the use of Rituxan for the treatment of RA is not yet an FDA
approved method, the recent research results and the current
enrollment for a Phase III clinical trial look encouraging. Of
course, when helping your father decide whether or not to consent to
this treatment, it's important to discuss every aspect of his care and
any attendant risk factors with his physician.
Whatever course you decide, please pass along my best wishes for a
speedy recovery.
I hope you find this information helpful. If I can be of further
assistance, please just ask for clarification. I'll be happy to help.
--Missy
Search terms: [ Rituxan ], [ Rituxan arthritis ] |
