|[June 18, 2014]
Two-Year Results From Pfizer's XELJANZ® (Tofacitinib Citrate) ORAL Start Study Published in The New England Journal of Medicine
NEW YORK --(Business Wire)--
Pfizer Inc. (NYSE:PFE) announced today the publication of two-year
results from the ORAL Start study in the June 19 issue of The New
England Journal of Medicine. ORAL Start is a 24-month Phase 3 study
in patients with moderately to severely active rheumatoid arthritis who
had not previously received methotrexate. The study showed that XELJANZ
(tofacitinib citrate) 5 mg and 10 mg twice daily, as monotherapy (e.g.,
taken without methotrexate), inhibited the progression of structural
damage and reduced the signs and symptoms of rheumatoid arthritis, and
was statistically significantly superior to methotrexate on these
measures at Month 6 (primary endpoint) and at all measured time points
up to 24 months. XELJANZ is not indicated in patients who had not
previously received methotrexate. The safety profile of XELJANZ in the
ORAL Start study was consistent with that seen previously in the
clinical development program.
In the United States, XELJANZ 5 mg tablets are indicated for the
treatment of adults with moderately to severely active rheumatoid
arthritis who have had an inadequate response or intolerance to
methotrexate. XELJANZ may be used alone or in combination with
methotrexate or other non-biologic, disease-modifying antirheumatic
drugs (DMARDs). Use of XELJANZ in combination with biologic DMARDs or
potent immunosuppressants, such as azathioprine and cyclosporine, is not
recommended. The recommended dose is a 5 mg pill taken twice daily.
"This study showed that XELJANZ taken by itself was statistically
significantly superior to methotrexate in measures of clinical,
radiographic and functional efficacy rheumatoid arthritis outcomes, and
these results were sustained over two years," said lead investigator Roy
M. Fleischmann, MD, professor, Metroplex Clinical Research Center,
Dallas, Texas. "These results also add to the information on the
efficacy and safety of XELJANZ as monotherapy."
The ORAL Start study was a 24-month Phase 3 randomized, double-blind,
controlled trial in which 956 patients with moderately to severely
active rheumatoid arthritis who had not previously received methotrexate
were randomized to receive XELJANZ 5 mg or 10 mg twice daily or to
methotrexate dose-titrated over 8 weeks to 20 mg weekly. As previously
announced, both doses of XELJANZ met the study's co-primary efficacy
endpoints: reduction of progression of radiographic measures of disease
as measured by average change from baseline in van der Heijde modified
Total Sharp (News - Alert) Score (mTSS)[0.18 and 0.04 (both P<0.001) for XELJANZ 5 mg
and 10 mg twice daily, respectively, versus 0.84 for methotrexate], and
clinical response as measured by ACR70 response rates, a measure of at
least 70% reduction in signs and symptoms of rheumatoid arthritis [25.5%
and 37.7% for XELJANZ 5 mg and 10 mg twice daily, respectively (both
P<0.001), versus 12.0% for methotrexate], at Month 6. ORAL Start also
evaluated improvement in physical function as measured by mean change
from baseline in the Health Assessment Questionnaire Disability Index
(HAQ-DI)[-0.83 and -0.94 (both P<0.001) for XELJANZ 5 mg and 10 mg
twice-daily, respectively, versus -0.58 for methotrexate], at Month 6.
These results were sustained at all measured time points up to 24 months.
The six- and 12-month radiographic data from this study were recently
added to the XELJANZ U.S. label (February, 2014) as part of an FDA
approved label update.
"The publication of the ORAL Start data in The New England
Journal of Medicine marks the sixth Phase 3 study in the XELJANZ
clinical program to be published in a major medical journal," said Dr.
Steven Romano, Global Medicines Development Lead for the Pfizer Global
Innovative Pharmaceutical business. "The publication of all of the
completed XELJANZ Phase 3 rheumatoid arthritis clinical studies in such
respected publications speaks to the significance and clinical relevance
of the data for XELJANZ."
The safety profile of XELJANZ in the ORAL Start study was consistent
with that seen previously in the clinical development program. The
incidence of adverse events, serious adverse events and discontinuations
due to adverse events were similar across groups. Most adverse events
were mild or moderate and the most frequently reported adverse events in
all groups were infections. Herpes zoster (shingles) occurred in 4.0% of
patients on XELJANZ and 1.1% of patients on methotrexate. Confirmed
malignancies developed in five patients treated with XELJANZ and one
patient treated with methotrexate. XELJANZ was associated with increases
in average serum creatinine and lipid levels.
XELJANZ U.S. Label Information
XELJANZ is a prescription medicine called a Janus kinase (JAK)
inhibitor. XELJANZ is used to treat adults with moderately to severely
active rheumatoid arthritis in which methotrexate did not work well.
It is not known if XELJANZ is safe and effective in people with
Hepatitis B or C.
XELJANZ isnot for people with severe liver problems.
It is not known if XELJANZ is safe and effective in children.
Important Safety Information
XELJANZ can lower the ability of the immune system to fight
infections. Some people have serious infections while taking XELJANZ,
including tuberculosis (TB), and infections caused by bacteria, fungi,
or viruses that can spread throughout the body. Some people have died
from these infections. Healthcare providers should test patients for
TB before starting XELJANZ, and monitor them closely for signs and
symptoms of TB and other infections during treatment. People should
not start taking XELJANZ if they have any kind of infection unless
their healthcare provider tells them it is okay.
XELJANZ may increase the risk of certain cancers by changing the
way the immune system works. Malignancies were observed in clinical
studies of XELJANZ.
The risks and benefits of treatment should be considered prior to
initiating XELJANZ in patients with chronic or recurrent infection;
who have been exposed to tuberculosis; with a history of a serious or
an opportunistic infection; who have resided or traveled in areas of
endemic tuberculosis or endemic mycoses; or with underlying conditions
that may predispose them to infection.
Viral reactivation, including cases of herpes virus reactivation
(e.g., herpes zoster), was observed in clinical studies with XELJANZ.
Use of live vaccines should be avoided concurrently with XELJANZ.
Update immunizations in agreement with current immunization guidelines
prior to initiating XELJANZ therapy.
Some people who have taken XELJANZ with certain other medicines to
prevent kidney transplant rejection have had a problem with certain
white blood cells growing out of control (Epstein Barr
virus-associated post-transplant lymphoproliferative disorder).
Some people taking XELJANZ get tears in their stomach or intestines.
This happens most often in people who also take nonsteroidal
anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate.
Patients should tell their healthcare provider right away if they have
fever and stomach-area pain that does not go away, or a change in
bowel habits. XELJANZ should be used with caution in patients who may
be at increased risk for gastrointestinal perforation (e.g., patients
with a history of diverticulitis).
XELJANZ can cause changes in certain lab test results including low
blood cell counts, increases in certain liver tests, and increases in
cholesterol levels. Healthcare providers should do blood tests before
starting patients on XELJANZ and while they are taking XELJANZ, to
check for these side effects. Normal cholesterol levels are important
to good heart health. Healthcare providers may stop XELJANZ treatment
because of changes in blood cell counts or liver test results.
Use of XELJANZ in patients with severe hepatic impairment is not
Patients should tell their healthcare providers if they plan to become
pregnant or are pregnant.
It is not known if XELJANZ will harm an unborn baby. To monitor the
outcomes of pregnant women exposed to XELJANZ, a registry has been
established. Physicians are encouraged to register patients and pregnant
women are encouraged to register themselves by calling 1-877-311-8972.
Patients should tell their healthcare providers if they plan to
breastfeed or are breastfeeding. Patients and their healthcare
provider should decide if they will take XELJANZ or breastfeed. They
should not do both.
In carriers of the hepatitis B or C virus (viruses that affect the
liver), the virus may become active while using XELJANZ. Healthcare
providers may do blood tests before and during treatment with XELJANZ.
Common side effects include upper respiratory tract infections (common
cold, sinus infections), headache, diarrhea, and nasal congestion,
sore throat, and runny nose (nasopharyngitis).
Please click the direct link to the full prescribing information for
XELJANZ, including boxed warning and Medication Guide: http://labeling.pfizer.com/ShowLabeling.aspx?id=959.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease
that typically affects the hands and feet, although any joint lined by
the synovial membrane can be affected.1 RA causes a range of
symptoms, including stiffness and swelling in the joints,2
particularly those in the hands, feet and knees.1 Although
the exact cause of RA is unknown,1 it is considered to be an
autoimmune disease, because the immune system in people with RA mistakes
the body's healthy tissues for a threat and attacks them.1 Some
people are at increased risk of developing RA, including people with a
family history of RA, smokers and women.3 Three times as many
women are affected by RA compared to men.2 RA affects
approximately 23.7 million people4 worldwide and 1.6 million
people in the United States.5,6 It can develop at any time
during adulthood, but it usually occurs between 40 and 70 years of age.2
Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world's
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world's
premier innovative biopharmaceutical companies, we collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world. For
more than 150 years, Pfizer has worked to make a difference for all who
rely on us. To learn more, please visit us at www.pfizer.com.
DISCLOSURE NOTICE: The information contained in this release
is as of June 18, 2014. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result of
new information or future events or developments.
This release contains forward-looking information about XELJANZ
(tofacitinib citrate), including its potential benefits, that involves
substantial risks and uncertainties. Such risks and uncertainties
include, among other things, whether and when the FDA will assess the
benefit: risk profile of the 10 mg twice-daily dose; and competitive
A further description of risks and uncertainties can be found in
Pfizer's Annual Report on Form 10-K for the fiscal year ended December
31, 2013 and in its subsequent reports on Form 10-Q and Form 8-K.
1 Medline Plus, "Rheumatoid Arthritis" Accessed 11 October 2011.
Available at http://www.nlm.nih.gov/medlineplus/ency/article/000431.htm.
2 Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001; 358:903-911.
3 Mayo Clinic, "Rheumatoid Arthritis." Accessed 14 September 2011.
Available at http://www.mayoclinic.com/health/rheumatoid-arthritis/DS00020/DSECTION=risk-factors.
4 World Health Organization, "The Global Burden of Disease, 2004
Update." Accessed 13 March 2012. Available at http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf.
5 Sacks, J., Lou, Y., Helmick, C. Prevalence of Specific Types of
Arthritis and Other Rheumatic Conditions in the Ambulatory Health Care
System in the United States 2001-2005. Arthritis Care and Research.
2010. 62(4): 460- 464.
6 Howden, L., Meyer, J., 2010 U.S. Census Bureau results --- U.S. Census
Bureau, 2010 Census Summary File 1.
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