Pfizer Announces FDA Approval to Include Radiographic Data on Reduction of
Progression of Structural Joint Damage for Adults with Moderately to
Severely Active Rheumatoid Arthritis in Labeling for XELJANZ® (tofacitinib
NEW YORK -- February 24, 2014
Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug
Administration (FDA) has approved a supplemental New Drug Application (sNDA)
to update the current label of XELJANZ^® (tofacitinib citrate) 5 mg tablets to
include radiographic data from two Phase 3 studies, ORAL Scan (A3921044) and
ORAL Start (A3921069). “XELJANZ is the first oral JAK inhibitor for moderately
to severely active rheumatoid arthritis. The reduction of radiographic
progression seen in ORAL Scan and ORAL Start represents a clinically
meaningful outcome for patients,” said Dr. Steven Romano, Global Medicines
Development Lead for the Pfizer Global Innovative Pharmaceutical business.
XELJANZ is indicated for the treatment of adults with moderately to severely
active rheumatoid arthritis (RA) who have had an inadequate response or
intolerance to methotrexate (MTX). XELJANZ may be used as a single agent or in
combination with MTX 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 5 mg twice-daily (BID).
The U.S. Prescribing Information contains a boxed warning for serious
infections and malignancies. Patients treated with XELJANZ are at increased
risk for developing serious infections that may lead to hospitalization or
death. Most patients who developed these infections were taking concomitant
immunosuppressants, such as MTX or corticosteroids. Lymphoma and other
malignancies have been observed in patients treated with XELJANZ.
The updated U.S. label now includes the radiographic response data from ORAL
Scan (Study IV) at 6 months and ORAL Start (Study VI) at 6 and 12 months (see
detailed study descriptions below the table). These studies evaluated the
effect of XELJANZ on the progression of structural joint damage as measured by
mean change from baseline in van der Heijde modified Total Sharp Score (mTSS)
and its components, erosion score and joint space narrowing (JSN) score. The
proportion of patients with no radiographic progression (mTSS change from
baseline less than or equal to 0) was also assessed.
Radiographic Changes at Months 6 and 12
Study IV (ORAL Scan)
XELJANZ 5 mg
Placebo XELJANZ 5 mg
Mean (SD)^a Mean (SD)^a
Baseline 33 (42) 31 (48) -
Month 6 0.5 (2.0) 0.1 (1.7) -0.3 (-0.7, 0.0)
Study VI (ORAL Start)
XELJANZ 5 mg
MTX XELJANZ 5 mg
Mean (SD)^a Mean (SD)^a
Baseline 17 (29) 20 (40) -
Month 6 0.8 (2.7) 0.2 (2.3) -0.7 (-1.0, -0.3)
Month 12 1.3 (3.7) 0.4 (3.0) -0.9 (-1.4, -0.4)
^aSD = Standard Deviation
^bDifference between least squares means XELJANZ minus placebo or MTX (95% CI
= 95% confidence interval)
^CMonth 6 and Month 12 data are mean change from baseline.
In the placebo plus MTX group in ORAL Scan (Study IV), 74 percent of patients
experienced no radiographic progression at Month 6 compared to 84 percent of
patients treated with XELJANZ 5 mg BID plus MTX.
In the MTX group of ORAL Start (Study VI), 55 percent of patients experienced
no radiographic progression at Month 6 compared to 73 percent of patients
treated with XELJANZ 5 mg BID.
It is important to note that the U.S. label specifies that use of live
vaccines should be avoided concurrently with XELJANZ. Update immunizations in
agreement with current immunization guidelines prior to initiating XELJANZ
The ORAL Start study showed that XELJANZ 5 mg BID, as a single agent, was
statistically significantly superior to MTX, providing a greater inhibition of
progression of structural joint damage, as measured by mean change from
baseline in mTSS at Month 6 (primary endpoint), and sustained at 12 months
(refer to table above). The study was conducted in MTX-naïve patients with
moderately to severely active RA who were randomized to receive XELJANZ 5 or
10 mg BID or to MTX dose-titrated over 8 weeks to 20 mg weekly. XELJANZ is not
indicated for use in MTX-naïve patients. The safety experience of the patients
in ORAL Start was consistent with the results of the five Phase 3 pivotal
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.
The ORAL Scan study demonstrated that XELJANZ 10 mg BID provided statistically
significantly greater reduction of progression of structural joint damage as
measured by mean change from baseline in mTSS compared to placebo at 6 months
(primary endpoint – refer to table above). Results for the 5 mg BID dose
exhibited similar effects on mean progression of structural damage but were
not statistically significant (refer to table above). The ORAL Scan study was
conducted in patients with moderately to severely active RA who had an
inadequate response to MTX. Patients were randomized to receive XELJANZ 5 or
10 mg BID or placebo, and all treatments were added to background MTX. The
controlled period for the study ended at 6 months. The 10 mg BID dose is not
It is important to note that the U.S. label says viral reactivation, including
cases of herpes virus reactivation (e.g., herpes zoster), was observed in
clinical studies with XELJANZ. 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 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 is not 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
*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 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:
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