Abbott's HUMIRA Receives FDA Approval For Inhibiting Structural Joint Damage & Improving Physical Function In Patients w/Arthritis

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Abbott's HUMIRA Receives FDA Approval For Inhibiting Structural Joint Damage

And Improving Physical Function In Patients With Arthritis

http://www.medicalnewstoday.com/medicalnews.php?newsid=57432 & nfid=nl

Abbott announced today that the U.S. Food and Drug Administration (FDA)

approved an expanded indication for HUMIRA (adalimumab) that includes

inhibiting structural joint damage and improving physical function in

patients with psoriatic arthritis (PsA). The expanded indication is in

addition to the psoriatic arthritis approval granted in October 2005.

HUMIRA is also approved in the U.S. for use in moderate to severe rheumatoid

arthritis (RA) and active ankylosing spondylitis (AS).

PsA is a chronic disease that combines symptoms of arthritis, including

joint pain and inflammation, and those of psoriatic skin disease, such as

painful, raised red lesions covered by silvery white scales. Approximately

one million men and women suffer from PsA in the United States and, when

left untreated, the disease can be potentially disabling. Early recognition,

diagnosis and treatment of PsA can relieve pain and inflammation and

possibly help inhibit extensive joint involvement and damage in later stages

of the disease.

" Psoriatic arthritis can be debilitating for many people, hindering everyday

activities. For these people, and others, the new indication for HUMIRA is

welcome news to our community, " said Gail Zimmerman, president and CEO of

the National Psoriasis Foundation.

Study Results

The expanded indication is based on results from an extension of the

Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), the largest

randomized, placebo-controlled biologic trial in PsA. ADEPT was a Phase III,

controlled study in 313 patients with moderate to severe PsA, who had an

inadequate response to NSAID (non-steroidal anti-inflammatory drug) therapy.

Patients were randomized to receive either HUMIRA 40 mg every other week or

placebo. At week 24, 285 patients elected to enroll in a 24-week open-label

extension.

Progression of Structural Joint Damage

Patients taking HUMIRA experienced significantly less joint damage than

patients taking placebo. Joint damage was assessed with X-rays taken at

baseline and weeks 24 and 48, using the modified total Sharp score (mTSS), a

measure of joint damage progression. A smaller change in mTSS reflects less

progression of joint damage, with a positive score indicating worse

radiographic damage. At week 24, the co-primary endpoint (the average change

in joint damage, as measured by a mean change in mTSS) was 10 times greater

in the placebo arm than in the HUMIRA arm (0.9 and -0.1, respectively;

p<0.001). More than three times as many patients on placebo (29 percent)

experienced joint damage compared to patients taking HUMIRA (9 percent) at

week 24. Results in the HUMIRA group were maintained through 48 weeks, the

mean change in mTSS compared to baseline was -0.2 at 48 weeks.

Physical Function

Patients taking HUMIRA showed significant improvement in physical function

as assessed by the Health Assessment Questionnaire Disability Index (HAQ)

score and the Short Form-36 Health Status Survey (SF-36). HAQ scores assess

a patient's ability to perform daily activities such as getting dressed,

walking and climbing stairs. Statistically significant improvements in HAQ

were achieved by patients in the HUMIRA group compared to placebo at week 24

(p<0.001). Patients taking HUMIRA also showed statistically significant

improvement compared to placebo in the SF-36 Physical Component Score

(p<0.001). The SF-36 is a broad questionnaire that examines the physical and

mental impact on patients. Improvements in physical function were maintained

through week 84.

Joint and Skin Symptoms

The October 2005 FDA approval of HUMIRA for active arthritis in psoriatic

arthritis was based on two studies including ADEPT 24-week results measuring

joint symptoms with American College of Rheumatology (ACR) scores and skin

disease symptoms with the Psoriasis Area Severity Index (PASI). Patients'

arthritic symptoms responded to HUMIRA, with nearly 60 percent of patients

achieving ACR20 through week 24. An ACR20 score indicates a 20 percent or

greater improvement in tender and swollen joint counts and several other

clinical measures. The primary endpoint was ACR20 at week 12 in the ADEPT

trial.

ADEPT also studied the ability of HUMIRA to improve the psoriatic skin

symptoms associated with PsA. Sixty-nine patients in the HUMIRA group had

skin lesions on greater than 3 percent of their body skin surface at the

onset of the trial. (The palm of an adult hand represents approximately 1

percent.) Of these patients, approximately three out of five achieved 75

percent improvement, and more than two out of five achieved 90 percent

improvement at 24 weeks (called PASI 75 or 90 responses, respectively in the

study; p<0.001).

Joint results were maintained for patients in the HUMIRA group through week

48. Patients in the placebo group achieved similar results after receiving

HUMIRA from week 24 through week 48. Skin results were also maintained in

the HUMIRA group through week 48, when nearly three out of five patients

achieved PASI 75 skin clearance and nearly one out of two patients achieved

PASI 90 skin clearance response at week 48. Patients in the placebo group

achieved similar results after receiving HUMIRA in the 24-week, open-label

extension.

" Psoriatic arthritis is a multifaceted disease in which patients can

experience joint and skin symptoms that may lead to disability and decreased

quality of life, " said Eugene Sun, M.D., vice president, Global

Pharmaceutical Clinical Development, Abbott. " HUMIRA effectively treats

multiple aspects of the disease, making it a promising comprehensive

treatment for these patients. "

About Psoriatic Arthritis

Psoriatic arthritis combines skin symptoms, such as dry, scaly skin and

painful patches of red, raised skin known as plaques, with arthritis

symptoms including joint pain and inflammation. Common symptoms of psoriatic

arthritis include varying degrees of skin involvement along with stiffness,

pain, swelling and tenderness of the joints that can lead to a reduced range

of motion and potential severe joint destruction.

Left untreated, psoriatic arthritis can be a progressively disabling

disease. The arthritic manifestations often include debilitating disease of

the hands and feet, as seen in rheumatoid arthritis, as well as painful

inflammation of the tendon insertions (the part of the tendon that attaches

to the bone) and arthritis of the spine. Psoriatic arthritis is often found

in patients who suffer from psoriasis, a chronic skin disease that affects

nearly 3 percent of the world's population. It is estimated that up to 30

percent of people with psoriasis also develop psoriatic arthritis.

Like RA, psoriatic arthritis is an autoimmune disorder in which a human

protein, tumor necrosis factor-alpha (TNF-alpha), has been suggested to play

a role in disease development. HUMIRA, which is a fully human monoclonal

antibody that resembles antibodies normally found in the body, works by

specifically blocking TNF-alpha.

Important Safety Information

Serious infections, sepsis, tuberculosis (TB) and rare cases of

opportunistic infections, including fatalities, have been reported with the

use of TNF-blocking agents, including HUMIRA. Many of these serious

infections have occurred in patients also taking other immunosuppressive

agents that in addition to their underlying disease could predispose them to

infections. Treatment with HUMIRA should not be initiated in patients with

active infections. TNF-blocking agents, including HUMIRA, have been

associated with reactivation of hepatitis B (HBV) in patients who are

chronic carriers of this virus. Some cases have been fatal. Patients at risk

for HBV infections should be evaluated for prior evidence of HBV infections

before initiating HUMIRA. The combination of HUMIRA and anakinra is not

recommended.

TNF-blocking agents, including HUMIRA, have been associated in rare cases

with demyelinating disease and severe allergic reactions. Infrequent reports

of serious blood disorders have been reported with TNF-blocking agents. More

cases of malignancies have been observed among patients receiving TNF

blockers, including HUMIRA, compared to control patients in clinical trials.

These malignancies, other than lymphoma and non-melanoma skin cancer, were

similar in type and number to what would be expected in the general

population. There was an approximately four fold higher rate of lymphoma in

combined controlled and uncontrolled open-label portions of HUMIRA clinical

trials. The potential role of TNF-blocking therapy in the development of

malignancies is not known.

The most frequent adverse events seen in the placebo-controlled clinical

trials in rheumatoid arthritis (HUMIRA vs. placebo) were injection site

reactions (20 percent vs. 14 percent), upper respiratory infection (17

percent vs. 13 percent), injection site pain (12 percent vs. 12 percent),

headache (12 percent vs. 8 percent), rash (12 percent vs. 6 percent) and

sinusitis (11 percent vs. 9 percent). Discontinuations due to adverse events

were 7 percent for HUMIRA and 4 percent for placebo. As with any treatment

program, the benefits and risks of HUMIRA should be carefully considered

before initiating therapy.

In HUMIRA clinical trials for ankylosing spondylitis and psoriatic

arthritis, the safety profile for patients treated with HUMIRA was similar

to the safety profile seen in patients with rheumatoid arthritis.

About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved for the

treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and

ankylosing spondylitis (AS) in the U.S. and Europe. HUMIRA resembles

antibodies normally found in the body. It works by blocking tumor necrosis

factor alpha (TNF-a), a protein that plays a central role in the

inflammatory responses of autoimmune diseases. To date, HUMIRA has been

approved in 67 countries and more than 160,000 people worldwide are

currently being treated with HUMIRA. Clinical trials are currently under way

evaluating the potential of HUMIRA in other autoimmune diseases.

In the U.S., HUMIRA is approved by the FDA for reducing signs and symptoms,

inducing major clinical response, inhibiting the progression of joint

structural damage, and improving physical function in adult patients with

moderately to severely active RA. HUMIRA is indicated for reducing the signs

and symptoms of active arthritis, inhibiting the progression of structural

damage and improving physical function in patients with psoriatic arthritis.

HUMIRA can be used alone or in combination with methotrexate or other

disease-modifying anti-rheumatic drugs (DMARDs). HUMIRA was also approved on

July 28, 2006 for reducing signs and symptoms in patients with active AS.