Humira/Crohns/Reduced Hospitalization

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New Analysis Of Data Shows Treatment With Abbott's HUMIRA®

Significantly Reduced Disease-Related Hospitalization For Patients

With Crohn's

Article Date: 24 May 2007 - 12:00 PDT

Abbott today announced results from a post-hoc analysis of a pivotal

study presented at the Digestive Disease Week annual meeting in

Washington, D.C. showing patients with moderate to severely active

Crohn's disease treated with HUMIRA® (adalimumab) maintenance therapy

were almost 60 percent less likely than patients on placebo to be

hospitalised due to their disease at one year (5.9 percent versus

13.9 percent; p<0.01).

Crohn's disease is a serious, chronic, inflammatory disease of the

gastrointestinal (GI) tract that affects more than one million people

in North America and Europe. It affects people of all ages but it is

primarily a disease of young adults, with onset typically before age

40. There is no medical or surgical cure for Crohn's disease, so

maintenance of remission from disease flares is one of the primary

goals of treatment.

People with Crohn's disease may be hospitalised for a variety of

reasons, from fever and vomiting to intestinal obstruction and

infections, sometimes leading to surgery. Previous studies have shown

that hospitalisation is responsible for approximately 60 percent of

the direct cost of Crohn's disease and that the average cost per

hospital stay is estimated (based on published cost data from 1997)

to be about $37,000 per patient in 2006 dollars. Hospitalisation is

also associated with a negative impact on health-related quality of

life in patients with Crohn's disease.

Data from the Phase III, pivotal study, called CHARM, were evaluated

to assess the effect of ongoing treatment with HUMIRA on the risk of

hospitalisation. At one year, this analysis showed that patients

taking placebo (13.9 percent) were more than twice as likely as

patients on HUMIRA (5.9 percent; p<0.01) to be hospitalised from

Crohn's disease.

" Patients on HUMIRA throughout the one-year analysis were

significantly less likely to be hospitalised because of their Crohn's

disease. Maintaining treatment with HUMIRA was the only independent

factor in this analysis that helped patients reduce the risk of

Crohn's related hospitalisation, " said G. Feagan, M.D., lead

investigator of the analysis, Department of Medicine, Epidemiology

and Biostatistics, University of Western Ontario, London Health

Sciences Centre, London, ON, Canada.

About HUMIRA Hospitalisation Data

In this analysis, week 4 randomised responders on either dose of

HUMIRA (40 mg every week or 40 mg every other week) were analysed for

hospitalisation risk as a single group versus placebo. Results were

generated using Kaplan-Meier estimates, a tool for measuring the

timing of significant events from real-life data. A proportional-

hazards model, which is a model used to determine the underlying rate

of risk, was used to control for other factors, such as demographics,

disease duration, presence of draining cutaneous fistula (abnormal

connections that form between the intestine and the skin in patients

with Crohn's disease), steroid use at baseline, stenosis (narrowing

of the bowel), and CDAI at week 4. A proportional-hazards model

showed HUMIRA was associated with a significantly lower risk of

hospitalisation (hazard ratio=0.31, p < 0.01).

At 56 weeks, Crohn's disease-related hospital admission rates for

patients treated with HUMIRA were 5.9 percent, compared to 13.9

percent for those on placebo (p<0.01). A difference in the risk of

hospitalisation between HUMIRA and placebo was also observed at two

weeks after patients were randomised into treatment groups. At three

months, patients on either dose of HUMIRA had a 78 percent lower risk

(1.6 percent) of being hospitalised for Crohn's-related symptoms than

those on placebo (7.3 percent; p<0.01).

" A flare-up of Crohn's disease that requires hospitalisation can take

a heavy toll on a person's life, " said J. Geswell, president

of the Crohn's & Colitis Foundation of America (CCFA). " The average

length of hospitalisation is about nine days. In addition to

suffering from the pain of the flare, patients lose time with their

families, miss work and incur medical costs for the hospital stay. "

About CHARM

CHARM was a 56-week trial that assessed the effectiveness of HUMIRA

in maintaining clinical remission (CDAI<150). CDAI is the Crohn's

Disease Activity Index, a weighted composite score of eight clinical

factors that evaluate patient wellness, including daily number of

liquid or very soft stools, severity of abdominal pain, level of

general well-being, and other measures.

CHARM enrolled 854 adult patients with moderately to severely active

Crohn's disease. The 499 patients who demonstrated clinical response

(a CDAI decrease >70 from baseline) to HUMIRA during a four-week open-

label induction phase were randomised to receive either HUMIRA or

placebo. The co-primary endpoints evaluated the maintenance of

clinical remission at weeks 26 and 56 for each HUMIRA group compared

to those on placebo. A significantly greater percentage of patients

treated with HUMIRA maintained clinical remission at one year

compared to placebo.

Approval of HUMIRA for Crohn's disease

In February 2007, the U.S. Food and Drug Administration approved

HUMIRA as a treatment for reducing the signs and symptoms and

inducing and maintaining clinical remission in adult patients with

moderately to severely active Crohn's disease who have had an

inadequate response to conventional therapy. HUMIRA is also indicated

for reducing the signs and symptoms and inducing clinical remission

in these patients if they have also lost response to or are

intolerant to infliximab, the only other approved biologic for

treatment of Crohn's disease. In the U.S., the recommended HUMIRA

dose regimen for adult patients with Crohn's disease is 160 mg

initially at week 0, 80 mg at week 2, followed by a maintenance dose

of 40 mg every other week beginning at week 4.

HUMIRA is the first and only self-administered biologic for the

treatment of moderate to severe Crohn's disease. Crohn's disease is

the fourth FDA approval in immune-mediated diseases for HUMIRA.

On April 26, 2007, the Committee for Medicinal Products for Human Use

(CHMP) of the European Medicines Agency granted a positive opinion

recommending approval of HUMIRA for the treatment of severe Crohn's

disease.

" For people with Crohn's disease, hospitalisation can disrupt their

active lives, " said Eugene Sun, M.D., vice president, Global

Pharmaceutical Clinical Development at Abbott. " The recent FDA

approval of and positive opinion for HUMIRA was based on clinical

data showing that HUMIRA induced and maintained remission in people

with Crohn's disease. This hospitalisation data further demonstrates

the importance of maintaining remission in these patients. "

Important Safety Information

Serious infections, sepsis, tuberculosis (TB) and 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. Infections have also been

reported in patients receiving HUMIRA alone. 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 infection should be evaluated for prior evidence of HBV

infection before initiating HUMIRA. The combination of HUMIRA and

anakinra is not recommended and patients using HUMIRA should not

receive live vaccines. 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 3.5 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. 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.

Worsening congestive heart failure (CHF) has been observed with TNF-

blocking agents, including HUMIRA, and new onset CHF has been

reported with TNF-blocking agents. Treatment with HUMIRA may result

in the formation of autoantibodies and rarely, in development of a

lupus-like syndrome.

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, psoriatic

arthritis and Crohn's disease, 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, an arthritis of the spine) in the U.S.

and Europe, and the only fully human monoclonal antibody approved for

Crohn's disease in the U.S. HUMIRA resembles antibodies normally

found in the body. It works by blocking tumor necrosis factor alpha

(TNF-á), a protein that when produced in excess, plays a central role

in the inflammatory responses of immune-mediated diseases. To date,

HUMIRA has been approved in 67 countries with more than 180,000

people worldwide currently treated with HUMIRA. Clinical trials are

currently under way evaluating the potential of HUMIRA in other

immune-mediated diseases.

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

symptoms, inducing major clinical response, inhibiting the

progression of 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 is

also indicated for reducing signs and symptoms in patients with

active ankylosing spondylitis. HUMIRA is also indicated for reducing

the signs and symptoms and inducing and maintaining clinical

remission in adult patients with moderately to severely active

Crohn's disease who have had an inadequate response to conventional

therapy, and reducing signs and symptoms and inducing clinical

remission in these patients if they have also lost response to or are

intolerant to infliximab.

Abbott's Commitment to Immunology

Abbott is focused on the discovery and development of innovative

treatments for immunologic diseases. The Abbott Bioresearch Center,

founded in 1989 in Worcester, Mass., United States, is a world-class

discovery and basic research facility supporting research and

development of biologic treatments. Abbott Biotechnology Limited,

which opened April 10, 2007, in Barceloneta, Puerto Rico, is the main

production facility for HUMIRA.

More information about HUMIRA, including full prescribing

information, is available on the Web site www.HUMIRA.com or in the

United States by calling Abbott Medical Information at 1-800-633-

9110.

About Abbott

Abbott is a global, broad-based health care company devoted to the

discovery, development, manufacture and marketing of pharmaceuticals

and medical products, including nutritionals and devices. The company

employs 65,000 people and markets its products in more than 130

countries. Abbott's news releases and other information are available

on the company's Web site at www.abbott.com.