Data Show that Abbott’s HUMIRA® (adalimumab) Reduced the Signs and Symptoms of Ankylosing Spondylitis Up to Three Years

Paris — Abbott (NYSE: ABT) announced new data from the open-label extension of the ATLAS (Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS) phase III clinical trial, which showed HUMIRA® (adalimumab) reduced the signs and symptoms of ankylosing spondylitis (AS) for up to three years of treatment among 74 percent of patients tested. AS is a type of arthritis that primarily causes inflammation of the spine and the spinal joints. These data were presented at the European League Against Rheumatism (EULAR) annual meeting in Paris.

"There is no cure for ankylosing spondylitis and the goal of therapy is to relieve back and joint pain" said Désirée van der Heijde, M.D., co-lead investigator of ATLAS and Professor of Rheumatology at Leiden University Medical Center, The Netherlands. "Even partial remission of AS can have a considerable positive impact on a patient’s symptoms. These data are reassuring for patients because they demonstrate that adalimumab can be an effective treatment for ankylosing spondylitis"
Three-Year ATLAS Data Summary

ATLAS was a randomized, placebo-controlled, double-blind, Phase III study conducted in the U.S. and Europe. The study involved 315 patients with active AS who had an inadequate response to at least one non-steroidal anti-inflammatory drug (NSAID) or disease modifying anti-rheumatic drug (DMARD). Patients received HUMIRA 40mg subcutaneously or placebo every other week (EOW). Results at 12 and 24 weeks showed HUMIRA patients experienced a statistically significant reduction in signs and symptoms according to the Assessment in SpondyloArthritis International Society (ASAS) measure, or ASAS20 compared to placebo. ASAS20 represents at least a 20 percent improvement in at least three of the four assessments to measure patient improvement and response to therapy. At 24 weeks, all patients were switched to an open-label HUMIRA 40mg EOW dose trial for an additional 236 weeks. Improvement was observed through three years of treatment.
Efficacy

* After three years, 74 percent (174/234) of patients achieved ASAS20.
* After three years, 42 percent (97/234) of patients achieved ASAS partial remission.

Physicians measure the severity of AS on a scale of 0-100 for level of pain, function, inflammation and a general overall assessment by the patient. Partial remission of the disease is classified as a score of less than 20 on a 0-100 scale in each of those four assessments.
Safety

* The most common adverse experiences occurring in greater than or equal to five percent of patients during three years of exposure were nasopharyngitis, upper respiratory tract infection and headache.
* There were no cases of tuberculosis or demyelinating disorders. There was one death caused by malignancy.

About Ankylosing Spondylitis (AS)

AS is a rheumatic condition that affects young adults, and is more common in men than in women. Ankylosis means "fusion" and spondylitis means "inflammation of the spine" Advanced AS can lead to new bone formation on the spine causing it to fuse in a fixed position. It commonly begins before the age of 35. It is estimated that nearly three million people in Europe and at least half a million people in the United States are affected by AS or a related spondyloarthropathy. However, there are likely more people affected by AS because it is under-recognized and under-diagnosed.
Important Safety Information

Globally, prescribing information varies; refer to the individual country product label for complete information.

Serious infections, sepsis, rare cases of tuberculosis (TB), and opportunistic infections, including fatalities, have been reported with the use of TNF antagonists, including HUMIRA. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease could predispose them to infections. Patients must be monitored closely for infections, including tuberculosis, before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.

TNF-blocking agents have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of the 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 combinations of HUMIRA and anakinra as well as HUMIRA and abatacept is not recommended.

TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease and serious allergic reactions. Rare reports of pancytopenia including aplastic anemia have been reported with TNF-blocking agents. Adverse events of the haematologic system, including medically significant cytopenia have been infrequently reported with HUMIRA.

More cases of malignancies including lymphoma have been observed among patients receiving a TNF antagonist compared with control patients in clinical trials. The size of the control group and limited duration of the controlled portions of studies precludes the ability to draw firm conclusions. Furthermore, there is an increased background lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation. During the long-term open-label trials with HUMIRA, the overall rate of malignancies was similar to what would be expected for an age, gender and race matched general population. With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF antagonist cannot be excluded. All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of Psoralen Ultra-Violet A (PUVA) treatment, should be examined for the presence of non-melanoma skin cancer prior to and during treatment with HUMIRA.

In clinical studies with another TNF antagonist, a higher rate of serious congestive heart failure (CHF) related adverse events including worsening CHF and new onset CHF have been reported. Cases of worsening CHF have also been reported in patients receiving HUMIRA. Physicians should exercise caution when using HUMIRA in patients who have heart failure and monitor them carefully. HUMIRA should not be used in patients with moderate or severe heart failure.

The most frequently reported adverse event (1/10 patients) at least possibly causally related to HUMIRA is injection site reaction (including pain, swelling, redness or pruritus). Other common adverse events (reported by 1/100 patients) at least possibly causally related to HUMIRA include lower respiratory infections (including pneumonia, bronchitis), viral infections (including influenza, herpes infections), candidiasis, bacterial infection (including urinary tract infections), upper respiratory infection, dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias), cough, nasopharyngeal pain, diarrhea, abdominal pain, stomatitis and mouth ulceration, nausea, hepatic enzymes increased, rash, pruritus, musculoskeletal pain, pyrexia, fatigue (including asthenia and malaise).
About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis, ankylosing spondylitis (AS) and Crohn’s disease in the United States and Europe. HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-α), a protein that, when produced in excess, plays a central role in the inflammatory responses of many immune-mediated diseases. To date, HUMIRA has been approved in 75 countries and more than 250,000 people worldwide are currently being treated with HUMIRA. Clinical trials are also under way evaluating the potential of HUMIRA in ulcerative colitis.

In Europe, HUMIRA in combination with methotrexate, is indicated for the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate.

HUMIRA is also indicated for the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. HUMIRA can be given as monotherapy in case of intolerance to methotrexate or when continued

treatment with methotrexate is inappropriate. HUMIRA has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate. In the United States, HUMIRA is also approved for the treatment of juvenile idiopathic arthritis (JIA).

HUMIRA is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying anti‑rheumatic drug therapy has been inadequate. HUMIRA has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease and to improve physical function.

HUMIRA is indicated for the treatment of adults with severe, active ankylosing spondylitis who have had an inadequate response to conventional therapy.

HUMIRA is indicated for treatment of severe, active Crohn’s disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. For induction treatment, HUMIRA should be given in combination with corticosteroids. HUMIRA can be given as monotherapy in case of intolerance to corticosteroids or when continued treatment with corticosteroids is inappropriate.

HUMIRA is indicated for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA.