Humira(reg) (Adalimumab) Significantly Reduces Signs and Symptoms in Rheumatoid Arthritis Patients

Main Category: Arthritis / Rheumatology
Article Date: 10 Jun 2004 - 22:00 PDT


New data about HUMIRA(reg) (adalimumab) from the largest anti-TNF clinical study ever conducted in Europe, the ReAct trial (Research in Active Rheumatoid Arthritis), reaffirms the drug's safety and efficacy seen in pivotal clinical trials. These results along with other key data about HUMIRA's sustained benefit beyond five years and ability to inhibit the progression of rheumatoid arthritis (RA) were presented this week at the European League Against Rheumatism (EULAR) annual congress in Berlin.

Results from the ReAct trial's first 2,000 patients treated with Abbott Laboratories' HUMIRA indicate:

-- Approximately one in four patients treated with HUMIRA 40 mg every other week, in addition to their existing therapies, achieved clinical remission within three months.

-- The safety profile of HUMIRA in this trial was consistent with the overall safety database from pivotal RA HUMIRA trials.

-- Forty-two percent of the patients responded favorably to HUMIRA within two weeks after the first dose.

-- HUMIRA proved effective in RA patients who had previous experience with other disease modifying anti-rheumatic drugs (DMARDs).

"The data on safety and efficacy from such a large trial confirm the favorable outcomes seen in the initial HUMIRA pivotal trials in RA," said G. R. Burmester, M.D., professor of medicine, Charite Humboldt University, Berlin, Germany.

ReAct Data Show HUMIRA Safe and Effective Treatment in Real-Life Setting

In this open-label study, patients with long-standing moderate to severe RA were treated with HUMIRA 40 mg every other week in addition to their existing therapies. The ReAct trial was considered a "real-life" study because patients met national treatment guidelines, meaning they represented different stages of the disease, as well as varying treatment experiences. The trial also explored the benefits of an "add-on" therapy, in this case HUMIRA, to the current standard of RA care, which is methotrexate. Finally, ReAct captured data from a broad patient population representing individuals from 11 European countries. Other trials may not be considered real-life because of restrictions in patient eligibility requirements, as well as patient population size and diversity.

Twenty-four percent of the ReAct patients achieved clinical remission, DAS28<2.6, at three months, as measured by Disease Activity Scores 28 (DAS28). DAS28 measures disease activity responses for RA by assessing tender and swollen joint counts, general health status and an inflammatory marker.

The ReAct trial continues to gather data with more than 6,000 patients now enrolled in the study.

HUMIRA Provides Reduction in Signs and Symptoms After First Dose

The positive effect of HUMIRA was observed two weeks after the first dose was given, with 42 percent of patients achieving an ACR 20 response. ACR (American College of Rheumatology) 20, 50 and 70 criteria are used to define improvement. ACR 20 represents a 20 percent improvement in tender and swollen joint counts, plus a 20 percent improvement in three of five other key clinical measures.

Also after the first dose, 6 percent of patients achieved clinical remission in disease activity (DAS28 score of <2.6).

Results from Additional HUMIRA Studies Presented at EULAR

Other new HUMIRA data presented this week at EULAR not associated with the ReAct trial include:

-- HUMIRA shows sustained benefit beyond five years. Patients with long-standing RA were observed to exhibit sustained improvement of signs and symptoms with HUMIRA 40 mg every other week treatment over a five-year period. Study participants received HUMIRA plus methotrexate and were seen and evaluated on a routine basis. Twenty-nine percent of patients achieved clinical remission (DAS28<2.6) between two months and four years of treatment. Among these, remission was sustained for a minimum of nine months and up to four years, with the average time of remission being 28 months.

-- Significant inhibition of radiographic progression. An analysis of 619 patients showed that treatment with HUMIRA 40 mg every other week and methotrexate over a 52-week period resulted in significantly less radiographic progression compared to patients who received placebo. In the overall study population, the HUMIRA group demonstrated statistically significant smaller mean changes from baseline in total Sharp score at one year (0.1) compared to patients receiving placebo (2.7). Modified total Sharp scores assess changes in bone erosion and joint-space narrowing on X-rays. A lower change in total Sharp score indicates less disease progression. Patients with moderate disease had an even greater inhibition of radiographic progression, with mean change from baseline in total Sharp score of 1.7 compared to 2.5 in patients receiving placebo. HUMIRA therapy was also associated with reductions in joint space narrowing and joint erosion in patients with moderate disease.

About RA

More than 5 million people worldwide suffer from RA, a chronic autoimmune disease that causes pain, swelling and stiffness in the joints of the hands, feet and wrists and often leads to the destruction of joints. Unlike osteoarthritis, the most common form of arthritis, RA is an autoimmune disease where joints are inflamed, often resulting in eventual destruction of the joint's interior and the surrounding bone.

More information about RA, the latest treatment options and helpful resources for patients is available at http://www.RA.com.

About HUMIRA

HUMIRA is the first human monoclonal antibody available in Europe for RA, and the first tumor necrosis factor alpha (TNF-α) antagonist approved in Europe with an indication for use with methotrexate or as monotherapy. HUMIRA resembles antibodies normally found in the body. It works by blocking TNF-α, a protein that plays a central role in the inflammatory responses of autoimmune diseases such as RA.

In the European Union, HUMIRA is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease modifying anti-rheumatic drugs (DMARD), including methotrexate, has been inadequate. To ensure maximum efficacy, HUMIRA is given in combination with methotrexate. In Europe, HUMIRA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. The European Medicines Evaluation Agency (EMEA) issued a positive opinion in April to authorize a label extension for HUMIRA for use in the treatment of adult RA patients for reducing the rate of progression of joint damage and to improve physical function. Such authorizations generally occur approximately 90 days after the issuance of the EMEA opinion.

Abbott received a positive opinion from the EMEA in May 2003 for the treatment of adult RA and was granted European Union approval to market HUMIRA in September 2003. HUMIRA received approval from the U.S. Food and Drug Administration on December 31, 2002. To date, HUMIRA has been approved in 41 countries and launched in 26.

The recommended dose of HUMIRA is 40 mg every other week by subcutaneous injection (a shot beneath the skin). Abbott offers HUMIRA in specially designed pre-filled syringes so patients do not have to mix and measure the medicine or leave their homes for treatment. The pre-filled syringe features handles and a plunger head designed for use by patients whose hands have been affected by their RA.

Clinical trials are also currently underway evaluating the potential of HUMIRA in other autoimmune diseases.

Important Safety Information

Common adverse events (>1/100 and <1/10) at least possibly causally related to HUMIRA include headache, dizziness, respiratory tract and urinary tract infection, nausea, diarrhea, sore throat, herpes simplex, abdominal pain, rash, pruritis and anemia. Injection site pain was reported by >1/10 patients.

Patients must be monitored closely for infections, including tuberculosis (TB), before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. 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-antagonists, including HUMIRA, have been associated in rare cases with exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease. Prescribers should exercise caution in considering the use of HUMIRA in patients with pre-existing or recent-onset central nervous system demyelinating disorders.

HUMIRA should be used with caution in patients with mild heart failure, and is contraindicated in patients with moderate or severe heart failure. HUMIRA must be discontinued in patients who develop new or worse

ning symptoms of congestive heart failure.

About Abbott Abbott Laboratories is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 55,000 people and markets its products in more than 130 countries.

For more information about Abbott Immunology is available on http://www.abbottimmunology.com web site.

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