Promising Phase III Psoriatic Arthritis Data for Humira® (Adalimumab)

Main Category: Arthritis
Article Date: 19 Oct 2004 - 11:00 PDT

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New Phase III study findings show that patients with active psoriatic arthritis who had failed a previous non-steroidal anti-inflammatory drug (NSAID) therapy achieved significant improvement in both joint and skin signs and symptoms after treatment with Abbott's HUMIRA®. The study, presented this week at the American College of Rheumatology (ACR) annual meeting, found that patients experienced sustained response with HUMIRA therapy beyond the 12-week primary endpoint. At the 24-week follow-up, nearly one-fourth of patients achieved a 70 percent improvement in arthritis signs and symptoms, and 42 percent of patients achieved at least a 90 percent reduction in psoriasis activity.

Patients in the trial experienced marked improvement in both arthritis and psoriasis response as early as two weeks after initiation of therapy and patient response was sustained through 24 weeks. These results were statistically significant.

"Psoriatic arthritis takes an enormous toll on patients' quality of life," said Philip Mease, M.D., lead study investigator of Swedish Medical Center and University of Washington School of Medicine, Seattle. "In this study, patients on HUMIRA achieved rapid improvement in arthritis symptoms as well as quality of life and function. Even more encouraging, they also displayed significant improvement in skin symptoms."

Psoriatic arthritis is an autoimmune disorder that combines symptoms of psoriasis, such as dry, scaly skin and 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 psoriasis activity along with stiffness, pain, swelling and tenderness of the joints that can lead to a reduced range of motion and potential severe joint destruction.

Study Overview

This placebo-controlled, double-blind study assessed the efficacy and tolerability of HUMIRA in 313 adults with active psoriatic arthritis (defined as three or more swollen joints and three or more tender joints) who had failed therapy with NSAIDs. Patients received 40 mg of HUMIRA or placebo administered subcutaneously every other week. Efficacy was assessed using ACR20 response (20 percent improvement in tender and swollen joint count and other clinical measures), one of the primary study endpoints.

Secondary endpoints included ACR50/70, Psoriasis Area and Severity Index (PASI) (which measures the extent and severity of psoriasis) measurement in patients with more than three percent body surface area involvement and other clinical assessments.

Arthritis Response

In the HUMIRA treatment group, improvement in arthritis signs and symptoms was rapid, with 27 percent of patients achieving an ACR20 response after two weeks and 52 percent of patients achieving an ACR20 response after just four weeks, compared with six percent and nine percent for patients taking placebo. At 24 weeks, 39 percent of patients treated with HUMIRA achieved an ACR50 response and 23 percent achieved ACR70, compared to six percent and one percent, respectively, in the placebo group.

Psoriasis Response

In patients with more than three percent body surface area involvement, 42 percent of patients taking HUMIRA achieved a PASI 90 response at 24 weeks, which reflects at least 90 percent improvement in psoriasis symptoms assessed by the PASI. Nearly one-third (30 percent) achieved 90 percent improvement at the week 12 visit. At 24 weeks, 59 percent of patients in the HUMIRA arm achieved a PASI 75 response (75 percent improvement), compared with one percent of patients taking placebo.

"These results are important for both rheumatologists and dermatologists, but more importantly the patients who suffer from both the joint and skin symptoms of psoriatic arthritis," said Jeffrey Leiden, M.D., Ph.D., president and chief operating officer, Pharmaceutical Products Group, and chief scientific officer, Abbott. "The promising results of this trial reinforce our plan to submit applications to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) by the end of the year to request approval for this new use."

The rates of adverse events and serious adverse events were comparable between HUMIRA and the placebo. Among patients taking HUMIRA, the most common adverse events (those affecting at least five percent of patients) were upper respiratory infection, nasopharyngitis, injection site reaction, headache and hypertension. The safety profile of HUMIRA in the psoriatic arthritis population was similar to that observed in the rheumatoid arthritis population.

About Psoriatic Arthritis

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 tendonitis and arthritis of the spine. Psoriatic arthritis affects between 10 and 30 percent of the 4.5 million Americans who have psoriasis, a non-contagious, chronic skin disease characterized by red plaques covered with silvery scales. Most people with psoriatic arthritis first developed psoriasis.

Important Safety Information

Cases of tuberculosis (TB) have been observed in patients receiving HUMIRA. Serious infections and sepsis, including fatalities, have been reported with the use of TNF-blocking agents, including HUMIRA. Many of these infections occurred in patients also taking other immunosuppressive agents that in addition to their underlying disease could predispose them to infections. 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 and rare reports of lymphoma have been reported with TNF-blocking agents. Patients with rheumatoid arthritis, particularly those with highly active disease are at a higher risk for the development of lymphoma. 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.

About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved by the FDA for reducing the signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adults with moderately to severely active rheumatoid arthritis (RA) who have had insufficient response to one or more disease-modifying antirheumatic drugs (DMARDs). HUMIRA can be used alone or in combination with methotrexate or other DMARDs. HUMIRA offers convenient every-other-week dosing by subcutaneous injection (shot beneath the skin) via a specially designed, pre-filled syringe.

Clinical trials are currently underway evaluating the potential of HUMIRA in other autoimmune diseases, including juvenile rheumatoid arthritis (JRA), psoriasis, psoriatic arthritis, Crohn's disease and ankylosing spondylitis.

HUMIRA was discovered through a broad scientific collaboration between Abbott and Cambridge Antibody Technology (CAT). As part of the collaboration, Abbott had the right to select several target antigens for which a joint Abbott/CAT research team would discover human antibody therapeutics. HUMIRA was isolated and optimized by Abbott and CAT as part of this collaboration. Abbott owns exclusive worldwide rights to HUMIRA, including responsibility for clinical development, manufacturing, sales and marketing. Abbott will book all revenues for HUMIRA, and CAT will receive a royalty fee based on HUMIRA sales.

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, Massachusetts, United States, is a world-class discovery and basic research facility committed to finding new treatments for autoimmune diseases. More information about Abbott Immunology and HUMIRA, including full prescribing information, is available on the Web sites www.abbottimmunology.com and www.HUMIRA.com, or in the United States by calling Abbott Medical Information at (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, devices and diagnostics. The company employs more than 55,000 people and markets its products in more than 130 countries.