Psoriasis patients receiving Humira® (adalimumab) achieved significant improvement in disease activity and quality of life through 60 weeks of treatment, according to new Phase II study results released today. The study, which assessed Humira in patients with moderate to severe chronic plaque psoriasis, showed that nearly 70 percent of patients receiving Humira 40 mg every other week (eow) experienced a 75 percent improvement in disease activity (known as a PASI 75 response) at week 60.

Psoriasis is a chronic, non-contagious autoimmune skin disease characterized by very dry, scaly and cracked skin; skin pain; and patches of red, raised skin known as “plaques.”

Despite many available treatment options for the disease, some biologic treatments that target specific aspects of the immune system and help prevent the rapid growth of skin cells and formation of plaques are proving to be effective for those with moderate to severe forms of psoriasis - which accounts for approximately one-third of the 4.5 million people in the U.S. who suffer from the disease.

“The findings of this study are significant, with nearly 70 percent of patients experiencing sustained improvement in their disease with Humira,” said Richard Langley, M.D., lead study investigator, Dalhousie University, Halifax, Nova Scotia. “Psoriasis can be unpredictable and challenging to treat, which is why it is important that we continue to seek out additional treatment options for patients, especially those who suffer from moderate to severe forms of the disease.”

In the study, 67 percent of patients taking Humira 40 mg eow achieved at least a 75 percent improvement in disease extent and severity after 60 weeks, as measured by the Psoriasis Area and Severity Index (PASI) score, which measures improvements in the severity and lesional characteristics of chronic plaque psoriasis. Furthermore, after 60 weeks more than one-third (36 percent) of patients taking Humira 40 mg eow achieved PASI 90 - a measurement that correlates to at least a 90 percent reduction in disease activity and severity score and is considered a significant skin measurement that goes beyond what is typically highlighted in clinical trials. Additionally, almost two-thirds (63 percent) of patients were determined to be “clear” or “almost clear” of their psoriasis as measured by the Physician’s Global Assessment, another measurement tool used by physicians to assess severity of disease.

Patients also recorded significant improvement in quality of life measures after 60 weeks of treatment with Humira 40 mg eow with 34.3 percent of patients reporting their quality of life was “not at all” affected by their psoriasis, as measured by the Dermatology Life Quality Index (DLQI) - a measure of patient-reported outcomes in dermatology.

“The study results are encouraging for patients whose lives continue to be negatively impacted by the effects of psoriasis,” said Rebecca Hoffman, M.D., global project head for Immunology Development at Abbott. “As we move forward into Phase III development, we are optimistic about the potential of Humira in the treatment of psoriasis.”

Disease Activity: Study Design and Results

Humira was evaluated in a 48-week Phase II extension trial conducted at 18 sites in the U.S. and Canada. Prior to inclusion in this extension trial, patients were enrolled in a 12-week, double-blind, placebo-controlled trial and randomized to receive either Humira 80 mg at week-0 and 40 mg eow, 80 mg at week-0 and -1 and 40 mg weekly, or placebo. A total of 137 patients who completed the 12-week randomized trial enrolled in the extension trial. Patients initially randomized to active treatment continued on their assigned dose. Placebo patients were switched to receive Humira 80 mg the first week followed by Humira 40 mg eow. After 60 weeks of continuous treatment (n=95), results indicated:

- 67 percent of patients receiving Humira 40 mg eow achieved PASI 75. - 73 percent of patients receiving Humira 40 mg weekly achieved PASI 75. - 36 percent of patients receiving Humira 40 mg eow and 55 percent of patients receiving Humira 40 mg weekly achieved PASI 90.

For those patients who switched from placebo to 40 mg eow at the beginning of this extension study, 50 percent achieved a PASI 75 response and 41 percent achieved a PASI 90 response after 48 weeks of continuous therapy.

Disease activity also was measured by the Physician’s Global Assessment. Results showed that 63 percent of patients receiving Humira 40 mg eow were “clear” or “almost clear” of their psoriasis, as were 79 percent of patients taking Humira 40 mg weekly after 60 weeks of therapy.

The types and rates of adverse events in this study were similar to those previously reported in adalimumab rheumatoid arthritis and psoriatic arthritis trials. Adverse events occurring in >5 percent of patients included headache, nasopharyngitis, triglyceride increase, upper respiratory infection, back pain, muscle strain, contact dermatitis and bronchitis.

Quality of Life: Study Design and Results

Quality of life was assessed using several measurements including SF-36 - to assess mental and physical health status on a scale of 0-100, with higher scores indicating better quality of life; EuroQoL 5D (EQ-5D) - to assess the impact on patient mobility, self-care, usual activities, pain/discomfort, anxiety/depression and global assessment of health; and the Dermatology Life Quality Index (DLQI) - to assess the impact of dermatologic conditions on psychosocial, social, and sexual functioning, and the performance of everyday activities. A 5-point change in the DLQI total score has been suggested as a minimal clinically important difference in disease-specific quality of life.

Patients formerly randomized to receive placebo demonstrated improved quality of life on Humira that was maintained through week 48. Patients receiving either dose of Humira (40 mg weekly or eow) continued to experience statistically significant improvements in DLQI. The DLQI index ranges from 0-30, with higher scores indicating worse quality of life for psoriasis patients. Results after 60 weeks of Humira therapy indicate:

- Changes in DLQI were greater than the suggested minimal clinically important difference of a five-point change in total score. - Patients continued to demonstrate an improved quality of life as measured by SF-36 achieving the suggested minimal clinically important difference for both physical and mental health scores at week 48. - Improvements in most domains of the SF-36 were sustained over the 60 weeks of Humira therapy.

Placebo patients who switched to Humira 40 mg eow at week 12 demonstrated an improved quality of life, as measured by the EQ-5D index, comparable to those initially randomized to active treatment. The mean change from baseline in placebo patients switched to Humira 40 mg eow was 9.4 at week 48.

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 and the EMEA 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 an inadequate 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.

Humira is the first fully human monoclonal antibody approved in Europe for RA, and the first tumor necrosis factor alpha (TNF-a) antagonist approved with an indication for use with methotrexate or as monotherapy. To date, Humira has been approved in 57 countries and prescribed to more than 83,000 patients suffering from RA worldwide.

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

SOURCE: Abbott