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Continued Improvement in Disease Activity Reported in Phase 2 Trial of Adalimumab
NEW YORK, July 29 /PRNewswire-FirstCall/ -- New Phase II study results of HUMIRA® (adalimumab) in patients with moderate to severe chronic plaque psoriasis showed that patients achieved significant and continued improvement in disease activity and quality of life over 24 weeks of treatment, with nearly half of patients experiencing a 90 percent improvement in disease activity. These data were presented today at the American Academy of Dermatology (AAD) summer meeting in New York City.
Psoriasis is a chronic, non-contagious skin disease characterized by very dry, scaly and cracked skin; skin pain; and patches of red, raised skin known as "plaques." This debilitating disease, which currently has no cure, affects more than 4.5 million people in the United States.
In the study, 64 percent of patients taking HUMIRA 40 mg every other week (eow) achieved at least a 75 percent improvement in disease extent and severity after 24 weeks. Furthermore, 42 percent of patients taking HUMIRA 40 mg eow experienced at least a 90 percent improvement in their disease. Patients also recorded significant improvement in quality of life measures: after 24 weeks, 40 percent of patients reported 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.
"Psoriasis can be a serious disease with enormous quality of life implications, so it is important that we continue to seek out effective treatment options for patients," said lead investigator Kenneth Gordon, M.D., Associate Professor of Medicine, Loyola University, Chicago Stritch School of Medicine. "In this study, patients on HUMIRA experienced a clinically significant response, in addition to quality of life improvements. Even more encouraging is the number of patients in the trial who achieved 90 percent improvement in their disease -- an important measure that goes beyond what is typically highlighted in clinical trials."
This double-blind study measured the effectiveness and tolerability of HUMIRA after a total of 24 weeks of treatment. It was the continuation of a 12-week trial in which participants (n=148) with a diagnosis of moderate to severe chronic plaque psoriasis for at least one year and an affected body surface area of greater than or equal to 5 percent were randomized to receive HUMIRA or placebo administered by subcutaneous injection (under the skin).
The results for the first 12 weeks of therapy were reported at the AAD meeting in February 2004.
Patients completing the first 12 weeks of the trial (n=137) were eligible to continue. Patients who had been receiving HUMIRA 40 mg eow, and patients receiving HUMIRA 40 mg weekly, continued with treatment at the same dosing for the additional 12 weeks. Beginning at week 12, patients in the placebo arm received 12 weeks of therapy, with an initial dose of 80 mg of HUMIRA followed by 40 mg eow beginning at week 13. Patients and physicians remained blinded to dose until week 24, at which point patients were evaluated.
Measuring Efficacy and Tolerability
The primary efficacy endpoint was the percentage of patients achieving at least a 75 percent reduction in disease activity after 24 weeks of treatment as measured by the Psoriasis Area and Severity Index Score (PASI 75) compared to the baseline value at week 0. PASI measures the extent and severity of psoriasis. Results at 24 weeks show that 64 percent of patients receiving HUMIRA 40 mg eow achieved PASI 75. Seventy-two percent of patients who received HUMIRA 40 mg weekly achieved PASI 75. Results also demonstrate that 55 percent of the patients who were switched from placebo to the 40 mg eow regimen beginning at week 12 achieved PASI 75 after 12 weeks of therapy. These data are similar to the results of patients receiving HUMIRA 40 mg eow in the first 12 weeks of the initial trial, where responses were seen as early as the first week of therapy.
The percentage of patients achieving PASI 90 -- a measurement that correlates to at least a 90 percent reduction in disease activity -- also was significant. Results at 24 weeks show that 42 percent of patients receiving HUMIRA 40 mg eow and 62 percent of patients receiving HUMIRA 40 mg weekly achieved PASI 90. For those patients who began taking HUMIRA 40 mg eow at week 12, 32 percent achieved PASI 90, marking a significant improvement in disease activity.
Disease activity was also measured by the Physician's Global Assessment, a measurement tool used by physicians to assess severity of disease. Results showed that 45 percent of patients receiving placebo/40 mg eow (placebo for 12 weeks followed by HUMIRA 80 mg then 40 mg eow) were "clear" (representing no signs of psoriasis) or "almost clear" after 12 weeks of therapy. At 24 weeks, 64 percent of patients receiving HUMIRA 40 mg eow were "clear" or "almost clear" of their psoriasis, as were 72 percent of patients taking HUMIRA 40 mg weekly.
There were no new safety concerns in the psoriasis population compared with those observed in the rheumatoid arthritis population. Adverse events occurring in >5 percent of patients included headache, injection site pain, nasopharyngitis, triglyceride increase, dyspepsia, skin papilloma, nausea, nonspecific upper respiratory infection and fatigue.
Quality of Life Results
Patients receiving either dose of HUMIRA reported significantly greater improvements in DLQI at 12 weeks than those receiving placebo, and those improvements continued over 24 weeks.
At 24 weeks, 40 percent of patients receiving HUMIRA 40 mg eow reported a DLQI of "0", meaning they were "not at all" affected by their psoriasis. Nearly 55 percent of patients on weekly dosing and 26 percent of those on placebo/40 mg eow reported they were "not at all" affected by their psoriasis after receiving HUMIRA.
The DLQI index ranges from 0-30, with 30 representing the worst quality of life for psoriasis patients. A mean change of greater than or equal to -5 represents a minimal clinically important difference in DLQI.
At baseline, the mean DLQI was between 12.2 and 13.6, and patients in all groups experienced improved quality of life at the end of treatment. Patients taking placebo/HUMIRA 40 mg eow experienced a mean change in DLQI of -8.2 after 24 weeks. Patients receiving HUMIRA 40 mg eow showed a mean DLQI change of -10.2 at week 24. Those taking HUMIRA 40 mg weekly experienced a mean change of -11.6 after 24 weeks.
"We are pleased to see patients in this study experience improvements in the physical and emotional effects of psoriasis through treatment with HUMIRA and are encouraged by the promising results we have seen so far in our psoriasis trials," said Jim Lefkowith, M.D., divisional vice president, Immunology Development, Abbott Laboratories.
According to a 2001 survey conducted by the National Psoriasis Foundation, 75 percent of people with moderate to severe psoriasis report that their disease has a moderate to large impact on their everyday lives, with 26 percent of people altering their normal daily activities and 21 percent stopping their normal daily activities.
HUMIRA is not indicated for treatment of psoriasis. Clinical trials are underway evaluating the potential of HUMIRA in psoriasis and other autoimmune diseases.
Important Safety Information
Cases of tuberculosis (TB), frequently disseminated or extra pulmonary at clinical presentation, 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 on concomitant immunosuppressive therapy that in addition to their underlying disease could predispose them to infections. Other invasive opportunistic fungal infections have also been observed in patients treated with TNF-blocking agents, including HUMIRA.
TNF-blocking agents, including HUMIRA, have been associated in rare cases with exacerbation of demyelinating disease. Lymphoma has been observed in patients treated with TNF-blocking agents. 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.
HUMIRA is the only fully human monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) for reducing the signs and symptoms and inhibiting the progression of structural damage in adults with moderately to severely active 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 (MTX) or other DMARDs. The efficacy and safety of HUMIRA have been studied in 23 clinical trials and in more than 2,300 patients, making it the most-studied TNF antagonist for RA at the time of regulatory submission. HUMIRA was approved by the FDA on Dec. 31, 2002.
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-alpha) antagonist approved with an indication for use with methotrexate or as monotherapy. In April 2004, the European Medicines Evaluation Agency (EMEA) granted a positive opinion for a HUMIRA label extension for reducing the rate of progression of joint damage as measured by X-ray and improving physical function in adults with RA.
To date, HUMIRA has been approved in 51 countries and prescribed to more than 75,000 patients worldwide suffering from rheumatoid arthritis.
Source: Abbott Laboratories