Abbott's HUMIRA(R) Significantly Reduces Key Marker Of Inflammation In Patients With Moderate To Severe Psoriasis

Main Category: Dermatology
Article Date: 18 Sep 2008 - 3:00 PDT

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Abbott's HUMIRA® (adalimumab) significantly reduces levels of C-reactive protein (CRP) in adult patients with moderate to severe plaque psoriasis, according to a post-hoc analysis presented today at the European Academy of Dermatology and Venereology (EADV) Congress in Paris. CRP is a key marker of inflammation that is used to assess disease activity in patients with autoimmune conditions.

Psoriasis is a chronic autoimmune disease resulting in thick, scaly areas of skin that are often itchy or painful. Patients with moderate to severe psoriasis often have elevated CRP levels.

"It is recognized that elevated CRP levels are seen in people with psoriasis," said William Abramovits, M.D., lead study researcher, Dermatology Treatment and Research Center, Dallas, Texas. "This analysis shows that HUMIRA reduces CRP levels in patients with moderate to severe psoriasis, including patients who had the highest levels - those with obesity or with psoriatic arthritis."

Study Results

A post-hoc analysis of the first 16 weeks of Abbott's pivotal, 52-week REVEAL trial was conducted to evaluate CRP concentrations in patients with moderate to severe psoriasis before and after HUMIRA treatment.

- During the REVEAL trial, 814 patients were given HUMIRA and 398 patients were given placebo.
- At the beginning of the study, 206 patients had elevated levels of CRP - 139 in the HUMIRA group and 67 in the placebo group.
- After 16 weeks, 67 percent of the HUMIRA group had normalized CRP levels, compared to only 37 percent of the placebo group.

The study also evaluated changes in CRP levels in two subgroups of patients that tend to have high levels of CRP - those with obesity and psoriatic arthritis (PsA), which are common co-morbidities of psoriasis. Treatment with HUMIRA in these two subgroups led to significant reductions in CRP.

Sub-analysis: Obesity

A growing body of research suggests there is a direct link between obesity and psoriasis.

- At the start of the study, 396 patients in the HUMIRA group and 211 patients in the placebo group were obese (Body Mass Index of 30 or above).
- Among obese patients, 92 in the HUMIRA group and 50 in the placebo group had elevated CRP levels.
- After 16 weeks, 64 percent of patients in the HUMIRA group had normal CRP levels, compared to 36 percent of the patients who received placebo.

Sub-analysis: PsA

Up to 30 percent of psoriasis patients develop PsA, which combines skin symptoms with arthritis symptoms, including joint pain and inflammation.

- At the start of the study, 224 patients in the HUMRA group and 113 patients in the placebo group had PsA.
- Among patients with PsA, 57 in the HUMIRA group and 28 in the placebo group had elevated CRP levels.
- After 16 weeks, 72 percent of patients in the HUMIRA group had normal CRP levels, compared to 43 percent in the placebo group.

About REVEAL

The REVEAL study was a 52-week, double blind, randomized, placebo-controlled Phase III trial to evaluate the efficacy and safety of HUMIRA in 1,212 patients with moderate to severe chronic psoriasis in the United States and Canada.

About Psoriasis

Psoriasis affects an estimated 125 million people worldwide. The severity of the disease varies from person to person with approximately 25 percent of people with psoriasis experiencing moderate to severe disease.

Psoriasis can develop anywhere on the skin and most commonly appears on the scalp, knees, elbows, lower back, hands and feet. It may even occur in the fingernails and toenails. While psoriasis occurs in people of all ages, it typically first appears in people between the ages of 15 and 25.

Psoriasis can be a very isolating disease and people with psoriasis may suffer from poor self-image, depression and an increased risk of premature death.

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. If latent tuberculosis is diagnosed, appropriate treatment for latent tuberculosis must be initiated with anti-tuberculosis prophylaxis therapy before starting treatment with HUMIRA, and in accordance with local recommendations. 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 combination of HUMIRA and anakinra and HUMIRA and abatacept is not recommended.

TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease including multiple sclerosis, Guillain-Barré syndrome and optic neuritis, 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 PUVA treatment, should be examined for the presence of non-melanoma skin cancer prior to and during treatment with HUMIRA.

Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Some of these hepatosplenic T-cell lymphomas with Humira have occurred in young adult patients on concomitant treatment with azathioprine or 6-mercaptopurine used for Crohn's disease. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with HUMIRA cannot be excluded.

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). Adverse drug reactions reported post-marketing include intestinal perforation, interstitial lung disease including pulmonary fibrosis and cutaneous vasculitis.

About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, ankylosing spondylitis (AS), Crohn's disease and juvenile idiopathic arthritis (JIA) 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 76 countries and more than 270,000 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 (MTX), is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease-modifying anti-rheumatic drugs (DMARDs) including MTX has been inadequate, and for the treatment of severe, active and progressive RA in adults not previously treated with MTX. HUMIRA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX 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 MTX.

Also in Europe, HUMIRA is indicated for the treatment of active and progressive PsA in adults when the response to previous DMARD 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 severe, active AS in adults 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 cortiocosteroids. 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.

Humira in combination with methotrexate is indicated for the treatment of active polyarticular juvenile idiopathic arthritis, in adolescents aged 13 to 17 years who have had an inadequate response to one or more DMARDs. Humira can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.

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, Mass., United States, is a world-class discovery and basic research facility committed to finding new treatments for autoimmune diseases.

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 68,000 people and markets its products in more than 130 countries.

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