Healthcare Industry News: ulcerative colitis
News Release - February 2, 2007
New Analyses Reinforce Efficacy of REMICADE(R) in Treatment of Severe PsoriasisData Show Patients with Severe Psoriasis Affecting the Nails Experienced Significant Improvements with REMICADE Therapy
WASHINGTON, Feb. 2 (HSMN NewsFeed) -- Findings from an integrated analysis of data from three pivotal, randomized, placebo-controlled trials showed that at week 10 more than three-quarters of patients with severe psoriasis receiving REMICADE® (infliximab) 3 mg/kg or 5 mg/kg achieved a 75 percent improvement in the chronic, inflammatory skin disease as measured by the Psoriasis Area Severity Index (PASI 75). In addition, in a separate analysis, investigators presented findings from a Phase 3 study, which showed that patients treated with REMICADE experienced significant and progressive improvements in psoriasis affecting the nails. Nail disease occurs in up to 50 percent of people with psoriasis.(1) These findings were presented today at the 65th Annual Meeting of the American Academy of Dermatology.
"The integrated data show the substantial efficacy of REMICADE and present great hope for patients with severe psoriasis, particularly those patients burdened with this chronic disease who previously failed phototherapy or systemic therapy," said Alan Menter, MD, dermatologist, Baylor Research Institute, Dallas, and lead study investigator.
In the analysis of 1462 randomized patients, 991 patients (68 percent) met criteria for severe disease as defined by a body surface area (BSA) of at least 20 percent. Out of the 991 patients, 73 percent and 69 percent of study patients had received previous phototherapy or systemic therapy, respectively. At week 10, among patients with severe psoriasis treated with REMICADE (combined 3 mg/kg and 5 mg/kg groups), 79 percent of patients who had received prior phototherapy and 76 percent who had been previously treated with one or more systemic agents achieved PASI 75, compared with three percent and one percent, respectively, of placebo patients (P < 0.001, for both). In a separate analysis from the Evaluation of Infliximab for Psoriasis in a [REMICADE] Efficacy and Safety Study (EXPRESS II), among patients with severe psoriasis who were either dissatisfied with or were intolerant to phototherapy, 73 percent of those treated with REMICADE achieved PASI 75 at week 10, compared with two percent of patients receiving placebo (P < 0.001). Sixty-nine percent of patients who were dissatisfied with or were intolerant to one or more systemic therapies prior to starting REMICADE achieved PASI 75 at week 10, compared with zero patients in the placebo group (P < 0.001).
A separate analysis from the European Infliximab for Psoriasis [REMICADE] Efficacy and Safety Study (EXPRESS) trial showed that among study patients with psoriasis affecting the nails at baseline who were treated with REMICADE 5 mg/kg, seven percent, 26 percent and 45 percent had clearance of nail psoriasis at weeks 10, 24 and 50, respectively, compared with 5 percent of patients in the placebo group at week 24 (P = 0.0002). In addition, at weeks 10 and 24, the mean percent improvements in the Nail Psoriasis Severity Index (NAPSI) scores were 27 percent and 57 percent, respectively, among patients in the REMICADE 5 mg/kg group compared with disease worsening observed among patients receiving placebo with increases in NAPSI scores of eight percent and four percent, respectively (P < 0.001, for both).
"These data are promising because the results demonstrate the efficacy of REMICADE in psoriasis patients whose disease is affecting the nails, a difficult-to-treat and chronic manifestation that can affect a large proportion of patients with psoriasis," said Phoebe Rich, MD, associate professor of dermatology, Oregon Health Sciences University. "Symptoms associated with nail disease may include deep holes in the nails or separation of the nails from the nail beds, which often result in pain and discomfort and may affect an individual's ability to perform daily activities. Given the nature of these symptoms, effectively treating both skin disease and nail disease, may greatly lessen the patients' overall burden of disease."
The progressive improvements in nail psoriasis observed in patients receiving REMICADE 5 mg/kg were consistent with normal nail growth rates, and the improvement was sustained over time. Treatment also resulted in significant improvements in nail matrix and nail bed signs of the disease, as measured by the NAPSI scoring system, including lunular red spots and splinter hemorrhages (small areas of bleeding under the nails), which completely resolved in two-thirds of REMICADE-treated patients at 10 weeks. The NAPSI scoring system evaluates nail bed psoriasis and nail matrix psoriasis by area of involvement in the nail unit and assesses eight characteristic features of psoriatic nail involvement, including pitting, leukonychia (discoloration), nail plate crumbling, red spots in the lunula (crescent-shaped area at bottom of nail), onycholysis (separation of nail from nail bed), nail bed hyperkeratosis (thickening of skin), splinter hemorrhages and oil drop discoloration.(2)
In September 2006, REMICADE was approved in the U.S. for the treatment of adult patients with chronic severe (i.e. extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. The recommended dose is an infusion of 5 mg/kg followed by additional doses at two and six weeks after the first infusion and then every eight weeks thereafter.
The European Infliximab for Psoriasis [REMICADE] Efficacy and Safety Study (EXPRESS) was a Phase 3, multi-center, randomized, double-blind, placebo-controlled trial that evaluated the safety and efficacy of REMICADE induction and maintenance therapy in 378 adult patients with chronic, stable plaque psoriasis involving at least 10 percent body surface area (BSA), a minimum PASI score of 12 and who were candidates for phototherapy or systemic therapy. Patients received either REMICADE 5 mg/kg or placebo administered at weeks 0, 2 and 6, followed by maintenance treatment every eight weeks. The REMICADE group continued on maintenance treatments every eight weeks. Patients in the placebo group were crossed over at week 24 to receive REMICADE 5 mg/kg at weeks 24, 26 and 30, then every eight weeks through week 46.
In EXPRESS, through week 24, adverse events (AEs) occurred at a higher incidence in the REMICADE group (82 percent) compared with the placebo group (71 percent). The only clinically significant laboratory abnormalities that occurred more frequently in the REMICADE group compared with the placebo group were elevated liver enzyme tests. There were more serious AEs (six percent), including one fatal infection, in the REMICADE group than in the placebo group (three percent). AEs observed were generally consistent with those described in the prescribing information, including information regarding serious infections. Please see "Important Safety Information" below.
About EXPRESS II
The Evaluation of Infliximab for Psoriasis in a [REMICADE] Efficacy and Safety Study (EXPRESS II) was a Phase 3, multi-center, randomized, double- blind, placebo-controlled trial that evaluated the safety and efficacy of REMICADE in 835 adult patients with chronic, stable plaque psoriasis involving at least 10 percent BSA, a minimum PASI score of 12 and who were candidates for phototherapy or systemic therapy. Patients were randomized to induction doses of REMICADE 3 mg/kg or 5 mg/kg or placebo at weeks 0, 2 and 6. Patients in the active induction treatment groups were randomized again at week 14 to receive either scheduled or "as-needed" maintenance treatment at the same dose administered during the induction phase. Patients in the placebo group were crossed over at week 16 to receive REMICADE 5 mg/kg at weeks 16, 18 and 22, then every eight weeks through week 46.
In EXPRESS II, through week 14 (the placebo-controlled period), AEs occurred at a higher incidence in the REMICADE groups (63 percent and 69 percent with 3 mg/kg and 5 mg/kg, respectively), compared with the placebo group (56 percent). The only clinically significant laboratory abnormalities that occurred more frequently in the REMICADE group compared with the placebo group were elevated liver enzyme tests. Serious AEs occurred at rates of two percent in the placebo group, three percent in the 5 mg/kg group and one percent in the 3 mg/kg group. AEs observed were generally consistent with those described in the prescribing information, including information regarding serious infections. Please see "Important Safety Information" below.
Study of Psoriasis with Infliximab [REMICADE] Induction Therapy (SPIRIT) was a Phase 2, multi-center, double-blind, placebo-controlled study evaluating the use of REMICADE induction therapy in 249 people with severe plaque psoriasis who had previously received psoralen plus ultraviolet light A (PUVA) or systemic therapy for psoriasis. Trial participants were randomized to receive REMICADE 3 mg/kg, REMICADE 5 mg/kg or placebo at weeks 0, 2, and 6 and were assessed biweekly for 10 weeks. At week 26, 114 patients whose Physician Global Assessment (PGA) score indicated moderate to severe disease were eligible for one additional infusion of their assigned treatment to assess the safety of re-treatment after a 20-week treatment-free period.
In the SPIRIT trial, the percentage of patients with one or more AE was higher in the REMICADE groups compared with placebo. Through week 30 of the SPIRIT trial, 63 percent, 78 percent and 79 percent of patients in the placebo, REMICADE 3 mg/kg and 5 mg/kg groups, respectively, reported one or more AE. The most commonly reported side effects versus placebo were upper respiratory tract infection (15 percent versus 14 percent), headache (15 percent versus 8 percent) and itching (12 percent versus 0 percent). A total of six percent of REMICADE-treated patients reported serious AEs, compared with zero patients in the placebo group. Overall, the AEs were consistent with those seen in previous trials. Please see "Important Safety Information" below.
Psoriasis is a chronic, immune-mediated disease, which results from inflammation in the skin and overproduction of skin cells that accumulate on the surface causing red, scaly plaques that may itch and bleed. This chronic inflammation is driven in part by tumor necrosis factor alpha, or TNF-alpha, a cytokine involved in the body's normal immune response. TNF-alpha is found at increased levels in psoriatic plaques and plays a crucial part in their formation and continued existence. It is estimated that two percent of the U.S. population has psoriasis, and about 30 percent of people with psoriasis have cases that are considered moderate to severe.
REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and is the only anti-TNF-alpha treatment approved in three different therapeutic areas: gastroenterology, rheumatology and dermatology. REMICADE has demonstrated broad clinical utility in Crohn's disease (CD), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), ulcerative colitis (UC), pediatric Crohn's disease (PCD) and psoriasis (PsO). The safety and efficacy of REMICADE have been well established in clinical trials over the past 14 years and with more than 843,000 patients treated worldwide through commercial experience.
In the U.S., REMICADE, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active RA. REMICADE is the only biologic indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately to severely active CD who have had an inadequate response to conventional therapy. REMICADE is also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing CD. In December 2004, REMICADE was approved for reducing signs and symptoms in patients with active AS. In May 2005, REMICADE was approved for reducing signs and symptoms of active arthritis in patients with PsA. Additionally, in September 2005, REMICADE was approved for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. This approval makes REMICADE the first and only biologic approved for the treatment of moderate to severe UC. In addition, on May 19, 2006, REMICADE was approved for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. This approval establishes REMICADE as the first and only biologic therapy approved for the treatment of PCD. In August 2006, REMICADE received the expanded indication for inhibiting the progression of structural damage and improving physical function in patients with psoriatic arthritis. In September 2006, REMICADE was approved for the treatment of adult patients with chronic severe plaque psoriasis. In October 2006, REMICADE was approved for maintaining clinical remission and mucosal healing in patients with moderately to severely active UC, who have had an inadequate response to conventional therapy.
REMICADE is unique among available anti-TNF biologic therapies. Unlike self-administered therapies that require patients to inject themselves frequently, REMICADE is the only anti-TNF biologic administered directly by caregivers in the clinic or office setting. In RA (3 mg/kg), CD (5 mg/kg), PsA (5 mg/kg), UC (5 mg/kg), PCD (5 mg/kg), and PsO (5 mg/kg), REMICADE is a two-hour infusion administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients may require as few as six treatments each year. In AS (5 mg/kg), REMICADE is a two-hour infusion administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6.
Important Safety Information
There are reports of serious infections, including tuberculosis (TB), sepsis and pneumonia. Some of these infections have been fatal. Tell your doctor if you have had recent or past exposure to people with TB. Your doctor will evaluate you for TB and perform a TB test. If you have latent (inactive) TB, your doctor should begin TB treatment before you start REMICADE. REMICADE can lower your ability to fight infections, so if you are prone to or have a history of infections, or develop any signs of an infection such as fever, fatigue, cough, flu or warm, red or painful skin while taking REMICADE, tell your doctor right away. Also, tell your doctor if you are scheduled to receive a vaccine or if you have lived in a region where histoplasmosis or coccidioidomycosis is common.
Reports of a type of blood cancer called lymphoma in patients on REMICADE or other TNF blockers are rare but occur more often than expected for people in general. People who have been treated for rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis for a long time, particularly those with highly active disease may be more prone to develop lymphoma. Cancers, other than lymphoma, have also been reported. Children and young adults who have been treated for Crohn's disease with REMICADE have developed a rare type of lymphoma that often results in death. These patients also were receiving drugs known as azathioprine or 6-mercaptopurine. If you take REMICADE or other TNF blockers, your risk for developing lymphoma or other cancers may increase. You should also tell your doctor if you have had or develop lymphoma or other cancers or if you have a lung disease called chronic obstructive pulmonary disease (COPD).
Many people with heart failure should not take REMICADE; so prior to treatment you should discuss any heart condition with your doctor. Tell your doctor right away if you develop new or worsening symptoms of heart failure (such as shortness of breath, swelling of your ankles or feet, or sudden weight gain.
Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF blockers, such as REMICADE. Some of these cases have been fatal. Tell your doctor if you know or think you may be a carrier of hepatitis B virus or if you experience signs of hepatitis B infection, such as feeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain.
There have been rare cases of serious liver injury in people taking REMICADE, some fatal. Tell your doctor if you have liver problems and contact your doctor immediately if you develop symptoms such as jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe fatigue.
Blood disorders have been reported, some fatal. Tell your doctor if you develop possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking REMICADE. Nervous system disorders have also been reported. Tell your doctor if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, visual disturbances or seizures while taking REMICADE.
Allergic reactions, some severe, have been reported during or after infusions with REMICADE. Signs of an allergic reaction include hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, and fever or chills. Tell your doctor if you have experienced a severe allergic reaction. The most common side effects of REMICADE are: respiratory infections, such as sinus infections and sore throat, headache, rash, coughing, and stomach pain.
Please read the Medication Guide for REMICADE and discuss it with your doctor.
Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.
The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary of Johnson & Johnson.
(1) National Psoriasis Foundation. Psoriasis of the Nails. http://www.psoriasis.org/about/psoriasis/sites/nails.php. Accessed 12/27/06.
(2) Kavanaugh A, Cassell S: Assessment of disease activity and outcomes in PsA. Clin Exp Rheumatol 2005; 23 (Suppl. 39): S142-S147.
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