SAN ANTONIO, TX, February 1, 2008 -- Data from an integrated analysis of three randomized, placebo-controlled trials showed patients with moderate to severe plaque psoriasis receiving REMICADE (infliximab) achieved a consistently high level of skin clearance in each of the four body regions (head, trunk, lower and upper extremities) as measured by the Psoriasis Area Severity Index (PASI). At week 10 of the analysis, which included nearly 1,500 subjects, 71 percent of patients receiving REMICADE 3 mg/kg and 79 percent of patients receiving REMICADE 5 mg/kg achieved a PASI 75, or at least a 75 percent improvement in the chronic inflammatory condition, compared with three percent of patients receiving placebo (both P<0.001). Additionally, 39 percent and 52 percent of patients receiving REMICADE 3 mg/kg and 5 mg/kg, respectively, achieved a PASI 90, or nearly complete skin clearance, versus one percent of patients receiving placebo (both P<0.001). Investigators reported these findings at the 66th Annual Meeting of the American Academy of Dermatology.
In September 2006, the U.S. Food and Drug Administration (FDA) approved REMICADE (5 mg/kg) for the treatment of chronic severe plaque psoriasis. Following an initial three infusion treatments (induction regimen), REMICADE is given once every eight weeks, or as few as six times a year.
“This analysis shows that treatment with REMICADE resulted in a consistently high level of clinical response in each quadrant of the body evaluated by PASI, and the results were consistent with patients’ overall psoriasis improvement,” said Alan Menter, MD, dermatologist, Baylor Research Institute, Dallas. “REMICADE remains an important advancement and biologic treatment option for a broad spectrum of patients with severe psoriasis.“
According to findings presented by investigators, in each of the three psoriasis clinical trials evaluated, the Study of Psoriasis with Infliximab [REMICADE] Induction Therapy (SPIRIT), the European Infliximab for Psoriasis [REMICADE] Efficacy and Safety Study (EXPRESS), and the Evaluation of Infliximab for Psoriasis in a [REMICADE] Efficacy and Safety Study (EXPRESS II), a substantial proportion of REMICADE-treated patients experienced dramatic improvements in head- and neck-related psoriasis, trunk psoriasis and psoriasis of the lower and upper extremities as compared with the placebo group. Additionally, the improvements in each body region were generally consistent with the overall PASI response. At week 10, the proportions of patients achieving at least a 75 percent improvement or at least a 90 percent improvement of head and neck-related psoriasis in the combined REMICADE groups (3 mg/kg and 5 mg/kg) versus placebo were as follows: SPIRIT, 86 percent versus 22 percent achieved at least 75 percent improvement and 69 percent versus 12 percent achieved at least 90 percent improvement; EXPRESS, 85 percent versus 13 percent achieved at least 75 percent improvement and 73 percent versus 8 percent achieved at least 90 percent improvement; EXPRESS II, 79 percent versus 10 percent achieved at least 75 percent improvement and 67 percent versus 6 percent achieved at least 90 percent improvement.
PASI responses for trunk psoriasis in the combined REMICADE groups (3 mg/kg and 5 mg/kg) versus placebo were as follows: SPIRIT, 86 percent versus 12 percent achieved at least 75 percent improvement and 66 percent versus 4 percent achieved at least 90 percent improvement; EXPRESS, 87 percent versus 5 percent achieved at least 75 percent improvement and 72 percent versus 1 percent achieved at least 90 percent improvement; EXPRESS II, 79 percent versus 7 percent achieved at least 75 percent improvement and 59 percent versus 4 percent achieved at least 90 percent improvement.
Patients in the combined REMICADE groups (3mg/kg and 5 mg/kg) experienced similar improvement in PASI scores of the upper and lower extremities. For the upper extremities the proportions of patients achieving at least 75 percent improvement or at least 90 percent improvement versus placebo were as follows: SPIRIT, 77 percent versus 6 percent achieved at least 75 percent improvement and 49 percent versus 2 percent achieved at least 90 percent improvement; EXPRESS, 82 percent versus 4 percent achieved at least 75 percent improvement and 56 percent versus 1 percent achieved at least 90 percent improvement; EXPRESS II, 72 percent versus 2 percent achieved at least 75 percent improvement and 46 percent versus 0.5 percent achieved at least 90 percent improvement. Results for the lower extremities were: SPIRIT, 72 percent versus 8 percent achieved at least 75 percent improvement and 49 percent versus 2 percent achieved at least 90 percent improvement; EXPRESS, 75 percent versus 3 percent achieved at least 75 percent improvement and 50 percent versus 1 percent achieved at least 90 percent improvement; EXPRESS II, 65 percent versus 4 percent achieved at least 75 percent improvement and 35 percent versus 0.5 percent achieved at least 90 percent improvement.
Further results from the integrated analysis were published in the summer 2007 issue of the Psoriasis Forum, a journal of the National Psoriasis Foundation, and showed the consistency of REMICADE response across subgroups defined by a variety of baseline demographic and disease characteristics in patients with psoriasis. REMICADE was similarly effective regardless of previous use of phototherapy or major conventional systemic therapies.
About EXPRESS
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 8 weeks. The REMICADE group continued on maintenance treatments every 8 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 8 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 (6 percent), including one fatal infection, in the REMICADE group than in the placebo group (3 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
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 8 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 2 percent in the placebo group, 3 percent in the 5 mg/kg group and 1 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.
About SPIRIT
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, patients whose Physician Global Assessment (PGA) score indicated moderate to severe disease (n=114) were eligible for one additional infusion of their assigned treatment to assess the safety of retreatment 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 6 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.
About Psoriasis
Psoriasis is a chronic, immune-mediated disorder, 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 2 percent of the U.S. population has psoriasis, and about 30 percent of people with psoriasis have cases that are considered moderate to severe.
About REMICADE
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 one million patients treated worldwide through commercial experience.In the U.S., REMICADE is approved for the following indications:
- Reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active RA, when administered in combination with methotrexate.
- Reducing signs and symptoms in patients with active AS.
- 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.
- Reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing CD.
- Reducing signs and symptoms, inducing and maintaining 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.
- Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function in patients with PsA.
- Treatment of adult patients with chronic severe plaque PsO who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.
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. REMICADE is a two-hour infusion administered every 6 or 8 weeks (indication-dependent), 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.
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.
About Centocor
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.
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