LAS VEGAS, Nev., October 23, 2006 -- Patients with ulcerative colitis (UC) treated with REMICADE® (infliximab) had an approximate 50 percent reduction in mean number of hospitalizations per year compared with placebo, according to an analysis of long-term data from a Phase 3 clinical trial (Active Ulcerative Colitis Trial 1, ACT 1) presented at the American College of Gastroenterology (ACG) meeting. Patients who responded and those who were in remission at one year had lower mean number of hospitalizations (no hospitalizations) vs. non-responders (23 per 100 patients, P <0.001) through one year of treatment.
"Severe ulcerative colitis is a disease characterized by high costs, as it often results in extended hospitalizations and surgery," said Stephen Hanauer, M.D., Professor of Medicine and Clinical Pharmacology; Chief, section of Gastroenterology and Nutrition at the University of Chicago Hospitals. "Results from this analysis suggest that patients who did not respond to REMICADE were more likely to be hospitalized than patients who responded."
A separate analysis of a medical claims database (PharMetrics), also presented at ACG, shows that individuals with moderate to severe UC who require hospitalization have 80 percent higher average yearly healthcare costs compared with healthy individuals. A review of the claims records of 13,856 patients with UC shows that individuals who require inpatient hospitalizations have the greatest overall healthcare costs. In fact, inpatient hospitalizations account for approximately 42 percent of UC patients' total healthcare costs annually.
Reduction of hospitalizations was sustained through one year in ACT I with approximately 50 percent lower mean number of hospitalizations for REMICADE-treated patients (12 per 100 patients) compared with placebo (22 per 100 patients, P = 0.061). Furthermore, the time to the first hospitalization among REMICADE patients was longer compared with patients who received placebo (P = 0.032).
Combined long-term data from ACT 1 and ACT 2 indicate that at week 30, patients who were treated with REMICADE experienced fewer hospitalizations requiring high-dose corticosteroids than those treated with placebo. Among 484 REMICADE-treated patients, there were 13 hospitalizations. Among 244 patients in the placebo group there were 19 hospitalizations (P = 0.025).
The analysis of UC patients registered in the PharMetrics database revealed that patients requiring hospitalization for UC (Group 1) incurred mean costs more than three times greater than UC patients requiring chronic aggressive pharmacotherapy (Group 2) and more than five times greater than costs for all other patients with UC (Group 3), indicating the high cost-burden of poorly controlled UC. Costs associated with hospitalization constituted the largest component of resource utilization at approximately $5,300 per patient for all UC patients. Inpatient healthcare costs per individual in Group1 were $24,693, compared with $1,842 and $1,016 per patient in Groups 2 and 3, respectively. Patients with UC requiring hospitalization also incurred higher costs relating to outpatient hospital care, emergency room visits, physician visits and laboratory tests than patients with UC who did not require hospitalization. On average, patients in Group 2 whose UC was controlled effectively with aggressive pharmacotherapy incurred $4,283 in prescription drug costs, compared with $3,502 and $1,508 per patient in Groups 1 and 3, respectively. The overall healthcare cost per patient in Group 2 was approximately $20,000 less than the per-patient cost among patients in Group 1, illustrating the benefits of aggressive pharmacotherapy in reducing overall UC-related healthcare costs.
About ACT 1 & ACT 2
REMICADE was approved by the FDA for the treatment of UC in September 2005 based on positive results from two randomized, placebo-controlled, pivotal Phase 3 clinical trials, ACT 1 and ACT 2. Fifty-four week results from the ACT 1 trial further demonstrated the long-term safety and efficacy of REMICADE in patients with moderately to severely active UC and found that REMICADE therapy not only induces clinical remission, but also maintains remission of symptoms up to one year.
In each trial, 364 patients with active UC who were unresponsive to at least one standard therapy- including corticosteroids, immunosuppressants or 5-ASAs- were enrolled. Patients in ACT 1 and ACT 2 had evidence of moderate or severe UC (total Mayo score of 6 to 12 and an endoscopy score ?2). In both trials, patients were randomized to one of three groups: continued conventional therapy plus placebo infusions, continued conventional therapy plus REMICADE 5 mg/kg infusions or continued conventional therapy plus REMICADE 10 mg/kg infusions. ACT 1 patients received the study agent at weeks 0, 2 and 6 and then every 8 weeks through week 46 and had their last evaluations at week 54. ACT 2 patients received the study agent at weeks 0, 2 and 6 and then every 8 weeks through week 22 and had their last evaluations at week 30.
In ACT 1, significantly higher proportions of patients receiving REMICADE 5 mg/kg (69 percent) and 10 mg/kg (62 percent) achieved clinical response at week 8 versus patients receiving placebo infusions (37 percent; P <0.001 for both). In addition, at week 30, 52 percent of patients in the 5 mg/kg and 51 percent of patients in the 10 mg/kg REMICADE treatment group were in clinical response versus 30 percent of placebo infusion group (P <0.001 and P <0.01, respectively). At week 8, 39 percent and 32 percent of patients treated with REMICADE 5 mg/kg and 10 mg/kg, respectively, were in clinical remission compared with 15 percent of the placebo infusion group (P <0.001 and P <0.01). These differences in remission rates persisted at week 30 (34 percent, 5 mg/kg; 37 percent, 10 mg/kg versus 16 percent, placebo; P <0.001 for both). Mucosal healing was achieved at week 8 in 62 percent and 59 percent of patients receiving REMICADE 5 mg/kg and 10 mg/kg, respectively, versus 34 percent of patients given placebo infusions (P <0.001 for both). This difference in mucosal healing was maintained at week 30 (50 percent, 5 mg/kg; 49 percent, 10 mg/kg versus 25 percent, placebo; P <0.001 for both). The proportion of patients who were able to discontinue corticosteroids while in clinical remission at week 30 was greater in both REMICADE groups compared with the placebo infusion group (24 percent, 5 mg/kg; 19 percent, 10 mg/kg; 10 percent, placebo; P =0.030 and P =0.125, respectively).
In ACT 2, significantly higher proportions of patients receiving REMICADE 5 mg/kg (65 percent) and 10 mg/kg (69 percent) were in clinical response at week 8 versus 29 percent who received placebo infusions (P <0.001 for both). At week 30, 47 percent of patients receiving REMICADE 5 mg/kg and 60 percent receiving 10 mg/kg were in clinical response versus 26 percent of patients receiving placebo infusions (P <0.001 for both). Clinical remission was achieved at week 8 in 34 percent and 28 percent of REMICADE 5 and 10 mg/kg patients, respectively, compared with 6 percent of the placebo infusion group (P <0.001 for both). Differences in remission rates persisted at week 30 (26 percent, 5 mg/kg; 36 percent, 10 mg/kg; 11 percent, placebo; P <0.01 and P <0.001). Mucosal healing was achieved at week 8 in 60 percent and 62 percent of patients receiving REMICADE 5 mg/kg and 10 mg/kg, respectively, compared with 31 percent of patients receiving placebo infusions (P <0.001 for both). Mucosal healing at week 30 was achieved in 46 percent and 57 percent of patients receiving REMICADE 5 and 10 mg/kg, respectively, compared with 30 percent of the placebo infusion group (P <0.01 and P <0.001). The proportion of patients who were able to discontinue corticosteroids while in clinical remission at week 30 was significantly greater in both REMICADE groups compared with the placebo infusion group (18 percent, 5 mg/kg; 27 percent, 10 mg/kg; 3 percent, placebo; P =0.010 and P <0.001, respectively).
By week 54 of ACT 1, 46 percent of patients receiving 5 mg/kg and 44 percent of patients receiving 10 mg/kg REMICADE treatments had achieved clinical response versus 20 percent for placebo (P <0.001 and P <0.01, respectively). A sustained long-term response from week 8 through 54 was seen in 39 percent of the 5 mg/kg and 37 percent of 10 mg/kg REMICADE patients versus 14 percent for placebo (P <0.001 and P <0.001, respectively). In addition, by week 54, 35 percent of patients receiving 5 mg/kg and 34 percent receiving 10 mg/kg REMICADE treatments had achieved clinical remission versus 16 percent for placebo (P =0.001 and P =0.001, respectively). Sustained remission from week 8 through 54 was seen in 20 percent of patients receiving 5 mg/kg and 10 mg/kg REMICADE treatments versus a 7 percent sustained remission rate for placebo (P =0.002 and P =0.002, respectively). Forty-six percent of patients in the 5 mg/kg and 47 percent of patients in the 10 mg/kg REMICADE treatment groups had achieved mucosal healing by week 54 of the ACT 1 trial versus just 18 percent for placebo (P <0.001 and P <0.001, respectively). Of 364 patients in the ACT trial, 61 percent were on concomitant corticosteroids at baseline. By week 54, 21 percent of REMICADE patients who were on corticosteroids at baseline were in clinical remission and had discontinued corticosteroid use compared with 9 percent for placebo (P =0.022).
The serious adverse events reported in these trials were similar to those reported in previous REMICADE clinical trials. (See Important Safety Information below).
About the PharMetrics Database Analysis
Utilizing a control group of 55,186 patients randomly selected by age and gender, a retrospective analysis of the PharMetrics database, including 13,856 UC patients between the ages of 18 to 64 and diagnosed between January 1, 2000 and June 30, 2005, was conducted. UC patients had to be continuously enrolled for six months pre-UC diagnosis and 12 months post-UC diagnosis, and have two distinct claims for UC. Mean per-patient healthcare resource utilization and cost were calculated for each patient sorted by disease severity group in the year following their initial UC diagnosis. Group 1 required hospitalization for UC; Group 2 required chronic aggressive pharmacotherapy, defined as corticosteroids or immunosuppressants, for greater than 4 months; and Group 3 consisted of all remaining patients.
The average age of patients was 44 years and 54 percent were females. Mean annual total costs for all adult patients with UC were $12,693, compared with $3,661 for non-UC patients. Group 1 patients incurred the highest mean cost ($36,155), while Groups 2 and 3 incurred $11,401 and $6,493, respectively. Inpatient hospitalization costs constituted the largest component ($5,276, 42 percent) of the mean annual total costs for all patients. The next highest cost components were prescription medications ($2,469, 19 percent), outpatient hospital care ($1,276, 10 percent), physician office visits ($884, 7 percent) and laboratory procedures ($467, 3.7 percent). Resource utilization was also highest in Group 1.
REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and 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 770,000 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 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 CD 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 was approved for inhibiting progression of structural damage and improving physical function in patients with psoriatic arthritis. In September 2006, REMICADE was approved for the treatment of adults 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. 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.
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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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