SAN DIEGO, Oct. 26 /PRNewswire/ -- New data from an open-label extension study evaluating the long-term safety and efficacy of CIMZIA® (certolizumab pegol) in moderate to severe Crohn's disease patients demonstrate that 82 percent of patients actively treated with CIMZIA - the only PEGylated anti-TNF-alpha (Tumor Necrosis Factor alpha) - remained in long-term remission without dose escalation up to 3.5 years. In a separate analysis, CIMZIA significantly improved patients' symptoms as early as day 8 as reported in a post-hoc responder analysis of PRECiSE 2, the original double-blind placebo controlled study. These data from PRECiSE 2 and the open-label extension PRECiSE 3 studies are being presented this week at the American College of Gastroenterology (ACG) Annual Meeting in San Diego, Calif.
CIMZIA is indicated for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
"These data further demonstrate that treatment with a stable dose of CIMZIA enables patients with Crohn's disease to have sustained symptom relief," said study investigator Gary R. Lichtenstein, M.D., Director, Inflammatory Bowel Disease Program, University of Pennsylvania in Philadelphia. "Long-term relief and control of symptoms are vital to helping Crohn's patients manage their disease."
At the start of the open-label extension study, PRECiSE 3, 75 percent of CIMZIA-treated patients (105 out of 141 patients who continued in PRECiSE 3) were in clinical remission. Eighty-two percent of patients who continued in the long-term extension trial on active treatment maintained remission for up to 3.5 years based upon responder analysis. Disease activity was measured by the Harvey-Bradshaw Index (HBI), which tallies the incidence of five clinical items, including general well-being, abdominal pain and number of liquid stools per day, during the previous 24 hours before the assessment. Each item is scored from 0 to 3 and total scores of less than or equal to 4 signify remission. Most reported adverse events were of mild to moderate intensity. The most serious adverse events (some leading to death) reported were exacerbation of Crohn's disease, serious infections (3 of which were tuberculosis) and malignancies. (Abstract #P716)
In the original PRECiSE 2 trial, moderate to severe Crohn's patients who responded to CIMZIA after an open-label induction phase were randomized to receive CIMZIA or placebo and evaluated for maintenance of clinical response by week 26, of which a significant majority (62 percent) of CIMZIA treated patients maintained their overall clinical response compared to placebo (34 percent, p<0.001). In the separate post-hoc analysis of the PRECiSE 2 trial, three patient-reported Crohn's Disease Activity Index (CDAI) components (number of loose/liquid stools, abdominal pain, and general well-being) were examined from baseline (day 0) to day 8 to 14, comparing week 6 responders and nonresponders to CIMZIA treatment. The CDAI is a patient/physician questionnaire which incorporates eight CD-related variables. Patients completed a diary card daily for 7 days prior to each clinic visit. Scores of <150 indicate remission and scores of >450 indicate severe illness along the 600 point scale. There was a 31 percent (95% CI: -1.7, -1.2) reduction of mean number of loose/liquid stools among responders versus a 14 percent (95% CI: -1.0, -0.3) reduction for nonresponders by day 8. Twenty percent of CIMZIA responders reported no abdominal pain by day 8 versus 16 percent of nonresponders (p= 0.002). Approximately 21 percent of CIMZIA responders reported improvement in general well-being scores versus 14 percent of nonresponders (p=0.001). (Abstract #P286)
"These data further underscore the value of CIMZIA as a therapeutic option for those living with this devastating and debilitating disease. The long-term efficacy data solidify CIMZIA's potential to help many patients throughout the course of their disease," said David Robinson, vice president and general manager of UCB's Immunology Business Unit.
Earlier this year, UCB announced that CIMZIA is available to moderate to severe Crohn's patients in a pre-filled syringe, developed in partnership with OXO Good Grips®( )for subcutaneous self-administration once every four weeks after initial dosing. CIMZIA, manufactured by UCB, was approved by the U.S. Food and Drug Administration on April 22, 2008 for reducing signs and symptoms of moderate to severe Crohn's disease and maintaining clinical response in adult patients who have had an inadequate response to conventional therapy.
About the PRECiSE Clinical Trial Program
PRECiSE (PEGylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy), one of the largest, most comprehensive development programs for an anti-TNF for Crohn's disease, is composed of two placebo-controlled studies and two open-label safety follow-up studies. In 2007, the two former studies were published in the New England Journal of Medicine (NEJM). The studies demonstrated that patients with moderate to severe Crohn's disease achieved and sustained clinical response with CIMZIA for up to six months, compared to placebo. In the first follow-up study, patients completing both initial studies were to be given CIMZIA every four weeks for up to seven years. In the second follow-up study, patients who relapsed in either initial study (defined as an increase in CDAI of >70 or absolute CDAI of >350) were re-introduced to CIMZIA every four weeks to be continued for up to seven years, with a single additional dose at week 2. The most common adverse events reported were headache, nasopharyngitis, cough and abdominal pain. The incidence of serious adverse events (SAEs) was 5.6 percent, including one case each of tuberculosis, pyelonephritis, and pneumonia.
About Crohn's Disease
Crohn's disease is a chronic, progressive, destructive disorder that causes inflammation of the gastrointestinal (GI) tract, most commonly at the end of the small intestine (the ileum) and beginning of the large intestine (the colon). The inflammation may be caused by the presence of high levels of Tumor Necrosis Factor (TNF) found in people with Crohn's disease. If not effectively treated, it may result in the need for surgery and hospitalization. Crohn's disease has been estimated to affect as many as half a million Americans. People with Crohn's can experience an ongoing cycle of flare-up and remission throughout their lives. Together with ulcerative colitis, Crohn's disease is an inflammatory bowel disease (IBD).
About CIMZIA® (certolizumab pegol)
CIMZIA is the only PEGylated anti-TNF (Tumor Necrosis Factor). CIMZIA( )has a high affinity for human TNF-alpha, selectively neutralising the pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha has emerged as a major target of basic research and clinical investigation. This cytokine plays a key role in mediating pathological inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of immunological diseases. The U.S. Food and Drug Administration (FDA) has approved CIMZIA for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderate to severe active disease who have had an inadequate response to conventional therapy and for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). CIMZIA was approved in Switzerland for induction of a clinical response and for the maintenance of a clinical response and remission in patients with active Crohn's disease who have not responded adequately to conventional treatment in September 2007. Health Canada and the European Commission have both approved CIMZIA in combination with methotrexate (MTX), for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying antirheumatic drugs (DMARDs) including MTX. UCB is also developing CIMZIA in other autoimmune disease indications. CIMZIA is a registered trademark of UCB PHARMA S.A.
IMPORTANT SAFETY INFORMATION
Risk of Serious Infections
Patients treated with CIMZIA are at an increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. CIMZIA should be discontinued if a patient develops a serious infection or sepsis. Reported infections include:
The risks and benefits of treatment with CIMZIA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
Serious and sometimes fatal infection due to bacterial, mycobacterial, invasive fungal, viral or other opportunistic pathogens has been reported in patients receiving TNF-blocking agents. Among opportunistic infections, tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis were the most common. Treatment with CIMZIA should not be initiated in patients with an active infection, including clinically important localized infections. CIMZIA should be discontinued if a patient develops a serious infection or sepsis. Patients who develop a new infection during treatment with CIMZIA should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for immunocompromised patients, and appropriate antimicrobial therapy should be initiated. Appropriate empiric antifungal therapy should also be considered while a diagnostic workup is performed for patients who develop a serious systemic illness and reside or travel in regions where mycoses are endemic.
During controlled and open-labeled portions of CIMZIA studies of Crohn's disease and other diseases , malignancies (excluding non-melanoma skin cancer) were observed at a rate of 0.5 per 100 patient-years among 4,650 CIMZIA-treated patients versus a rate of 0.6 per 100 patient-years among 1,319 placebo-treated patients. In studies of CIMZIA for Crohn's disease and other investigational uses, there was one case of lymphoma among 2,657 CIMZIA-treated patients and one case of Hodgkin lymphoma among 1,319 placebo-treated patients. In CIMZIA RA clinical trials (placebo-controlled and open label) a total of three cases of lymphoma were observed among 2,367 patients. This is approximately 2-fold higher than expected in the general population. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of TNF blocker therapy in the development of malignancies is not known.
Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. CIMZIA has not been formally studied in patients with CHF. Exercise caution when using CIMZIA in patients who have heart failure and monitor them carefully.
Symptoms compatible with hypersensitivity reactions, including angioedema, dyspnea, hypotension, rash, serum sickness, and urticaria, have been reported rarely following CIMZIA administration. If such reactions occur, discontinue further administration of CIMZIA and institute appropriate therapy.
Hepatitis B Reactivation
Use of TNF blockers, including CIMZIA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. Some cases have been fatal. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating CIMZIA therapy. Exercise caution in prescribing CIMZIA for patients identified as carriers of HBV, with careful evaluation and monitoring prior to and during treatment. In patients who develop HBV reactivation, discontinue CIMZIA and initiate effective anti-viral therapy with appropriate supportive treatment.
Use of TNF blockers, including CIMZIA, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease. Rare cases of neurological disorders, including seizure disorder, optic neuritis, and peripheral neuropathy have been reported in patients treated with CIMZIA. Exercise caution in considering the use of CIMZIA in patients with these disorders.
Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia (e.g., leukopenia, pancytopenia, thrombocytopenia) has been infrequently reported with CIMZIA. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on CIMZIA. Consider discontinuation of CIMZIA therapy in patients with confirmed significant hematologic abnormalities.
An increased risk of serious infections has been seen in clinical trials of other TNF blocking agents used in combination with anakinra or abatacept. Formal drug interaction studies have not been performed with rituximab or natalizumab; however because of the nature of the adverse events seen with these combinations with TNF blocker therapy, similar toxicities may also result from the use of CIMZIA in these combinations. Therefore, the combination of CIMZIA with anakinra, abatcept, rituximab, or natalizumab is not recommended. Interference with certain coagulation assays has been detected in patients treated with CIMZIA. There is no evidence that CIMZIA therapy has an effect on in vivo coagulation. CIMZIA may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities.
Treatment with CIMZIA may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if symptoms of lupus-like syndrome develop.
Do not administer live vaccines or attenuated vaccines concurrently with CIMZIA.
In controlled Crohn's clinical trials, the most common adverse events that occurred in greater than or equal to 5% of CIMZIA patients (n=620) and more frequently than with placebo (n=614) were upper respiratory infection (20% CIMZIA, 13% placebo), urinary tract infection (7% CIMZIA, 6% placebo), and arthralgia (6% CIMZIA, 4% placebo). The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 8% for CIMZIA and 7% for placebo.
In controlled RA clinical trials, the most common adverse events that occurred in greater than or equal to 3% of patients taking CIMZIA 200 mg every other week with concomitant methotrexate (n=640) and more frequently than with placebo with concomitant methotrexate (n=324) were upper respiratory tract infection (6% CIMZIA, 2% placebo), headache (5% CIMZIA, 4% placebo), hypertension (5% CIMZIA, 2% placebo), nasopharyngitis (5% CIMZIA, 1% placebo), back pain (4% CIMZIA, 1% placebo), pyrexia (3% CIMZIA, 2% placebo), pharyngitis (3% CIMZIA, 1% placebo), rash (3% CIMZIA, 1% placebo), acute bronchitis (3% CIMZIA, 1% placebo), fatigue (3% CIMZIA, 1% placebo). Hypertensive adverse reactions were observed more frequently in patients receiving CIMZIA than in controls. These adverse reactions occurred more frequently among patients with a baseline history of hypertension and among patients receiving concomitant corticosteroids and non-steroidal anti-inflammatory drugs. Patients receiving CIMZIA 400mg as monotherapy every 4 weeks in RA controlled clinical trials had similar adverse reactions to those patients receiving CIMZIA 200mg every other week. The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 5% for CIMZIA and 2.5% for placebo.
Please visit http://cimzia.com/crohns-disease/pdf/Prescribing_Information.pdf for full prescribing information.
UCB, Brussels, Belgium (www.ucb.com) is a biopharmaceutical company dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing approximately 10 000 people in over 40 countries, UCB generated revenue of EUR 3.6 billion in 2008. UCB is listed on Euronext Brussels (symbol: UCB).
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. Such statements are subject to risks and uncertainties that may cause actual results to be materially different from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, effects of future judicial decisions, changes in regulation, exchange rate fluctuations and hiring and retention of its employees.
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