Healthcare Industry News: Inflammatory Bowel Disease
News Release - October 6, 2008
CIMZIA(R) (certolizumab pegol) Reduces Intestinal Lesions and Induces Endoscopic Improvement in Crohn's PatientsMore than 60 percent of moderate to severe patients achieved endoscopic response and more than 40 percent achieved endoscopic remission at Week 10 in data from a 54-week open-label study presented at the American College of Gastroenterology (ACG) Annual Scientific Meeting
ORLANDO, Fla., Oct. 6 -- (Healthcare Sales & Marketing Network) -- UCB today presented data from a large, prospective study investigating endoscopic improvement in Crohn's disease (CD) with a biologic compound. The data presented at the American College of Gastroenterology Annual Scientific Meeting demonstrates that CIMZIA® (certolizumab pegol) -- the only PEGylated anti-TNF alpha (Tumor Necrosis Factor alpha) -- significantly improved endoscopic lesions and induced endoscopic response (as assessed by the Crohn's Disease Endoscopic Index of Severity (CDEIS)) within ten weeks of treatment in more than 60 percent of the moderate to severe Crohn's disease patients studied.
"Even though the study was uncontrolled, it is interesting to see evidence of endoscopic improvement so early in the course of treatment," said lead study investigator Jean-Frederic Colombel, M.D., Hepatogastroenterology, CHRU Lille, the Regional Hospital Center of the University of Lille, France. "Long-term follow up of these patients will allow us to determine the clinical impact of endoscopic improvement on modifying the course of the disease."
Data from the 54-week, open-label Phase IIIb MUSIC trial showed significant improvement by Week 10 in CDEIS scores, the primary endpoint of the study. Scores dropped from 14.7 to 8.2 -- a reduction of 6.5 points, or 44 percent improvement compared to baseline. The CDEIS, which ranges from 0 to 44 points, is used to assess the presence of mucosal lesions associated with inflammation along the lining of the gut (ileum, colon and rectum). Mucosal healing has been associated with a lower rate of hospitalization and lower need for surgery.
Improvements in secondary endpoints, including endoscopic remission and response rates, histological CD score, clinical remission rate and decrease in C-reactive protein level, also were achieved in this study. Specifically, the Crohn's Disease Activity Index (CDAI), showed nearly half (46 percent) of the patients achieved clinical remission at Week 10.
More than 40% of study participants achieved endoscopic remission (CDEIS score <6 points) by Week 10. Meanwhile, more than 60% of the patients responded (defined as a reduction of 5 or more points in CDEIS scores) to CIMZIA treatment. Significant improvements also were shown by histological analysis.
"These data underscore the importance of CIMZIA as a comprehensive treatment option for people fighting Crohn's disease," said Dr. Colombel.
CIMZIA is approved for reducing the signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderate to severe active disease who have an inadequate response to conventional therapy. CIMZIA, manufactured by UCB, was approved by the U.S. Food and Drug Administration on April 22, 2008. The approval was based on safety and efficacy data from clinical trials in more than 1,500 patients with Crohn's disease.
The most common adverse events seen in this study were headache, arthralgia, nausea and anal fissure. The incidence of serious adverse events (SAEs) was nine percent and there were no unexpected safety concerns identified during this study.
The MUSIC trial (endoscopic MUcoSal Improvement in patients with active Crohn's disease treated with certolizumab pegol) is an 89-patient Phase IIIb open-label 54-week trial designed to evaluate the efficacy of certolizumab pegol on resolving the intestinal mucosal lesions in patients with active Crohn's disease. CIMZIA was administered subcutaneously at Weeks 0, 2, 4 and then every four weeks. Adverse events (AEs) were assessed at each visit. The change in CDEIS score from baseline to Week 10 was -6.5 points (from 14.7 to 8.2 on the 44-point scale), which was highly significant (95% confidence interval: -7.6 to -5.3; P<0.0001). In addition to remission and responses rates with CIMZIA, secondary endpoints included histological scores of sections of the gut, which also showed significant improvement compared to baseline: -2.7 points (95% confidence interval: -3.5 to -1.9) for the colon, and -2.8 points (95% confidence interval -3.9 to -1.8) for the ileum. (Note: in this context, a confidence interval that does not include zero is considered to indicate a statistically significant change).
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). 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-TNFa (Tumour Necrosis Factor). CIMZIA is an effective, rapid-acting and long lasting treatment option for people with RA. CIMZIA has a high affinity for human TNF-alpha, selectively neutralizing 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 diseases. UCB is developing CIMZIA in rheumatoid arthritis and other autoimmune disease indications. CIMZIA was approved in April 2008 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. CIMZIA is a registered trademark of UCB PHARMA S.A. For full prescribing information, please visit www.ucb-group.com.
Tuberculosis (frequently disseminated or extrapulmonary at clinical presentation), invasive fungal infections, and other opportunistic infections, have been observed in patients receiving CIMZIA. Some of these infections have been fatal. Anti-tuberculosis treatment of patients with latent tuberculosis infection reduces the risk of reactivation in patients receiving treatment with TNF blockers such as CIMZIA. However, active tuberculosis has developed in patients receiving CIMZIA whose tuberculin test was negative. Evaluate patients for tuberculosis risk factors and test for latent tuberculosis infection prior to initiating CIMZIA and during therapy. Initiate treatment of latent tuberculosis infection prior to therapy with CIMZIA. Monitor patients receiving CIMZIA for signs and symptoms of active tuberculosis, including patients who tested negative for latent tuberculosis infection. Consider anti-tuberculosis therapy prior to initiation of CIMZIA in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.
Serious infections, sepsis, and cases of opportunistic infections, including fatalities, have been reported in patients receiving TNF blockers, including CIMZIA. Infections have been reported in patients receiving CIMZIA alone or in conjunction with immunosuppressive agents. Do not initiate treatment with CIMZIA in patients with active infections, including chronic or localized infections. Patients who develop a new infection while undergoing treatment with CIMZIA should be monitored closely. Discontinue administration of CIMZIA if a patient develops a serious infection. Exercise caution when considering the use of CIMZIA in patients with a history of recurrent infection, concomitant immunosuppressive therapy, or underlying conditions that may predispose them to infections, or patients who have resided in regions where tuberculosis and histoplasmosis are endemic.
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. Patients who are carriers of HBV and require treatment with CIMZIA should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, discontinue CIMZIA and initiate effective anti-viral therapy with appropriate supportive treatment.
During controlled and open-labeled portions of CIMZIA studies of Crohn's disease and other investigational uses, malignancies were observed at a rate (95% confidence interval) of 0.6 (0.4, 0.8) per 100 patient-years among 4,650 CIMZIA-treated patients verses a rate of 0.6 (0.2, 1.7) per 100 patient-years among 1,319 placebo-treated patients. The size of the control group and limited duration of the controlled portions of the studies preclude the ability to draw firm conclusions. 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. The potential role of TNF blocker therapy in the development of malignancies is not known.
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.
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; the causal relationship to CIMZIA remains unclear. 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. The causal relationship of these events to CIMZIA remains unclear. 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.
Serious infections were seen in clinical studies with concurrent use of anakinra (an interleukin-1 antagonist) and another TNF blocker, with no added benefit. Therefore, the combination of CIMZIA and anakinra 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.
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.
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.
CIMZIA should be administered by a healthcare professional.
UCB, Brussels, Belgium (www.ucb-group.com) is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing around 12,000 people in over 40 countries, UCB achieved revenue of 3.6 billion euro in 2007. 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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