ATLANTA, Oct. 18 /PRNewswire/ -- Findings from the PRECiSE 3 (P3) open label extension study for Cimzia® (certolizumab pegol; CZP), demonstrating the longest continuously running maintenance trial for an anti-TNF in Crohn's disease, will be exhibited at the 2010 Annual Scientific Meeting of the American College of Gastroenterology (ACG), taking place in San Antonio from October 15 – 20. Additionally, long-term efficacy data from the PRECiSE 4 (P4) clinical trial also will be presented at the meeting.
Results of the P3 open-label extension study showed that continuous therapy with Cimzia provided long-term remission for more than 4.5 years in patients who initially responded to Cimzia in the six-month PRECiSE 2 study (P2). In the PRECISE 2 double blind, placebo controlled clinical trial, 48% of patients achieved remission at six months. Sustained long-term remission was observed among patients who had previous anti-TNF exposure (77% remission), as well as anti-TNF naive patients (73% remission).
Similarly, results of the P4 open-label extension study showed long-term remission rates among patients treated with Cimzia (naive – 63%; non-naive – 50%). For some patients, disease remission was achieved in as early as 4 weeks (38% of patient population). Additionally, the data demonstrates that patients who are losing response to Cimzia or experience an interruption in therapy can be recaptured with one additional dose of Cimzia. The data suggests re-induction therapy may have long-term benefits in helping patients who experienced drug interruption or loss of initial response achieve response and maintain remission.
"Collectively, these Cimzia data findings are important for patients living with moderate to severe Crohn's disease and the gastroenterologists treating them, as long-term remission is the ultimate goal of treatment," said Cem Kayhan, MD, Medical Director at UCB. "It also is encouraging that Cimzia data demonstrated a simple recapture strategy to help patients who may have active Crohn's disease and begin to lose response achieve response and maintain remission."
Cimzia is indicated for reducing the 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.
PRECiSE 3 Study:
PRECiSE 3 is a long-term open-label continuation of the Phase III PRECiSE 2 (P2) subpopulation assessing the long-term efficacy, safety and tolerability of CZP for more than 4.5 years. PRECiSE 3 was open to patients from the Cimzia treatment arm of P2. At the end of the P2 study (week 26), 48% of Cimzia treated patients were in remission. In P3, patients received a 400mg dose of Cimzia every four weeks.
Disease remission was measured using the Harvey-Bradshaw Index (HBI)* at 1, 2, 3, 4, 4.5 and 5 years among all 141 patients, and, separately, a subset of 114 patients with no previous infliximab (IFX) exposure. These data support the use of Cimzia long term in moderate to severe Crohn's disease patients.
Remission rates, calculated using observed case (OC) analyses were as follows:
PRECiSE 4 Study:
PRECiSE 4 is a long-term open-label continuation of the PRECISE clinical program, including the P2 subpopulation assessing the long-term efficacy and safety of Cimzia in patients who were withdrawn from P2 due to Crohn's disease exacerbation. PRECiSE 4 was open to patients from the Cimzia or placebo arm of P2. Patients from the treatment arm of P2 received an additional 400mg dose at week 2 and continued 400mg every four weeks thereafter. Patients from the placebo arm received 400mg doses at weeks 0, 2 and 4 and every 4 weeks thereafter.
Disease response and remission were measured using the HBI at 1, 2, 3 and 4 years among all 124 patients, and, separately, a subset of 84 patients with no previous IFX exposure. These data support the use of Cimzia long term in moderate to severe Crohn's disease patients who experienced Crohn's disease exacerbation.
Remission rates, calculated using OC analyses were as follows:
Remission rates over four years were comparable among CD patients previously enrolled in the P2 Phase III study in patients previously treated with IFX and IFX-naive patients.
* The Harvey-Bradshaw Index is a simplified, closely correlated version of the Crohn's Disease Activity Index (CDAI) used to measure Crohn's disease activity over a 24-hour period based on clinical parameters. Serious and sometimes fatal side effects have been reported with CIMZIA. These include tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis) and infections due to other opportunistic pathogens. Lymphoma and other malignancies also have been reported in children and adolescents. CIMZIA is not indicated for use in pediatric patients. In pre-marketing controlled trials of all patient populations combined the most common adverse reactions (greater than or equal to 8%) were upper respiratory infections (18%), rash (9%) and urinary tract infections (8%).
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 are 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. For more information on the PRECiSE program, visit: http://tinyurl.com/2avpwg5.
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.
Certolizumab pegol is the only PEGylated anti-TNF (Tumor Necrosis Factor). It 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. The U.S. Food and Drug Administration (FDA) has approved certolizumab pegol 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. It is also approved for the treatment of adults with moderately to severely active rheumatoid arthritis. Certolizumab pegol 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.
Please visit www.cimzia.com for full prescribing information for CIMZIA®.
IMPORTANT SAFETY INFORMATION
Risk of Serious Infections and Malignancy
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:
- Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before CIMZIA use and during therapy. Treatment for latent infection should be initiated prior to CIMZIA use.
- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness .
- Bacterial, viral and other infections due to opportunistic pathogens.
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.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member. CIMZIA is not indicated for use in pediatric patients.
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.
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy less than or equal to 18 years of age), of which CIMZIA is a member. Approximately half of the cases were lymphoma (including Hodgkin's and non-Hodgkin's lymphoma, while the other cases represented a variety of different malignancies and included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.
Cases of acute and chronic leukemia have been reported with TNF-blocker use. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for developing leukemia.
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 central nervous system demyelinating disease, including multiple sclerosis, and with peripheral demyelinating disease, including Guillain-Barre syndrome. 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 see full prescribing information at www.cimzia.com before prescribing.
For further Information:
Bert Kelly, Communication and Public Relations Manager, UCB
Sarah Fox, Cooney/Waters Group
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 8 000 people in about 40 countries, the company generated revenue of EUR 3.1 billion in 2009. UCB is listed on Euronext Brussels (symbol: UCB).
Forward looking statement
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