Improved outcomes for fistula closures observed in PRECiSE 2 trial under maintenance therapy with stable dosing of CIMZIA® every four weeks
HOLLYWOOD, FL, USA | December 5, 2008 | Data presented this week by UCB at Advances in Inflammatory Bowel Diseases 2008, the Crohn’s & Colitis Foundation’s Clinical & Research Conference, demonstrated more than half (53.6%) of those moderate to severe Crohn’s disease patients who had open fistulas at baseline had closure of fistulas by Week 26 following short-term induction therapy with CIMZIA® (certolizumab pegol) – the only PEGylated anti-TNFa (Tumor Necrosis Factor alpha). Additionally, the data showed that fistulas in most of these patients treated continuously with CIMZIA® stayed closed with a majority of patients achieving clinical remission.
CIMZIA® is indicated 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 had an inadequate response to conventional therapy.
Fistulas are abnormal tunnels or tracts that develop in response to inflammation and ulceration associated with CD. Fistulas may originate from the intestinal tract or rectum and connect to the bladder, vagina, skin or other intestinal areas. If left untreated, fistulas may cause a decrease in absorption of nutrients from food, abnormal drainage of bowel contents into other organs, or a life-threatening infection or abscess.
These results focus on a subpopulation of adult, moderate to severe Crohn’s disease patients with fistulizing disease who took part in PRECiSE 2, the Phase III maintenance study of CIMZIA®. In PRECiSE 2, patients received an open-label induction with subcutaneous CIMZIA® 400 mg at Weeks 0, 2 and 4. Those who responded to treatment (reduction of less than or equal to 100 points from baseline on the Crohn’s Disease Activity Index (CDAI)) at Week 6 were randomized to CIMZIA® 400 mg or placebo every 4 weeks until Week 24 with final assessment at Week 26. Of the patients in the intent-to-treat population who responded to CIMZIA® induction, 13.6% (58 of 425) had open fistulas at baseline: 30 of these patients were randomized to placebo and 28 to CIMZIA® 400 mg.
Among patients who had fistula closure (the absence of drainage on gentle compression) during the study, a higher proportion of those treated continuously with CIMZIA® 400 mg (73.3%) maintained 50% fistula closure at Week 26 versus patients receiving placebo (38.5%). More than two-thirds (66.7%) of the CIMZIA®-treated patients maintained 100% closure of fistulas compared to placebo (30.8%) at Week 26.
Of the adult, moderate to severe Crohn’s disease patients with open fistula at baseline, a higher percentage of patients in the CIMZIA® versus placebo group achieved CDAI response of 100 points from baseline (71.4% versus 33.3%, respectively) and CDAI remission (53.6% versus 20%, respectively). The CDAI is a patient/physician questionnaire which incorporates eight CD-related variables. Scores of <150 indicate remission, and scores of >450 indicate severe illness along the 600 point scale.
Health-related quality of life measurements was assessed by the 32-question Inflammatory Bowel Disease Questionnaire (IBDQ), which measures social, systemic, emotional and bowel related symptoms on a scale of 32 to 224 points (higher scores denote better well-being). In this study, mean change in IBDQ scores from baseline were greater in CIMZIA® (36.7 points) than placebo-treated groups (20.7 points).
There was a higher rate of discontinuation from treatment in the placebo group (50%) compared to the CIMZIA® group (14%). In the PRECiSE 2 trial, the most common AEs in the CIMZIA® group were headache (7%), nasopharyngitis (6%) and cough (6%). For the placebo group AEs included headache (7%), nasopharyngitis (4%) and cough (<1%). The incidence of injection site pain was lower in the CIMZIA® group (<1%) compared to in the placebo group (5%). Serious AEs were broadly similar in both groups (6% CIMZIA® versus 7% placebo). Three percent and less than 1% respectively were due to infection or infestation; 2% and 4% respectively were due to gastrointestinal disorder.
About the PRECiSE Clinical Trial Program
PRECiSE, 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. The safety and tolerability of CIMZIA® was consistent with that expected of an anti-TNF agent. 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.
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 results 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 alpha). 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 http://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.
About UCB
UCB 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 approximately 12,000 people in more than 40 countries, UCB achieved revenue of 3.6 billion euro in 2007. UCB is listed on NYSE Euronext (symbol: UCB). Worldwide headquarters is located in Brussels, Belgium; U.S. headquarters is located in Atlanta, Georgia. For more information about UCB, visit www.ucb-group.com.
SOURCE: UCB
Post Views: 53
Improved outcomes for fistula closures observed in PRECiSE 2 trial under maintenance therapy with stable dosing of CIMZIA® every four weeks
HOLLYWOOD, FL, USA | December 5, 2008 | Data presented this week by UCB at Advances in Inflammatory Bowel Diseases 2008, the Crohn’s & Colitis Foundation’s Clinical & Research Conference, demonstrated more than half (53.6%) of those moderate to severe Crohn’s disease patients who had open fistulas at baseline had closure of fistulas by Week 26 following short-term induction therapy with CIMZIA® (certolizumab pegol) – the only PEGylated anti-TNFa (Tumor Necrosis Factor alpha). Additionally, the data showed that fistulas in most of these patients treated continuously with CIMZIA® stayed closed with a majority of patients achieving clinical remission.
CIMZIA® is indicated 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 had an inadequate response to conventional therapy.
Fistulas are abnormal tunnels or tracts that develop in response to inflammation and ulceration associated with CD. Fistulas may originate from the intestinal tract or rectum and connect to the bladder, vagina, skin or other intestinal areas. If left untreated, fistulas may cause a decrease in absorption of nutrients from food, abnormal drainage of bowel contents into other organs, or a life-threatening infection or abscess.
These results focus on a subpopulation of adult, moderate to severe Crohn’s disease patients with fistulizing disease who took part in PRECiSE 2, the Phase III maintenance study of CIMZIA®. In PRECiSE 2, patients received an open-label induction with subcutaneous CIMZIA® 400 mg at Weeks 0, 2 and 4. Those who responded to treatment (reduction of less than or equal to 100 points from baseline on the Crohn’s Disease Activity Index (CDAI)) at Week 6 were randomized to CIMZIA® 400 mg or placebo every 4 weeks until Week 24 with final assessment at Week 26. Of the patients in the intent-to-treat population who responded to CIMZIA® induction, 13.6% (58 of 425) had open fistulas at baseline: 30 of these patients were randomized to placebo and 28 to CIMZIA® 400 mg.
Among patients who had fistula closure (the absence of drainage on gentle compression) during the study, a higher proportion of those treated continuously with CIMZIA® 400 mg (73.3%) maintained 50% fistula closure at Week 26 versus patients receiving placebo (38.5%). More than two-thirds (66.7%) of the CIMZIA®-treated patients maintained 100% closure of fistulas compared to placebo (30.8%) at Week 26.
Of the adult, moderate to severe Crohn’s disease patients with open fistula at baseline, a higher percentage of patients in the CIMZIA® versus placebo group achieved CDAI response of 100 points from baseline (71.4% versus 33.3%, respectively) and CDAI remission (53.6% versus 20%, respectively). The CDAI is a patient/physician questionnaire which incorporates eight CD-related variables. Scores of <150 indicate remission, and scores of >450 indicate severe illness along the 600 point scale.
Health-related quality of life measurements was assessed by the 32-question Inflammatory Bowel Disease Questionnaire (IBDQ), which measures social, systemic, emotional and bowel related symptoms on a scale of 32 to 224 points (higher scores denote better well-being). In this study, mean change in IBDQ scores from baseline were greater in CIMZIA® (36.7 points) than placebo-treated groups (20.7 points).
There was a higher rate of discontinuation from treatment in the placebo group (50%) compared to the CIMZIA® group (14%). In the PRECiSE 2 trial, the most common AEs in the CIMZIA® group were headache (7%), nasopharyngitis (6%) and cough (6%). For the placebo group AEs included headache (7%), nasopharyngitis (4%) and cough (<1%). The incidence of injection site pain was lower in the CIMZIA® group (<1%) compared to in the placebo group (5%). Serious AEs were broadly similar in both groups (6% CIMZIA® versus 7% placebo). Three percent and less than 1% respectively were due to infection or infestation; 2% and 4% respectively were due to gastrointestinal disorder.
About the PRECiSE Clinical Trial Program
PRECiSE, 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. The safety and tolerability of CIMZIA® was consistent with that expected of an anti-TNF agent. 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.
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 results 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 alpha). 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 http://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.
About UCB
UCB 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 approximately 12,000 people in more than 40 countries, UCB achieved revenue of 3.6 billion euro in 2007. UCB is listed on NYSE Euronext (symbol: UCB). Worldwide headquarters is located in Brussels, Belgium; U.S. headquarters is located in Atlanta, Georgia. For more information about UCB, visit www.ucb-group.com.
SOURCE: UCB
Post Views: 53
