New Cimzia (certolizumab pegol) Data Show a Significant, Rapid Clinical Response and Reduced Disease Activity Among Diverse Patient Populations With Active Rheumatoid Arthritis (RA)
- The REALISTIC phase IIIb
clinical trial demonstrated statistically significant improvements
among a broad active RA patient population representing routine
clinical practice meeting its primary endpoint at week 12
- Trial results showed Cimzia® provided rapid improvements in disease activity and physical function as early as week 2 of treatment and through week 12
ATLANTA, Nov. 9, 2010 /PRNewswire/ -- The addition of Cimzia® (certolizumab pegol; CZP) to current therapy was associated with a rapid clinical response, improved function and reduced disease activity in a diverse group of adult rheumatoid arthritis (RA) patients reflecting those seen in daily clinical practice (including those with prior TNF-inhibitor use). These positive clinical trial data were presented during the American College of Rheumatology's (ACR) 2010 Annual Scientific Meeting in Atlanta, November 7-11. Cimzia® is approved for the treatment of adults with moderately to severely active rheumatoid arthritis.
"There are patients who live with little relief from the painful symptoms of rheumatoid arthritis due to failed therapies or the severity of the condition," said Roy Fleischmann, MD, clinical professor in the Department of Internal Medicine at the University of Texas Southwestern Medical School. "These data emphasize that treatment with Cimzia® can substantially provide rapid improvements and help reduce disease activity regardless of the patient's disease history in many of these patients."
The data presented were from the REALISTIC (RA Evaluation in Subjects Receiving TNF Inhibitor Certolizumab Pegol) multicenter phase IIIb study, which included a 12-week, randomized, double-blind (DB), placebo-controlled phase followed by an open-label extension (OLE) (greater than or equal to 16 weeks). REALISTIC was designed to investigate the safety and efficacy of CZP in a broad patient population with active RA more closely resembling routine clinical practice, versus the pivotal trials, including patients with/without prior TNF-inhibitor exposure, with/without concomitant methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs); and varying lengths of disease duration.
The primary endpoint of an ACR20 score at week 12 was met. At week 12, more than half (51.1%) of patients in the CZP treatment group achieved ACR20 response versus the control group (25.9%). Additional efficacy evaluated in the trial included ACR50/70 response rates, as well as the DAS28[CRP] disease activity score and the Health Assessment Questionnaire-Disability Index (HAQ-DI) measuring physical function.
Clinical responses among patients in the CZP treatment group were rapid. ACR 20/50 responses were significantly superior to control (31.8% vs 8.5% and 9.6% vs 1.4%, p<0.001 for both) from the first time point (week 2) onwards. Significant improvements in DAS28[CRP] were reported among patients treated with CZP vs. the placebo group. In addition, CZP patients reported rapid and significant improvements in HAQ-DI vs. placebo at the first time point measured (week 2).
Similar ACR20 responses were seen across the various patient populations regardless of baseline disease duration or activity; baseline use of methotrexate; or prior use of TNF- inhibitors. ACR50 and ACR70 responses at week 12 were 26.6% and 13% for patients treated with CZP compared to the placebo group (9.9% and 2.8% respectively).
Treatment with CZP was generally well tolerated. Adverse and serious adverse event rates were comparable between CZP and placebo treatment groups with no new safety signals observed through week 12. The most common serious infections were lower respiratory tract and lung infections. The most common adverse events were infections and infestations, musculoskeletal and connective tissue disorders, and nervous system disorders.
For full study information, please see: http://www.abstracts2view.com/acr/titleindex.php?num=E&page=2
For further information
Bert Kelly, Communication and Public Relations Manager, UCB
Sarah Fox, Cooney/Waters Group
About Rheumatoid Arthritis
RA affects more than 1.3 million Americans, and it is estimated that 5 million people suffer from RA globally. Prevalence is not split evenly between genders, since women are three times more likely to be affected than men. Although RA can affect people of all ages, the onset of the disease usually occurs between 35-55 years of age.
About REALISTIC Study
REALISTIC (RA Evaluation in Subjects Receiving TNF Inhibitor Certolizumab Pegol) is a multicenter phase IIIb trial in patients with active rheumatoid arthritis who have shown inadequate response to disease-modifying antirheumatic drugs, including patients with/without prior TNF-inhibitor exposure, with/without concomitant methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs); and varying lengths of disease duration. The study demonstrated that – in a diverse group of RA patients reflecting those seen in daily clinical practice (including those with prior TNF- inhibitor use) – addition of CZP to current therapy was associated with a rapid clinical response consistent in all strata, improved function and reduced disease activity.
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 certolizumab pegol 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. Certolizumab Pegol 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 certolizumab pegol use and during therapy. Treatment for latent infection should be initiated prior to certolizumab pegol 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 certolizumab pegol 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 certolizumab pegol, 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 certolizumab pegol is a member. Certolizumab pegol 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 certolizumab pegol should not be initiated in patients with an active infection, including clinically important localized infections. Certolizumab pegol should be discontinued if a patient develops a serious infection or sepsis. Patients who develop a new infection during treatment with certolizumab pegol 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 certolizumab pegol 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 certolizumab pegol-treated patients versus a rate of 0.6 per 100 patient-years among 1,319 placebo-treated patients. In studies of certolizumab pegol for Crohn's disease and other investigational uses, there was one case of lymphoma among 2,657 certolizumab pegol-treated patients and one case of Hodgkin lymphoma among 1,319 placebo- treated patients. In certolizumab pegol 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 certolizumab pegol 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. Certolizumab pegol has not been formally studied in patients with CHF. Exercise caution when using certolizumab pegol 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 certolizumab pegol administration. If such reactions occur, discontinue further administration of certolizumab pegol and institute appropriate therapy.
Hepatitis B Reactivation
Use of TNF blockers, including certolizumab pegol, 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 certolizumab pegol therapy. Exercise caution in prescribing certolizumab pegol for patients identified as carriers of HBV, with careful evaluation and monitoring prior to and during treatment. In patients who develop HBV reactivation, discontinue certolizumab pegol and initiate effective anti-viral therapy with appropriate supportive treatment.
Use of TNF blockers, including certolizumab pegol, 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 certolizumab pegol. Exercise caution in considering the use of certolizumab pegol 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 certolizumab pegol. 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 certolizumab pegol. Consider discontinuation of certolizumab pegol 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 certolizumab pegol in these combinations. Therefore, the combination of certolizumab pegol with anakinra, abatacept, rituximab, or natalizumab is not recommended. Interference with certain coagulation assays has been detected in patients treated with certolizumab pegol. There is no evidence that certolizumab pegol therapy has an effect on in vivo coagulation. Certolizumab pegol may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities.
Treatment with certolizumab pegol 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 certolizumab pegol.
In controlled Crohn's clinical trials, the most common adverse events that occurred in greater than or equal to 5% of certolizumab Pegol patients (n=620) and more frequently than with placebo (n=614) were upper respiratory infection (20% certolizumab pegol, 13% placebo), urinary tract infection (7% certolizumab pegol, 6% placebo), and arthralgia (6% certolizumab pegol, 4% placebo). The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 8% for certolizumab pegol 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 certolizumab pegol 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% certolizumab pegol, 2% placebo), headache (5% certolizumab pegol, 4% placebo), hypertension (5% certolizumab pegol, 2% placebo), nasopharyngitis (5% certolizumab pegol, 1% placebo), back pain (4% certolizumab pegol, 1% placebo), pyrexia (3% certolizumab pegol, 2% placebo), pharyngitis (3% certolizumab pegol, 1% placebo), rash (3% certolizumab pegol, 1% placebo), acute bronchitis (3% certolizumab pegol,1% placebo), fatigue (3% certolizumab pegol, 1% placebo). Hypertensive adverse reactions were observed more frequently in patients receiving certolizumab pegol than in controls. These adverse reactions occurred more frequently among patients with a baseline history of hypertension and among patients receiving concomitant corticosteroids and nonsteroidal anti-inflammatory drugs. Patients receiving certolizumab pegol 400mg as monotherapy every 4 weeks in RA controlled clinical trials had similar adverse reactions to those patients receiving certolizumab pegol 200mg every other week. The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 5% for certolizumab pegol and 2.5% for placebo.
Please see full prescribing information at www.cimzia.com before prescribing.
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
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.
CONTACT: Bert Kelly,
Communication and Public Relations Manager, UCB, +1-404-784-6303,
Bert.Kelly@ucb.com; or Sarah Fox, Cooney/Waters Group,
Web Site: http://www.cimzia.com
Posted: November 2010