New data from REALISTIC study showed Cimzia® (certolizumab pegol) provided rapid and sustained efficacy, over 28 weeks, in a broad population of patients with moderate to severe rheumatoid arthritis (RA) including those who discontinued prior anti-TNF the
BRUSSELS/CHICAGO, 7th Nov, 2011 – UCB today announced new data which showed that treatment with Cimzia® (certolizumab pegol) was associated with a rapid and sustained clinical response over 28 weeks in a broad population of moderate to severe rheumatoid arthritis (RA) patients.1 The results, presented during the American College of Rheumatology’s (ACR) 2011 Annual Scientific Meeting in Chicago, November 5-9, are from an open-label extension of the REALISTIC (RA EvALuation In Subjects receiving TNF Inhibitor Certolizumab pegol) study, and demonstrated consistent efficacy and improved physical function irrespective of prior anti-TNF therapy, concomitant disease modifying antirheumatic drugs (DMARDs), or duration of disease.1
“These results are encouraging because they show that the rapid improvement in disease activity, as a result of the clinical response to certolizumab pegol, is sustained in patients who failed on previous therapies,” said co-lead investigator Maxime Dougados, MD, Professor of Rheumatology, Rene Descartes University, Department of Rheumatology B, Cochin Hospital, Paris. “The data from the REALISTIC study is of interest because the trial included a broad RA patient population, which reflects aspects of the diversity we see day-to-day in clinical practice.”*
Patients (n=1,063) who had participated in the 12-week randomized, double-blind, placebo-controlled REALISTIC study, either on certolizumab pegol or placebo plus DMARD, were given the option of participating in an open-label extension (OLE) study for a further 16 weeks (28 weeks in total). In total 954 patients entered the extension study and were given certolizumab pegol, including those patients that were previously treated with placebo in the 12-week controlled period of the trial. At Week 28, positive efficacy results were comparable between patients who had received certolizumab pegol for 28 weeks in total and those that switched from placebo to certolizumab pegol after 12 weeks.1*
A total of 770 patients who had previously been given certolizumab pegol, and 184 patients who had been given placebo, entered the extension study. At 28 weeks, ACR20 response rates were 59.7% (n=770) for patients taking certolizumab pegol for 28 weeks and 53.3% (n=184) for those taking it for 16 weeks following the initial placebo phase. DAS28(CRP) remission (DAS28 <2.6) was achieved in 22.9% and 21.7% (p=no significant difference) of patients, respectively, while DAS28(ESR) remission (DAS28 <2.6) was achieved in 15.2% and 11.4% (p=no significant difference) of completers, respectively.1
Treatment with certolizumab pegol was associated with rapid and consistent efficacy and sustained improvements in disease activity and physical function up to Week 28 in a diverse group of patients with RA closely resembling those seen in routine clinical practice. Rapid efficacy was also seen across patients receiving concomitant DMARDs at baseline, regardless of the number or type of concomitant DMARDs.1
In the placebo controlled portion of the trial, 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. Incidence of adverse in the OLE phase was 305.8 events per 100 patient years in patients randomised to certolizumab pegol in the double blind period compared to 406.2 in patients randomised to placebo and switched to certolizumab pegol in the OLE. Incidence of serious adverse events per 100 patient years was 14.7 vs 16.3, respectively.
* Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
For further Information:
Scott Fleming, Global Communications Manager – Immunology
T +44 770.277.7378, scott.fleming@ucb.com
Andrea Levin, Senior PR Manager, US Communications and Public Relations
T +1 770 970 8352, andrea.Levin@ucb.com
Antje Witte, Investor Relations, UCB
T +32.2.559.9414, antje.witte@ucb.com
About REALISTIC
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 Cimzia® to current therapy was associated with a rapid clinical response consistent in all strata, improved function and reduced disease activity.
A sub-analysis investigated Cimzia® as monotherapy or concomitantly with DMARDs in subgroups of patients with or without prior TNF inhibitor use. Active RA patients with inadequate response to ≥1 DMARD were randomised 4:1 to Cimzia® 400mg at Weeks 0, 2 and 4 followed by 200mg every 2 weeks or placebo injection (control) every 2 weeks + current therapy. Primary outcome was ACR20 at Week 12. Randomisation was stratified by prior TNF inhibitor use, concomitant use of methotrexate (MTX), and disease duration (<2 y vs ≥2 y). Treatment effect differences between subgroups were assessed by interactions (treatment by covariate) at 10% significance level.
Active RA patients with inadequate response to ≥1 DMARD were randomised 4:1 to CZP 400mg (n=851) at Weeks 0, 2 and 4 followed by 200mg every 2 weeks or placebo injection (control, n=212) every 2 weeks added to current therapy. PROs included fatigue (Fatigue Assessment Scale [FAS; 0–10 numeric rating scale]), pain (0–100mm visual analogue scale [VAS]), and patient’s global assessment of disease activity (PtGA, 0–100mm VAS). The minimal clinically important difference (MCID) is a clinically relevant change in a patient’s status. The percentage of patients reporting MCIDs was determined: ≥1 for FAS, ≥6 for MOS-SPI, and ≥10mm for pain-VAS and PtGA. Correlations between PROs and DAS28 were also assessed (Pearson correlations [rho], CZP group only).
About CIMZIA®
Cimzia® is the only PEGylated anti-TNF (Tumor Necrosis Factor). 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. 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 moderately to severely active disease who have had an inadequate response to conventional therapy and for the treatment of adults with moderately to severely active rheumatoid arthritis. Cimzia® in combination with MTX, is approved in the EU for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying antirheumatic drugs (DMARDs) including MTX. Cimzia® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. UCB is also developing Cimzia® in other autoimmune disease indications. Cimzia® is a registered trademark of UCB PHARMA S.A.
About UCB
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 8 500 people in about 40 countries, the company generated revenue of EUR 3.2 billion in 2010. UCB is listed on Euronext Brussels (symbol: UCB).
Forward-looking statements
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.
Cimzia® (certolizumab pegol) in European Union/ EEA important safety information
Cimzia® was studied in 2367 patients with RA in controlled and open label trials for up to 57 months. The commonly reported adverse reactions (1-10%) in clinical trials with Cimzia® and post-marketing were viral infections (includes herpes, papillomavirus, influenza), bacterial infections (including abscess), rash, headache (including migraine), asthenia, leukopaenia (including lymphopaenia, neutropaenia), eosinophilic disorder, pain (any sites), pyrexia, sensory abnormalities, hypertension, pruritis (any sites), hepatitis (including hepatic enzyme increase), injection site reactions. Serious adverse reactions include sepsis, opportunistic infections, tuberculosis, herpes zoster, lymphoma, leukaemia, solid organ tumours, angioneurotic edema, cardiomyopathies (includes heart failure), ischemic coronary artery disorders, pancytopaenia, hypercoagulation (including thrombophlebitis, pulmonary embolism), cerebrovascular accident, vasculitis, hepatitis/hepatopathy (includes cirrhosis), and renal impairment/nephropathy (includes nephritis). In RA controlled clinical trials, 5% of patients discontinued taking Cimzia® due to adverse events vs. 2.5% for placebo.
Cimzia® is contraindicated in patients with hypersensitivity to the active substance or any of the excipients, active tuberculosis or other severe infections such as sepsis or opportunistic infections, moderate to severe heart failure.
Before initiation of Cimzia®, evaluate patients for both active or inactive (latent) tuberculosis infection. Monitor patients for the development of signs and symptoms of infection during and after treatment with Cimzia®. If an infection develops, monitor carefully, and stop Cimzia® if infection becomes serious.
TNF blockers including Cimzia® may increase the risk: of reactivation of Hepatitis B Virus (HBV) in patients who are chronic carriers of the virus; of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease; of formation of autoantibodies and uncommonly of the development of a lupus-like syndrome; of severe hypersensitivity reactions. If a patient develops any of these adverse reactions, Cimzia® should be discontinued and appropriate therapy instituted.
With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with a TNF antagonist cannot be excluded. Rare cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have been reported in patients treated with Cimzia®.
Adverse reactions of the hematologic system, including medically significant cytopenia, have 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 haematological abnormalities.
The use of Cimzia® in combination with anakinra or abatacept is not recommended due to a potential increased risk of serious infections. As no data are available, Cimzia® should not be administered concurrently with live vaccines or attenuated vaccines. The 14-day half-life of Cimzia® should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on Cimzia® should be closely monitored for infections.
Please consult the full prescribing information in relation to other side effects, full safety and prescribing information. European SmPC date of revision February 2011.
References
- Weinblatt M, Fleischmann R, van Vollenhoven RF et al. Efficacy and Safety of Certolizumab Pegol in a Broad Population of Patients With Active Rheumatoid Arthritis: Week 28 Results From a Phase IIIb Randomized Controlled Study. Poster #1253
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