New RAPID 1 post-hoc analysis showed early response to Cimzia® (certolizumab pegol) at Week 12 was predictive of Week 52 response
BRUSSELS/CHICAGO, 7th Nov, 2011 – UCB today announced findings from a post-hoc analysis suggesting that disease activity response rates to Cimzia® (certolizumab pegol) plus methotrexate (MTX) as early as Week 12 helped predict the effect on structural joint damage in patients with moderate to severe rheumatoid arthritis (RA) at one year.2 Comparable responses were found by both RAPID3 (Routine Assessment of Patient Index Data 3) and EULAR (European League Against Rheumatism), suggesting that either response criteria could be used as predictors of structural joint damage in patients with moderate to severe RA. The analysis examined patients treated with certolizumab pegol plus MTX compared to placebo plus MTX. The data were presented at the American College of Rheumatology’s 2011 Annual Scientific Meeting in Chicago, IL (November 5-9, 2011).
“This post-hoc analysis is consistent with previous evidence that suggested an opportunity for healthcare professionals to predict clinical outcomes as early as Week 12 when treating rheumatoid arthritis patients with certolizumab pegol,” said Edward Keystone, M.D., The Rebecca MacDonald Center for Arthritis, Mount Sinai Hospital, The University of Toronto. “Moreover, the results indicated that if a patient responds to treatment at 12 Weeks, it may predict disease progression at one year.”
Both RAPID3 and EULAR response criteria are measures of disease activity in RA.3,4,5 RAPID3 is an index of three patient self-report measures—physical function, pain, and patient global estimate of status—that can be quickly calculated by a healthcare professional. RAPID3 and its components are seen as markers that may alert a healthcare professional to unanticipated patient problems, provide a baseline measure to support a change in treatment, and numerically document improvement or worsening over time to complement clinical impressions.1 EULAR response criteria classify individual patients as non-, moderate, or good responders, depending on the extent of change and the level of disease activity reached.3
The RAPID3 patient-derived assessment of disease activity has been shown to correlate with disease activity score, DAS28, in patients treated with certolizumab pegol.2 DAS28 is defined as a clinical index of RA disease activity that combines information from swollen joints, tender joints, an acute phase response, and general health.3
Previous post-hoc analyses with certolizumab pegol have demonstrated that a lack of improvement in DAS28 (≥ 1.2) by Week 12 predicts failure to achieve low disease activity at one year.6 The analysis presented here examined whether RAPID3 or EULAR responses at Week 12 predicted structural joint damage at one year (defined as change from baseline in modified Total Sharp Score [mTSS]) in patients treated with certolizumab pegol plus MTX or placebo plus MTX. The mTSS assesses bone erosion and joint space narrowing measured by X-ray. A smaller change in mTSS reflects less progression of joint damage.
In this post-hoc analysis, patients taking certolizumab pegol 200mg two weekly plus MTX or MTX alone in the RAPID 1 study were evaluated. RAPID 1 was a Phase III double-blind placebo-controlled trial designed to establish the efficacy and tolerability of certolizumab pegol plus MTX in the treatment of moderate to severely active RA in patients who did not adequately respond to treatment. RAPID 1 met the co-primary endpoints which were ACR20 score at Week 24 and change in mTSS at Week 52. At Week 12, patients were categorized according to good, moderate or poor based on RAPID3 or EULAR response criteria. Data were pooled for patients in each group achieving a good or moderate RAPID3 or EULAR response, and progression of joint damage was evaluated in good/moderate versus poor RAPID3 or EULAR responders.1
The analysis showed that the rate of mTSS non-progressors at Week 52 was higher in patients with good/moderate RAPID3 (79.7%, n=246) or EULAR (78.5%, n=284) responses compared to those with poor RAPID3 (70.1%, n=117) or EULAR (68.4%, n=79) responses in the certolizumab pegol plus MTX group, according to Week 12 responses (last observation carried forward (LOCF)). At Week 52, good/moderate RAPID3 or EULAR responses were higher for those treated with certolizumab pegol plus MTX versus the RAPID3 (63.6%, n=44) or EULAR (69.2%, n=52) responses for those treated with placebo plus MTX, according to Week 12 responses (LOCF).1
The analysis showed greater inhibition of radiographic progression in patients treated with certolizumab pegol plus MTX versus those treated with placebo plus MTX, regardless of the level of response (good, moderate, or poor) at Week 12 and how the response was determined (RAPID3 or DAS28). The analysis suggested that for patients receiving MTX, assessing RAPID3 response at Week 12 may be beneficial in aiding clinicians in treatment decisions.1
Furthermore, the analysis revealed that at Week 12, the majority of certolizumab pegol plus MTX patients had good/moderate RAPID3 or EULAR responses (66.8% and 77.6% respectively, versus 23.5% and 29.1% for placebo plus MTX). At baseline, mean and median mTSS were similar between Week 12 response groups, and at one year, patients with a poor RAPID3 or EULAR response at Week 12 had a greater increase in mTSS from baseline than those patients with a good/moderate response. Differences between categories were greatest in the MTX alone group.1
RAPID 1 showed certolizumab pegol had a low incidence of injection site pain (n=<3 new cases /100 years) and discontinuations due to adverse events (AEs). The most commonly occurring AEs were headache, nasopharyngitis, and upper respiratory tract infections. Reported serious adverse reactions were infections (including tuberculosis) and malignancies (including lymphoma), consistent with findings from other trials in the anti-TNF class.2
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
Michael Tuck-Sherman, Investor Relations, UCB
T +32.2.559.9712, Michael.tuck-sherman@ucb.com
Dena Koklanaris, Cooney/Waters Group
212.886.2228, dkoklanaris@cooneywaters.com
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 RAPID 1
The double-blind placebo-controlled trial, involving 982 adults, was designed to establish the efficacy and tolerability of Cimzia® together with MTX, in the treatment of active RA in patients who did not adequately respond to conventional treatment. Patients were randomly allocated to receive one of three treatment regimens: 393 patients received Cimzia® 400mg and at Weeks 0, 2 and 4, then 200mg every two weeks; 390 patients received Cimzia® 400mg every 2 weeks; 199 patients received placebo every 2 weeks. RAPID 1 met co-primary endpoints: ACR20 response rate at Week 24 and change from baseline in mTSS at Week 52.
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
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
1. Keystone E, Davies O, Luijtens K. RAPID3 (Routine Assesment of Patient Index Data 3) at Week 12 Predicts Progression of Joint Damage at Year 1 in Rheumatoid Arthritis Patients Treated With Certolizumab Pegol Plus Methotrexate. Presented at the American College of Rheumatology’s 2011 Annual Scientific Meeting in Chicago, IL (November 5-9, 2011).
2. Keystone E, van der Heijde D, Mason D, Landewe R, van Vollenhoven R, Combe B, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 2008;58:3319-29.
3. Fransen, J., van Riel, P. L. C. M. The Disease Activity Score and the EULAR Response Criteria. Clinical and Experimental Rheumatology. 2005; 23(39): S93-S99
4. Pincus T, Swearingen CJ, Bergman M, Yazici Y. RAPID3 (Routine Assessment of Patient Index Data 3), a rheumatoid arthritis index without formal joint counts for routine care: proposed severity categories compared to DAS and CDAI categories. J Rheumatol 2008;35:2136–47.
5. Pincus T, Bergman MJ, Yazici Y, Hines P, Raghupathi K, Maclean R. An index of only patient-reported outcome measures, Routine Assessment of Patient Index Data 3 (RAPID3), in two abatacept clinical trials: similar results to Disease Activity Score (DAS28) and other RAPID indices that include physician-reported measures. Rheumatology (Oxford) 2008; 47:345–9.
6. Keystone E et al. Rapid improvement in the signs and symptoms of rheumatoid arthritis following certolizumab pegol treatment predicts better longterm outcomes: post-hoc analysis of a randomized controlled trial. J Rheumatol 2011; 38: 990-6
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