Cimzia® Is The First Anti-TNF Shown To Inhibit Progression Of Joint Damage As Early As 16 Weeks In Rheumatoid Arthritis

Main Category: Arthritis / Rheumatology
Also Included In: Clinical Trials / Drug Trials
Article Date: 18 Jun 2008 - 1:00 PDT

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UCB has announced new data showing that Cimzia® (certolizumab pegol), the only PEGylated, Fc-Free anti-TNF (Tumor Necrosis Factor), combined with methotrexate (MTX), significantly inhibits progression of joint damage in patients with active rheumatoid arthritis (RA) as early as 16 weeks after the start of treatment. Presented at the European League Against Rheumatism (EULAR) meeting in Paris, these data are the first to show such rapid inhibition of progression of structural damage in patients receiving an anti-TNF.

These findings are from a post-hoc analysis of the RAPID 1 and 2 trials, two large, international, multi-centre placebo-controlled RA studies, of 52 and 24 weeks' duration, respectively. Previously-presented results from these studies have shown that Cimzia®, in combination with MTX, significantly inhibited progression of structural damage at Week 24 (RAPID 1: Cimzia® 200 and 400mg p<0.001. RAPID 2: Cimzia® 200mg p=0.003 and Cimzia® 400mg p<0.001) and 52 (RAPID 1 Cimzia® 200 and 400mg p<0.001) when compared to MTX alone. Additionally, Cimzia® also demonstrated a rapid and significant reduction in the signs and symptoms of active RA as early as the first dose as measured at Week 1.

Furthermore, the new Week 16 radiographic analysis in patients who did not meet the clinical response criteria showed that patients on Cimzia® (200mg or 400mg) combined with MTX experienced significantly lower changes from baseline in modified Total Sharp Score (mTSS)a, erosion score (ES) and joint space narrowing score (JSN) compared to patients receiving placebo (p≤0.05). These results support previous observations that radiographic response is not always associated with clinical response criteria. In addition, the demonstrated early inhibition of radiographic progression supports performing shorter term imaging studies in RA.

"Prevention of long-term structural damage is a key concern for rheumatologists when treating patients with active rheumatoid arthritis," said Dr van der Heijde, Professor of Rheumatology, Leiden University Medical Centre. "These data from the RAPID trials confirm that certolizumab pegol is both fast and effective at preventing this structural damage."

These results are part of a package of two oral presentations and 10 posters regarding Cimzia® which are being presented by UCB at the congress. This package includes the latest clinical data and post-hoc analyses from the RAPID trials plus new home and work productivity studies.

A pooled analysis of the safety data from the two RAPID studies showed there was a low incidence of injection site pain (n=<3 new cases/ 100 patient-years) and low level of 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.

On April 22, 2008, the US Food and Drug Administration (FDA) approved Cimzia® 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. The U.S. FDA also agreed to accept, for filing and review, a Biologics License Application (BLA) for Cimzia® for the treatment of adult patients with active rheumatoid arthritis (RA) in February, 2008. Preparation for submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA) for Cimzia® in the treatment of RA is ongoing, with filing planned by mid 2008.

About RAPID

The RAPID series of clinical trials were designed to establish the efficacy and tolerability of Cimzia® (certolizumab pegol) in the treatment of rheumatoid arthritis. The RAPID clinical trial program is comprised of two large, international, multi-centre placebo-controlled studies - RAPID 1 (027) and RAPID 2 (050).

In the year-long RAPID 1 trial, 982 patients were randomly allocated to receive one of three treatment regimens: Cimzia® 400 mg at the start of the study and at Weeks 2 and 4, then 200 mg given every 2 weeks, together with MTX; Cimzia® 400 mg every 2 weeks, together with MTX; or placebo every 2 weeks, together with methotrexate. In all three arms of the study, the dose of methotrexate was 10-30 mg per week.

Co-primary endpoints for RAPID 1 were the ACR20 response rateb at Week 24 and the change from baseline in the mTSS at Week 52.

Six month ACR response rates for RAPID 1

	Placebo & MTX	Cimzia® (certolizumab pegol) 200mg & MTX	Cimzia® (certolizumab pegol) 400mg & MTX
Six months
ACR 20	13.6	58.8*	60.8*
ACR 50	7.6	37.1*	39.9*
ACR 70	3.0	21.4*	20.6*

Six and 12 month mean mTSS changes from baseline for RAPID 1

	Placebo & MTX	Cimzia® (certolizumab pegol) 200mg & MTX	Cimzia® (certolizumab pegol) 400mg & MTX
Six months	1.3	0.2*	0.2*
12 months	2.8	0.4*	0.2*

* p<0.001

In the six-month RAPID 2 trial, 619 patients were randomly allocated to receive one of three treatment regimens: Cimzia® 400 mg at the start of the study and at Weeks 2 and 4, then 200 mg given every 2 weeks, together with MTX; Cimzia® 400 mg every 2 weeks, together with MTX; or placebo every 2 weeks, together with MTX. In all three arms of the study the dose of methotrexate was 10-30mg per week.

Patients were assessed for improvement in signs and symptoms of RA. The primary endpoint for RAPID 2 was the ACR20 response rate at Week 24.

In both studies, Cimzia® given at a dosage of 200mg every 2 weeks was clinically as effective as a dosage of 400mg every 2weeks.

Six month ACR response rates for RAPID 2

	Placebo & MTX	Cimzia® (certolizumab pegol) 200mg & MTX	Cimzia® (certolizumab pegol) 400mg & MTX
ACR 20	8.7	57.3*	57.6*
ACR 50	3.1	32.5*	33.1*
ACR 70	0.8	15.9**	10.6†

* p<0.001 **p= 0.002 †p=0.008 versus Placebo

Six month mean mTSS changes from baseline for RAPID 2

	Placebo & MTX	Cimzia® (certolizumab pegol) 200mg & MTX	Cimzia® (certolizumab pegol) 400mg & MTX
Six months	1.2	0.2**	-0.4*

* p<0.001 **p= 0.003

About Rheumatoid Arthritis (RA)

RA is a progressive autoimmune disease that causes chronic inflammation of the joints. It is estimated that five million people suffer from RA globally with 0.3 percent to 1 percent of the population in industrialized countries suffering from the disease. Women are three times more likely to be affected than men. Although it can affect people of all ages, the onset of RA usually occurs between the ages of 35-55.

Traditional treatments for RA include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs (DMARDs), with biological therapies a more recent addition.

About Cimzia® (certolizumab pegol)

Cimzia® is the first and 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 inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of diseases. UCB is developing Cimzia® in Crohn's disease, rheumatoid arthritis and other autoimmune disease indications. Cimzia® is a registered trademark of UCB Inc.

About UCB's Inflammatory Disorders Portfolio

UCB has developed Cimzia® which was approved by the FDA in April 2008 to reduce signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderate to severe active disease who have an inadequate response to conventional therapy, and is also being investigated for use in RA and other autoimmune disease indications. Cimzia® is one of three investigational therapies for the treatment of inflammatory in UCB's clinical development portfolio, alongside epratuzumab and anti-sclerostin. UCB presented data on Cimzia® and phase II data on epratuzumab at EULAR 2008.

About UCB

UCB (Brussels, Belgium) (http://www.ucb-group.com) is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialization of innovative pharmaceutical and biotechnology products in the fields of central nervous system disorders, allergy/respiratory diseases, immune and inflammatory disorders and oncology. UCB focuses on securing a leading position in severe disease categories. Employing around 12 000 people in over 40 countries, UCB achieved revenue of 3.6 billion euro in 2007. UCB S.A. is listed on Euronext Brussels.

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 regulations, exchange rate fluctuations and hiring and retention of its employees.

Footnotes

a. The mTSS (modified Total Sharp Score) assesses erosion and joint space narrowing measured by X-rays of the hands and the feet. A smaller change in mTSS reflects less progression of joint damage.

b. The ACR (American College of Rheumatology) response criteria assess improvement in the tender and swollen joint count and also include assessment of the following five parameters: patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of arthritis pain, degree of disability as measured by the Health Assessment Questionnaire-Disability Index, and level of an acute-phase reactant (i.e. erythrocyte sedimentation rate or C-reactive protein). ACR20 is achieved when there is at least a 20 percent improvement in each tender and swollen joint count as well as at least a 20 percent improvement in at least three of the five parameters. ACR50 and ACR70 are an extension of these criteria corresponding to at least a 50 percent and 70 percent improvement respectively.

Source:
Scott Fleming,
http://www.ucb-group.com