Tests Suggest Certolizumab Pegol Plus Methotrexate Effective In Reducing Rheumatoid Arthritis Signs/Symptoms In Patients Refractory To Methotrexate

Main Category: Arthritis / Rheumatology
Also Included In: Clinical Trials / Drug Trials
Article Date: 16 Jun 2007 - 1:00 PDT

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59% of patients receiving certolizumab pegol 200mg plus methotrexate, and 61% of patients receiving certolizumab pegol 400mg plus methotrexate every two weeks achieved a 20% improvement in symptoms (known as an American College of Rheumatology (ACR) 20 response) after 24 weeks. treatment, according to a study presented today at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain. Only 14% of patients receiving methotrexate alone achieved an ACR20 response over the same period, highlighting the superiority of the treatment combination at both doses of certolizumab pegol in patients refractory to methotrexate.

In a Phase III trial of the anti tumour necrosis factor alpha (TNF-α) certolizumab pegol, the treatment was administered to 982 patients whose rheumatoid arthritis (RA) was not being adequately controlled by methotrexate alone; 572 patients completed the study. Patients who had been taking methotrexate for more than six months were randomised to certolizumab pegol 200mg, 400mg or placebo. The treated arms of the study both received three initial doses of certolizumab pegol 400mg at two weekly intervals then 200mg or 400mg of the treatment every two weeks for 52 weeks. A third arm received placebo in addition to methotrexate at the same time intervals.

Preliminary results at 24 weeks show that 21% of patients treated with certolizumab 200mg plus methotrexate and 21% of patients receiving certolizumab pegol 400mg plus methotrexate achieved a 70% improvement in symptoms (ACR70), compared to only 3% for patients taking placebo.

Interestingly, in patients treated with 400mg certolizumab pegol compared to the 200mg dose, a significant difference in outcomes was not observed in any of the ACR criteria (20, 50 and 70% response).

Lead researcher Dr Edward Keystone, of the University of Toronto, Canada, commented: .Where treatment with methotrexate as monotherapy is not achieving sufficient results, we have shown that adding certolizumab pegol can achieve a significant improvement in symptoms.

Certolizumab pegol is the first anti TNF treatment which has been coupled to polyethylene glycol (.PEGylated.). This process slows the body.s clearance of the active compound from the blood, thereby prolonging its active period and possibly also resulting in differential accumulation in inflamed tissue over normal tissue.

Certolizumab pegol works by targeting TNF-α in inflamed tissue, reducing associated symptoms and the disease progression of RA. The molecule is Fc-free, which means that the Fc region of the antibody, found in conventional anti-TNFs, has been removed. Although it has now been shown in RAPID 1 that the Fc region is not required for efficacy in RA, it does have functions which could potentially be detrimental, including Fc-mediated cytotoxicity and transport across the placenta.

Adverse Events (AEs) were monitored in all patients at two weekly intervals. Discontinuation due to AEs was low at 4.3%, 5.7% and 1.5% for certolizumab pegol 200mg, 400mg and placebo respectively.

About EULAR

• The European League Against Rheumatism (EULAR) is the organization which represents the patient, health professional and scientific societies of rheumatology of all the European nations.

• The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.

• Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.

• As new treatments emerge and cellular mechanisms are discovered, the 8th Annual European Congress of Rheumatology in Barcelona (EULAR 2007) brings together more than 10,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.

• To find out more information about the activities of EULAR, visit: http://www.eular.org

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