UCB, 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 CNS, has initiated the Exxelerate study which will evaluate the short- and long-term efficacy of Cimzia (certolizumab pegol) plus methotrexate (MTX) compared with that of Humira (adalimumab) plus MTX in the treatment of moderate to severe rheumatoid arthritis (RA). The start of this study confirms previously announced plans.
"This head-to-head study is an important milestone. We believe that Exxelerate should help to provide additional evidence to support early, informed management decisions for people living with this chronic, progressive disease," said Professor Dr. Iris Loew-Friedrich, chief medical officer and executive vice president, UCB.
The primary objectives of the study are to compare the relative efficacy of the two anti-TNF therapies during short- and long-term treatment (12 and 104 weeks, respectively).
"While meta-analyses from placebo controlled trials suggest differences in efficacy among anti-TNFs in RA, results from the Exxelerate study should help to provide additional insights to support the current lack of head-to-head data and to guide treatment decisions," said Roy Fleischmann, MD, Clinical Professor of Medicine, The University of Texas South Western Medical Center, Dallas, Texas, US. "As recent guidelines on biological agents recommend rapid treatment to target for RA patients, it is also timely for Exxelerate to explore the comparative long term benefits of anti-TNF therapies, related to early response-driven treatment decisions."
The European League Against Rheumatism (EULAR) and the international Treat-to-Target Expert Committee recommend appropriate therapeutic adaptation of disease-modifying anti-rheumatic drugs to reach targets of remission or low disease activity within three to six months of starting treatment.
Persistent active disease is a predisposing factor of subsequent disease severity, such as progressive joint damage, irreversible disability and increased mortality. Therefore, stopping inflammation rapidly can be an important therapeutic goal and studies have shown that achieving control of disease activity, ideally rapid control, has led to improved long-term outcomes for patients with RA.
Exxelerate is a multi-centre, single-blind, randomized, parallel-group study which will randomize patients to either certolizumab pegol plus MTX or adalimumab plus MTX. After 12 weeks, patients who respond will continue their initial treatment, whereas non-responders will switch to the alternative treatment arm until study end at 104 weeks. By including a week 12 response-based therapeutic decision, Exxelerate aims to assess the impact of early response-driven treatment on long-term (104 weeks) clinical and patient outcomes. The study aims to enroll approximately 900 adult patients with moderate to severe RA in multiple geographies including the US, Canada and Europe, who have inadequately responded to MTX and who have not previously received anti-TNF treatment. The headline results from the study are expected in 2016.
Cimzia is indicated for the treatment of adult patients with moderately to severely active RA. Serious and sometimes fatal side effects have been reported with Cimzia, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens (such as Legionella or Listeria). Patients should be closely monitored for the signs and symptoms of infection during and after treatment with Cimzia. Lymphoma and other malignancies also have been reported in children and adolescents. Cimzia is not indicated for use in paediatric patients.
Cimzia is the only PEGylated anti-TNF (Tumour 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 US 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 SA.