UC CARES study highlights impact of flare-ups in patients with moderate-to-severe ulcerative colitis
New analyses of the pan-European Ulcerative Colitis Condition, Attitude, Resources and Educational Study (UC CARES) presented at the 10th Congress of the European Crohn’s and Colitis Organisation (ECCO) in Barcelona, Spain show that 91% of biologic-naïve patients with moderate-to-severe ulcerative colitis (UC) across 11 European countries believe their UC to be disruptive when experiencing a flare-up, whereas 40% of patients reported disruption when they were in remission.1
Dr Paul Robinson, Medical Director, MSD UK, says: “The UC CARES data remind us that regular flare-ups significantly disrupt quality of life. Most patients with UC want to get their disease under control without intermittent flares but many are still failing to achieve full disease control with conventional therapies. Understanding the impact of UC is important in the management of the disease, and clinicians need a focus on sustained symptom relief.”
Room for Better Control in UC
Outcomes from UC CARES found that 84% of patients were ‘somewhat to very knowledgeable’ about their disease.1 However, not all patients receiving UC treatment were well-controlled and maintaining remission of their disease, suggesting that a disconnect can occur between patients’ perceived disease control, and that measured objectively. Approximately 63% of patients reported seeking information about UC and/or various treatment options, and 96% acknowledge their physician as the main source of medical information relating to UC treatment options.1
Earlier findings from the UC CARES Study, which was funded by MSD, suggested that the majority of biologic naïve moderate-to-severe active UC patients treated with conventional therapies were not well-controlled (83%), and nearly half of patients were not satisfied with their current UC treatment.2
Predictors of Continuous Clinical Response with Anti-TNF Therapy
Also presented at ECCO were data from a post-hoc analysis of PURSUIT (Programme of Ulcerative Colitis Research Studies Utilising an Investigational Treatment) which showed that maintenance of SIMPONI (golimumab) versus withdrawal and calprotectin level at six weeks were significant predictors of continuous clinical response in moderate-to-severe UC patients who responded to SIMPONI induction treatment at week six. Continuous clinical response was defined as sustained clinical response without clinical flare and loss of response through week 54.3
Dr Robinson explains: “PURSUIT raises the bar for the concept of continuous response and a role for patient self-monitoring through patient-reported outcomes. Physicians need to adopt practice to aim for full symptom relief.”
UC is a form of inflammatory bowel disease (IBD), that causes inflammation and ulceration in the inner lining of the large intestine (colon) or rectum (proctitis).4 The most common symptoms of UC include abdominal pain and bloody diarrhoea. Patients also may experience fatigue, weight loss, loss of appetite and rectal bleeding.4 When conventional medications do not control the disease, surgery may be considered as an option to remove the affected colon (colectomy). About one in five (20%) people with UC will undergo a colectomy at some point.5
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About UC CARES1
UC CARES is an observational, non-interventional, multinational, multi-center, cross-sectional study that assessed disease control and treatment satisfaction among patients with moderate-to-severe, active UC. The sub-analysis was designed to describe the knowledge of patients regarding moderate-to-severe UC and to evaluate the consistency of the patients and physicians assessment of disease activity. Patients were enrolled from 46 study sites in 11 European countries, including Belgium, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden, Switzerland, Turkey and the United Kingdom. Participants (n=250) included a sample of patients aged 18 years or older, diagnosed with moderate-to-severe, active UC (defined by clinical Mayo score ?6), naïve to biologic therapy, who had received UC related conventional treatments, including thiopurines, 5-ASA or corticosteroids. Data were collected from patient questionnaires at the date of enrolment and medical charts.1
Remission was defined as full Mayo score < =2 with no individual sub-score >1. Patients completed questionnaires by rating their knowledge about UC disease by using a 4-point Likert scale; from one, as being very knowledgeable to four, having no knowledge of the disease. A weighted kappa was calculated to assess the agreement of disease activity (mild, moderate, and severe) between patient and physician.1 The study was commissioned by MSD in collaboration with IMS Health, a CRO based in Barcelona, Spain.1
PURSUIT (Program of Ulcerative Colitis Research Studies Utilising an Investigational Treatment) is a Phase 3 multicentre, randomised, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of subcutaneous SIMPONI (golimumab) in adults with moderately to severely active UC. All trial patients had failed to respond to or had failed to tolerate one or more of the following conventional therapies: 6-mercaptopurine (6-MP), azathioprine (AZA), corticosteroids and/or 5-aminosalicylate (5-ASA); or were corticosteroid dependent. Study participants were naïve to treatment with TNF inhibitors and had a baseline Mayo score between 6 and 12 and endoscopic subscore greater than or equal to 2.6
The PURSUIT SC-Induction trial had an adaptive design with Phase 2 dose ranging followed by a confirmatory Phase 3 component. Patients were randomised to receive SC injections of SIMPONI 100 mg/50 mg (prior to dose selection only), placebo or SIMPONI 200 mg/100 mg or 400 mg/200 mg at weeks 0 and 2. The primary endpoint was clinical response at week 6. Secondary endpoints at week 6 included clinical remission, mucosal healing and a change from baseline in IBDQ scores. Overall, 1065 patients were treated in the study; 774 of these patients were randomised into the Phase 3 component of the study. Patients responding to induction treatment with SIMPONI were eligible to continue in the Phase 3 PURSUIT maintenance study.6
The PURSUIT-Maintenance trial included patients who responded to induction treatment with SIMPONI. A total of 464 patients were randomised to placebo or subcutaneous injections of SIMPONI 50mg or 100mg every four weeks through week 52. Patients were assessed for UC disease activity using the Mayo score at weeks 30 and 54 and by partial Mayo score every 4 weeks. The primary endpoint was maintenance of clinical response through week 54 among SIMPONI-induction responders. Major secondary endpoints of the maintenance study included clinical remission and mucosal healing at both weeks 30 and week 54; clinical remission at both weeks 30 and 54 among patients who were in clinical remission at week 0 of the maintenance trial; and corticosteroid-free clinical remission at week 54 among patients receiving concomitant corticosteroids at week 0 of the maintenance study.7
The post-hoc analysis included 456 patients from PURSUIT who were responders at week 6 after SIMPONI induction and entered maintenance treatment. Potential predictors evaluated included, age; gender; disease duration (?5y versus >5y); disease extent (extensive versus limited); Mayo score at induction week 0 (<9 versus ?9); Mayo score at induction week 6; stool frequency and rectal bleeding at induction week 6; CRP, calprotectin and lactoferrin at induction week 6 and change from induction week 0-6; Mayo change from induction week 0-6; CRP normalisation at induction week 6; mucosal healing (Mayo endoscopy score 0 or 1) at induction week 6; and SIMPONI maintenance versus withdrawal.3
SIMPONI is a human monoclonal antibody that targets and neutralises tumour necrosis factor (TNF)-alpha, a protein that when overproduced in the body due to chronic inflammatory diseases can cause inflammation and damage to bones, cartilage and tissue. SIMPONI is the first four-weekly, subcutaneous biologic therapy approved for the treatment of adult patients with moderately to severely active UC who have had an inadequate response to conventional therapy, including corticosteroids and 6-mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies. The approved dose of SIMPONI for a person weighing less than 80kg is an initial dose of 200mg, followed by 100mg at week 2 and then 50mg every 4 weeks thereafter. For patients weighing 80kg or more, SIMPONI is given as an initial dose of 200mg, followed by 100mg at week 2 and then 100mg every 4 weeks thereafter. SIMPONI is available either through the SmartJect autoinjector/prefilled pen or a prefilled syringe as a SC administered injection. Other licensed indications for SIMPONI include the three rheumatology diseases: rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.8 SIMPONI is a Registered Trademark owned by Centocor, Inc. and licensed to Merck and Co., Inc., Whitehouse Station, New Jersey, USA.
Please refer to the Summary of Product Characteristics for full information on ‘SIMPONI’ including contraindications, precautions, special warnings and side effect information. Available from: www.medicines.org.uk/emc/medicine/28316/SPC/SIMPONI+100+mg+solution+for+injection//
1. ECCO 2015. Poster Presentation: Van Assche, G., et al. Knowledge and attitude of patient toward Ulcerative Colitis and disease activity in Europe: The UC CARES (Ulcerative Colitis Condition, Attitude, Resources and Educational Study).
2. ECCO 2014 Poster Presentation. Van Assche, G., et al. Disease control and unmet needs among moderate to severe ulcerative colitis patients treated with conventional therapies in Europe: The UC Cares (Ulcerative Colitis Condition, Attitude, Resources and Educational Study) study.
3. ECCO 2015 Poster Presentation: Reinisch, W., et al. Golimumab maintenance treatment and fecal calprotection predict continuous clinical response in ulcerative colitis.
4. Crohn’s and Colitis UK. Ulcerative Colitis. Available at: www.crohnsandcolitis.org.uk/Resources/CrohnsAndColitisUK/Documents/Publications/Booklets/living-with-ibd.pdf. Last accessed: September 2014.
5. Crohn’s and Colitis UK. Surgery for Ulcerative Colitis (UC). Available at: www.crohnsandcolitis.org.uk/Resources/CrohnsAndColitisUK/Documents/Publications/Info-Sheets/surgery-for-ulcerative-colitis.pdf. Last accessed: September 2014.
6. Sandborn, W.J. et. al.Subcutaneous Golimumab Induces Clinical Response and Remission in Patients With Moderate-to-Severe Ulcerative Colitis. Gastroenterology 2014;146:85–95.
7. Sandborn, W.J. et. al. Subcutaneous Golimumab Maintains Clinical Response in Patients With Moderate-to-Severe Ulcerative Colitis. Gastroenterology 2014;146:96-109.
8. SIMPONI. Summary of Product Characteristics. January 2015. Available from: www.medicines.org.uk/emc/medicine/28316/SPC/Simponi+100+mg+solution+for+injection. Last accessed: February 2015.