Certolizumab pegol a monthly subcutaneously admin

Authors: Paul Rutgeerts Stefan Schreiber Brian Feagan Dorothy L Keininger Liz O’Neil Richard N Fedorak CDP870 Crohn’s Disease Study Group

Publish Date: 2007/12/11

Volume: 23, Issue: 3, Pages: 289-296

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Abstract

Certolizumab pegol a polyethylene glycolated Fcfree Fab’ was efficacious and well tolerated in patients with moderatetosevere Crohn’s disease in a previously reported randomized placebocontrolled study In this paper we report the effect of certolizumab pegol on healthrelated quality of life HRQoLPatients with moderatetosevere active Crohn’s disease n = 292 received subcutaneous certolizumab pegol 100 200 or 400 mg or placebo at weeks 0 4 and 8 A post hoc analysis of the intenttotreat population 290 patients with HRQoL data assessed HRQoL by evaluating patients’ responses to the selfadministered inflammatory bowel disease questionnaire IBDQ at baseline and weeks 2 4 6 8 10 and 12Patients receiving certolizumab pegol 400 mg at weeks 0 4 and 8 demonstrated via their IBDQ total score significantly P ≤ 005 greater improvement in HRQoL from baseline to week 12 and at all other time points compared with placebo Moreover HRQoL improved over time in all certolizumab pegol groups irrespective of baseline Creactive protein levels Emotional wellbeing IBDQ Emotional Function domain improved throughout the study for patients receiving certolizumab pegol 400 mg This improvement was significantly P ≤ 005 greater than for patients receiving placebo at all time points In addition systemic symptoms IBDQ Systemic Symptoms domain improved significantly more in patients receiving certolizumab pegol 400 mg than in those receiving placebo at weeks 4 8 10 and 12 P ≤ 005 and approached statistical significance at week 2 P = 0054Crohn’s disease is a chronic relapsing and remitting inflammatory bowel disease IBD that has a significant impact on healthrelated quality of life HRQoL 1 2 HRQoL has been recognized as an important health outcome and has been defined in the medical setting as “a concept encompassing a broad range of physical and psychological characteristics and limitations which describe an individual’s ability to function and derive satisfaction from doing so” 3 Crohn’s disease frequently begins in early adulthood causing a heavy disease burden in a relatively young patient population Consequently many patients will be affected for most of their adult lifeIn Crohn’s disease health status is affected as much by psychosocial factors and functional status as by disease activity 4 For example the need to wear an ostomy bag may adversely affect selfimage and this has been reported to be a common worry for patients with Crohn’s disease 5 Moreover previous studies have demonstrated a high correlation between disease severity as measured by the Crohn’s Disease Activity Index CDAI 6 and HRQoL as assessed using the Inflammatory Bowel Disease Questionnaire IBDQ 7 8 A large longitudinal study prospectively assessed the HRQoL of patients with Crohn’s disease over 1 year and determined influencing factors 9 The following factors were associated with a negative impact on overall HRQoL female gender tobacco use active Crohn’s disease involvement of the colon hospitalization corticosteroid treatment and surgery in the past 3 months order does not indicate priority These findings were reflected in a survey of patients with a longterm diagnosis of Crohn’s disease 10 It is therefore important to include improvement in HRQoL as a key therapeutic goal in the treatment of patients with Crohn’s diseaseConventional treatment options for Crohn’s disease include aminosalicylates antibiotics corticosteroids immunomodulators and surgery However in some patients the disease can be refractory or unresponsive to certain pharmacologic treatments Furthermore corticosteroids are associated with a risk of dependency and potentially serious side effects eg diabetes osteoporosis moon face and acne which are detrimental to a patient’s HRQoL and may negatively affect selfesteem 11 12 13 Such treatments therefore require careful management Additionally it is rarely possible to achieve longterm relief from Crohn’s disease with a single surgical procedure and as a result patients with Crohn’s disease fear surgery so much that their HRQoL is reduced 14It is now well accepted that tumor necrosis factor α TNFα plays a pivotal role in the underlying inflammatory pathophysiology of Crohn’s disease 15 Furthermore neutralization of TNFα has been shown to improve the symptoms of this debilitating illness 13 16 Infliximab has been shown to improve HRQoL as measured by the IBDQ and the ShortForm Health Survey SF36 8 17 but the occurrence of infusion reactions along with the risk of developing antiinfliximab antibodies which can reduce longterm efficacy 18 could negatively impact HRQoL over time Patients may feel that subcutaneous treatment has advantages over treatments requiring infusion a long stay at the clinic may negatively impact a patient’s daily life This increased freedom in patient treatment management may lead to improved treatment compliance with a consequent impact on therapeutic outcomes Thus there is a need for alternative longterm therapies for moderatetosevere Crohn’s disease that have minimal negative impact on patients’ everyday life while also reducing the impact of the disease on patients’ HRQoL 19

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