Quality of life improvements with Natalizumab induction therapy in patients exposed to or failing TNF-alpha inhibitor therapy in the ENCORE Trial

To investigate the impact of natalizumab (NAT) induction therapy on the health-related quality of life (HRQoL) of Crohn's disease (CD) patients who had prior exposure to tumor necrosis factor-alpha (TNF-alpha) inhibitor therapy or had failed prior TNF-alpha inhibitor therapy. NAT is a humanized antibody against alpha-4 integrin indicated for patients with active inflammation who have had an inadequate response to TNF-alpha inhibitors. NAT was studied as an induction therapy for CD in ENCORE, a 12-week, randomized, controlled trial in patients with moderate to severe CD with elevated C-reactive protein levels. HRQoL was measured using both the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ) and the Short-form 36 (SF-36), a general measure of HRQoL. For this analysis, 2 groups of patients were identified: 1) patients previously exposed to TNF-alpha inhibitor therapy (“exposed” patients), and 2) patients previously exposed to TNF-alpha inhibitor therapy who were primary efficacy failures, secondary efficacy failures, or failed due to an adverse event or intolerance (“failed” patients). Changes in HRQoL from the baseline measure to Week 12 among those treated with NAT and those treated with placebo (PBO) were compared within the exposed and failed patient groups. Patients receiving NAT (n = 127) experienced significantly greater improvements in HRQoL as measured by the IBDQ (P<0.001) and each of the 4 domains of the IBDQ (Bowel Symptoms: P<0.001, Systemic Symptoms: P<0.001, Emotional Function: P=0.001, Social Function: P=0.003) compared with patients receiving PBO (n = 109). Improvements in HRQoL as measured by the SF-36 were also evident. Specifically, NAT patients had a significantly greater increase in the Physical Component Summary score of the SF-36 (P<0.001) and significantly greater improvement on 6 of the 8 individual scales of the SF-36 (Physical Functioning: P<0.001, Bodily Pain: P<0.001, General Health: P=0.004, Vitality: P=0.004, Social Functioning: P=0.013, Mental Health: P=0.047). The HRQoL outcomes among the subset of TNF-alpha inhibitor exposed patients who were treatment failures were similar. The improvement in HRQoL measured with the IBDQ scale was significantly greater (P<0.001) for the NAT-treated patients (n = 89) compared with those receiving PBO (n = 83). The changes in each of the 4 domains of the IBDQ were also significantly greater for the NAT-treated patients (Bowel Symptoms: P<0.001, Systemic Symptoms: P<0.001, Emotional Function: P=0.002, Social Function: P=0.027). Among this TNF-alpha inhibitor failure subset, increases in the scores of both the SF-36 Physical Component Summary and Mental Component Summary were found to be significantly greater for the NAT patients (P=0.002 and P=0.016, respectively). Significantly greater improvements were found on each of the same 6 individual scales of the SF-36 as for the larger group of TNF-alpha inhibitor exposed patients (P value range: <0.001 to 0.036). In ENCORE, NAT-treated patients who had previously been exposed to or had “failed” TNF-alpha inhibitor therapy demonstrated significant improvements in HRQoL as measured by the IBDQ and SF-36. Importantly, HRQoL improvement was found to be independent of the reason for TNF-alpha inhibitor discontinuation.

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