Infliximab Therapy on Quality of Life in Ulcerative Colitis Patients
Objectives: The impact of infliximab induction and maintenance therapy on health-related quality of life (HRQL) was evaluated in patients with ulcerative colitis (UC).
Methods: In two placebo-controlled, double-blind studies (the Active Ulcerative Colitis Trials 1 and 2 [ACT 1 and 2]), 728 patients were randomized to placebo or infliximab 5 mg/kg or 10 mg/kg. Infusions were administered at weeks 0, 2, 6, and every 8 wk thereafter, up to week 22 (ACT 2) or 46 (ACT 1). Changes in Inflammatory Bowel Disease Questionnaire (IBDQ) and Medical Outcomes Study 36-Item Short Form Health Survey physical and mental component summary (PCS and MCS, respectively) scores were analyzed.
Results: Baseline scores for the pooled patient population indicated substantial impairment in HRQL. Improvement at week 8 in the total IBDQ score was significantly greater in the infliximab 5-mg/kg (40, P < 0.001) and 10-mg/kg (36, P < 0.001) groups compared with the placebo group (28). Improvement at week 8 was also significantly greater in the infliximab 5- and 10-mg/kg groups for the PCS (6.8 and 5.9, respectively) and MCS (5.9 and 6.4, respectively) compared with placebo (PCS = 3.7, MCS = 3.0, P < 0.01 for all comparisons). Continued benefit was seen at weeks 30 and 54 with infliximab maintenance therapy (P < 0.001 for all comparisons). Improvement in total IBDQ score correlated significantly (P < 0.001) with improvement in both PCS and MCS scores, and Mayo score.
Conclusions: Infliximab therapy substantially improved HRQL in patients with UC. This benefit was sustained through 1 yr with maintenance infliximab therapy.
Ulcerative colitis (UC) is a chronic disorder characterized by an inflammatory reaction involving the colonic mucosa. Patients with UC experience substantial impairment in health-related quality of life (HRQL) from the typical symptoms of abdominal pain, bloody diarrhea, and fatigue. Moreover, current treatments for patients with UC, such as corticosteroids, frequently cause adverse effects that may also negatively affect patient HRQL.
Tumor necrosis factor-alpha (TNFα) is a proinflammatory cytokine found at increased concentrations in the blood, colonic tissue, and stools of UC patients. Infliximab (REMICADE, Centocor, Inc., Malvern, PA) is a monoclonal antibody that binds with high affinity and specificity to human TNFα. This binding process, which lessens the biological availability of TNFα, results in down-regulation of a pathological immune response through several mechanisms. The Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and 2, respectively) were large multicenter clinical studies that demonstrated the efficacy of infliximab therapy for inducing and maintaining clinical response, disease remission, and mucosal healing in patients with moderately to severely active UC.
Although traditional measures of disease activity such as the Mayo score have been used to assess the efficacy of new drug treatments, these indices do not evaluate the overall illness experience from a patient perspective. HRQL assessments can play a complementary role to such clinical assessments by providing a more comprehensive evaluation of the effects of drug therapy on the well-being of patients. However, evaluation of HRQL requires the use of valid instruments that detect clinically meaningful differences in health status.
In these studies, we used two validated HRQL instruments, the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific questionnaire, and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), a general questionnaire. The use of such measures facilitates the documentation of impairment of HRQL in patients with UC, and allows for the assessment of the impact of treatment on HRQL. This paper examines the impact of infliximab induction and maintenance therapy on HRQL in patients with UC using data from the ACT 1 and ACT 2 studies.
Abstract and Introduction
Abstract
Objectives: The impact of infliximab induction and maintenance therapy on health-related quality of life (HRQL) was evaluated in patients with ulcerative colitis (UC).
Methods: In two placebo-controlled, double-blind studies (the Active Ulcerative Colitis Trials 1 and 2 [ACT 1 and 2]), 728 patients were randomized to placebo or infliximab 5 mg/kg or 10 mg/kg. Infusions were administered at weeks 0, 2, 6, and every 8 wk thereafter, up to week 22 (ACT 2) or 46 (ACT 1). Changes in Inflammatory Bowel Disease Questionnaire (IBDQ) and Medical Outcomes Study 36-Item Short Form Health Survey physical and mental component summary (PCS and MCS, respectively) scores were analyzed.
Results: Baseline scores for the pooled patient population indicated substantial impairment in HRQL. Improvement at week 8 in the total IBDQ score was significantly greater in the infliximab 5-mg/kg (40, P < 0.001) and 10-mg/kg (36, P < 0.001) groups compared with the placebo group (28). Improvement at week 8 was also significantly greater in the infliximab 5- and 10-mg/kg groups for the PCS (6.8 and 5.9, respectively) and MCS (5.9 and 6.4, respectively) compared with placebo (PCS = 3.7, MCS = 3.0, P < 0.01 for all comparisons). Continued benefit was seen at weeks 30 and 54 with infliximab maintenance therapy (P < 0.001 for all comparisons). Improvement in total IBDQ score correlated significantly (P < 0.001) with improvement in both PCS and MCS scores, and Mayo score.
Conclusions: Infliximab therapy substantially improved HRQL in patients with UC. This benefit was sustained through 1 yr with maintenance infliximab therapy.
Introduction
Ulcerative colitis (UC) is a chronic disorder characterized by an inflammatory reaction involving the colonic mucosa. Patients with UC experience substantial impairment in health-related quality of life (HRQL) from the typical symptoms of abdominal pain, bloody diarrhea, and fatigue. Moreover, current treatments for patients with UC, such as corticosteroids, frequently cause adverse effects that may also negatively affect patient HRQL.
Tumor necrosis factor-alpha (TNFα) is a proinflammatory cytokine found at increased concentrations in the blood, colonic tissue, and stools of UC patients. Infliximab (REMICADE, Centocor, Inc., Malvern, PA) is a monoclonal antibody that binds with high affinity and specificity to human TNFα. This binding process, which lessens the biological availability of TNFα, results in down-regulation of a pathological immune response through several mechanisms. The Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and 2, respectively) were large multicenter clinical studies that demonstrated the efficacy of infliximab therapy for inducing and maintaining clinical response, disease remission, and mucosal healing in patients with moderately to severely active UC.
Although traditional measures of disease activity such as the Mayo score have been used to assess the efficacy of new drug treatments, these indices do not evaluate the overall illness experience from a patient perspective. HRQL assessments can play a complementary role to such clinical assessments by providing a more comprehensive evaluation of the effects of drug therapy on the well-being of patients. However, evaluation of HRQL requires the use of valid instruments that detect clinically meaningful differences in health status.
In these studies, we used two validated HRQL instruments, the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific questionnaire, and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), a general questionnaire. The use of such measures facilitates the documentation of impairment of HRQL in patients with UC, and allows for the assessment of the impact of treatment on HRQL. This paper examines the impact of infliximab induction and maintenance therapy on HRQL in patients with UC using data from the ACT 1 and ACT 2 studies.
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