Systematic review and network meta-analysis: evaluating the impact of advanced therapies for moderate-to-severe ulcerative colitis on health-related quality of life.

P1154 Impact of pharmacological therapies for moderate to severe Ulcerative Colitis on health-related quality of life: a systematic review and network meta-analysis

Background Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon that has a relapsing-remitting course. Health related quality of life (HRQL) is significantly lower in patients with UC than the general population due to the negative effects of the disease on physical, psychological and social well-being. Randomized controlled trials (RCTs) evaluating medical interventions for UC have traditionally used clinical disease activity indices that focus on symptoms to define primary outcomes such as clinical remission or improvement. However, this approach does not evaluate benefits that are highly relevant to patients such as HRQL Objectives The primary objective was to assess the impact of biologic therapy on the HRQL of UC patients. Search methods We searched PubMed, MEDLINE, EMBASE and CENTRAL from inception to September, 2015. Conference abstracts and reference lists were also searched. Selection criteria RCTs that compared biologics to placebo in UC patients and reported on HRQL using the Inflammatory Bowel Disease Questionnaire (IBDQ), or the SF-36 or EQ-5D to measure HRQL were included. Data collection and analysis Two authors independently screened studies for inclusion, extracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was improvement in HRQL. For dichotomous outcomes we calculated the risk ratio (RR) and 95% confidence interval (CI). For continuous outcomes we calculated the mean difference (MD) and 95% CI. The overall quality of the evidence supporting the primary outcome was assessed using GRADE. Main results Nine RCTs (n = 4143) were included. Biologics included rituximab (one small study), interferon-s-1a (one study), vedolizumab (one study), and the tumor necrosis factor-alpha (TNF-α) antagonists infliximab (two studies), adalimumab (three studies), and golimumab (one study). Risk of bias was low in eight studies. The rituximab study was judged to be at high risk of bias due to attrition bias. The studies comparing interferon-s-1a and rituximab to placebo found no clear evidence of a difference in the proportion of patients who experienced an improvement in HRQL at 8 or 12 weeks respectively. The proportion of patients with a clinically meaningful improvement in HRQL at 6 or 52 weeks was significantly higher in vedolizumab patients compared to placebo. At 6 weeks 37% (83/225) of vedolizumab patients had an improvement in IBDQ score of at least 16 points from baseline compared to 23% (34/149) of placebo patients (RR 1.62, 95% CI 1.15 to 2.27; 1 study). At 52 weeks, 64% (157/247) of vedolizumab patients had an improvement in IBDQ score of at least 16 points from baseline compared to 38% (48/126) of placebo patients (RR 1.62, 95% CI 1.15 to 2.27; 1 study). A GRADE analysis indicated that the overall quality of the evidence supporting these outcomes was moderate due to sparse data ( 16 points from baseline compared to 50% of placebo patients (RR 1.39, 95% CI 1.21 to 1.60; 1 study). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was high. Similar results were found between infliximab and placebo when HRQL was measured using the SF-36 instrument. One small study (n = 43) found no difference in HRQL between infliximab and placebo when measured by the EQ-5D. Pooled analyses of TNF-α antagonists showed a benefit in HRQL favouring TNF-α over placebo. Authors' conclusions These results suggest that biologics have the potential to improve HRQL in UC patients. High quality evidence suggests that infliximab provides a clinically meaningful improvement in HRQL in UC patients receiving induction therapy. Moderate quality evidence suggests that vedolizumab provides a clinically meaningful improvement in HRQL in UC patients receiving maintenance therapy. These findings are important since there is a paucity of effective drugs for the treatment of UC that have the potential to both decrease disease activity and improve HRQL. More research is needed to assess the long-term effect of biologic therapy on HRQL in patients with UC. More research is needed to assess the impact of golimumab and adalimumab on HRQL in UC patients. Trials involving direct head to head comparisons of biologics would help determine which biologics provide optimum benefit for HRQL.

Patient-reported outcomes are important in the assessment of efficacy of intervention for ulcerative colitis (UC). To compare the impact of interventions for moderate-to-severe UC on health-related quality of life (HRQL). We searched Medline, Embase, CENTRAL and grey literature sources through October 2017. We included randomised controlled trials (RCTs) that compared infliximab, adalimumab, golimumab, vedolizumab or tofacitinib to each other or placebo. Outcomes included the change in quality of life scores and the proportion of patients with improvement in quality of life. We performed random-effect pairwise and network meta-analysis. We assessed confidence in estimates using the CINeMA (Confidence in Network Meta-Analysis) framework. Fourteen RCTs assessed HRQL using the Inflammatory Bowel Disease Questionnaire (IBDQ) (14 trials), the Short Form questionnaire-36 (SF-36) (seven trials) or the European Quality of Life-5 Dimensions questionnaire (EQ-5D) (three trials). At induction (13 trials), low to very low confidence evidence suggested that all agents significantly improved both generic and disease-specific HRQL scores compared to placebo. However, only infliximab (MD 18.58; 95% CI 13.19-23.97) and vedolizumab (MD 18.00; 95% CI 11.08-24.92) showed clinically meaningful improvement in IBDQ score. Differences among individual interventions were imprecise. For maintenance (four trials), very low confidence evidence suggested that vedolizumab, tofacitinib and adalimumab maintained improvement in HRQL. Induction treatment with infliximab, adalimumab, golimumab, vedolizumab or tofacitinib improves quality of life compared to placebo. Evidence on maintenance therapy is sparse and uncertain. Head-to-head comparisons could enhance confidence in conclusions about differences between drugs in terms of HRQL.

DOP56 Ustekinumab maintained clinically meaningful improvement in health-related quality of life in patients with moderate to severe ulcerative colitis: Results from the UNIFI long-term extension

Adalimumab 160-/80-mg Induction Regimen is Associated With Better Outcomes Compared With the 80-/40-mg Regimen During Maintenance Therapy in Patients With Crohn's Disease

Crohn's Disease Patients With Persistently Elevated CRP Plasma Concentration Have Higher Rates of Remission With Certolizumab Pegol 400 mg Every 2 Weeks vs. Every 4 Weeks

The comparative efficacy of advanced therapies to improve health-related quality of life (HR-QoL) in Crohn's disease (CD) is unknown. We aimed to compare the impact of approved advanced therapies for moderate-to-severe CD on HR-QoL. We searched MEDLINE, Embase, and Cochrane CENTRAL from inception to December 2023. We included randomized controlled trials that assessed approved advanced therapies for the treatment of adults with moderate-to-severe luminal CD. The primary outcome was change from baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ). Pairwise random-effects meta-analyses were conducted, and we reported results as mean differences (MDs) for continuous outcomes and risk ratios for binary outcomes, with corresponding 95% confidence intervals (CIs). A random-effects frequentist network meta-analysis was conducted, and the competing interventions were ranked using the P-score. Our search strategy included 34 records that fulfilled our eligibility criteria. In pairwise meta-analysis, advanced therapies were associated with improvements in IBDQ score (MD 16.07, 95% CI 12.59-19.54) after induction. In network meta-analysis, upadacitinib 45 mg ranked first for change in IBDQ after induction (MD 23.10, 95% CI 14.41-31.78, P-score 0.86). For maintenance studies, advanced therapies showed a significant improvement in IBDQ score in pairwise meta-analysis (MD 12.72, 95% CI 10.47-14.97). Infliximab 10 mg/kg ranked first for change in IBDQ after maintenance (MD 24.91, 95% CI 12.99-36.83, P-score 0.90). Advanced therapies were associated with improvements in HR-QoL after induction and maintenance. Upadacitinib 45 mg and infliximab 10 mg/kg ranked highest after induction and maintenance, respectively.

Adalimumab Improves Health-Related Quality of Life for 52 Weeks in Patients With Ulcerative Colitis

IntroductionWe investigated effects of adalimumab (ADA) maintenance therapy on health-related quality of life (HRQOL) through 52 weeks (wks) in patients (pts) with ulcerative colitis (UC).Methods494 pts with moderate to severe...

Health-related quality of life (HRQOL) is an important outcome factor in chronic diseases such as inflammatory bowel disease (IBD). This study used the Korean translation of the disease-specific, self-administered Inflammatory Bowel Disease Questionnaire (IBDQ) to compare HRQOL in ulcerative colitis (UC; n = 98), Crohn's disease (CD; n = 49), and intestinal Behçet's disease (BD; n = 34). In addition to the current status, patients were asked retrospectively to recall their symptoms at the beginning and during the worst period of their disease. Disease activity was measured by St. Mark's Activity Index, Crohn's disease Activity Index (CDAI), and the Harvey-Bradshaw Index (HBI). In all IBD patients, including those with BD, the IBDQ total score during the worst period was significantly lower than that at present and that at the beginning of the disease. However, there were no significant differences between groups regarding the total IBDQ score or its various dimensions. In UC a strong correlation between IBDQ scores and St. Mark's Activity Index was observed (r = -0.708, P < 0.001). IBDQ scores were also highly correlated with CDAI and HBI in both CD (r = -0.506, P < 0.001 for CDAI; r = -0.600, P < 0.001 for HBI) and BD (r = -0.687, P < 0.001 for CDAI; r = -0.531, P < 0.001 for HBI). However, the current IBDQ score was not related to demographic parameters such as gender, age, educational status, economic status, and marital status as well as disease factors such as duration of disease, history of operation or hospital admission, extent of disease in UC, involved region in CD, and clinical type in BD. We conclude that the Korean IBDQ is a responsive and promising instrument for measuring HRQOL of IBD patients in clinical trials. In addition, the IBDQ can be helpful in developing a disease-specific activity index in BD.

DOP075 Tofacitinib in active ulcerative colitis: Analysis of efficacy based on patient-reported outcomes

Background/AimsImproving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC.MethodsA multicenter, hospital-based, prospective study was performed using a Moderate-to-Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later.ResultsIn a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p<0.01). Inflammatory markers such as C-reactive protein (CRP) or erythrocyte sedimentation rate also showed a negative correlation on HRQL (p<0.05). Patients whose IBDQ score improved by 16 or more (71.2%) in 1 year were younger, tended to be nonsmokers, and had a lower partial Mayo score and CRP than those whose IBDQ score did not. There was no significant association between HRQL and disease extent, treatments at diagnosis, or the highest treatment step during the 1-year period.ConclusionsOptimally controlled disease status improves HRQL in patients with moderate-to-severe UC. The partial Mayo score and inflammatory markers may be potential indicators reflecting the influence of UC on patient`s daily lives.

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

INTRODUCTION: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Significant improvements have been reported in all Inflammatory Bowel Disease Questionnaire (IBDQ) domains for tofacitinib vs placebo (PBO) in patients (pts) with UC in OCTAVE Induction 1 &amp; 2 and OCTAVE Sustain. 1 The effect of tofacitinib on items within each IBDQ domain has not yet been analyzed. METHODS: We examined the effect of tofacitinib induction (10 mg twice daily [BID]) on individual IBDQ items in adults with moderate to severe UC. Data were pooled from the randomized, Phase 3 OCTAVE Induction 1 &amp; 2 studies (NCT01465763 &amp; NCT01458951). 2 Pts self-administered the IBDQ at baseline (BL), Week (Wk) 4, and Wk 8. IBDQ domains are: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items); higher scores indicate better health-related quality of life (HRQoL). 1,3 Change from BL (CFB) in IBDQ items was analyzed for tofacitinib vs PBO using a linear mixed-effects model, with fixed effects (treatment, study, prior tumor necrosis factor inhibitor treatment, BL corticosteroid use, geographical region, week, treatment-by-week interaction, and BL score) and a random effect (pts). No multiplicity adjustment was performed. RESULTS: Significant improvements (P &lt; 0.05) were observed in all IBDQ items with tofacitinib 10 mg BID vs PBO at Wks 4 and 8. The largest treatment differences (CFB; domain) were: “bowel movements been loose” at Wks 4 and 8 and also “problem with rectal bleeding” at Wk 8 (all 1.1 points) for the bowel symptoms domain; “getting a good night's sleep” at Wk 4 (0.8) and 8 (0.9) for the systemic symptoms domain; “fear of not finding a washroom” at Wk 4 (0.6) and 8 (0.8) and also “felt embarrassed” and “felt angry” at Wk 4 (both 0.6) for the emotional function domain; and “avoid attending events” at Wk 4 (0.8) and 8 (1.0) and also “difficulty doing leisure/sports” at Wk 8 (1.0) for the social function domain (Table 1). CONCLUSION: Tofacitinib improved all bowel-related and systemic symptoms, and all emotional and social functioning IBDQ items vs PBO, highlighting the broad impact of tofacitinib on HRQoL. This analysis provides a useful perspective on the most improved IBDQ domains with tofacitinib induction therapy, which may facilitate patient-physician dialogue.

ObjectiveMirikizumab, a monoclonal antibody targeting the interleukin-23 p19 subunit, was effective in a Phase 2 study (NCT02589665) of moderately-to-severely active ulcerative colitis (UC). We studied mirikizumab’s impact on health-related quality...