The impact of biological interventions on health-related quality of life in adults with Crohn's disease: a systematic review with meta-analysis

Abstract

Background: Health-related quality of life (HRQoL) is one of the main issues in Crohn's disease (CD). We systematically assessed the effects of a biological treatment on HRQoL in adults with CD.

Methods: We searched MEDLINE, EMBASE, and CENTRAL from inception to 26 Jul 2024 for randomised controlled trials (RCTs) investigating the effects of the biological agents approved for CD on HRQoL-related outcomes. Changes in IBDQ (Inflammatory Bowel Disease Questonnaire), SF-36 (The 36-Item Short Form Survey) and EQ-5D scores were evaluated using random-effects meta-analyses to determine if they met a clinically meaningful improvement (CMI). Cochrane's Risk of Bias tool 2 and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were applied to assess the quality and certainty of findings. PROSPERO registration: CRD42024573408.

Findings: Twenty-six RCTs involving 9013 participants were included in analysis. A clinically meaningful IBDQ score improvement was observed for infliximab (mean difference (MD) of 16.09 (95% CI: -0.13 to 32.31; 4 studies; 1162 participants, very low-certainty evidence)) and upadacitinib (MD 20.65, 95% CI 7.04-34.25; I² = 42.8%, P = 0.17; 3 studies; 1523 participants; high-certainty evidence). No significant IBDQ improvement was observed for adalimumab, certolizumab pegol, ustekinumab, or natalizumab compared to placebo (low-to high-certainty evidence). Due to considerable heterogeneity, data on vedolizumab and risankizumab could not be pooled.

Interpretation: Methodological issues in HRQoL measurement, including the need for larger sample sizes, standardized reporting, and uniform participant characteristics, contribute to the low methodological quality of current evidence on the impact of biological agents on HRQoL in CD. There is a large unmet need to investigate the association between clinical outcomes and HRQoL outcomes more thoroughly.

Funding: None.

Keywords: Antibody targeted therapy; Biologic drug; Crohn's disease; Inflammatory bowel diseases; Quality of life.

Fig. 1

PRISMA flow diagram of search results.

Fig. 2

Forest plot illustrating the mean differences of IBDQ score change between infliximab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; p, p-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Fig. 3

Forest plot illustrating the mean differences of IBDQ score change between adalimumab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Fig. 4

Forest plot illustrating the mean differences of IBDQ score change between certolizumab pegol and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Fig. 5

Forest plot illustrating the mean differences of IBDQ score change between ustekinumab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Fig. 6

Forest plot illustrating the mean differences of IBDQ score change between natalizumab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Fig. 7

Forest plot illustrating the mean differences of IBDQ score change between risankizumab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Fig. 8

Forest plot illustrating the mean differences of IBDQ score change between upadacitinib and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Fig. 9

Forest plot illustrating the mean differences of IBDQ score change between tumour necrosis factor-α antagonists (infliximab, adalimumab and certolizumab pegol) and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: IBDQ, Inflammatory Bowel Disease Questionnaire; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Supplementary Figure S1

Risk of bias in included studies. Abbreviations: +, low risk of bias; ? unclear risk of bias; -, high risk of bias.

Supplementary Figure S2

Forest plot illustrating the mean differences of SF-36 Mental Component Summary score change between infliximab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: SF-36, The 36-Item Short Form Survey; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Supplementary Figure S3

Forest plot illustrating the mean differences of SF-36 Physical Component Summary score change between certolizumab pegol and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: SF-36, The 36-Item Short Form Survey; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Supplementary Figure S4

Forest plot illustrating the mean differences of SF-36 Mental Component Summary score change between certolizumab pegol and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: SF-36, The 36-Item Short Form Survey; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Supplementary Figure S5

Forest plot illustrating the mean differences of SF-36 Physical Component Summary score change between ustekinumab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: SF-36, The 36-Item Short Form Survey; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Supplementary Figure S6

Forest plot illustrating the mean differences of SF-36 Mental Component Summary score change between ustekinumab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: SF-36, The 36-Item Short Form Survey; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Supplementary Figure S7

Forest plot illustrating the mean differences of SF-36 Physical Component Summary score change between risankizumab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: SF-36, The 36-Item Short Form Survey; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.

Supplementary Figure S8

Forest plot illustrating the mean differences of SF-36 Mental Component Summary score change between risankizumab and placebo groups across included studies. Squares represent individual study estimates of the mean difference, and horizontal lines (whiskers) indicate the 95% confidence intervals. The size of each square (box plot) reflects the weight of the corresponding study in the meta-analysis. The diamond at the bottom represents the overall mean difference and its 95% CI calculated using a random-effects model. Abbreviations: SF-36, The 36-Item Short Form Survey; CI, confidence interval; I², heterogeneity statistic; MD, mean difference; N, number of participants; P, P-value; SD, standard deviation; t, t-statistic for overall effect; τ², between-study variance.