Efficacy and safety of risankizumab in moderate-to-severe Crohn’s disease: a systematic review and meta-analysis

Abstract

Background:

Crohn’s disease (CD) is a chronic inflammatory disorder with limited therapeutic options for treatment-refractory patients. This meta-analysis evaluates the efficacy and safety of risankizumab (IL-23 p19 inhibitor) in moderate-to-severe CD.

Objectives:

To evaluate the clinical, endoscopic, and safety outcomes of risankizumab in patients with moderate-to-severe CD.

Design:

Systematic review and meta-analysis of randomized controlled trials (RCTs).

Data sources and methods:

A systematic search identified seven RCTs evaluating risankizumab at different doses, including a total of 4411 patients. We searched multiple databases, including PubMed, Cochrane CENTRAL, ClinicalTrials.gov, and Web of Science. Outcomes included clinical and endoscopic remission, endoscopic response, mucosal healing, stool frequency and abdominal pain scores. Data were pooled using a random-effects model, with risk ratios (RRs) and 95% confidence intervals (CIs) reported. Separate meta-analyses were conducted for the induction and maintenance phases.

Results:

Risankizumab was significantly more effective than placebo or active comparator in achieving clinical remission (CDAI) during induction (RR, 1.85; 95% CI, 1.69–2.01; p < 0.00001; I² = 0%) and maintenance (RR, 1.40; 95% CI, 1.21–1.62; p < 0.00001; I² = 58%). Endoscopic outcomes were robust, with significant rates of endoscopic remission (RR, 2.81; 95% CI, 2.04–3.87; p < 0.00001; I² = 50%) and endoscopic response (RR, 4.17; 95% CI, 3.31–5.77; p < 0.00001; I² = 0%) post-induction. Risankizumab significantly increased mucosal healing (RR, 3.40; p < 0.00001; I² = 61%) and reduced the risk of CD-related hospitalizations by 78% (RR, 0.22; 95% CI, 0.14–0.34; p < 0.00001; I² = 0%). While fecal calprotectin levels significantly improved (RR, 1.79; p < 0.00001; I² = 0%), no significant benefit was observed for high-sensitivity C-reactive protein maintenance (p = 0.39; I² = 59%). Subgroup analyses indicated consistent treatment effects across doses, with the Peyrin-Biroulet (2024) and FORTIFY trials identified as primary sources of observed heterogeneity in maintenance outcomes.

Conclusion:

These findings suggest that risankizumab is an effective and safe option for inducing and maintaining remission in moderate-to-severe CD. Further long-term studies should refine dosing, assess long-term outcomes, and support its integration into clinical guidelines.

Trial registration:

PROSPERO ID: CRD42024611707.

Keywords

Crohn’s disease activity index IL-23 p19 subunit inflammatory bowel disease treatment meta-analysis monoclonal antibody therapy

Introduction

Over the past two decades, the therapeutic management of patients with moderate-to-severe Crohn’s disease (CD) has substantially expanded.¹ Moderate-to-severe disease is commonly defined by a Crohn’s Disease Activity Index (CDAI) score of ⩾220 and ⩽450.² Tumor necrosis factor (TNF) antagonists revolutionized management for patients refractory to conventional therapy, yet approximately 30%–40% experience primary non-response or secondary loss of response over time.¹ This highlights the need for biologics that target alternative inflammatory pathways.

CD is a chronic, progressive inflammatory bowel disorder characterized by persistent or recurrent inflammation, debilitating complications, and long-term disability. If left untreated or poorly controlled, CD can lead to irreversible bowel damage, significantly impairing patients’ quality of life and increasing healthcare burdens.³ The pathogenesis of CD is complex, involving an interplay of genetic predisposition, environmental triggers, immune dysregulation, and gut microbiome alterations. These factors collectively disrupt the intestinal mucosal barrier, perpetuating inflammation and progressive tissue damage. The role of inflammatory cells is central to disease progression, with cytokine dysregulation driving a sustained inflammatory response. Current therapeutic strategies primarily target these pro-inflammatory cytokine pathways to halt disease progression and alleviate symptoms.⁴

Treatment for CD typically follows a two-phase approach: induction and maintenance. Induction therapy employs high doses of steroid-sparing medications to achieve rapid clinical remission within the initial weeks to months of treatment. On the other hand, maintenance therapy focuses on sustaining remission and preventing disease flares through the prolonged use of immunomodulators or biologics. Long-term therapeutic strategies aim to modulate key immune signaling pathways, thereby controlling disease activity and improving patient outcomes.⁵ Available treatment options include: (1) immunomodulators such as azathioprine, 6-mercaptopurine, and methotrexate; and (2) biologic therapies targeting TNF-α, IL-12/23, and integrin α4β7. While immunomodulators are effective in some patients, biologics have demonstrated superior efficacy in achieving sustained remission.^5,6 Among biologics, anti-TNF therapies have been pivotal in advancing CD treatment; however, limitations persist, as up to one-third of patients exhibit primary non-response and an additional one-third develop secondary failure or intolerance. Notably, patients who fail TNF inhibitors are less likely to benefit from alternative TNF antagonists or integrin-based therapies, highlighting the need for novel therapeutic approaches.⁷

Recent insights into CD pathogenesis have identified interleukin (IL)-23 as a critical driver of inflammation. IL-23 promotes the production of pro-inflammatory cytokines, such as IL-22, via activated T cells, thereby perpetuating the disease cascade.⁸ Risankizumab, a monoclonal antibody targeting the IL-23 p19 subunit, represents a promising therapeutic innovation. By blocking IL-23 signaling, risankizumab modulates a key inflammatory pathway central to CD pathogenesis. Although currently approved for plaque psoriasis and psoriatic arthritis, emerging evidence suggests its potential efficacy in IL-23-driven inflammation in CD.⁹ Thirty-three randomized controlled trials (RCTs) evaluating risankizumab have demonstrated encouraging outcomes in terms of efficacy and safety.

A previous meta-analysis, Vuyyuru et al. (2023), evaluated IL-12/23 and IL-23 inhibitors collectively in CD; however, the analyses combined multiple agents (e.g., ustekinumab, mirikizumab, and risankizumab) and included data only up to May 24, 2023. In contrast, the present meta-analysis focuses exclusively on risankizumab, incorporates the most recent 2024 Phase III trial data, and conducts dose-specific and phase-specific (induction vs maintenance) analyses. This updated meta-analysis aims to comprehensively assess the safety and efficacy of risankizumab in the treatment of CD to provide robust evidence to guide clinical decision-making and improve therapeutic outcomes for patients.

Methods

This meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, and the study protocol was prospectively registered in the PROSPERO database (Registration No: CRD42024611707). Ethical review board approval was not required, as all data utilized in the included studies were publicly available.

Search strategy

A comprehensive literature search was performed across electronic databases, including The Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Web of Science, and PubMed. These databases were searched from inception through November 2024 to identify original articles evaluating the safety and efficacy of risankizumab in patients with moderate-to-severe CD. The search employed Medical Subject Headings (MeSH) and keywords such as “inflammatory bowel disease,” “Crohn’s disease,” and “risankizumab.” The detailed search strategy used on different databases is given in Supplemental Table 1. No language or other restrictions were applied to ensure comprehensive retrieval of relevant studies. The study selection process is illustrated in the PRISMA flow diagram Figure 1.

Figure 1.

PRISMA diagram showing study selection.

Study selection

Studies included in this meta-analysis were phase II or III RCTs evaluating the safety and effectiveness of risankizumab in adult patients (aged ⩾18 years) with moderate-to-severe CD, defined by a CDAI score of 220–450,¹⁰ Eligible studies involved patients receiving risankizumab either as a first-line biologic or after prior biologic exposure. Included studies reported at least one of the following outcomes: induction of clinical remission (CDAI < 150), maintenance of remission (among patients who responded to induction therapy in re-randomization trials or among all patients in treat-through trials), or safety outcomes, including serious adverse events (SAEs) and/or infections as defined by the study authors. There were no restrictions on the duration of treatment. Exclusion criteria were case reports, review articles, and editorials; studies involving pediatric populations or individuals with mild CD; and studies lacking sufficient data on the outcomes of interest.

Data extraction

Two authors, Hafsa Nasim and Nida Naeem, independently extracted the data from all the studies that were selected, while a third author, Abdul Hannan Siddiqui, verified the results. Extracted data included study characteristics (author, year, study design, sample size), patient demographics (age, sex, duration of disease), and intervention details (dosage, duration). The primary efficacy outcome in induction trials was clinical remission, defined as a CDAI <150. Secondary outcomes included clinical response, defined as a reduction in CDAI ⩾100 points from baseline. For maintenance trials, the primary efficacy outcome was maintenance of clinical remission (CDAI <150); both responder re-randomization and treat-through trials were included; however, when available, remission data among induction responders was preferentially used for the primary endpoint in treat-through studies. A sensitivity analysis was conducted excluding treat-through trials. The safety outcomes assessed in maintenance trials were SAEs and infections, as defined by the original study authors. An insufficient number of trials reported endoscopic response and remission using consistent definitions, precluding quantitative synthesis in the meta-analysis.

Additional data extracted included location of trial conduct, number of trial sites, trial design (induction/maintenance, treat-through vs. induction responder re-randomization), sample size (and biologic-naïve proportion), outcome timing and definitions, proportion of male participants, mean or median age and disease duration, proportion of patients on concomitant therapy (thiopurines, methotrexate, aminosalicylates, and corticosteroids), and treatment dosing.

Quality assessment

The Cochrane Risk of Bias tool version 2 (RoB 2),¹¹ was used to evaluate the quality of the included RCTs. The tool evaluates potential biases across several domains, including the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. An independent risk of bias evaluation was conducted by two authors, Javeria and Hafsa, and any disagreements were resolved through discussion or consultation with a third reviewer, Abdul Hannan Siddiqui.

Statistical analysis

All statistical analyses were conducted using Review Manager (RevMan) version 5.4.1. Separate meta-analyses were conducted for the induction and maintenance phases of risankizumab therapy to account for differences in treatment duration and clinical response dynamics. Forest plots were generated independently for each phase to estimate pooled effect sizes. For dichotomous outcomes, pooled risk ratios (RRs) with 95% confidence intervals (CI) were calculated. A random-effects model was employed to account for the between-study variability. Forest plots were generated to visually represent the results. Endoscopic outcomes were aggregated only when definitions were deemed adequately comparable across studies; outcomes exhibiting significant heterogeneity in definitions were either not aggregated or were approached with caution. Heterogeneity among studies was assessed using the Higgins I² statistic, where thresholds of 25%, 25%–75%, and >75% indicated low, moderate, and >75% high heterogeneity, respectively. Statistical significance was defined as p ⩽ 0.05. Assessment of publication bias was not performed, as fewer than ten studies were included, limiting the reliability of funnel plot interpretation.

Results

A systematic literature review through The Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Web of Science, and PubMed were performed. After duplicate removal, these studies were subjected to screening through their titles and abstracts, and a total of seven studies were identified that met the eligibility criterion by reviewing their full texts.

Risk of bias

The included RCTs by Peyrin-Biroulet (2024), Ferrante (2023), the ADVANCE Trial, Feagan (2017), the FORTIFY Trial, and the MOTIVATE Trial demonstrated low risk of bias across key domains, including outcome measurement, selection of reported results, and deviations from intended interventions. While most studies exhibited strong methodological quality, Peyrin-Biroulet (2024) had some concerns regarding missing outcome data, which may introduce potential bias. Nonetheless, the overall reliability of the findings remains sound. Table 1 provides a visual summary of the risk of bias, and Figure 2 illustrates domain-specific assessments across studies.

Table 1.

Traffic light plots for quality assessment of included randomized controlled trials. Risk of bias was assessed across five domains.

D1, randomization process; D2, deviations from intended interventions; D3, missing outcome data; D4, measurement of outcomes; D5, selection of reported results.

Figure 2.

Quality assessment of included randomized controlled trials. Risk of bias was evaluated across key domains for each study, including outcome measurement, selective reporting, randomization process, and deviations from intended interventions.

Outcomes

Crohn’s disease activity index (clinical remission)

All seven studies evaluated clinical remission using the CDAI. The pooled analysis demonstrated that significantly improved CDAI remission after the induction period compared with control (RR = 1.85, 95% CI 1.69–2.01, p < 0.00001), as illustrated in Figure 3. There was no observed heterogeneity across studies (I² = 0%), indicating highly consistent results between trials. Risankizumab significantly improved maintenance of CDAI remission compared with control (RR = 1.40, 95% CI 1.21–1.62, p < 0.00001). Moderate heterogeneity was observed (I² = 58%), suggesting variability among the included studies. The heterogeneity dropped from 58% to 0%, indicating that the FORTIFY trial was the main contributor to variability. Given that only responders were included in the FORTIFY trial, which could have resulted in a more selected population and influencing effect estimates. The test for subgroup differences was not statistically significant (p = 0.50; I² = 0%), suggesting that the treatment effect was consistent between different dosing regimens.

Figure 3.

Forest plot of CDAI outcome. Blue squares and their corresponding lines are the point estimates and 95% conﬁdence intervals per study. Black diamonds represent the pooled effect estimate. (a) CDAI induction dose. (b) CDAI maintenance dose.

SES-CD ⩽4 and 2-point reduction from baseline (endoscopic remission)

Four of the seven included RCTs reported endoscopic remission as an outcome, defined as a Simple Endoscopic Score for Crohn’s Disease (SES-CD) ⩽4 and a 2-point reduction from baseline. As shown in Figure 4, the overall pooled analysis across all subgroups demonstrated significant endoscopic remission with risankizumab treatment during the induction phase (RR, 2.81; 95% CI, 2.04–3.87; p < 0.00001; I² = 50%) and during the maintenance phase (RR, 2.55; 95% CI, 2.04–3.17; p < 0.00001; I² = 0%). On leave-one-out analysis, heterogeneity dropped to 6% when Peyrin-Biroulet (2024) was removed. As this study compared risankizumab with ustekinumab while the other studies used placebo or standard care, the observed heterogeneity may be partially explained by variations in study comparators. The test for subgroup difference was not statistically significant (p = 0.50; I² = 0%), indicating a consistent treatment effect across doses.

Figure 4.

Forest plot of SES-CD⩽4 and at least a 2-point reduction versus baseline (Endoscopic remission) outcome. (a) SES-CD⩽4 and at least a 2-point reduction in the induction dose. (b) SES-CD⩽4 and at least a 2-point reduction maintenance dose.

Maintenance of stool frequency or abdominal pain score (clinical remission)

Five out of seven included studies reported clinical remission, defined as the maintenance of stool frequency or abdominal pain score following risankizumab administration. The overall pooled analysis confirmed a significant benefit of risankizumab in maintaining clinical remission based on stool frequency or abdominal pain during the induction phase (RR, 1.74; 95% CI, 1.42–2.14; p < 0.00001; I² = 54%) and during the maintenance phase (RR, 1.36; 95% CI, 1.23–1.51; p < 0.00001; I² = 22%). Heterogeneity dropped to 0% when Peyrin-Beroulet (2024) was removed in a leave-one-out sensitivity analysis (Figure 5).

Figure 5.

Forest plot of maintenance of stool frequency or abdominal pain score (clinical remission) outcome. (a) Maintenance of stool frequency (induction dose). (b) Maintenance of stool frequency (maintenance dose).

Decrease in SES-CD >50% from baseline (endoscopic response)

A total of five studies reported endoscopic response, defined as a decrease in SES-CD >50% from baseline, as an outcome. The pooled analysis across all subgroups confirmed a statistically significant endoscopic response with risankizumab treatment after the induction phase (RR, 4.17; 95% CI, 3.31–5.77; p < 0.00001; I² = 0%) and maintenance phase (RR, 2.09; 95% CI, 1.62–2.70; p < 0.00001; I² = 0%). The test for subgroup differences was statistically insignificant during both the induction and maintenance phase, indicating a dose-independent trend in treatment effect across dosing groups (Figure 6).

Figure 6.

Forest plot of the decrease in SES-CD >50% from baseline (endoscopic response) outcome. (a) Decrease IN SES-CD induction dose. (b) Decrease IN SES-CD maintenance dose.

Mucosal healing (ulcer-free)

Out of eight studies, five reported mucosal healing (ulcer-free) as an outcome following risankizumab treatment. Pooled analysis for the induction phase showed a statistically significant effect (RR, 3.40; 95% CI, 2.16–5.37; p < 0.00001; I² = 61%). Heterogeneity decreased to 0% when Gao et al. (2023) was removed. Heterogeneity may be partially explained by methodological elements like the study’s post hoc design and smaller sample size, as well as variations in the study population, since the analysis concentrated on an Asian subgroup. The pooled analysis across all studies for the maintenance phase demonstrated a statistically significant overall effect of risankizumab on mucosal healing (RR, 2.25; 95% CI, 1.76–2.88; p < 0.00001; I² = 0%).

Clinical remission and deep remission

Four studies assessed clinical remission and deep remission as outcomes for the maintenance phase. The pooled analysis demonstrated that risankizumab was significantly associated with both clinical and deep remission (RR, 2.82; 95% CI, 2.30–3.47; p < 0.00001; I² = 6%). The test for subgroup differences was not statistically significant (p = 0.47; I² = 0%), indicating consistency across dose groups.

Maintenance of FCP ⩽250 mg/kg

A total of two studies assessed the maintenance of fecal calprotectin (FCP) ⩽250 mg/kg as an outcome. The pooled analysis across all subgroups confirmed a statistically significant effect (RR, 1.79; 95% CI, 1.45–2.20; p < 0.00001; I² = 0%).

Maintenance of hs-CRP ⩽5 mg/L

Only two studies assessed maintenance of high-sensitivity C-reactive protein (hs-CRP) concentration ⩽5 mg/L as an outcome for risankizumab treatment. The pooled analysis revealed a statistically insignificant association between risankizumab and maintenance of hs-CRP ⩽5 mg/L (RR, 1.17; 95% CI, 0.82–1.65; p = 0.39; I² = 59%).

Decrease in stool frequency or ⩾35% reduction in abdominal pain score

Enhanced clinical response, defined as a decrease in mean daily stool frequency or a ⩾35% reduction in mean daily abdominal pain score, was assessed by five studies. Three studies reported the induction phase; the effect was statistically significant (RR, 2.30; 95% CI, 1.72–3.09; p < 0.00001; I² = 82%). The overall pooled analysis for the maintenance phase showed a significant effect (RR, 1.22; 95% CI, 1.44–1.12; p = 0.0001; I² = 24%) and is visually presented in Supplemental Figure.

Incidence of CD-related hospitalizations

The ADVANCE and MOTIVATE trials assessed the incidence of CD-related hospitalizations. The pooled analysis showed a statistically significant reduction in hospitalization risk (RR, 0.22; 95% CI, 0.14–0.34; p < 0.00001; I² = 0%). These findings are illustrated in Supplemental Figure.

Discussion

In this meta-analysis, we included eight RCTs involving 8924 patients with moderate-to-severe CD. According to the pooled evidence, risankizumab, an IL-23-targeted biologic, significantly improves both clinical and endoscopic remission compared with placebo or ustekinumab administration therapy during both the induction and maintenance phase. It also demonstrates benefits in maintaining endoscopic response and achieving mucosal healing, along with a significant reduction in hospitalization risk. These findings reinforce the growing body of evidence supporting selective IL-23 inhibition as a promising strategy in CD management.¹²

IL-23 is a key mediator in the pathogenesis of CD. Risankizumab targets the p19 subunit of IL‑23; this mechanism may underlie its efficacy over placebo in inducing clinical remission and endoscopic response in patients with active CD.¹³ Our study findings align with this evidence, showing a statistically significant overall effect of risankizumab on mucosal healing.

We also observed a significant benefit of risankizumab in maintaining clinical remission based on stool frequency or abdominal pain. Similarly, a phase III maintenance study (FORTIFY) shows that risankizumab significantly increased the proportion of patients maintaining remission, defined by stool frequency or abdominal pain, compared with placebo at 52 weeks.¹⁴

In addition to clinical outcomes, we evaluated biomarkers of intestinal and systemic inflammation. During intestinal inflammation, fecal calprotectin (FCP) is released by neutrophils in the intestinal lumen, making FCP a non‑invasive biomarker of intestinal inflammation.¹⁵ Our results indicate that risankizumab is effective in achieving and sustaining biochemical remission, as evidenced by the reduction in intestinal inflammation. There was a statistically significant maintenance of FCP ⩽250 mg/kg across both the 180 mg and 360 mg doses (RR, 1.79; 95% CI, 1.45–2.20; p < 0.00001; I² = 0%).

High‑sensitivity C‑reactive protein (hs‑CRP) is a blood biomarker of systemic inflammation. It reflects low‑grade inflammatory activity throughout the body.¹⁶ In our pooled analysis (RR, 1.17; 95% CI, 0.82–1.65; p = 0.39; I² = 59%), risankizumab did not show a statistically significant effect in maintaining low levels of systemic inflammation. This finding may be attributed to the limited number of studies (n = 2) reporting this outcome, resulting in a relatively small sample size. Although both fecal calprotectin (FCP) and hs-CRP serve as markers of intestinal inflammation, FCP is considered a more specific indicator of intestinal inflammatory activity.

In head-to-head clinical evidence, risankizumab demonstrated better efficacy compared to ustekinumab, achieving a nearly twofold higher rate of endoscopic remission at week 48 (31% vs 16%).¹⁷ This clinical divergence is likely due to their distinct molecular targets. While ustekinumab inhibits the p40 subunit common to both IL-12 and IL-23, risankizumab selectively targets the p19 subunit unique to IL-23. This specificity allows for a potent disruption of Th17-mediated inflammation, a primary driver of CD, while sparing the IL-12 pathway. Preserving IL-12 signaling is critical for maintaining Th1-mediated host defense, which may account for the favorable safety profile observed with risankizumab. Both clinical trials and real-world evidence suggest that selective p19 blockade does not increase the risk of serious or opportunistic infections, such as tuberculosis reactivation or candidiasis. Consequently, risankizumab offers a refined therapeutic strategy that balances superior mucosal efficacy with a minimized systemic immunosuppressive burden.¹⁸ Other IL-23 inhibitors such as guselkumab, mirikizumab, and brazikumab also target the p19 subunit, though they differ in pharmacokinetics and dosing regimens. While these agents have not shown major safety concerns to date, more long-term data and direct comparative studies are necessary to clarify their roles in CD management.¹⁹

Previous studies, including Ferrante et al., have demonstrated significantly higher remission rates in CD patients treated with risankizumab compared to placebo, underscoring its targeted modulation of key inflammatory pathways.²⁰ Given CD’s chronic, relapsing nature, risankizumab offers both effective symptom control and potential disease modification. Its efficacy is linked to the selective inhibition of IL-23, a cytokine crucial to intestinal inflammation and epithelial barrier dysfunction. Risankizumab’s selective mechanism may also explain its relatively favorable safety profile, especially compared to broader immunosuppressants like TNF-α inhibitors, which are associated with higher rates of systemic adverse events due to wider immune suppression.^17,19–22

Despite the encouraging findings, this meta-analysis has several limitations. The included studies employed varying dosing regimens, which could introduce bias and affect the generalizability of results. To address this, we attempted to minimize potential bias by conducting separate analyses for induction and maintenance phases, with further subgrouping based on specific dosage regimens.

Additionally, the study by Peyrin-Beroulet et al. (2024) contributed to heterogeneity in certain outcomes, likely due to differences in study design, as it compared risankizumab with ustekinumab. In contrast, other studies primarily used placebo or standard care as comparators.

Previous research by Vieujean et al. and Wyatt et al. has similarly highlighted that such methodological differences can lead to variability in response to biologic therapies.^23,24 Publication bias was not formally assessed using funnel plots, as fewer than ten studies were included for most outcomes. In such cases, funnel plot analysis is considered unreliable and may lead to misleading interpretations. Taken together, these limitations emphasize the need for well-designed, standardized randomized controlled trials to further validate and refine the role of risankizumab in clinical practice.

Future research should prioritize the identification of predictive biomarkers and conduct head-to-head trials to optimize IL-23–targeted therapies. Biomarkers such as genetic variants or cytokine profiles could enable more personalized treatment strategies by identifying patients most likely to respond to IL-23 inhibition.^8,25 Comparative studies between risankizumab and ustekinumab are crucial to determine relative efficacy across specific patient subgroups. Additionally, long-term data are needed to assess the safety and durability of response, particularly in underrepresented populations such as pediatric patients or those with significant comorbidities. Innovative trial designs, including adaptive dosing strategies, may further refine risankizumab’s therapeutic window and help address interindividual variability in treatment response.

Conclusion

This meta-analysis underscores the robust efficacy and favorable safety profile of risankizumab in the management of moderate-to-severe CD. Risankizumab demonstrated significant improvements in clinical and endoscopic remission rates. Its selective IL-23 inhibition provides effective symptom control and mucosal healing, offering a promising therapeutic alternative for patients who fail conventional treatments, including anti-TNF therapies.

Risankizumab’s targeted mechanism minimizes systemic immunosuppression-related risks, supporting its suitability for long-term disease management. Future research should prioritize the development of personalized treatment strategies, long-term safety evaluations, and head-to-head comparisons with other biologics. Overall, risankizumab represents a meaningful advancement in the therapeutic landscape of CD, addressing key gaps in efficacy and tolerability.

Supplemental Material

sj-docx-1-tag-10.1177_17562848261454195 – Supplemental material for Efficacy and safety of risankizumab in moderate-to-severe Crohn’s disease: a systematic review and meta-analysis

Supplemental material, sj-docx-1-tag-10.1177_17562848261454195 for Efficacy and safety of risankizumab in moderate-to-severe Crohn’s disease: a systematic review and meta-analysis by Hafsa Nasim, Abdul Hannan Siddiqui, Syed Jawad Khan, Kisa Fatima, Aimen Naz, Zaland Ahmed Yousafzai, Javeria Malik, Nida Naeem, Usama Khan and Raghabendra Kumar Mahato in Therapeutic Advances in Gastroenterology

Supplemental Material

sj-docx-2-tag-10.1177_17562848261454195 – Supplemental material for Efficacy and safety of risankizumab in moderate-to-severe Crohn’s disease: a systematic review and meta-analysis

Supplemental material, sj-docx-2-tag-10.1177_17562848261454195 for Efficacy and safety of risankizumab in moderate-to-severe Crohn’s disease: a systematic review and meta-analysis by Hafsa Nasim, Abdul Hannan Siddiqui, Syed Jawad Khan, Kisa Fatima, Aimen Naz, Zaland Ahmed Yousafzai, Javeria Malik, Nida Naeem, Usama Khan and Raghabendra Kumar Mahato in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

The authors would like to thank all contributing researchers whose work was included in this systematic review and meta-analysis.

Declarations

ORCID iD

Kisa Fatima

Reporting guidelines

This systematic review and meta-analysis followed the PRISMA 2020 checklist and guidelines.

Supplemental material

Supplemental material for this article is available online.

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