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. 2025 Dec 1;12(1):e002034. doi: 10.1136/bmjgast-2025-002034

Utilisation and real-world effectiveness of advanced therapies for inflammatory bowel disease in Middle Eastern populations: a systematic review

Mohammed Nabil Quraishi 1,2,3,✉, Maryam A Alahmad 1, Ala I Sharara 4, Palak J Trivedi 5,6,7, Badr Al-Bawardy 8,9,10, Laith Alrubaiy 11,12
PMCID: PMC12673545  PMID: 41330599

Abstract

Objectives

We aimed to systematically review the real-world evidence (RWE) on the effectiveness and utilisation of advanced therapies for inflammatory bowel disease (IBD) in Middle Eastern populations.

Design

Systematic review.

Data sources

PubMed/MEDLINE, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials were searched up to May 2025.

Eligibility criteria

Observational RWE studies investigating biologics or small molecules in Middle Eastern IBD patients (adult and paediatric) were included. Randomised controlled trials and case series with fewer than 10 patients were excluded. No language restrictions were applied.

Data extraction and synthesis

Data were independently extracted by two reviewers. Due to significant heterogeneity in study design, populations and outcome reporting, a narrative synthesis was performed.

Results

From 884 records, 23 studies were included, originating primarily from Saudi Arabia (n=8) and Iran (n=4). For anti-tumour necrosis factor (TNF) therapy, a Kuwaiti study of biologic-naive patients found 12-month endoscopic remission rates with infliximab of 56% for ulcerative colitis (UC) and 53% for Crohn’s disease (CD), while a Saudi study reported higher odds of treatment failure with adalimumab versus infliximab (OR=26.91). Ustekinumab demonstrated strong efficacy, achieving 76.9% clinical remission at 52 weeks in a Saudi paediatric anti-TNF refractory IBD cohort and showing higher probability of effectiveness than vedolizumab in another Saudi study. In contrast, vedolizumab remission rates in advanced therapy-experienced UC patients were 89.3% with intensified dosing. Newer agents also showed promise; risankizumab induction led to 43.2% clinical remission in an Emirati CD cohort, while tofacitinib achieved clinical remission rates of 56.4% and 61.1% at 52 weeks in Lebanese and Iranian UC cohorts, respectively.

Conclusions

Advanced therapies for IBD appear to be effective in Middle Eastern cohorts; however, the available evidence is methodologically diverse, with substantial heterogeneity in study design, population characteristics and outcome reporting, which limits the ability to draw strong conclusions and highlights the need for further robust evaluation. Prospective, collaborative regional registries are imperative to address these gaps and inform local guidelines.

PROSPERO registration number

CRD420251083256.

Keywords: INFLAMMATORY BOWEL DISEASE, CROHN'S DISEASE, ULCERATIVE COLITIS

WHAT IS ALREADY KNOWN ON THIS TOPIC

  • The incidence of inflammatory bowel disease is rapidly increasing across the Middle East, but patients from this region have been historically under-represented in pivotal clinical trials for advanced therapies.

WHAT THIS STUDY ADDS

  • This systematic review of 23 real-world studies reveals that while advanced therapies are effective, the evidence is fragmented, originates mainly from a few countries like Saudi Arabia and Iran, and is sparse for newer agents.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • These findings underscore an urgent need for collaborative, pan-Middle Eastern registries to generate robust local data, which is essential for developing region-specific clinical guidelines and informing health policy.

Introduction

Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), is an escalating global health issue. Its incidence and prevalence are notably increasing in newly industrialised nations, particularly across the Middle East.1 2 This trend, which includes reports of a nearly 13-fold increase in new diagnoses at a single tertiary centre in the United Arab Emirates (UAE) over the last two decades, likely driven by genetics and Westernisation-linked environmental factors, presents significant challenges to regional healthcare systems and underscores the urgent need for optimised, evidence-based treatment approaches as prevalence is projected to surge.3,6 The growing availability of biologics and small molecule therapies has transformed IBD care globally. However, patients in the Middle East have historically been under-represented in clinical trials, limiting the applicability of international data to regional populations.3 7 8 Furthermore, access to these advanced therapies, funding models and the availability of specialist expertise to deliver them vary significantly across the region. While some countries have unrestricted access and high utilisation rates, others may face limitations due to payer restrictions or infrastructure, further complicating the regional management landscape and necessitating local real-world evidence (RWE).

RWE from routine clinical practice is consequently crucial for understanding long-term effectiveness, safety in diverse populations and overall value, particularly in varied healthcare contexts. A significant gap exists in robust RWE regarding the application and outcomes of these advanced therapies specifically within Middle Eastern populations. Regional clinical decisions often rely on data from Western cohorts, which may not be directly applicable due to potential genetic, environmental and healthcare system differences. This evidence deficit hinders tailored IBD management for these therapies locally.

While numerous systematic reviews have explored the real-world effectiveness of biologics and small molecules globally, the Middle East remains under-represented in global registries, randomised trials and RWE publications.9 This manuscript is the first systematic review that comprehensively examines real-world data on advanced therapies for IBD in Middle Eastern populations. The unique sociogenetic, environmental and healthcare system characteristics of this region may influence treatment response and healthcare utilisation, thus necessitating region-specific evidence. By systematically mapping existing data and identifying gaps, this review will support future strategic research investment and clinical guideline development tailored to Middle Eastern populations, which currently rely mainly on data extrapolated from western populations.10,13

This systematic review, therefore, aims to comprehensively synthesise and critically appraise the available RWE on the use and outcomes of advanced IBD therapies in Middle Eastern populations. A primary objective is to explore the current landscape of regional RWE, characterising its extent, nature and quality. This will identify areas where evidence may be abundant or lacking, thereby highlighting potential evidence gaps.

Methods

This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. A detailed protocol outlining the study’s objectives and methods was established a priori and registered with the International Prospective Register of Systematic Reviews prior to the commencement of the literature search (Registration No: CRD420251083256).14 The completed PRISMA 2020 checklist is provided in online supplemental document 1.

Eligibility criteria

Studies were included based on the Population, Intervention, Comparator, Outcomes framework:

  • Population: adult and/or paediatric patients with a confirmed diagnosis of IBD (including UC or CD), residing in or receiving care in the Middle East. For the purposes of this review, we adopted the WHO Eastern Mediterranean Region as the definition for the study area, which includes Afghanistan, Bahrain, Djibouti, Egypt, Iran (Islamic Republic of), Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syrian Arab Republic, Tunisia, UAE and Yemen.

  • Intervention: real-world use of advanced IBD therapies, including biologics (anti-tumour necrosis factors (anti-TNFs), anti-integrins, anti-interleukins (anti-IL12/23, anti-IL-23) and small molecules (Janus kinase (JAK inhibitors), S1P receptor (S1PR) modulators).

  • Comparators: real-world comparators, including conventional therapies, no active advanced therapy or another advanced therapy.

  • Outcomes

    • Primary outcomes: treatment effectiveness. Due to anticipated heterogeneity in outcome reporting across real-world studies, definitions for effectiveness were accepted as reported by the individual studies. These included, but were not limited to: clinical remission/response, steroid-free remission, endoscopic improvement/remission (also termed mucosal healing), histological healing and biomarker reduction (eg, C reactive protein, faecal calprotectin).

    • Secondary outcomes: utilisation (defined as drug durability, persistence, adherence, discontinuation and switching patterns) and reduction in hospitalisations or surgeries.

  • Study designs: Observational RWE studies, such as cohort studies and patient registry analyses.

Studies were excluded if they were randomised controlled trials (RCTs, unless providing long-term extension data with data that can be clearly disaggregated for the Middle Eastern populations), case series with fewer than 10 patients, narrative reviews, editorials, letters without original data or studies where data from Middle Eastern populations could not be disaggregated. Conference abstracts were included only if published in the last 12 months (June 2024 to May 2025).

Search strategy and study selection

A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify all relevant studies published up to May 2025, with no language restrictions. Although RCTs were excluded, CENTRAL was searched to ensure the identification of relevant observational long-term extension phases of interventional trials, as specified in our eligibility criteria. Search terms combined concepts for IBD, specific advanced therapies, RWE study types, and the specified Middle Eastern countries. The full Medline and Embase search strategies are provided in the online supplemental material (online supplemental document 2). The search was supplemented by screening reference lists of included articles and relevant reviews.

Following the removal of duplicates, two reviewers (MNQ and MAA) independently screened the titles and abstracts of all identified records against the eligibility criteria. The full texts of potentially relevant articles were then retrieved and assessed for final inclusion. Any disagreements between reviewers were resolved through discussion and consensus, with a third senior reviewer arbitrating if needed. The selection process was documented using a PRISMA flow diagram.

Data extraction and quality assessment

Two reviewers independently extracted data from all included studies using a standardised data extraction form. Extracted information included: (1) study characteristics (eg, author, year, country, study design); (2) patient characteristics (eg, IBD type, age, disease severity, prior treatments); (3) intervention details; and (4) outcome data.

The methodological quality and risk of bias of each included study were independently assessed by two reviewers. The Newcastle-Ottawa Scale (NOS) was used for non-randomised cohort and case–control studies. For comparative effectiveness studies, the Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I) tool was used. The results of the quality assessment were used to inform the synthesis and interpretation of the findings. Where the primary studies did not provide sufficient information to permit a judgement for a specific risk of bias domain, it was rated as ‘no information’. The results of the quality assessment were used to inform the synthesis and interpretation of the findings.

Data synthesis and analysis

A narrative synthesis was employed to summarise the findings from the included studies. The results were described and grouped thematically by the type of advanced therapy, IBD type and specific outcomes to provide a structured overview of the evidence landscape.

Although we explored quantitative pooling, the marked heterogeneity in study populations (adult vs paediatric), prior biologic exposure, outcome definitions (clinical vs endoscopic remission), follow-up durations and non-standardised reporting precluded formal meta-analysis. Given these constraints, we opted for a narrative synthesis to address the aim of the study.

Results

The systematic search of five major databases (PubMed/MEDLINE, Embase, Scopus, Web of Science and CENTRAL) initially identified 884 records as shown in the PRISMA flowchart (figure 1). No additional records were identified from other sources such as grey literature, citation searching or expert consultation. After the removal of 313 duplicates, 571 unique records underwent title and abstract screening. During this stage, 524 records were excluded primarily because they were not RWE (n=277), pertained to the wrong population (n=156), did not investigate advanced therapies as defined (n=30), did not report relevant outcomes (n=48) or were conference abstracts older than 1 year (n=13). On full-text assessment for eligibility, a further 24 reports were excluded. The main reasons for exclusion at this stage were wrong intervention (n=12), wrong outcomes (n=5), not being RWE (n=4) or the inability to disaggregate data for the Middle Eastern population (n=3). A total of 23 studies met the final inclusion criteria as summarised in online supplemental table 1) (online supplemental document 2), among which 21 were full papers and two were recent conference abstracts.15 16 These 23 studies included an aggregate population of 3683 patients from the region.

Figure 1. PRISMA 2020 flow diagram. The diagram illustrates the study selection process. It details the number of records identified through database searching, records remaining after duplicates were removed, records screened, reports sought for retrieval, reports assessed for eligibility and the final number of studies included in the systematic review, with reasons for exclusion at each stage. PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses; RWE, real-world evidence. **excluded following title and abstract screening.

Figure 1

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As shown in table 1, the included studies originated primarily from Saudi Arabia (n=8). Iran was the next most represented country with four studies, followed by Kuwait and Egypt with two studies each. The UAE, Lebanon, Bahrain and Iraq each contributed a single study. Additionally, three multinational studies with cohorts from the region were included. The temporal distribution of this focused research shows data collection periods spanning from the late 2010s to 2023, reflecting the evolving landscape of advanced IBD therapy. Earlier studies often focused on anti-TNF agents, while more recent research explores newer mechanisms of action. There were no RWE studies reporting on S1PR modulators in this specific population. The bulk of the evidence from this revised cohort relies on retrospective observational designs, though prospective cohort studies and registry-based analyses are emerging from several countries, including Saudi Arabia, the UAE and Lebanon.

Table 1. Distribution of real-world evidence studies on advanced therapies for IBD in the Middle East, by country and drug class.

Country Anti-TNF (IFX, ADA) Vedolizumab Ustekinumab Risankizumab JAK inhibitors (tofacitinib, upadacitinib) Total studies Notes
Saudi Arabia 6 3 3 0 1 10 Single-centre dominant; growing interest in newer agents
Iran 3 0 0 0 1 4 Older agents; includes prospective small studies
Kuwait 3 2 1 0 0 3 ENROLL study prominent; mostly biologic-naive populations
UAE 0 0 0 1 0 1 Only study on risankizumab; prospective design
Lebanon 0 0 0 0 1 1 Tofacitinib-focused; biologic-experienced cohort
Egypt 1 0 0 0 0 1 Single-centre infliximab retrospective study
Bahrain 1 0 0 0 0 1 Focus on early biologic discontinuation
Iraq 1 0 0 0 0 1 Small cohort; mixed UC and CD
Multinational (Middle East sites) 5+ 2+ 1 1 1 10+ Often in collaboration with Europe
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This table summarises the distribution of RWE studies on advanced therapies for IBD across various countries in the Middle East and by specific drug class.

IFX (Infliximab), ADA (Adalimumab), and ENROLL (Effectiveness of biologic therapies in achieving treatment targets in inflammatory bowel disease; real-world data from the Middle East).

CD, Crohn’s disease; IBD, inflammatory bowel disease; JAK, Janus kinase; RWE, real-world evidence; TNF, tumour necrosis factor; UC, ulcerative colitis.

Online supplemental tables 2,3 (online supplemental document 2) show the risk of bias assessed using the NOS and ROBINS-I tools, respectively. For non-comparative studies, the NOS was used, with scores ranging from 6 to 9. The majority of these studies scored 7 or higher, indicating a low to moderate risk of bias. For comparative studies, the ROBINS-I tool was used, with the overall risk of bias judged to be ‘moderate’ or ‘serious’ for most studies. Confounding due to a lack of adjustment for important prognostic factors and potential selection bias were the most frequent domains contributing to the risk of bias across the comparative studies.

Effectiveness of infliximab

Saudi Arabia

The infliximab biosimilar CT-P13 showed promising efficacy in 156 IBD patients. For naive CD, week 46 remission was 70.6%; for fistulising CD 25.0% (defined as clinical remission, not fistula healing); and for naive UC, 50.0%. Disease control in switched patients (from originator infliximab to biosimilar) was high (93%–100%).16 In contrast, another study found infliximab was associated with lower odds of treatment failure (defined endoscopically) compared with adalimumab in anti-TNF naive IBD patients in a cohort of 146 patients.17

Iran

In 44 adult CD patients refractory to anti-TNF monotherapy, adding methotrexate to infliximab (or other anti-TNFs) led to complete remission in 68.2% (defined by Harvey Bradshaw Index (HBI)).18 For very early onset severe UC, infliximab induction led to remission in 14% at week 54, with 43% having primary failure in 14 patients.19 A prospective study in 29 refractory UC patients showed infliximab-induced clinical remission in 58.6% (defined by Mayo score) and reduced disease extent in 34.5%.20

Iraq

In 32 IBD patients, infliximab resulted in good clinical response in 42.1% of UC patients and 61.5% of CD patients, with significant reductions in Mayo and CDI scores, respectively.21

Kuwait

The ENROLL (Effectiveness of biologic therapies in achieving treatment targets in inflammatory bowel disease) study in 422 biologic-naive IBD reported 12-month endoscopic remission rates with infliximab of 53% for CD and 56% for UC.22 In 44 refractory UC patients, infliximab induction led to clinical remission (defined by Mayo score ≤2) in 54.5% and mucosal healing (defined by Mayo endoscopic subscore≤1) in 65.9% at week 12.23

Iran (methotrexate+anti-TNF therapy)

In 44 adult Iranian CD patients refractory to anti-TNF monotherapy, combination therapy with methotrexate and anti-TNF resulted in complete remission in 68.2% (defined by HBI).18

Multinational/regional (including Middle Eastern sites)

The HARIR study (Algeria, Egypt, Kuwait, Qatar, Saudi Arabia) found a 29.2% clinical response (defined by CDAI (Crohn's Disease Activity Index) reduction ≤70) to infliximab at month 3 in CD patients from a total of 86 patients, though many had low baseline activity.24 The EXPLORE study (RME) reported suboptimal response rates to first-line anti-TNFs (including infliximab) in 1674 patients overall.25

Effectiveness of adalimumab

Saudi Arabia

In a study of 146 IBD patients naive to monoclonal antibodies, adalimumab was associated with higher odds of treatment failure (endoscopically defined) compared with infliximab (OR=26.91).17 The specific timeframe for this analysis, however, was not reported.

Kuwait

In the biologic-naive Kuwaiti ENROLL cohort of 422 patients, 12-month endoscopic remission rates for adalimumab were 52% for CD and 61% for UC.22

Iran

In 14 children with very early onset severe UC refractory to conventional treatment, 6 who failed infliximab were switched to adalimumab. At 52 weeks on adalimumab, 17% (1/6) achieved remission, while 50% (3/6) required colectomy.19

Regional (RME—Russia, Saudi Arabia, Turkey)

The EXPLORE study reported that for patients initiating first-line anti-TNF therapy (including adalimumab), the cumulative incidence of suboptimal response at 24 months was 29.5% for CD and 23.8% for UC in the RME cohort, which included 1674 patients overall.25

Effectiveness of vedolizumab

Saudi Arabia

In 101 adult CD patients who failed anti-TNF therapy, vedolizumab (n=30) was found to be potentially less effective than ustekinumab (n=71) for achieving clinical improvement (defined by HBI scores) at 12 weeks.26 A study from the IBD-ME Registry (implying Saudi Arabia/Kuwait) on 153 advanced therapy-experienced UC patients reported vedolizumab clinical remission rates (defined by P-SCCAI ≤3) of 61.9% (Q8 weeks) and 89.3% (Q4 weeks).27 In 16 IBD patients, 29.4% achieved clinical remission (defined by pMayo for UC or CDAI/HBI for CD) by week 14 with vedolizumab, with higher week 6 drug levels in remitters.28

Kuwait

The ENROLL study reported 12-month endoscopic remission rates with vedolizumab of 51% for CD and 53% for UC in biologic-naive patients among 422 total patients.22 The IBD-ME registry study also included Kuwaiti patients.27

Effectiveness of ustekinumab

Saudi Arabia

In 13 paediatric IBD patients (8 CD, 5 UC) refractory to anti-TNF, ustekinumab achieved clinical remission in 76.9% at week 52 (defined by PCDAI (Pediatric Crohn Disease Activity Index) /PUCAI (Pediatric Ulcerative Colitis Activity Index) ≤10).29 In 71 adult CD patients post-anti-TNF failure, ustekinumab showed a higher probability of effectiveness at 12 weeks compared with vedolizumab.26 In 30 anti-TNF-experienced adult CD patients, ustekinumab led to 66.7% clinical remission at week 12 (defined by HBI ≤4) and 76.7% clinical response at week 52 (defined by HBI decrease ≥3).30

Kuwait

The ENROLL study in biologic-naive patients reported 12-month endoscopic remission rates with ustekinumab of 56% for CD and 55% for UC among 422 total patients.22

Effectiveness of risankizumab

United Arab Emirates

In an Emirati cohort of 37 CD patients, risankizumab induction led to clinical remission (CDAI <150) in 43.2% (53.8% AT-naive, 37.5% AT-exposed) and clinical response (CDAI improvement by 100 points) in 89.2%.15 Among 15 patients with>12 months follow-up, clinical remission was 60%. In patients with available data, endoscopic response (≥50% SES-CD improvement) was 81.8% (n=9/11).

Effectiveness of JAK inhibitors (tofacitinib and upadacitinib)

Saudi Arabia

A prospective cohort in Riyadh evaluating upadacitinib in 26 IBD patients (18 UC, 8 CD) reported that among 6 CD patients completing induction, 4 achieved clinical remission at 3 months and maintained it at 6 months.31 For 14 UC patients completing induction, significant reductions in stool frequency and rectal bleeding were seen at 8 weeks, with a non-specified number of patients (reported as ‘significant patients’ in the abstract) achieving clinical remission at 6 months and endoscopic healing in 10/16 (data from conference abstract).

Lebanon

In 60 UC patients (58.3% prior biologic exposure), tofacitinib achieved clinical remission in 41.7% at week 8, rising to 56.4% at week 52 (defined as Mayo score 0–1 or SCCAI≤2). Endoscopic remission (defined as Mayo endoscopic score 0 or 1) at week 52 was 58.3%. However, 31.7% discontinued by 1 year.32

Iran

A prospective trial in 50 adult UC patients (failed conventional/anti-TNF) showed tofacitinib induction (10 mg two times per day) led to 84% clinical response and 9.5% clinical remission (total Mayo) at week 8.33 At week 52 (maintenance 5 mg two times per day), among week 8 responders, 61.1% were in clinical remission and 44.4% had endoscopic healing (defined as Mayo endoscopic subscore≤1).

Utilisation patterns and other key outcomes

Beyond direct effectiveness measures like remission and response, the reviewed studies provide insights into several other important aspects of advanced therapy use in the Middle East. Reasons for discontinuation included LOR/ineffectiveness, adverse events or sustained remission. In Lebanon, 31.7% of UC patients on tofacitinib stopped by 1 year due to LOR/ineffectiveness among 60 patients.32 Early biological discontinuation (within 6 months) in Bahrain was most commonly due to ineffectiveness, with older age at initiation being a risk factor in the 188 patients studied.34 The EXPLORE study (RME) characterised suboptimal response to anti-TNFs, with dose escalation being one component, among 1674 patients overall.25 One study linked higher trough levels of vedolizumab to better clinical outcomes.28 Data on the secondary outcomes of hospitalisation and surgery rates were sparsely and heterogeneously reported. The EXPLORE study (RME) identified IBD-related hospitalisation as the most frequent first indicator of suboptimal response to anti-TNFs in both UC (50.7%) and CD (37.3%) patients.25 In an Iranian paediatric UC cohort, 50% (3/6) of patients who failed infliximab subsequently required colectomy after switching to adalimumab.19 The ENROLL study (Kuwait) listed hospitalisations and surgeries as measured outcomes, but this specific data were not reported in the final abstract.22

Discussion

This systematic review is the first comprehensive effort to collate and synthesise available RWE on the utilisation and effectiveness of advanced therapies for IBD from a core group of Middle Eastern nations. This initiative is critical due to the rapidly escalating IBD burden in this region. Historically considered a disease of Western nations, IBD incidence and prevalence are markedly increasing across the Middle East, with recent estimates suggesting rising incidence rates and projections indicating a potential 2.3-fold increase in prevalence between 2020 and 2035.12 35,39 This escalating disease burden places an increasing strain on regional healthcare systems and underscores the urgent need for optimised, cost-effective treatment strategies informed by robust, locally generated RWE.

The studies highlighted in this review, predominantly observational and originating mainly from Saudi Arabia with growing contributions from other nations like the UAE, Kuwait and Iran, reveal an evolving but fragmented landscape. It is important to note that a significant body of RWE originates from neighbouring countries such as Israel and Turkey, which were excluded based on a strict regional definition. This excluded literature is extensive, particularly from Israel, and includes large, nationwide registry-based studies assessing long-term outcomes like surgery rates, prospective therapeutic drug monitoring trials and robust drug durability analyses. While outside the scope of this review, this parallel research landscape highlights the advanced state of IBD research in the broader geographical vicinity and provides a valuable comparator for future regional analyses. Within the included cohort, while many studies report positive efficacy outcomes, significant heterogeneity in study design, patient populations and outcome definitions makes direct comparisons challenging.

This review underscores several critical evidence gaps in the RWE landscape for advanced IBD therapies in the Middle East. Geographically, robust data are still sparse or absent from most countries in the region. Therapeutically, while older biologics have some evidence base, RWE for newer agents is lacking from many Middle Eastern cohorts. Outcome-related gaps are prominent, with a scarcity of long-term effectiveness, safety, patient-reported outcomes (PROs) and comprehensive healthcare resource utilisation and local cost-effectiveness data. Methodologically, studies were often retrospective and performed in a single centre, lacking standardised data collection and outcome reporting, which limits robust comparative analysis and quantitative synthesis. The reasons for these persistent methodological and data gaps are likely multifactorial, reflecting historical underprioritisation of IBD research, a lack of dedicated national funding streams for RWE, and an underdeveloped infrastructure for multicentre collaboration and clinical trial expertise in some nations. Furthermore, publication bias may contribute to the perceived lack of RWE, as smaller cohorts or studies with findings that do not significantly diverge from existing Western literature often face challenges in acceptance at international scientific congresses and peer-reviewed journals. These methodological constraints, particularly the reliance on retrospective data and the high degree of heterogeneity, fundamentally limit the generalisability of the effectiveness data and preclude any quantitative synthesis or meta-analysis, reinforcing our conclusion that the evidence is fragmented.

The available data from the Middle East suggest some potentially distinct characteristics. There is emerging evidence of aggressive CD phenotypes, with reports from the region indicating high rates of stricturing, penetrating and perianal disease, often noted at diagnosis or in higher proportions than typically reported in some Western cohorts.6 35 37 However, these observations may, in part, reflect referral bias towards tertiary centres that manage more severe or complex cases. Additionally, a high rate of advanced therapy utilisation has been observed in several regional cohorts across the broader MENA region, reflecting increasing availability, earlier intervention strategies or potentially more severe disease requiring such treatments. While direct comparisons with Western RWE must be made with caution, these regional observations highlight the need for local data to understand and manage IBD effectively.

The synthesised evidence and the identified gaps have significant implications for clinical practice and health policy in the Middle East. There is a clear need for the development or adaptation of region-specific clinical practice guidelines for IBD management, informed by local RWE to account for unique patient characteristics, disease phenotypes and healthcare system contexts. Such guidelines can help standardise care, optimise treatment selection and improve outcomes. Furthermore, robust local RWE is crucial for Health Technology Assessment bodies and payers to make informed reimbursement decisions for often costly advanced therapies. To address these gaps, a systematic and collaborative region-wide approach is vital, building on nascent collaborative efforts like the IBD-ME registry and the MIRAGE study (multinational cross-sectional study exploring demographics and clinical characteristics of IBD across the Middle East and North Africa) are vital first steps and drawing lessons from successful Western registries such as GETAID, ENEIDA, the UK IBD BioResource, REBOOT IBD and the VICTORY Consortium.3740,47

Compared with Western registries, our review found regional differences not only in study design and patient selection but also in outcomes reporting. For instance, the 1-year continuation rate of anti-TNFs in Middle Eastern cohorts is often lower than that reported in Western studies, which may reflect more severe disease phenotypes, later treatment initiation or health system differences. Moreover, while TDM is well integrated in some Saudi cohorts, it remains underutilised across much of the region. Demonstrating the real-world clinical and economic value of these treatments within the local setting can facilitate equitable patient access.7

This systematic review provides a strong case for a strategic vision to advance IBD research across the Middle East with a phased, collaborative approach forming its foundation. The initial phase must focus on strengthening regional networks among IBD centres and societies to establish consensus on a core dataset, harmonising key definitions for disease activity and outcomes. This must be paired with capacity-building programmes in RWE methodologies for local researchers. Subsequently, these efforts can mature into pilot multicentre prospective registries in key countries, which should prioritise the collection of PROs from the outset using culturally validated tools. Ultimately, the goal should be to scale these pilots into a sustainable, pan-Middle Eastern IBD registry network, supported by diversified funding and robust, transparent governance. Such a network will enable robust comparative effectiveness research to guide therapeutic sequencing decisions, currently a major gap in the region. Addressing the identified evidence gaps through such a robust, collaborative and large-scale RWE generation is imperative to inform region-specific clinical guidelines, optimise resource allocation, ensure equitable access to effective therapies and ultimately improve the lives of patients with IBD across the Middle East.

Supplementary material

online supplemental file 1
bmjgast-12-1-s001.docx (40.2KB, docx)
DOI: 10.1136/bmjgast-2025-002034
online supplemental file 2
bmjgast-12-1-s002.docx (31.7KB, docx)
DOI: 10.1136/bmjgast-2025-002034

Footnotes

Funding: This work was supported by the UAE Department of Health Ma’an Research Grant (DOH/ADHRTC/2025/360) that was awarded to MNQ.

Provenance and peer review: Not commissioned; externally peer-reviewed.

Patient consent for publication: Not applicable.

Ethics approval: Not applicable.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

online supplemental file 1
bmjgast-12-1-s001.docx (40.2KB, docx)
DOI: 10.1136/bmjgast-2025-002034
online supplemental file 2
bmjgast-12-1-s002.docx (31.7KB, docx)
DOI: 10.1136/bmjgast-2025-002034

Data Availability Statement

All data relevant to the study are included in the article or uploaded as supplementary information.

Articles from BMJ Open Gastroenterology are provided here courtesy of BMJ Publishing Group

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