Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking agent, was approved in Europe and the USA for the treatment of moderate-to-severe Crohn’s disease (CD) in 2014. Real-world evidence is essential for understanding the effectiveness and benefit–risk profile of VDZ for CD outside clinical trial settings. A systematic literature review and meta-analysis published in 2018 confirmed the real-world effectiveness and positive benefit–risk profile of VDZ treatment for up to 12 months in patients with inflammatory bowel disease.¹ However, there are limited real-world evidence on the long-term (> 12 months) effectiveness of VDZ in patients with CD.

Aims & Methods

A systematic literature review was performed using MEDLINE, MEDLINE In-Process, Embase, Cochrane Library, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform to identify relevant studies published from May 2014 to July 2022. In addition, if the congress abstracts were not indexed in Embase, key congresses from 2015 to July 2022 were hand-searched. Data from adults (aged ≥ 18 years) with CD treated with VDZ in a real-world setting were extracted for meta-analysis. Depending on data availability, the analysis was conducted using the DerSimonian-Laird random-effects model to obtain weighted mean rates (percentage of patients) and the corresponding 95% confidence interval (CI) for each outcome of interest, as per the 2018 meta-analysis.¹ The aims of the current analysis were to evaluate the rates of treatment persistence at 12 and 24 months and mucosal healing at 12 months (overall and stratified by biologic-naïve versus biologic-experienced patients) to address the paucity of long-term data available on these outcomes.

Results

Overall, data from 78 studies of 30 158 patients with CD had at least one outcome of interest for analysis. Using the reported number of patients as the weight, the baseline weighted mean age was 39.3 years (standard error [SE] 2.7; 15 studies), weighted mean disease duration was 12.5 years (SE 0.5; 8 studies), weighted mean CD activity index score was 177 (SE 4.3; 3 studies), and weighted mean Harvey-Bradshaw index score was 7.9 (SE 0.7; 5 studies). In the 32 and 13 studies that assessed treatment persistence at 12 and 24 months, respectively, the rates of treatment persistence were 62.8% (95% CI 56.6–68.9) and 54.9% (95% CI 44.3–65.4), and were higher in biologic-naïve patients than biologic-experienced patients at both time points (Table). The rate of mucosal healing at 12 months (assessed in 20 studies) was 38.4% (95% CI 30.2–46.5) and was higher in biologic-naïve patients than biologic-experienced patients at both time points (Table).

	Patients with CD		Biologic-naïve patients with CD		Biologic-experienced patients with CD
	Na (studies)	%b (95% CI)	Na (studies)	%b (95% CI)	Na (studies)	%b (95% CI)
12-month VDZ treatment persistence	6312 (32)	62.8 (56.6, 68.9)	846 (5)	81.0 (70.5–91.6)	1653 (6)	60.4 (52.9–67.8)
24-month VDZ treatment persistence	3271 (13)	54.9 (44.3–65.4)	575 (3)	70.4 (61.3–79.6)	1060 (2)	41.9 (8.3–75.6)
12-month mucosal healing	1390 (20)	38.4 (30.2–46.5)	164 (6)	48.6 (30.5–66.7)	239 (5)	29.6 (19.3–39.9)
aNumber of patients assessed in studies that assessed treatment persistence or mucosal healing, respectively. bEvents per 100 patients.

Conclusion

This meta-analysis of real-world studies of VDZ demonstrated high rates of robust, long-term treatment persistence and mucosal healing in patients with CD, particularly in biologic-naïve versus biologic-experienced patients. Over a third of patients achieved mucosal healing at 12 months, confirming the effectiveness of VDZ for achieving this important treatment outcome.

References

1. Schreiber S et al. J Gastroenterol 2018;53:1048–64.

Disclosure

This study was funded by Takeda Pharmaceuticals International AG. Medical writing services were provided by Matthew Reynolds, of Oxford PharmaGenesis, and funded by Takeda Pharmaceuticals International AG.
SS: Personal fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Fresenius, Galapagos/Gilead, Hikma, I-Mab, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, ProventionBio, Takeda and Theravance Biopharma.
PB: Employee and stockholder of Takeda Pharmaceuticals International AG, Zurich, Switzerland.
RJB: Employee of PHMR Ltd., who received funding for this study from Takeda Pharmaceuticals International AG.
MN: Employee and stockholder of Takeda Pharmaceuticals International AG, Zurich, Switzerland.
SW: Employee and stockholder of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
AA Advisory board/lecture fees from AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda.

Introduction

Patients with inflammatory bowel disease (IBD) are at increased risk of reduced bone mineral density (BMD), often linked to chronic inflammation, corticosteroid use, biologics, and vitamin D deficiency. 25-hydroxyvitamin D (25(OH)D) is a fat-soluble vitamin essential for calcium and phosphorus homeostasis, and its deficiency is common in IBD due to malabsorption, dietary, altered metabolism, or impaired VDR signaling.

Aims & Methods

This cross-sectional study aimed to evaluate the relationship between serum 25(OH)D levels, BMD, and body composition in IBD patients. A total of 73 outpatients with IBD (38 ulcerative colitis, 35 Crohn’s disease) were assessed. Body composition was evaluated using BMI and bioelectrical impedance analysis (BIA). BMD was measured using whole-body dual-energy X-ray absorptiometry (DEXA), and vitamin D status was assessed by serum 25(OH)D concentration. Statistical analysis included descriptive and comparative tests (Chi-square and t-test).

Results

Participants had a mean age of 45.27±11.37 years, with 67.1% being female and a mean disease duration of 10.22±7.54 years. Most patients (93.15%) were in clinical and endoscopic remission. The average BMI was 26.85±4.51 kg/m², with 39.7% classified as overweight. DEXA revealed a high prevalence of osteopenia (39.7%) and osteoporosis (19.0%). Mean BMD Z-scores were whole body -1.32±1.13, spine -0.92±1.19, and femoral neck -0.34±1.02. Mean serum 25(OH)D level was 31.20±8.78 ng/mL; 52.1% had insufficient levels and 47.9% were sufficient. Vitamin D insufficiency was significantly associated with osteopenia/osteoporosis (p=0.0144) and with overweight/obesity (p=0.0265). No significant associations were observed between vitamin D levels and age (p=0.6476), sex (p=0.4565), lean mass (p=0.2941), fat mass (p=0.1218), phase angle (p=0.3154), or regional BMD (total body p=0.5001; spine p=0.3067; femoral neck p=0.2364).

Conclusion

IBD patients are vulnerable to low serum vitamin D levels and present a high prevalence of low BMD. Vitamin D insufficiency was associated with altered BMI and increased risk of osteopenia/osteoporosis, though not with other body composition metrics. Further studies are needed with larger and more clinically heterogeneous samples to confirm these associations and guide screening and supplementation strategies.

References

Khan, ZAW, Shetty, S., Pai, GC, Acharya, KKV, & Nagaraja, R. (2020). Prevalence of low bone mineral density in inflammatory bowel disease and factors associated with it. Indian journal of gastroenterology: official journal of the Indian Society of Gastroenterology, 39(4), 346–353. https://doi.org/10.1007/s12664-020-01048-5
Kuo, YW, Kuo, CJ, Le, PH, Chang, ML, Lin, CY, Hsu, CM, Lin, WP, Chen, CW, Lin, WR, Ho, YP, Su, MY, and Chiu, CT (2025). Risk factors and awareness of bone fragility in inflammatory bowel disease in Taiwan: a cross-sectional study. Biomedicines, 13(3), 638. https://doi.org/10.3390/biomedicines13030638
Chauhan, G., & Rieder, F. (2025). The Pathogenesis of Inflammatory Bowel Diseases. Surgical Clinics of North America, 105(2), 201–215. https://doi.org/10.1016/j.suc.2024.10.008
Kärnsund, S., Lo, B., Bendtsen, F., Holm, J., & Burisch, J. (2020). Systematic review of the prevalence and development of osteoporosis or low bone mineral density and its risk factors in patients with inflammatory bowel disease. World Journal of Gastroenterology, 26(35), 5362–5374. https://doi.org/10.3748/wjg.v26.i35.5362
Aaseth, JO, Finnes, TE, Askim, M., & Alexander, J. (2024). The importance of vitamin K and the combination of vitamins K and D for calcium metabolism and bone health: a review. Nutrients, 16(15), 2420. https://doi.org/10.3390/nu16152420

Introduction

Type 1 AIP is the most common presentation of IgG4-related disease. Serum IgG4 levels are widely used in initial screening and diagnosis, with levels ≥135 mg/dL recommended as part of the diagnostic criteria. However, its diagnostic specificity is limited as it can be elevated in a broad spectrum of neoplastic, infectious, and autoimmune diseases. Histological diagnosis though definitive, remains challenging in real life clinical practice. In recent years, IgG4/IgG ratio has been proposed as a promising alternative serum biomarker.

Aims & Methods

We aimed to study the diagnostic utility of serum IgG4/IgG ratio compared to serum IgG4 alone in the diagnosis of Type 1 AIP. We identified a cohort of patients from 2015 to 2021 who had raised serum IgG4 levels in Tan Tock Seng Hospital, Singapore. Associations between serum IgG4 level and IgG4/IgG ratio were compared to confirmed AIP diagnosis and characteristic computed tomography (CT) and magnetic resonance imaging (MRI) features (diffuse pancreatic swelling, rim-like enhancement). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at IgG4/IgG thresholds of ≥15% and ≥20%.

Results

Our sample included a total of 60 patients with raised serum IgG4 levels. 21 patients had been diagnosed with Type 1 AIP, and 39 patients had not.
The majority of our patients had serum IgG4 ≥135 mg/dL (n=53, 88.3%). However, there was no significant association between the conventional serum IgG4 cut off of ≥135 mg/dL and the diagnosis of AIP (p = 0.687). In contrast, serum IgG4/IgG ratio demonstrated significantly higher values in patients with AIP compared to those without (median 23.2% vs 13.9%; p < 0.001). Analysis by logistic regression of IgG4/IgG ratio showed an acceptable performance with an area under the curve of 0.779, sensitivity of 92.3%, and specificity of 52.4%.

Variable	Type 1 AIP Present (n=21)	Type 1 AIP Absent (n=39)	Test Statistic	p-value
IgG4/IgG ratio	23.2 (24.0 ± 14.2)	13.9 (13.4 ± 4.5)	U = 184	<0.001
Serum IgG4 ≥135 mg/dL	18/21 (85.7%)	35/39 (89.7%)	Fisher's exact	0.687

We performed further analysis to determine a threshold for diagnostic utility of serum IgG4/IgG ratio. A ratio of ≥20% was strongly associated with AIP diagnosis (OR = 13.2, 95% CI: 3.08–56.5; p < 0.001), with high specificity (92.3%) and PPV (78.6%). Reducing the diagnostic threshold to ≥15% increased sensitivity to 76.2% (vs 52.4% at ≥20%) and improved NPV 84.4%, however this reduced specificity to 69.2%.

Subset analysis was performed among patients with Type 1 AIP (n=21) to evaluate for relationship between serum biomarkers and typical imaging findings (diffuse pancreatic swelling, rim-like enhancement). When stratified to a cut off of ≥135 mg/dL, the association between serum IgG4 levels with imaging findings trended towards positivity, but was not statistically significant (OR 3.14, p = 0.0553, φ 0.196). The IgG4/IgG ratio demonstrated a stronger association with typical imaging findings, although still not achieving statistical significance (OR = 1.065, p = 0.129). This subset analysis is likely limited by the small sample size.

Conclusion

This study demonstrates that serum IgG4/IgG ratio is a superior serological marker compared to serum IgG4 alone, particularly in the diagnosis of type 1 AIP. A threshold ratio of ≥20% demonstrated strong association with AIP diagnosis, with high specificity and PPV.
Our findings support the incorporation of IgG4/IgG ratio - particularly at a cut-off of 20% - as a valuable adjunct in diagnosis of suspected type 1 AIP, and we recommend further research in a larger cohort to validate this data.

References

1. Wallace ZS, Naden RP, Chari S, Choi HK, Della-Torre E, Dicaire JF, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020;72(1):7–19.
2. Umehara H, Okazaki K, Kawa S, Takahashi H, Yoshino T, Matsui S, et al. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-related disease. Mod Rheumatol. 2021;31(3):529–33.
3. Lanzillotta M, Mancuso G, Della-Torre E. Advances in the diagnosis and management of IgG4-related disease. BMJ. 2020;369:m1067.
4. Uchida K, Okazaki K. Current status of type 1 (IgG4-related) autoimmune pancreatitis. J Gastroenterol. 2022;57(10):695–708.
5. Xia CS, Zhang S, Duan L, Zhao CW, Zhang F. Diagnostic performances of serum IgG4 concentration and IgG4/IgG ratio in IgG4-related disease. Clin Rheumatol. 2017;36(11):2769–74.