Introduction

The risk of colorectal advanced adenomas (CAAs) and colorectal cancer (CRC) in siblings aged ≤ 50 years of patients diagnosed with early-onset CAAs (E-CAAs), defined as having CAA at or below the age of 50 years​, is poorly understood.

Aims & Methods

This study aimed to compare the risks of adenomas, CAA, and CRC in siblings aged ≤ 50 years of patients diagnosed with E-CAA to those in individuals aged ≤ 50 without such a family history.
This case-control study was conducted at a tertiary hospital in Vietnam. The participants included 96 cases who were siblings aged ≤ 50 years of patients diagnosed with E-CAA. Controls were randomly selected from consecutive patients aged ≤ 50 years who did not have siblings diagnosed with E-CAA. The absence of a family history of CAA in the control group was confirmed through comprehensive history taking. ​The controls were matched to cases in a 2:1 ratio for age (±3 years), sex, and smoking status. Individuals with alarming features of CRC or a family history of CRC were excluded. All the participants underwent standard bowel preparation and colonoscopy.

Results

The mean age was similar between cases (40.9 ± 6.0 years) and controls (41.1 ± 6.0 years). Except for the indications for colonoscopy, there were no significant differences in the baseline demographics between the two groups. A higher risk of CAA was documented in cases compared with controls (odds ratio [OR] = 6.33; 95% confidence interval [CI], 1.43–43.8; P = 0.018). This increased risk of CAA was more pronounced among male participants (OR = 13.7; 95% CI, 1.23–262; P = 0.006). Higher risks of colorectal adenomas (OR = 2.43; 95% CI, 1.27–4.67; P = 0.009) and colorectal neoplasia (OR = 2.23; 95% CI, 1.24–4.40; P = 0.011) were also found in cases compared with controls. CRC was found in one case and two controls.

Conclusion

Siblings aged ≤ 50 years of patients diagnosed with E-CAA have an increased risk of adenomas, CAA, and colorectal neoplasia. CRC screening should be initiated early in high-risk individuals.

Table 1. Risk of Colorectal Neoplasia among Siblings of Patients Diagnosed with Advanced Adenomas (n = 288)

References

Ng SC, Lau JY, Chan FK, et al. Risk of Advanced Adenomas in Siblings of Individuals With Advanced Adenomas: A Cross-Sectional Study. Gastroenterology. 2016;150(3):608-e17.
Cottet V, Pariente A, Nalet B, et al. Colonoscopic screening of first-degree relatives of patients with large adenomas: increased risk of colorectal tumors. Gastroenterology. 2007;133(4):1086-1092.

Introduction

We conducted a retrospective analysis of a large U.S. based administrative claims database comparing the risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) among patients with inflammatory bowel disease (IBD) initiating advanced biological therapies.

Aims & Methods

Patients with CD and UC who were incident users of advanced biological agents from 2013 to 2023 were identified within the Optum Labs® database. The therapeutic agents included either tumor necrosis factor-α (TNF) antagonists (infliximab, adalimumab, and certolizumab pegol), IL-12/23 antagonists (ustekinumab), IL-23 antagonists (risankizumab), anti-integrin agents (vedolizumab), Janus kinase (JAK) inhibitors (tofacitinib and upadacitinib), or S1PR modulators (ozanimod). Eligible patients were required to have continuous insurance coverage for at least one year before and after treatment initiation. We estimated incidence rates (IRs) and compared risks for VTE and MACE (myocardial infarction and stroke). Fatal cardiovascular outcomes were excluded due to limited specificity and data constraints.
To account for baseline confounding, we applied stabilized inverse probability of treatment weighting (IPTW) using multinomial propensity scores. Hazard ratios were estimated using Cox proportional hazard models.

Results

We included 12,245 patients with CD (mean age: 44.5 ± 17.5 years; 54.2% female; 30.9% using concomitant steroids), and 9,430 patients with UC (mean age: 47.5 ± 17.7 years; 49.2% female; 50% on concomitant corticosteroids). Patients receiving JAK inhibitors and vedolizumab were more likely to have higher comorbidity burden than others for CD while those receiving IL-23 antagonists had the most comorbid burden for UC patients, when assessed through proportion of patients with Charlson comorbidity index of ≥ 5. In UC patients, VTE incidence rates ranged from 1.69 to 2.01 for VTE and MACE rates from 0.52 to 0.99 per 100 person-years. For CD, VTE incidence rates ranged from 0.89 to 2.33 and for MACE, 0.68 to 1.73. Hazard ratios comparing the risk of events across therapies is presented in table 1.

Table 1: Hazard ratios for risk of VTE and MACE in patients with Crohn’s disease and Ulcerative colitis receiving advanced biological therapies and small molecules

Conclusion

In this large real-world IBD cohort, there was no difference in risk of adverse cardiovascular and thrombotic events between any biological agent or small molecule, in compairosn to TNF antagnoists.

Disclosure

• CM: Consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Mirador Therapeutics, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Eli Lilly, Ferring, Pfizer.
• VJ: Consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome,Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi
• SS: Research grants from Pfizer

Introduction

Alternate day oral iron therapy is better than daily oral iron therapy in Iron deficiency anemia (IDA) as it increases the fractional absorption of iron. In Ulcerative colitis (UC) with IDA increased fractional absorption of iron with alternate day iron may not only be better in improvement of anemia but also results in reduced unabsorbed iron delivery to distal bowel and may hence reduce adverse effects.

Aims & Methods

In a randomized, open label trial, from February 2023 to December 2024 patients of UC in remission (Mayo ≤2 OR partial Mayo ≤1 with fecal calprotectin <150mcg/gm for last 3 months) with IDA (ferritin <30mcg/l, transferrin saturation <20%, Hb 8-12 gm/dl) were randomized to every other day 132mg (EOD group) or daily 66mg (OD group) elemental oral iron given as ferrous fumarate for 8 weeks. Primary outcome was the difference in mean change in Hemoglobin (Hb) at 8 weeks. Secondary outcomes were the difference in mean change in RBC indices, iron indices and adverse events at 8 weeks.

Results

54 patients were randomized between both groups. One patient in EOD and 2 in OD group withdrew before treatment initiation. Eleven patients had disease flare on oral iron therapy (5 in EOD and 6 in OD group) p= 0.62 and two patients in EOD group had intolerance requiring oral iron stoppage. Thirty-eight patients completed treatment. The mean change in Hb at 8 weeks in EOD and OD groups was 2.08±1.0gm/dl and 2.09±1.11gm/dl respectively in per protocol analysis (p=0.797). The mean change in serum ferritin, serum iron, transferrin saturation and total iron binding capacity in both the groups is not significant. Disease flare within 6 months prior to oral iron therapy correlated with increased incidence of flare on oral iron therapy. (P=0.04)

Conclusion

Alternate day oral iron is not better than daily oral iron in improving Hb levels, iron indices and with similar incidence of adverse events in patients of UC in remission. A recent flare has increased chances of disease flare with oral iron therapy