Clinical Case Summary

Aims: TNFα antagonists are effective therapeutic options for induction and maintenance of remission in patients with moderate to severe Crohn’s disease. However, these agents have been linked to immunogenicity and few case reports have described the onset of IgAN after such treatment.
Methods: We report the case of a 27-year-old male patient with CD who developed an Infliximab-induced IgA nephropathy.
Case Presentation: We report a man who, at the age of 16, manifested with a perianal abscess. The patient underwent ileocolonoscopy which revealed ileocolitis with histological investigations suggestive of Crohn’s disease and was treated with pos mesalamine and pos prednisolone (with tapering). Τhe patient had a poor response so he was administered a combo therapy with iv Infliximab and pos azathioprine. Four years later (monotherapy with Infliximab) the patient manifested enteropathic spondyloarthritis so he received additionally inj methotrexate with remission of the disease. After six years, being on remission, in a routine laboratory test he had hypoalbuminemia (Alb: 2,8 gr/dL), proteinuria and hematuria (hemoglobin +3 and protein +4 on dipstick). The rest lab values showed anemia (Hct: 31,50%, Hb: 11 g/dL), normal platelets and leukocytes and normal kidney function without markers of inflammation. Urine analysis demonstrated loss of 1 g of protein per day in 24-hour urine collection. Clinical examination and abdominal ultrasound were unremarkable. Kidney biopsy was performed, revealing findings consistent with IgA nephropathy (Figure). Upon the diagnosis was confirmed, Infliximab, as a potential inducer of IgAN, was discontinued and after the induction of corticosteroid therapy the patient made a remarkable recovery.
Conclusions: In the present case, the patient has been in deep remission for years therefore, Crohn’s disease alone was presumably not the cause of IgAN. Biological agent, specifically Infliximab, has been identified as the potential cause for IgAN.

References

1. Mertelj T, Smrekar N, Kojc N, Lindič J, Kovač D. IgA Nephropathy in a Patient Treated with Adalimumab. Case Rep Nephrol Dial. 2021 Jul 28;11(2):233-240. doi: 10.1159/000515585.
2. Terasaka T, Uchida HA, Umebayashi R, Tsukamoto K, Tanaka K, Kitagawa M, Sugiyama H, Tanioka H, Wada J. The possible involvement of intestine-derived IgA1: a case of IgA nephropathy associated with Crohn's disease. BMC Nephrol. 2016 Sep 5;17(1):122. doi: 10.1186/s12882-016-0344-1.
3. Bhagat Singh AK, Jeyaruban AS, Wilson GJ, Ranganathan D. Adalimumab-induced IgA nephropathy. BMJ Case Rep. 2019 Mar 31;12(3):e226442. doi: 10.1136/bcr-2018-226442.
4. Joher N, Gosset C, Guerrot D, Pillebout E, Hummel A, Boffa JJ, Faguer S, Rabant M, Higgins S, Moktefi A, Delmas Y, Karras A, Lapidus N, Amiot A, Audard V, El Karoui K. Immunoglobulin A nephropathy in association with inflammatory bowel diseases: results from a national study and systematic literature review. Nephrol Dial Transplant. 2022 Feb 25;37(3):531-539. doi: 10.1093/ndt/gfaa378.

Disclosure

Nothing to disclose.

Introduction

The treatment of complex perianal fistulas (cPAF) in Crohn’s disease remains challenging. Diversion stoma is typically reserved for patients with advanced disease and for palliation. However, data regarding its contribution to radiological remission (RR) in the era of biologic therapies are limited. This study aimed to evaluate effects of diversion stoma on RR.

Aims & Methods

After identifying RR-associated factors in entire cPAF cohort(n:236), a control group was generated using propensity score matching(PSM), accounting for these variables. Stoma(n:60) and control(n:59) groups were assessed for demographic and treatment-related characteristics. In the study group (n:60+59) univariate time-dependent anlayses were conducted for RR. Than, RR-related factors (p<0.1 in univariate analyses) were evaluated in multivariate Cox regression analysis. Cinical remission (CR) was defined as the absence of fistula drainage ≥3 months, confirmed by gentle compression. RR was defined as fibrotic closure of all fistula tracts in MRI. MRI assessments were reevaluated and confirmed by two radiologists.

Results

Among 236 patients with cPAF, factors associated with RR included multiple fistulas, branched morphology, trans-sphincteric fistulas (TSF), frequent need for antibiotics, and use of multiple anti-TNF agents. A total of 60 patients who underwent stoma formation were matched via PSM to 59 patients in the control cPAF group.
Stoma creation occurred at a relatively late stage, with a median fistula duration of 29 months (IQR: 69). The median stoma duration was 24 months (IQR:46). With stoma, CR was achieved in 77% and RR in 60% of patients. The median time to CR was 20 months (range: 3–196; IQR:13), and the median time to RR was 29 months (range: 6–208; IQR:28). The stoma was reversed in 45.8% of cases (n:27).
While multiple fistulas, TSF, and a history of multiple anti-TNF use were associated with RR in the entire cohort, their distribution was similar between stoma and control groups. However, the stoma group had a higher proportion of females (51.7% vs. 32.2%), more frequent history of seton use (53.3% vs. 35.6%), and longer IBD duration at the time of fistula development (30 vs. 5 months). These factors may be considered negative influencers in IBD and could compromise the success of the stoma group from the beginning. Both radiologic response and RR rates were significantly higher in the stoma group. In Kaplan-Meier analysis, diversion stoma was significantly associated with RR (log-rank: 0.02) (Table 1). Cox regression analysis showed that the presence of multiple fistulas and TSF were independently associated with poor RR, while diversion stoma was independently associated with achieving RR (Table 1). Among patients with a stoma, only multiple fistulas (p = 0.03) and TSF (p = 0.004) were associated with poor RR.

Conclusion

Diversion stoma in patients with cPAF, after adjusting for key prognostic factors, was independently associated with RR. Despite having unfavorable prognostic features such as TSF, multiple fistula tracts, and other negative influencers, the success of even relatively late-stage stoma formation may encourage consideration of earlier stoma creation to achieve RR.

Introduction

Colorectal endoscopic mucosal resection (EMR) is the treatment of choice for large colorectal lesions, but it has an important recurrence risk, requiring endoscopic surveillance. This study aims to identify factors associated with relapse and complications, by analysing the 5-year follow-up.

Aims & Methods

Prospective cohort study conducted in a single centre, including all patients submitted to colorectal pEMR between 2009 and 2021 with follow-up ≥3 months. We analysed lesion characteristics, calculated Sydney EMR recurrence tool (SERT) and SMSA (size, morphology, site, access) scores and compared complication and recurrence rates and respective risk factors.

Results

Included 568 mucosal resections, median age 69.5 years (IQR 62.3-76.0), male sex 58.1%. From the lesions included: 32.6% ≥40mm; 51.6% plane and 48.4% sessile; 35.9% in the right colon, 27.6% in the rectum, 23.2% in the transverse colon and 13.2% in the left colon. The median SMSA score was 4 (IQR 3-4) and median SERT score 1 (IQR 0-2), complication rate of 7.0% (bleeding, n=33; perforation, n=4; post-polypectomy syndrome, n=3) and overall recurrence rate of 20.3%: 15.1% in 3 months, 6.3% in 12 months, 2.5% in 36 months and 0% in 60 months.
The variables associated with recurrence were size ≥40mm (35.0% vs. 14.6%, p<0.001), anal location (35.1% vs. 19.7%, p<0.01), SERT score>0 (27.5% vs. 11.8%, p<0.001) and SMSA score=4 (30.6% vs. 11.5%, p<0.001), but not argon plasma therapy (22.8% vs. 18.7%, p=0.26). By logistic regression, size ≥40mm was associated with higher recurrence, but not statistically significant (OR 3.19, CI95% 0.69-1.63).
Use of anticoagulant/antiplatelet drugs was associated with higher risk of complications (12.7% vs. 4.7%, p<0.001), particularly bleeding (11.4% vs. 4.2%, p<0.01), with no difference for size ≥40mm (9.2% vs. 6.0%, p=0.17) or SMSA score=4 (7.6% vs. 6.5%, p=0.61).

Conclusion

The 5-year surveillance proved colorectal EMR’s efficacy. Recurrence is higher in lesions ≥40mm, with anal location, SERT score>0 and SMSA score=4, whereas bleeding is more frequent with the use of anticoagulant/antiplatelet drugs.

Introduction

Secondary loss of response to Infliximab(IFX) occurs in approximately half of patients with Inflammatory Bowel Disease(IBD), due to drug levels falling below the therapeutic range. This study evaluated IFX levels and related clinical and laboratory parameters and their impact on clinical outcomes.

Aims & Methods

Pre-infusion drug levels, associated laboratory data, and clinical parameters were evaluated in IBD patients receiving maintenance doses of IFX(5–15 mg/kg every 4–8 weeks) between Nov2021-Apr2025. Drug levels were measured using a bedside kit capable of quantitatively detecting values between 0.4–20µg/mL.

Results

A total of 1,059 single pre-infusion measurements from 455 patients and consecutive dual measurements at weeks 4 and 8 from 64 patients were evaluated. In the single and double measurement groups, 75.4% and 84.4% of patients had Crohn’s disease(CD), respectively. The most commonly used doses were 5 mg/8 weeks and 10 mg/4 weeks(Table 1) Drug levels were below 5 µg/mL in 33% of the measurements. Antibody positivity was present in 47.5% of 120 available measurements ranging from 0.4-20 µg/mL, showing no significant correlation with drug levels or immunomodulatory(IM) use (p=0.62 and p=0.61) However, for all positive antibody measurements drug levels were ≤ 3.5 µg/mL. CRP differed significantly across drug level groups, whereas albumin did not(Table 1). A weak negative correlation was found between IFX levels and CRP(r = -0.13, p = 0.001), with no correlation for albumin(p=0.54). In UC patients, the correlation between CRP and IFX levels was slightly stronger(r= -0.280, p=0.004).No significant associations were found between IM use and IFX levels >5 µg/mL(p=0.55), >10 µg/mL(p= 0.93), or >20µg/mL(p = 0.87). Abdominal pain was more common in patients with IFX levels <5 µg/mL (p=0.032) and <10 µg/mL (p=0.044). Smoking status was not associated with achieving IFX levels >5 µg/mL( p=0.57), >10 µg/mL (p=0.89), and >20 µg/mL (p=0.633). Among CD patients, those with IFX levels >5 µg/mL had significantly lower CDAI scores (p = 0.039), and lower daily stool frequency (p=0.002).Regression analysis showed that higher BMI (p=0.045), lower CRP(p < 0.001), higher IFX dose(p < 0.001), and CD diagnosis(p =0.014) to be independently associated with achieving IFX levels >5 µg/mL. These factors also predicted levels >10 µg/mL and >20 µg/mL, except for BMI at the >20 µg/mL threshold. In the dual measurement group, the median CRP levels at weeks 4 and 8 were 2.1(5.1) and 2.5(6.3), respectively (p = 0.108). Among patients with IFX >20 µg/mL at week 4, 75% maintained levels >5 µg/mL at week 8, whereas this rate was 64% for those with levels >10 µg/mL. Only 59.6% of those with >5 µg/mL at week 4 retained >5 µg/mL at week 8(all p <0.001). Week 4 IFX levels was 7.3 times higher than at week 8 for cases within measurable range.

Conclusion

One-third of patients demonstrated sub-therapeutic drug levels, which were associated with elevated CRP levels and worse clinical outcomes. Notably, the 5mg/4 weeks group exhibited higher drug concentrations compared to the 10mg/8 weeks group, suggesting that increased infusion frequency may contribute to achieving higher levels. Moreover, maintaining sufficient drug levels at week 8 requires substantially higher levels at week 4. Measurement of anti-TNF antibodies may not be fruitful if drug level is > 3.5µg/mL. These findings support the drug monitoring and personalized dosing to reduce the risk of loss of response and improve outcomes.

Introduction

The standard treatment for pT1 colorectal cancer classified as high risk (poor differentiation, deep submucosal invasion, intense tumor budding, resection margins that are positive or lymphovascular invasion) is surgery [1]. However, some studies have revealed that patients who undergo surgery and endoscopic treatment have similar disease progression outcomes, and it is also controversial which histological factors influence disease progression [2,3].

Aims & Methods

The aim of this study was to analyze the characteristics and evolution of patients undergoing surgery or endoscopic treatment after the resection of pT1 colorectal adenocarcinoma with histological findings considered high risk for lymph node metastasis.
We conducted an observational study of historical cohorts. We included patients with pT1 Adenocarcinoma and histological criteria of poor prognosis with at least six months of follow-up, and who were diagnosed between 2018 and 2024. The therapeutic approach was determined by a multidisciplinary committee.

Results

We included 54 patients (74.1% male) with a mean age of 65.3 years and mean follow-up time of 3.07 years; no significant differences in both groups. The indications for colonoscopy were screening (42.6%), alarm symptoms (38.9%), radiological findings (3.7%), prior polypectomy (9.3%), history of colorectal cancer (1.9%), and family history (3.7%). The rate of patients with endoscopic complications was 2.9% intraprocedural bleeding and 2.9% delayed bleeding.
The mean lesion size was 23.48 mm, and the most common location was the rectum.
Regarding the therapeutic approach, 63.0% of patients underwent surgery and 29.6% underwent endoscopic surveillance. Among the surgical patients, complications included suture dehiscence (6%), and hemorrhage (2%). In the surgical specimen analysis, residual lesion was found in 6 patients, and metastatic lymph nodes in 2. 5.55% required adjuvant therapy due to lymph node involvement, and 1.85% were stage IV at diagnosis, excluded from the comparative analysis.
Comparing both study groups, the surgical group had a significantly higher rate of submucosal invasion, with no differences in the remaining characteristics studied. During the study period, progression with lymph node involvement was observed in one patient who underwent surgery and two patients who underwent endoscopy treatment (average time 11 and 24.5 months, respectively). No patient has developed distant metastases to date.

Conclusion

In our study, patients who underwent endoscopic treatment did not present significant differences with respect to those who received surgery in terms of long-term tumor progression, despite having a higher rate of submucosal invasion. Further studies with larger sample sizes are needed to determine which factors and to what extent influence lymphatic and distant dissemination of pT1 adenocarcinoma.

References

1. Hassan C, Wysocki PT, Fuccio L, Seufferlein T, Dinis-Ribeiro M, Brandão C, et al. Endoscopic surveillance after surgical or endoscopic resection for colorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Digestive Oncology (ESDO) Guideline. Endoscopy 2019;51:266–77. https://doi.org/10.1055/a-0831-2522.
2. Ozeki T, Shimura T, Ozeki T, Ebi M, Iwasaki H, Kato H, et al. The risk analyses of lymph node metastasis and recurrence for submucosal invasive colorectal cancer: Novel criteria to skip completion surgery. Cancers (Basel) 2022;14:822. https://doi.org/10.3390/cancers14030822.
3. Zwager LW, Bastiaansen BAJ, Montazeri NSM, Hompes R, Barresi V, Ichimasa K, et al. Deep submucosal invasion is not an independent risk factor for lymph node metastasis in T1 colorectal cancer: A meta-analysis. Gastroenterology 2022;163:174–89. https://doi.org/10.1053/j.gastro.2022.04.010.

Introduction

Intestinal ultrasound (IUS) is a non-invasive modality for monitoring disease activity in inflammatory bowel disease (IBD). While widely used for long-term assessment, its utility in early response evaluation following biologic therapy initiation or modification remains underexplored.

Aims & Methods

This prospective study aimed to assess early ultrasonographic response at week 6 in ulcerative colitis (UC) and Crohn’s disease (CD) patients undergoing induction, dose escalation, or switching of biologic therapy. A total of 24 patients (mean age: 40.1 ± 12.8 years; 54.2% female) were included. Fourteen patients (58.3%) were initiating biologic treatment, 4 (16.7%) underwent dose escalation, and 6 (25%) were switched to another biologic agent. Biologic therapies included infliximab (70.8%), adalimumab (16.7%), and others (12.5%). IUS examination was performed at baseline and at week 6. The following parameters were assessed: bowel wall thickness (BWT), wall stratification, color doppler signal activity and mesenteric fat inflammation. IUS remission was defined as bowel wall thickness less than 3 mm and no color doppler signal. IUS improvement was defined as more than 25% decrease in bowel wall thickness without increase in color doppler signal. IUS activity assesment was performed at the same segment of the bowel at the 6th weeks.

Results

A total of 24 patients were included in the study, with a mean age of 40.1 ± 12.8 years; 13 (54.2%) were female. Seven patients (29.2%) had ulcerative colitis (UC), and 17 (70.8%) had Crohn’s disease (CD). Fourteen patients (58.3%) had newly initiated biologic therapy, 4 (16.7%) underwent dose escalation, and 6 (25%) were switched to a different biologic agent. Anti-TNF agents were used in 21 patients (87.5%), including infliximab in 17 (70.8%) and adalimumab in 4 (16.7%). The remaining 3 patients (12.5%) were treated with other biologic agents. At baseline, the most active intestinal segment on IUS was the terminal ileum in CD patients (9 patients, 52.9%) and the sigmoid colon in UC patients (4 patients, 57.1%) (p = 0.021). At week 6, 11 patients (45.8%) showed ultrasonographic improvement, 9 patients (37.5%) had no change, and 4 patients (16.7%) showed worsening. The baseline mean bowel wall thickness (BWT) of the most active segment was 5.5 ± 1.3 mm, which decreased to 4.4 ± 1.7 mm at week 6. A reduction in BWT was observed in 18 patients (75%), while an increase was seen in 6 patients (25%) (p = 0.002). In multivariate regression analysis, higher baseline bowel wall thickness was identified as an independent predictor of ultrasonographic improvement at week 6 (OR: 3.137; 95% CI: 1.005–9.790; p = 0.04). In patients who showed improvement, bowel wall thickness significantly decreased from baseline 6.2 ± 1.5 mm to 3.7 ± 1.6 mm at week 6 (to; p = 0.003), whereas in patients who worsened, an increase in wall thickness was observed (5.3 ± 1.0 mm to 6.7 ± 1.7 mm; p = 0.068). By disease group, 5 of the UC patients (71.4%) showed ultrasonographic improvement, 1 (14.3%) remained unchanged, and 1 (14.3%) worsened. Among CD patients, 6 (35.3%) showed improvement, 8 (47.1%) had no change, and 3 (17.6%) worsened. However, there was no statistically significant difference in response patterns between the UC and CD groups (p = 0.244).

Conclusion

Intestinal ultrasound at week 6 effectively detected early treatment response, with baseline bowel wall thickness emerging as a predictor of improvement. These results support its use in routine early monitoring of IBD patients on biologic therapy.

References

1. Calabrese E, Rispo A, Zorzi F, De Cristofaro E, Testa A, Costantino G, Viola A, Bezzio C, Ricci C, Prencipe S, Racchini C, Stefanelli G, Allocca M, Scotto di Santolo S, D'Auria MV, Balestrieri P, Ricchiuti A, Cappello M, Cavallaro F, Guarino AD, Maconi G, Spagnoli A, Monteleone G, Castiglione F. Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study. Clin Gastroenterol Hepatol. 2022 Apr;20(4):e711-e722.
2. Paredes JM, Moreno N, Latorre P, Ripollés T, Martinez MJ, Vizuete J, Moreno-Osset E. Clinical Impact of Sonographic Transmural Healing After Anti-TNF Antibody Treatment in Patients with Crohn's Disease. Dig Dis Sci. 2019 Sep;64(9):2600-2606.