Clinical Case Summary

Tofacitinib has recently been introduced into European guidelines for managing moderate-severe Ulcerative Colitis (UC). Among the various extra-intestinal manifestations of UC is Hidradenitis Suppurativa (HS), also called acne inversa. Unfortunately, there is no evidence on the efficacy of tofacitinib in HS, such that recommendations generally suggest anti-tumour necrosis factors, antibiotics, anakinra, ustekinumab or surgery. We report the case of a 26-year-old Caucasian non-smoking, nonalcohol-drinking, and non-obese woman diagnosed with UC E3 (i.e., pancolitis) according to Montreal classification with Mayo endoscopic subscore (ESS) of 2 at the age of 23 years old. At the time, the patient underwent conventional therapy with oral prednisone at the immunosuppressive dosage combined with oral mesalazine. Following this therapy, she achieved clinical-biochemical remission. A year later, she developed a UC relapse associated with steroid dependence, also received another colonoscopy (E3, ESS=2, C-Reactive protein 18.6 mg/L) and received a dermatologic diagnosis of HS (mainly localized to axillary folds, inguinal folds, intermammary groove) and treated employing topical triamcinolone/neomycin cream. In addition, we introduced Adalimumab. She then experienced primary failure. Due to the persistence of moderate-severe symptoms and iron-deficiency anaemia, we introduced tofacitinib therapy in March 2022. At that moment, the patient had an HS relapse which the previous dermatologic treatment failed. Therefore, the patient undertook tofacitinib induction with 20 mg daily for eight weeks. Because of clinical improvement with the halving of discharges and absence of blood, however, complete clinical remission was not achieved. Therefore, it was decided to continue this regimen for another eight weeks. At the end of the 16 weeks, we noted UC clinical and biochemical remission and a marked amelioration of HS. Today, the patient continues a 10 mg daily tofacitinib regimen.

References

- Chen W-T, Chi C-C. Association of Hidradenitis Suppurativa With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. JAMA Dermatol 2019;155:1022–7.
- Goldburg SR, Strober BE, Payette MJ. Hidradenitis suppurativa: Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol 2020;82:1045–58.
- Savage KT, Santillan MR, Flood KS, Charrow A, Porter ML, Kimball AB. Tofacitinib shows benefit in conjunction with other therapies in recalcitrant hidradenitis suppurativa patients. JAAD Case Rep 2020;6:99–102.
- Raine T, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, Bachmann O, Bettenworth D, Chaparro M, Czuber-Dochan W, Eder P, Ellul P, Fidalgo C, Fiorino G, Gionchetti P, Gisbert JP, Gordon H, Hedin C, Holubar S, Iacucci M, Karmiris K, Katsanos K, Kopylov U, Lakatos PL, Lytras T, Lyutakov I, Noor N, Pellino G, Piovani D, Savarino E, Selvaggi F, Verstockt B, Spinelli A, Panis Y, Doherty G. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J Crohns Colitis. 2022 Jan 28;16(1):2-17.

Introduction

ERCP is the cornerstone for managing biliary and pancreatic duct diseases. However, performing in patients with surgically altered anatomy poses significant challenges. Traditional ERCP techniques often fail in these cases due to difficulties in accessing the papilla. This has led to the development of alternative techniques like enteroscopy-assisted ERCP (e-ERCP) and endoscopic ultrasound-directed transenteric ERCP (EDEE).
e-ERCP while it can be successful, is technically demanding, time-consuming, and associated with a higher risk of complications while EDEE involves using EUS guidance to create a temporary anastomosis between the stomach and the intestinal segment containing the papilla. EDEE offers a more direct and stable route to the biliary tree, However, it requires specialized equipment (lumen-apposing stents) and expertise.

Aims & Methods

Retrospective observational, patients undergoing EDEE or e-ERCP at the CMN 20 de Noviembre between 2018-2024

Results

This study compared two endoscopic procedures, e-ERCP and EDEE, for accessing the biliary tract in patients with altered anatomy. The average age of the patients was 48 years, with a standard deviation of 14 years, and 61% were women. Most patients (81%) underwent e-ERCP, while only 9% underwent EDEE. Regarding the success of the procedure, e-ERCP had a technical success rate of 87%, endoscopic success rate of 93%, and clinical success rate of 75%. On the other hand, EDEE, although performed in a small number of patients, showed a 100% success rate in all three categories. Adverse events occurred in 5% of patients. 72% of patients had altered anatomy due to a pancreaticoduodenectomy, and 90% had a Roux-en-Y hepaticojejunostomy. In addition, dilations were performed in 72% of patients, stents were placed in 17%, and sphincterotomy or precut was performed in 17%.

Conclusion

The average cost of EDEE was 120,000 pesos (6,000 USD), while that of e-ERCP was 40,000 pesos (2,000 USD). Despite the difference in cost, EDEE showed a 100% success rate in this study, suggesting that it could be a cost-effective option for patients with altered anatomy in whom e-ERCP is not feasible or has failed. However, a cost-effectiveness analysis, considering the cost of the procedure divided by the proportion of clinical success, showed that e-ERCP was more cost-effective than EDEE.
Studies with a larger number of patients are needed to confirm these findings and to evaluate the safety and cost-effectiveness of EDEE compared to e-ERCP. This study is limited by the small number of patients with EDEE and the lack of information on the type of complications, the duration of the procedures, and long-term survival. It is recommended to expand the research with more patients and to perform a statistical analysis to formally compare the two procedures.

References

1. Khashab M. A. (2019). Endoscopic ultrasound-directed transenteric ERCP (EDEE) in patients with postsurgical anatomy - novel but challenging. Endoscopy, 51(12), 1119–1120. https://doi.org/10.1055/a-0958-2323
2. Ichkhanian, Y., Yang, J., James, T. W., Baron, T. H., Irani, S., Nasr, J., Sharaiha, R. Z., Law, R., Wannhoff, A., & Khashab, M. A. (2020). EUS-directed transenteric ERCP in non-Roux-en-Y gastric bypass surgical anatomy patients (with video). Gastrointestinal endoscopy, 91(5), 1188–1194.e2. https://doi.org/10.1016/j.gie.2019.12.043

Introduction

Direct oral anticoagulants (DOACs), particularly rivaroxaban and apixaban, are increasingly utilized to manage thromboembolic conditions due to their favorable efficacy and safety profiles. However, gastrointestinal bleeding (GIB) remains a significant concern associated with these medications, particularly considering pharmacogenetic variations among populations. This study aims to evaluate the frequency and identify risk factors associated with GIB in patients using rivaroxaban and apixaban in a Mexican healthcare setting.

Aims & Methods

This retrospective observational study analyzed data from January 2018 to December 2023 at the Centro Médico Nacional 20 de Noviembre, Mexico City. The cohort consisted of 278 patients: 136 on DOAC therapy (rivaroxaban or apixaban) and 142 controls without anticoagulation. Clinical data, demographic characteristics, comorbidities, and concomitant medications were systematically reviewed. Statistical methods employed included chi-square tests, Student's t-tests, and logistic regression analysis to assess the risk factors and association between anticoagulant type and incidence of GIB.

Results

The study population had a mean age of 67.36 ± 15.05 years, with an equal gender distribution (52.9% male). Rivaroxaban was significantly linked to increased GIB-related hospitalizations compared to controls (OR 1.29, 95% CI: 1.10–1.52, p < 0.001), while apixaban showed no statistically significant increase. NSAID co-administration dramatically raised the risk of GIB in rivaroxaban users (OR 16.1, 95% CI: 1.22–212.6, p = 0.03). Patients treated with DOACs experienced more hospitalizations (average 0.49 ± 0.80) and longer hospital stays (2.19 ± 3.54 days) compared to controls (0.30 ± 0.62 hospitalizations, 0.99 ± 2.68 days, respectively). Mortality rates were not significantly different between groups.

Conclusion

Rivaroxaban and apixaban present similar overall risks of gastrointestinal bleeding, although rivaroxaban is associated with higher hospitalization rates. Concomitant NSAID use substantially elevates the risk in patients on rivaroxaban. This underscores the necessity of individualized anticoagulant management strategies, especially in populations with distinct genetic and clinical characteristics, such as the Mexican demographic.

References

1. Lopes RD, Guimarães PO, Kolls BJ, et al. Gastrointestinal bleeding with novel oral anticoagulants: A systematic review and meta-analysis. BMJ. 2015;350:h1857.
2. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962.
3. Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.

Introduction

The eosinophilic esophagitis (EoE) endoscopic reference score (EREFS) is the validated scoring system for endoscopic findings of EoE. EREFS findings are currently scored cumulatively and correlate modestly with histological disease activity (HDA), symptoms, and adaptive behaviors. However, inflammatory and fibrotic findings may reflect different aspects of EoE, but this has never been evaluated.

Aims & Methods

We investigated the correlation of EREFS inflammatory and fibrotic subscores with HDA, symptoms and adaptive behaviors. In three tertiary referral centres for EoE, consecutive adults (>18 years) undergoing upper endoscopy for suspected or follow up EoE were prospectively enrolled. EREFS was scored as follows: edema 0-1; rings 0-3; exudates 0-2; furrows 0-2; stricture 0-1. The EREFS inflammatory sub-score (EREFS-i) combined the scores of edema, exudates and furrows. The EREFS fibrotic sub-score (EREFS-f) combined the scores of moderate-severe rings (score ≥2) and stricture. Subsequently, at least six esophageal biopsies were collected to assess HDA based on peak eosinophil count/high-power field (PEC/HPF) (active EoE PEC ≥15/HPF; EoE in remission: PEC<15/HPF). Symptoms were assessed using the dysphagia symptoms questionnaire (DSQ). Adaptive behaviors were assessed using the Pisa EoE Adaptation Questionnaire v1.0 (PiEAQ) [reference 1]. Clinical characteristics were recorded. Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons. ROC curve analysis was used to calculate the diagnostic accuracy (AUC). Spearman’s test and linear regression models were used to assess relationships between variables. Significance threshold was p<0.05.

Results

121 patients were included. 58% had active EoE, 42% were in histological remission. Baseline clinical data are reported in Table 1. The EREFS total score had modest AUC for predicting HDA (0.68) and did not show significant correlation with DSQ and PiEAQ. In contrast, EREFS-i had AUC of 0.73, with 88.2% sensitivity and 51.4% specificity for predicting HDA, being significantly more accurate compared to the EREFS-f (p<0.001; Figure 1). There was a significant correlation between EREFS-i and PEC/HPF with Spearman’s Rho=0.5 (p<0.001), with linear regression showing that an increase of 1 point of any inflammatory feature corresponded to an increase of 12 eosinophils/HPF (p<0.0001). In contrast, EREFS-f correlated significantly with the use of adaptive behaviors assessed with PiEAQ [Spearman’s Rho of 0.6 (p<0.001); Figure 2], with linear regression showing that an increase of 1 point of any fibrotic feature corresponded to an increase of one adaptive behavior (p=0.001). EREFS, EREFS-i, and EREFS-f had nonsignificant negative correlation with DSQ (p>0.05 for all).

Conclusion

We confirmed that, while total EREFS provides a global assessment of endoscopic disease severity, it lacks correlation with histological and clinical disease activity. However, we demonstrated that EREFS-i correlates significantly with PEC and predicts PEC/HPF and that EREFS-f correlates significantly with the use of adaptive behaviors assessed with PiEAQ, which represent known clinical markers of disease activity. Neither EREFS-i nor EREFS-f correlated significantly with DSQ. In conclusion, we showed that, compared to the total EREFS, EREFS sub-scores improve the correlation between endoscopy findings with histology and clinical disease activity markers. Applied to clinical practice, our results represent another step towards precision medicine in the setting of EoE.

References

[reference 1] Visaggi P, Del Corso G, Solinas I, Ovidi F, Adamo G, Dulmin I, Baiano Svizzero F, Bellini M, Savarino EV, de Bortoli N. Adaptive Behaviors, Esophageal Anxiety, and Hypervigilance Modify the Association Between Dysphagia Perception and Histological Disease Activity in Eosinophilic Esophagitis. Am J Gastroenterol. 2024 Dec 30. doi: 10.14309/ajg.0000000000003272. Epub ahead of print. PMID: 39787341.

Disclosure

Speaker or consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi