Introduction

Dermal lesions are often among patients with inflammatory bowel diseases (IBD), partialy could be associated with biological therapies [1,2]. Their occurrence frequently leading to dermatological consultations and causes diagnostic and therapeutic difficulties [3,4].

Aims & Methods

This is a retrospective, single-center analysis of occur dermal lesions in IBD patients treated with TNF at a tertiary center in Poland. A total of 541 IBD patients treated with TNF (case group) and 805 IBD patients without TNF therapy (control group) were included in the study since 2016 till 2022 in the study. The mean follow-up time last in the case group 19.86 vs. 20.78 months in the control group, p<0,46.

Results

Regular visits to the dermatologist during observation were performed in 531 (98,15%) cases vs. 92 (11.43%) controls, p<0,00001. Dermal lesions were presented in 34.75% (188) vs. 16.89% (136) during follow up, p<0,00001. The following dermal lesions were reported in the both groups: erythema nodosum 10 (1.8%) vs. 21 (2.6%), p<0,36; pyoderma gangrenosum 14 (2.58%) vs. 17 (2.11%), p p<0,57; psoriasis 9 (1.66%) vs. 9 (1.12%), p<0,39; hidradenitis suppurativa 9 (1.66%) vs. 15 (1.86%), p<0,79; vitiligo 4 (0.74%) vs. 5 (0.62%), p<0,79; phlebitis 1 (0.18%) vs. 1 (0.12%), p<0,78; urticaria 5 (0.92%) vs. 11 (1.37%), p<0,46; infusion reactions and injection site reaction 30 (5.55%) vs. 0 (0%)0, p<0,00001; xerosis and eczema 46 (8.5%) vs. 44 (5.47%), p<0,28; cutaneous infections 42 (7.76%) vs. 0 (0%), p<0,00001; psorasiform reactions 8 (1.48%) vs. 0 (0%), p<0,002; cutaneus malignancies 2 (0.37%) vs. 9 (1.12%), p<0,13; lupus-like symptoms 4 (0.74%) vs. 0 (0%), p<0,07; vasculitis 1 (0.18%) vs. 0 (0%), p<0,77; alopecia areata / totalis 2 (0.37%) vs. 2 (0.25%), p<0,96; lichenoid drug reactions 2 (0.37%) vs. 0 (0%), p<0,35. In 9 (1.66%) cases anti-TNF therapy led to drug change because of dermal lesions (alopecia, lupus-like syndrome, vasculitis or melanoma).

Conclusion

Dermal lesions during TNF therapy are common and often require dermatological consultation. Despite the lack of clear guidelines on dermatological supervision during biological therapy, its regular conduct seems to be justified and may facilitate the initiation of appropriate management at an early stage. Despite the commonness of dermal lesions, they are rarely the reason for changing treatment.

References

1. Antonelli E, Bassotti G, Tramontana M et al. Dermatological Manifestations in Inflammatory Bowel Diseases. J. Clin. Med. 2021; 10, 364.
2. Lambert J.L.W, De Schepper S, Speeckaert, R. Cutaneous Manifestations in Biological-Treated Inflammatory Bowel Disease Patients: A Narrative Review. J. Clin. Med. 2021; 10, 1040.
3. Cleynen I, Van Moerkercke W, Billiet T, et al. Characteristics of Skin Lesions Associated With Anti-Tumor Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease: A Cohort Study. Ann Intern Med. 2016; 164: 10-22.
4. Summaries for Patients. Rashes in Patients With Ulcerative Colitis or Crohn Disease Being Treated With Drugs That Block Tumor Necrosis Factor. Ann Intern Med. 2016; 164. doi: 10.7326/P16-9000. Epub 2015 Dec 8.

Introduction

Patients with Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) are at high risk of developing malignancies, so prevention and adherence to cancer screening may improve its detection.
The aim of this study was to assess the compliance with medical recommendations, especially primary and secondary prevention of cancer.

Aims & Methods

The aim of this study was to assess the compliance with medical recommendations, especially primary and secondary prevention of cancer.
This one-center cross-sectional study was carried out between June and December 2021r. amongst patients from the Department of Internal Medicine and Gastroenterology with IBD Division, National Health Institute of Ministry of Interior Affairs and Administrations or outpatient clinic. Patients were asked to complete anonymous questionnaire which included 42 questions concerning lifestyle, cancer risk factors, cancer history and checkups in patients with IBD. The results of the qualitative variables were expresses as frequencies and percentage. We used Fisher exact test, chi-squares test. p<0.05 was considered significant. Statistical analyses were performed with the SPSS statistical package.

Results

A total of 313 patients were enrolled into the study: 145 women and 168 men. In the group, 182 had Crohn’s disease (CD), 120 had ulcerative colitis (UC) and 11 with IBDU (unclassified IBD). Most participants had disease duration over 8 years, received biological treatment, corticoids or/and immunosuppressive therapy. Amongst respondents 17% (31) of patients with CD, 25.8% (31) with UC were overweight and 10.5% (19) with CD and 15.8% (19) with UC were obese (p= 0.017). We found that 16.3% of all respondents were smokers (79.6% (144) CD, 90.8% (109) UC and 72.7%(8); p 0.053) and 33.9% declared to consume alcohol (39.4%(71) CD, 26.9%(32) UC and 18.2%(2) IBDU; p 0.045). 25.4% were exposed to UV radiation, only 18.8% of them used sunblock. 58.8% (67) of patients with CD, 35.8% (19) and UC receiving immunosuppressants did regular laboratory tests regularly (p= 0.02). 41.4% (46) of UC, 27.1% (49) of CD and 70.0%(7) IBDU declared not to do any dermatological control (p =0.013). 77% of patients had abdominal ultrasound done. Out of 52.9% of patients who had colonoscopy recommended, only 27.3% had it performed (16.9%(30) with CD vs . 43.1%(50) with UC p< 0 .001). Most of examinations were ordered by gastroenterologists. Female patients had regular breast control (CD 78.6% (66), UC 91.2%(52) and 50% (2) IBDU p 0.034) and 93.8% (76) had gynaecological examination. 80.2% of patients knew about HPV but most declared not to be vaccinated. 17.9% of patients had urological control, but most had no important pathology detected.

Conclusion

According to our study, many patients are still exposed to risk factors, such as obesity, smoking or little physical activity, which are modifiable. Systematic control especially dermatological check-ups should be recommended. Additionally, not only gastrologists but also other specialists and GPs should remind patients about regular checkups. Primary prevention, such as HPV vaccinations, should be reminded to all patients.

References

1. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies [published correction appears in Lancet. 2020 Oct 3;396(10256):e56]. Lancet. 2017;390(10114):2769-2778
2. Eder P, Łodyga M, Gawron-Kiszka M, et al. Guidelines for the management of ulcerative colitis. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. Gastroenterology Review/Przegląd Gastroenterologiczny. 2023;18(1):1-42. doi:10.5114/pg.2023.125882.
3. Łodyga M, Eder P, Gawron-Kiszka M, et al. Guidelines for the management of patients with Crohn's disease. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. Prz Gastroenterol. 2021;16(4):257-296
4. Gordon H, Biancone L, Fiorino G, et al. ECCO Guidelines on Inflammatory Bowel Disease and Malignancies [published online ahead of print, 2022 Dec 18]. J Crohns Colitis. 2022Rozich JJ, Holmer A, Singh S. Effect of Lifestyle Factors on Outcomes in Patients With Inflammatory Bowel Diseases. Am J Gastroenterol. 2020;115(6):832-840.

Introduction

In the years to follow we anticipate a rise in the prevalence of an aging population of inflammatory bowel disease (IBD) patients and a rise in cancer incidence. We are in urgent need of data to help us manage these patients.
We therefore followed a cohort of patients from a referral oncology hospital with prior and active cancer who received biologic therapy to control their IBD.

Aims & Methods

We first recorded data regarding inflammatory bowel disease characteristics: disease type, disease duration, disease severity, previous surgery or hospitalization and received therapy: type and duration of biologic therapy, prior use of immunosuppressants. We also recorded all available data regarding cancer disease: cancer site, stage, virus related cancer, family history of cancer, smoking status and received therapy (curative surgery, chemotherapy, hormone therapy, radiotherapy, immunotherapy). We monitored outcomes of IBD (steroid free clinical remission, IBD-related surgery or hospitalization) and outcomes of cancer (recurrence free survival, progression free survival, overall survival).
A blinded oncologist was asked to retrospectively evaluate all available data regarding cancer prognosis (stage, histology, response to therapy) and to categorize patients in 3 groups: low, intermediate or high risk to recur or progress.

Results

A total of 30 patients were included, 57 % female, median age 60 years, 60% Crohn's Disease, median disease duration 9.5 years, 26% prior IBD surgery, 33% prior azathioprine use, 36% smokers. They were treated with anti-TNF therapy (n=19) anti-integrin therapy (n=8) and anti-IL 12/23 therapy (n=4). The majority (20%) of patients had a history of hematologic malignancy (lymphomas, myeloproliferative disorders, leukemias), 13% with a virus related cancer and 66% with curative surgery. Patients were classified retrospectively as 63% low risk, 13% intermediate risk and 10% high risk. Four patients ) with active cancer (2 with lung cancer and 2 with myeloproliferative disorders) continue to receive biologic therapy for IBD and oncological therapy with no signs of progression from both diseases. All but 3 patients have remained in steroid free clinical remission: 3 had IBD-related surgery. Median follow up under biologic therapy was 5.5 years: only 2 patients showed cancer recurrence: 1 patient with breast cancer developed bone metastases and finally died, and 1 patient with colon cancer developed bladder cancer and died as well. Both patients were classified as high risk.
In both patients biologic therapy was interrupted and that resulted in administration of high-dose steroids and IBD-related hospitalizations and infections (pneumonia, C Difficile colitis).

Conclusion

In this cohort of cancer patients with IBD treated with biologics and followed up for more than 5 years the risk of cancer recurrence was low and not unexpected in oncology terms.
Biologic therapy was successful in the majority of patients and kept them off surgeries and steroids for their underlying IBD. We need more smart and innovative ways to study this particular clinical scenario in the future.

Introduction

Patients with inflammatory bowel disease (IBD) have a 2-3 fold increased risk of venous thromboembolic events (VTE) compared to the general population. The relevance of this complication is underlined by increased morbidity, longer hospitalization, additional healthcare cost, the tendency of recurrence, and the potentially fatal outcome.
The etiology of VTE in IBD is complex, modulated by the interplay of disease- and treatment-specific factors. The additive effect of these may be supposed; the role of medication is not precisely defined.

Aims & Methods

The aim of our study was to assess the proportion of VTE in IBD patients treated with anti-tumor necrosis factor-alfa (anti-TNF-α) drugs and conventional anti-inflammatory therapy, namely corticosteroids (CS), immunomodulators (IM) and 5-aminosalicylates (5-ASA).
A systematic search was performed in 5 databases (Pubmed, Embase, Cochrane Library, Scopus, Web of Science) on the 22nd of November, 2022. Population-based data, retrospective cohort, and case-control studies were found eligible for inclusion. Our protocol was prospectively registered on PROSPERO (CRD42022376118).
Based on the number of VTE we determined the proportion of this complication in the mentioned treatment groups. We calculated the odds ratio (OR) with 95% confidence intervals (CI) in the distinct categories of medications. The Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies and the Risk of Bias in Non-randomized Studies of Interventions tool were used for quality evaluation.

Results

Out of 10.209 articles, 16 were included in the meta-analysis. A preliminary summary of analyzed data showed, that patients on anti-TNFs had less VTE compared with those treated with CS (proportion: 5%, 95%CI: 3-10 and 15%, 95%CI: 7-29, respectivelly). Comparing these treatments, the OR of VTE was 0.37 (95% CI: 0.21-0.66).
Among patients treated with anti-TNFs or IM we found similar proportions (5%, 95%CI: 3-10 vs. 7%, 95% CI: 4-11) and odds (OR: 0.88, 95% CI: 0.70-1.11) of VTE.
9% (95% CI: 5-17) of patients on 5-ASA medication had VTE; compared with TNF-inhibitors, OR was found to be 1.04 (95% CI: 0.75-0.44).

Conclusion

TNF-α is a driver of inflammation in IBD and may trigger coagulation as well. Inhibition of this key cytokine with biologicals is effective in induction and maintenance of remission in moderate and severe IBD. It may be presumed to have an effect on the risk of VTE as well.
Available literature and our summary of clinical data indicate, that CS therapy may increase the risk of VTE, while anti-TNF agents seem to be linked with decreased odds of these events. As a possible association between TNF-inhibitors and decreased risk of VTE compared with CS, we would like to underline the importance of „steroid-sparing” therapy in patients with high risk of VTE.
The rate of VTE was similar in patients on IM and 5-ASA, relative to TNF-inhibitors. This may be explained by the long-term disease remission maintained with conventional IBD therapy.
Prevention and treatment of VTE should always follow the recommandations of current guidelines.
Our work is limited by the retrospective desing of the studies, the relatively low number of VTE events, the heterogeneity of the IBD population, and the effect of concurrent anti-inflammatory medication used in IBD. To precisely assess the correlation between medication and VTE risk prospective, large, well-conducted studies are needed.

References

References:

1. Yuhara, H.; Steinmaus, C.; Corley, D.; Koike, J.; Igarashi, M.; Suzuki, T.; Mine, T. Meta-analysis: The risk of venous thromboembolism in patients with inflammatory bowel disease. Aliment. Pharmacol. Ther. 2013, 37, 953–962.
2. Fumery, M.; Xiaocang, C.; Dauchet, L.; Gower-Rousseau, C.; Peyrin-Biroulet, L.; Colombel, J.F. Thromboembolic events and cardiovascular mortality in inflammatory bowel diseases: A meta-analysis of observational studies. J. Crohns Colitis 2014, 8, 469–479.
3. Nguyen GC, Bernstein CN, Bitton A, et al. Consensus statements on the risk, prevention, and treatment of venous thromboem‐ bolism in inflammatory bowel disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146:835–848.e6.
4. Nguyen, G.C.; Sam, J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am. J. Gastroenterol. 2008, 103, 2272–2280.
5. Murthy SK, Nguyen GC. Venous thromboembolism in inflammatory bowel disease: an epidemiological review. Am J Gastroenterol. 2011;106:713–718.

Introduction

Biologic therapies such as anti-TNF-alpha agents (infliximab, adalimumab), interleukin modulators, and gut-selective integrin antagonists like vedolizumab have significantly improved outcomes in inflammatory bowel disease (IBD), leading to enduring remission, better quality of life, and reduced surgical intervention and hospitalizations. However, many patients may eventually lose response, often due to factors like the formation of anti-drug antibodies, altered drug metabolism, or individual patient characteristics. Dose escalation—by increasing dosage or reducing intervals—is commonly used to counteract this loss, especially for anti-TNF therapies guided by therapeutic drug monitoring. Vedolizumab poses a greater challenge in this regard due to the lack of standardized monitoring protocols. We aimed to investigate the effectiveness of dose-escalated infliximab, adalimumab, and vedolizumab in IBD patients who worsened after initial response, evaluating outcomes such as treatment persistence and clinical remission, to guide more personalized, cost-effective treatment strategies.

Aims & Methods

We conducted a retrospective analysis of IBD patients who underwent Infliximab (IFX), vedolizumab, or adalimumab (ADA) therapy dose escalation between 2020-2024 at a tertiary IBD centre. Primary outcomes included clinical remission using disease activity scores (Simple Clinical Colitis Activity/SCCAI Index for UC, Harvey-Bradshaw Index/HBI for CD), biochemical markers (CRP, faecal calprotectin) and treatment persistence, evaluated at 3-12 months, 12 months, and annually up to 36 months post-escalation.

Results

A total of 155 patients (median age 31 years, 46% female) were included, of which 89 patients (57%) were prescribed dose-escalated IFX, 48 patients (31%) were prescribed dose-escalated ADA and 18 patients (12%) were prescribed dose-escalated Vedolizumab. Of those included, 118 patients (76%) had Crohn’s disease, 36 patients (23%) had ulcerative colitis (UC) and 1 patient (1%) had indeterminate disease. Indications for dose escalation included secondary loss of response (SLOR) (105/155; 68%) and/or low drug levels (65/155; 42%). Dose-escalated IFX led to significant improvements in disease activity scores at 3 months (HBI: p=0.002; SCCAI: p=0.0003). Improvement in SCCAI was maintained at 12 months (p=0.00007), 2 years (p=0.0008) and 3 years (p=0.025). Improvement in HBI was maintained at 2 years (p=0.01) and 3 years (p=0.049). Significant improvement in CRP following dose-escalated IFX was reported at 3 months (p=0.011), 12 months (p=0.004), 2 years (p=0.006) and 3 years (p=0.03). Dose-escalated ADA led to a significant improvement in HBI at 3 months (p=0.023). This improvement was maintained at 12 months (p=0.005) and 2 years (p=0.008). Early improvement in faecal calprotectin was reported at 3 months (p=0.046). Significant initial improvement in SCCAI following dose-escalated Vedolizumab was reported at 3 months (p=0.043). This improvement was not maintained at any further follow-up points (p>0.05). Minor adverse events were reported in 3 patients receiving dose escalated ADA and in 6 patients receiving dose escalated IFX.

Conclusion

Our study demonstrates that biologic dose escalation is an effective and safe mechanism to recapture clinical remission, with high rates of treatment persistence.

Introduction

Intestinal Behçet’s disease (BD) is a rare chronic intestinal vasculitic disorder and it is often refractory to conventional therapies such as corticosteroids and immunomodulators. We aimed to assess the efficacy and tolerability of anti-tumor necrosis factor alpha (TNF ɑ) in intestinal BD.

Aims & Methods

We retrospectively reviewed 667 patients with intestinal BD registered at the Inflammatory Bowel Disease Clinic of Severance Hospital, Seoul, Korea. Response rates of anti-TNF ɑ treatment, predictive factors of sustained response and relapse were analyzed.

Results

A total of 46 patients with refractory moderate to severe intestinal BD were selected for the anti-TNF ɑ therapy. According to the intention-to-treat (ITT) principle, clinical remission rates were 8.7%, 21.7%, 6.5%, and 8.7%, clinical response rates were 76.1%, 71.7%, 39.1%, and 26.1%, and biological response rates were 60.9%, 60.9%, 39.1%, and 26.1%, respectively. According to the per-protocol (PP) principle, clinical remission rates were 8.7%, 25.6%, 13.0%, and 28.6%, clinical response rates were 76.1%, 84.6%, 78.3%, and 85.7%, and biological response rates were 60.9%, 71.8%, 78.2%, and 85.7%, respectively. Previous corticosteroid use more than 20 mg per day (HR: 4.781) and multiple number of ulcers (HR: 8.599) were more likely to have relapse of intestinal BD, and clinical response at 1 month (HR: 0.189) was associated with lowering the relapse. One patient had severe sepsis, 1 patient was diagnosed pneumonia and herpes zoster, and 1 patient experienced otitis externa.

Conclusion

Anti-TNF ɑ therapy could be a useful therapeutic option for refractory intestinal BD with an acceptable efficacy and tolerability profiles.

References

1. Fernandes C, Allocca M, Danese S, Fiorino G. Progress with anti-tumor necrosis factor therapeutics for the treatment of inflammatory bowel disease. Immunotherapy 2015;7(2):175-90.
2. Levin AD, Wildenberg ME, van den Brink GR. Mechanism of Action of Anti-TNF Therapy in Inflammatory Bowel Disease. J Crohns Colitis 2016;10(8):989-97.
3. Atreya R, Zimmer M, Bartsch B, Waldner MJ, Atreya I, Neumann H, et al. Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14(+) macrophages. Gastroenterology 2011;141(6):2026-38.
4. Vos AC, Wildenberg ME, Arijs I, Duijvestein M, Verhaar AP, de Hertogh G, et al. Regulatory macrophages induced by infliximab are involved in healing in vivo and in vitro. Inflamm Bowel Dis 2012;18(3):401-8.
5. Danese S, Vuitton L, Peyrin-Biroulet L. Biologic agents for IBD: practical insights. Nat Rev Gastroenterol Hepatol 2015;12(9):537-45.
6. Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet 1990;335(8697):1078-80.
7. Cheon JH, Kim ES, Shin SJ, Kim TI, Lee KM, Kim SW, et al. Development and validation of novel diagnostic criteria for intestinal Behcet's disease in Korean patients with ileocolonic ulcers. Am J Gastroenterol 2009;104(10):2492-9.

Introduction

Tumor necrosis factor inhibitors (anti-TNF) are associated with several adverse effects, including paradoxical reactions like psoriasiform lesions and less common drug-induced sarcoidosis-like reactions. They present significant diagnostic and therapeutic challenges, as they require careful differential diagnosis and often necessitate the discontinuation of treatment. Initially described in patients with inflammatory rheumatic diseases, sarcoidosis-like lesions induced by anti-TNF therapy have been sparsely documented only through case reports in the context of Inflammatory Bowel Diseases (IBD).

Aims & Methods

This study aimed to comprehensively describe epidemiological, diagnostic and therapeutic features of sarcoidosis-like lesions in IBD patients treated anti-TNF therapy, along with patient outcomes.
We conducted a nationwide observational case series across 59 institutions affiliated with the Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID). The diagnosis of anti-TNF-induced sarcoidosis was based on typical clinical and radiological signs, histological evidence of non-necrotizing granuloma, exclusion of differential diagnoses, and a timeline consistent with drug exposure. Each case was reviewed by a pharmacovigilance expert to confirm drug causality.

Results

We identified 12 cases of sarcoidosis-like lesions during anti-TNF therapy, with an equal distribution of male and female and a median age of 39 years (range 25-55). Underlying conditions were Crohn’s Disease (58.3%), Ulcerative Colitis (33.3%) and Inflammatory Bowel Disease Unclassified (8.3%). The median duration of IBD prior to diagnosis was 14 years (range 5-29).
The anti-TNF medications involved were infliximab (58.3%), adalimumab (33.3%) and golimumab (8.3%), with the majority of patients (75%) being first-time users of biotherapy.
6 patients had optimized treatment. The median time from anti-TNF initiation to diagnosis was 22.7 months (range 3-91).
The most commonly observed clinical manifestations were dyspnea (75%) and fever (58.3%). Affected organs included the lungs (100%), liver (16.7%), extrathoracic adenopathy (16.7%), spleen (16.7%), parotid gland (8.3%), and kidneys (8.3%). There was a case of Löfgren syndrome and one of meningitis. Eight patients discontinued anti-TNF therapy and started oral steroids, resulting in complete resolution of symptoms in five cases and improvement in two. One patient with multivisceral sarcoidosis required azathioprine addition due to renal insufficiency. Anti-TNF discontinuation was the only intervention in 2 cases, giving clinical remission in both. In 2 other cases, resolution of symptoms was observed with addition of steroids without anti-TNF discontinuation. Median time from steroid initiation (daily dose of 30 or 60 mg) to clinical remission was 91 days (range 11-305).
After a median follow-up of 48 months (range 18-175), one case showed persistent sarcoidosis activity, while no relapses were noted in the others. Anti-TNF therapy was resumed in only one patient, without recurrence of granulomatous lesions. Of the 10 patients who discontinued anti-TNF, all needed a new line of treatment, which was mostly vedolizumab. At last follow-up, IBD activity was noted in 4 patients.

Conclusion

Sarcoidosis-like lesions represent a rare but significant adverse reaction to anti-TNF therapy in IBD patients. This diagnosis should be considered when patients present with persistent respiratory or systemic symptoms after ruling out mycobacterial infection. Management involves discontinuation of anti-TNF and introduction of steroids.