Introduction

Anti-tumour necrosis factor-alpha (anti-TNF-alpha) therapy is an effective treatment for the management of Crohn’s disease (CD). However, treatment failure is common.

Aims & Methods

The aim of this study was to identify predictors of anti-TNF-alpha therapy failure.
Retrospective single-center study including anti-TNF-alpha naïve patients with CD, who started on intravenous infliximab, between January 2019 and December 2021. Biochemical parameters included erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), faecal calprotectin, infliximab serum concentrations and the presence of antibodies to infliximab (ATI). Anti-TNF-alpha therapy failure was defined as the development of ATI at 6 and 12 months, absence of clinical response at 6 months, absence of clinical remission or of objective response at 12 months. Clinical response was defined as a reduction in Harvey-Bradshaw index (HBI) of ≥ 3 points comparing with initial value or HBI < 5 points if initial HBI ≥ 7 points and clinical remission as HBI ≤ 4 points. Objective response was assessed by endoscopic studies, defined by improvement of mucosal inflammation and absence of deep ulcerations, or imaging, defined as improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyper-enhancement.

Results

A total of 53 CD patients were included, 30 were female (56.6%), with a mean age at the beginning of treatment of 39 ± 2 years. Considering the Montreal classification, 31 patients had ileal disease (58.5%), 7 colonic (13.2%) and 15 ileocolonic disease (28.3%); 22 patients had nonstricturing, nonpenetrating disease (41.5%), 22 stricturing (41.5%) and 9 penetrating disease (17.0%). Eleven patients had perianal disease (20.8%). A total of 26 patients (49.1%) were treated with combination of anti-TNF-alpha and immunomodulatory therapy (thiopurine or methotrexate). Anti-TNF-alpha therapy failure occurred in 21 patients (39.6%). At 6 months, the development of ATI occurred in 6 patients (11.3%) and absence of clinical response in 9 patients (17.0%). At 12 months, absence of clinical remission was seen in 13.6% of patients and absence of objective response in 27.0% of patients.
At 6 months, the development of ATI was significantly higher in patients with lower infliximab serum concentrations at week 14 (with antibodies 5.9±3.2 µg/mL vs without 14.3±7.7 µg/mL, p<0.001). Additionally, the development of ATI was significantly higher in patients with a higher initial value of ESR (with antibodies median 35 vs without median 13, p=0.045). The infliximab serum concentrations at week 14 (AUC 0.828; p=0.009; sensitivity 0.833 and specificity 0.404 for values ≤11.6) and the initial value of ESR (AUC 0.754; p=0.045; sensitivity 0.833 and specificity 0.468 for values ≥15) had very good and good discriminative capacity, respectively, in predicting the development of ATI. No statistically significant differences were found in initial values of CRP and faecal calprotectin, between both groups. Moreover, the other definers of anti-TNF-alpha therapy failure were not associated with the combination with immunomodulatory therapy, infliximab serum concentrations at week 14 or initial values of ESR, CRP and faecal calprotectin.

Conclusion

Infliximab serum concentration after induction therapy is the most important factor in the development of ATI, influencing treatment response, regardless of the combination of anti-TNF-alpha therapy with immunomodulatory therapy. A higher initial value of ESR can also predict the development of ATI.

Introduction

Recent developments in diagnostic imaging have increased the detection rate of lymphoma, for which a clear, histopathological diagnosis is critical for the subsequent choice of therapeutic regimen. Over the past decade, endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) has become widely-used means of tissue collection. However the open lymph node biopsy has conventionally been used to diagnose lymphoma histologically, and the evidence backing the use of EUS-FNA/B for this purpose is still limited.

Aims & Methods

The present study aimed to compare the performance of EUS-FNA/B and the open biopsy for diagnosing lymphoma by retrospectively analyzing 1113 patients with 1224 lesions who underwent either of the two methods at the study center between 2012 and 2024. The patients’ background, pathological diagnosis, procedural factors, and complications were evaluated. The performance of the open biopsy was compared with that of EUS-FNAB in diagnosing lymphoma in accordance with the 5^th edition of the World Health Organization classification of hematolymphoid tumours ¹⁾ (WHO classification).

Results

An open biopsy was performed for 943 lesions, 621 of which were malignant lymphomas, with the face, head, neck, axilla or groin, limb, and other areas being the site of 46, 556, 96, 225, 4, and 16 lesions, respectively. EUS-FNAB was performed for 281 lesions, 82 of which were malignant lymphomas, with the intra-abdominal area, mediastinum, and rectum being the site of 270, 10, and 1 lesion, respectively. The needle gauge used for FNA was 19G, 22G, and 25G in 1, 143, and 36 lesions, respectively, while and the needle gauge for FNB was 20G, 22G, and 25G in 3, 74, and 3 lesions, respectively. The mean number of punctures was 2.3 (range 1-9). EUS-FNAB involved significantly fewer, procedural complications than the open biopsy (14/943 vs 0/281; p=0.04). According to the WHO classification, the diagnostic performance (95% confidence interval) of the open biopsy has sensitivity 93.4 % (91.1-95.2), specificity 100.0 % (98.3-100.0), positive predictive value 100.0 % (99.0-100.0), and negative predictive value 88.7 % (85.0-91.8). The diagnostic performance (95% confidence interval) of EUS-FNAB according to the same classification has sensitivity 79.3 % (68.9-87.4), specificity 100.0 % (97.2-100.0), positive predictive value 100 % (91.8-100.0), and negative predictive value 92.1 % (87.7-95.3 %). Between the groups, there was no significant difference in the proportion of lesions for which immunostaining was able to be performed (615/621 vs 80/82; p = 0.24). The positive diagnosis rate was significantly higher for the open biopsy (580/621 vs 27/40; p < 0.001) but did not differ significantly for the EUS-FNB (580/621 vs 38/42; p = 0.52). Univariate and multivariate analyses found that needle type (FNB needle) was a procedural factor in EUS (needle type, gauge, number of punctures, stroke length) contributing to the diagnosis of lymphoma (odds ratio: 3.83; p = 0.037).

Conclusion

EUS was less complicated than the open biopsy as means of collecting tissue for histologically diagnosing lymphoma, and EUS-FNB had a positive diagnosis rate comparable to that of the open biopsy.

References

1. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022 Jul;36(7):1703-1719.

Introduction

The efficacy and safety of risankizumab (RZB), an anti-interleukin 23p19 monoclonal antibody, as induction and maintenance therapy for adults with moderately to severely active ulcerative colitis (UC) was recently reported.^1,2 Influences of baseline disease characteristics on clinical outcomes are important to consider when optimizing UC treatment. Herein we analyze the efficacy of RZB stratified by baseline UC disease characteristics.

Aims & Methods

In the 12-week phase 3 INSPIRE induction study (NCT03398148) patients with moderately to severely active UC were randomized 2:1 to receive intravenous (IV) RZB 1200 mg or placebo (PBO) at weeks 0, 4, and 8. Patients with clinical response to RZB IV induction at week 12 or 24 in the phase 2b/3 induction studies were randomized 1:1:1 to receive subcutaneous (SC) RZB 180 mg, RZB 360 mg, or PBO (RZB withdrawal) every 8 weeks in the 52-week phase 3 COMMAND maintenance study (NCT03398135). This post hoc analysis evaluates clinical response, clinical remission, endoscopic remission, endoscopic improvement, and histological-endoscopic mucosal improvement (HEMI) at week 12 and 52 in subgroups stratified by baseline disease characteristics (Adapted Mayo score, pancolitis, high‑sensitivity C‑reactive protein [hs‑CRP], Mayo endoscopic subscore [ES], and disease duration).

Results

The induction analysis included 650 and 325 patients who received RZB 1200 mg IV and PBO IV, respectively. The maintenance analysis included 179, 186, and 183 patients who received RZB 180 mg SC, RZB 360 mg SC, and PBO (RZB withdrawal) SC, respectively. At induction week 12, the proportions of patients receiving RZB 1200 mg IV who achieved clinical response were numerically higher for the following baseline characteristic subgroups: pancolitis absence (70.5%) vs pancolitis presence (58.4%), Mayo ES of 2 (75.5%) vs Mayo ES of 3 (59.0%), and hs-CRP ≤ 5 mg/mL (68.9%) vs hs-CRP > 5 mg/mL (57.3%); the proportions of patients receiving RZB 1200 mg IV who achieved clinical remission at induction week 12 were also numerically higher for subgroups with pancolitis absence (25.3%) vs pancolitis presence (15.6%), Mayo ES of 2 (31.7%) vs Mayo ES of 3 (14.9%), and hs-CRP ≤ 5 mg/mL (23.7%) vs hs-CRP > 5 mg/mL (14.5%; Table). Differences in outcomes were not observed between subgroups stratified by Adapted Mayo score or disease duration. At week 52 of the maintenance study, there was no impact of baseline disease characteristics on achievement of clinical response and clinical remission with RZB (Table).

Conclusion

RZB induction and maintenance therapy improved clinical outcomes, regardless of baseline disease characteristics. Numerically higher RZB induction efficacy was observed for patients with no baseline pancolitis, Mayo ES of 2, and hs‑CRP ≤ 5 mg/L. These trends are consistent with prior observations that patients with milder UC disease phenotypes tend to be more responsive to therapy.

References

1. Louis E, et al. United Eur Gastroenterol J . 2023;11(S8):26–28. Abstract OP021.
2. Louis E, et al. J Crohns Colitis. 2024;18(S1):i10–12. Abstract OP06.

Disclosure

CH has served as a consultant, advisor, and/or has received education funds from AbbVie, Bausch Health, BMS, the Helmsley Charitable Trust, Janssen, Pfizer, Roivant, and Takeda.
MDL has received consulting fees and/or research grants from AbbVie, BMS, Intercept, Janssen, Lilly, Pfizer, Prometheus, Takeda, and Target RWE.
SRF has served as a consultant or advisor for AbbVie, Janssen, MSD, Takeda, Tillots, and Vitoria.
TF has received research grants and/or speaking honoraria from AbbVie, Ajinomoto, Alfresa, BI, BMS, Celgene, Celltrion, Daiichi Sankyo, EA Pharma, Eisai, Gilead, Janssen, Kissei, Kyorin, Kyowa Hakko Kirin, Lilly, Mebix, Mitsubishi Tanabe, Mochida, Nichiiko, Nippon Kayaku, Pfizer, Sanofi, Taiho, Takeda, and Zeria.
ZR has no disclosures to report.
JK, PL, SC, LC, RV, and PMH are employees of AbbVie and may hold AbbVie stock and/or stock options.
FA-A has served as a consultant and/or has received grants and speaker fees from AbbVie, Celltrion, Kern, MSD, and Takeda.
RA has served as a consultant or advisor for AbbVie, AstraZeneca, BI, Biogen, BMS, CED-Service GmbH, Celltrion, Falk Foundation, Galapagos, Gilead, InDex, Janssen-Cilag, Lilly, MSD, Roche, and Takeda.
Funding
AbbVie funded this study and participated in the study design, research, data collection, analysis, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and the authors thank all trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Morgan A Gingerich, PhD, of JB Ashtin, and funded by AbbVie, and Karen Chien, PhD, of AbbVie.

Introduction

The therapeutic armamentarium for inflammatory bowel disease (IBD) is rapidly increasing recent years with newer therapies such as vedolizumab (VDZ). Their effectiveness has already been demonstrated against placebo, but head-to-head trials compared to tumour necrosis factor alpha inhibitors (anti-TNF) are scarce.

Aims & Methods

Aim: To compare the effectiveness of VDZ versus anti-TNF in bio-naïve IBD patients in a real world setting.
Methods: A retrospective monocentric study was performed in IBD patients treated with VDZ and anti-TNF at a Belgian University Hospital, from January 2018 to June 2021 with follow-up until December 2021. Primary endpoints considering efficacy after induction and after 1 year of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). Secondary endpoint was treatment survival during follow-up. For assessment of risk factors influencing efficacy and treatment survival, a multivariate logistic regression and Cox regression model were applied. Propensity scores for VDZ vs. anti-TNF were weighted for age at start biological, IBD type, perianal disease activity, disease duration and previous IBD-related intestinal resection.

Results

In total, 42 patients received VDZ and 57 anti-TNF. At baseline, the VDZ group had an older median age (38 vs. 31 years, P=0.024), longer disease duration (P=0.017) and more moderate to severe comorbidities (21.4% (9/42) vs. 0% (0/57), P<0.001). In the anti-TNF group, percentage of CD patients was higher (77.2% (44/57) vs. 57.1% (24/42),P=0.034), patients had more upper GI, penetrating or stricturing disease (P=0.013 for location and P=0.004 for behavior), perianal disease (P=0.034) and used more immunomodulators (IMM) during treatment (52.6% (30/57) vs. 16.7% (7/42), P<0.001). After treatment induction, CRp (P=0.311) and CRm (P=0.216) rate was not significantly different. The anti-TNF group had a significantly higher BRp rate compared to the VDZ group (87.8% (43/49) vs. (23/34), P=0.026). After adjusting for propensity score, age, IBD type, systemic corticosteroid (CS) or IMM use, the higher rate of BRp remained (aOR 3.83 [1.01-14.60], P=0.049). Similar results were found for BRm (87.8% (43/49) vs. 67.6% (23/34), P=0.026). After adjustment for the same confounders, the higher rate of BRm in the anti-TNF group remained (aOR 3.83 [1.01-14.60], P=0.049). No significant difference was seen for ERp (P=1.000) and ERm (P=0.338). After 1 year, univariate analysis showed no significant difference for CRp (P=0.736) and CRm (P=0.404), nor for BRp (P=0.907) and BRm (0.890) or for ERp (P=0.163) and ERm (P=0.533). Treatment survival using Cox regression model with adjustment for propensity and IMM or CS use, showed no significant longer treatment duration for anti-TNF compared to VDZ (aHR 0.947 [0.36-2.49], P=0.913).

Conclusion

In this tertiary real-world cohort of bio-naïve patients with IBD, anti-TNF and VDZ showed a similar efficacy, with an advantage of anti-TNF regarding onset of action.