Introduction

Optimal strategies for monitoring isolated small bowel’s Crohn’s Disease (CD) remain uncertain. In 2020, the APEX score was developed, with a value between 4 and 7 presenting an excellent accuracy at stratifying patients relapse risk following a small bowel capsule endoscopy (SBCE) showing mucosal healing (MH)¹.

Aims & Methods

Our aim was to prospectively validate APEX score accuracy in predicting disease flares on the year following SBCE.
Our study prospectively included patients with isolated small bowel CD (Montreal L1±L4) undergoing SBCE, who were in clinical remission (CDAI<150) and corticosteroid-free for the previous 6 months. A blood sample was collected within a maximum of 15 days of SBCE. The score APEX (Age ≤30 years +3 / Platelets ≥ 280 × 10³/L +2 / EXtraintestinal manifestations +2) was applied on patients whose SBCE reported MH. Disease flares were documented on the subsequent year.

Results

We have included 47 patients, from which 28 (59.6%) presented MH on SBCE. From these, 21 (75%) were female, with a mean age of 42±13 years. On the following year, a disease flare was documented on 4 (14.3%) patients. A high-risk APEX score was found in 5 (17.9%) of the patients.
The APEX score presented an excellent accuracy in predicting disease flares on the year following MH (AUC=0.97; 95%CI 0.92-1.00; p=0.003). The previously calculated optimal cut-off (APEX≥4) had a sensitivity of 100% and a specificity of 95.8% in predicting the outcome.

Conclusion

Patients with small bowel CD and MH still have a non-neglectable risk of disease flare on the subsequent year. The APEX score has prospectively demonstrated excellent accuracy at stratifying patients’ relapse risk. Thus, it emerges as a helpful tool in patients with MH, by identifying those who will need earlier evaluations and more frequent monitoring.

References

1. Macedo Silva V, Freitas M, Boal Carvalho P, et al. Apex Score: Predicting Flares in Small-Bowel Crohn's Disease After Mucosal Healing. Dig Dis Sci. 2022; 67: 1278-86.

Introduction

The correlation between fecal calprotectin (FC) levels and small bowel (SB) inflammation in patients with Crohn's Disease (CD) remains a subject of debate.

Aims & Methods

This study aims to investigate the relationship between FC levels and SB inflammatory activity in patients diagnosed with SB CD.
We conducted a retrospective cohort study involving patients with SB CD who underwent small bowel capsule endoscopy (SBCE) and FC testing. Patients with colon inflammation were excluded. Participants were categorized into four groups based on their SB inflammatory status: no inflammation (all three SB tertiles showed Lewis Score (LS) <135); proximal SB inflammation (first and/or second SB tertiles had LS ≥ 135, with no inflammation in the third SB tertile); distal SB inflammation (third SB tertile had LS ≥ 135, with no inflammation in the proximal SB); pan-SB inflammation (both proximal and distal SB with inflammation).

Results

A total of 87 patients were included in the study, with a median age of 35 years, 75.9% being female. The distribution of inflammation among the patients was as follows: no inflammation in 21.8%; proximal inflammation in 4.6%; distal inflammation in 33.3%; pan-SB inflammation in 40.4%.
FC median values exhibited an ascending trend along the SB axis: no inflammation 58 µg/g (33-180); proximal SB inflammation 65 µg/g (30-128); distal SB inflammation 122 µg/g (42-507); pan-SB inflammation 400 µg/g (205-852).
Statistically significant differences in FC levels were observed between pan-SB inflammation vs. isolated proximal inflammation (p = 0.014), and isolated distal inflammation (p = 0.012).
Additionally, FC showed a positive correlation with LS in the second (r = 0.464, p<0.001) and third tertiles (r = 0.435, p<0.001), but no correlation was noted in the first tertile.
FC demonstrated good predictive capacity for identifying inflammation in the distal SB and pan-SB vs. no inflammation and proximal inflammation, with an area under the curve of 0.790 (p < 0.001) and an optimal cutoff value of 228 µg/g.

Conclusion

FC levels correlate positively with the presence of SB lesions in the second and third tertiles of the small bowel. However, it is not a reliable marker for detecting inflammation in the first tertile, highlighting the importance of conducting a SBCE in these patients.

Introduction

Small-bowel (SB) inflammatory activity in Crohn's Disease (CD) is variable among patients. Capsule Enteroscopy (CE) allows for visualization of the entire SB, which may be divided into three parts, known as tertiles.

Aims & Methods

The aim of this study was to determine the association between SB inflammatory involvement in CD of the first and second tertiles and the impact on the clinical outcome. A total of 53 treatment-naive patients with SB CD submitted to CE as part of the diagnosis workup were selected. Data regarding SB inflammatory activity quantified by the Lewis Score (LS; < 135, normal; 135–790, mild; ≥790 moderate-to-severe) were collected. Individuals with any colonic involvement, as well as stricturing or fistulizing phenotypes, were excluded from the analysis.

Results

Thirty-six (67.9%) patients displayed inflammatory activity in the first and/or second tertile together with third tertile involvement (Proximal+T3 group). Seventeen (32.1%) had inflammation in the third tertile only (T3 group). The LS accounts for the SB tertile with the highest degree of inflammation, yet we found that individuals in the Proximal+T3 group exhibited higher inflammatory scores (p=0.031). We performed a subgroup analysis for those with mild inflammatory activity. There were no differences regarding age or sex distribution, smoking habits, frequency in relatives with CD, perianal disease, extra-intestinal manifestations, or laboratory values. Notably, we found that patients with mild disease in the Proximal+T3 group initiated biologic drugs more often in the five years following the initial diagnosis (p=0.036).

Conclusion

This study shows that involvement of the first and/or second tertiles of the SB is significantly associated with more severe inflammatory activity overall. Additionally, in those with mild disease and proximal inflammation the need for biologics occurred more frequently. This suggests that early detection of proximal SB CD using CE may contribute to timely treatment.

Introduction

Crohn’s disease (CD) often recurs after ileocolic resection, requiring reliable endoscopic assessment.
While the Rutgeerts score is standard, its limitations highlight the need for alternatives. Simplified Endoscopic Score for Crohn’s Disease (SES-CD) and Modified Multiplier SES-CD (MM-SES-CD) assess both ileal and colonic disease, potentially providing a more comprehensive evaluation.

Aims & Methods

This study evaluates their predictive value for postoperative disease progression compared to Rutgeerts score.
Longitudinal study of consecutive CD patients undergoing ileocolonoscopy for postoperative surveillance.
Receiver operating characteristic (ROC) curve analyses compared Rutgeerts, SES-CD, and MM-SES-CD scores for predicting disease progression within one year after ileocolonoscopy. Multivariate logistic regression assessed score cutoffs, adjusting for confounders. Disease progression was defined as a composite endpoint, including clinical recurrence (Harvey-Bradshaw Index≥4), therapy intensification, CD-related hospitalization, endoscopic balloon dilation, or surgery.

Results

A total of 81 patients (48±13years; 55.6% female) with 128 ileocolonoscopies were included. Regarding Montreal classification, 37 (45.7%) patients had ileal and 44 (54.3%) ileocolonic disease; 9 (11.1%) patients had nonstricturing, nonpenetrating disease, 35 (43.2%) structuring and 37 (45.7%) penetrating disease. Nineteen (23.5%) had perianal disease. The mean time between surgery and ileocolonoscopy was 133±83months.
Disease progression occurred in 44 (34.4%) cases at one-year follow-up. Rutgeerts score demonstrated fair accuracy (AUC 0.73; 95% CI 0.64-0.80), which was similar to SES-CD (AUC 0.72; 95%CI 0.63-0.79) and MM-SES-CD (AUC 0.72; 95%CI 0.63-0.80).
The optimal thresholds for predicting disease progression were SES-CD>4 (sensitivity 70.45%; specificity 69.05%) and MM-SES- CD>17 (sensitivity 59.09%; specificity 77.38%). However, comparing scores cutoffs, Rutgeerts score>1 showed the highest odds ratio for disease progression (OR 9.02, 95%CI 3.20- 25.46, p<0.001).

Conclusion

Rutgeerts score, SES-CD, and MM-SES-CD demonstrated similar predictive accuracy for postoperative disease progression. However, the Rutgeerts score>1 had the strongest predictive value, supporting its continued use while also suggesting that SES-CD and MM- SES-CD can serve as viable alternatives for monitoring postoperative recurrence.

References

Narula N, Wong ECL, Colombel JF, et al. Predicting endoscopic remission in Crohn's disease by the modified multiplier SES-CD (MM-SES-CD). Gut. 2022;71(6):1078-1087. doi:10.1136/gutjnl-2020-323799

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

Recurrence of Crohn’s disease (CD) after ileocolic resection is common. However, reliable non-invasive monitoring methods are lacking, for instance, the use of faecal calprotectin (FC) has showed inconsistent results in this subgroup of patients.

Aims & Methods

The aim of this study was to evaluate clinical and biochemical factors associated with post-operative endoscopic recurrence in CD patients.
Retrospective single-center study including patients with CD who underwent ileocolonoscopy for CD surveillance, after ileocolic resection. The patients’ clinical status was evaluated through Harvey-Bradshaw index (HBI), with clinical remission considered as ≤ 4 points. Biochemical parameters included erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and FC. Clinical and biochemical parameters were evaluated in the 6 months prior to ileocolonoscopy. Post-operative endoscopic recurrence was defined as a Rutgeerts score ≥ i2b.

Results

A total of 81 patients and 121 ileocolonoscopies were included. Most patients were female (55.6%), with a mean age of 48±13 years. Regarding the Montreal classification, 37 patients had ileal disease (45.7%) and 44 ileocolonic disease (54.3%); 9 patients had nonstricturing, nonpenetrating disease (11.1%), 35 stricturing (43.2%) and 37 penetrating disease (45.7%). Nineteen patients had perianal disease (23.5%). The mean time between the surgery and the endoscopic evaluation was 135±79 months. Post-operative endoscopic recurrence was observed in 52 ileocolonoscopies (43.0%).
Symptomatic patients (HBI > 4 points) were 11 times more likely to have post-operative endoscopic recurrence (OR 10.686, 95%CI 2.930-38.974, p<0.001). Those with post-operative endoscopic recurrence had a significantly higher FC values (median 189 vs 69 µg/g, p<0.001) and higher ESR values (median 14 vs 9 mm, p=0.002). In fact, patients with FC values ≥ 150 µg/g and those with ESR values > 12 mm were 4 and 3 times more likely to have post-operative endoscopic recurrence (OR 3.654, 95%CI 1.605-8.316, p=0.002 and OR 3.059, 95%CI 1.397-6.696, p=0.005, respectively). The presence of post-operative endoscopic recurrence was not associated with CRP values (median 2.9 vs 2.9 mg/L, p=0.466), and neither with mean time between the surgery and the endoscopic evaluation (mean 126±83 vs 142±75 months, p=0.263).

Conclusion

The presence of symptoms (HBI > 4 points), FC values ≥ 150 µg/g and ESR values > 12 mm was associated with post-operative endoscopic recurrence in CD. Therefore, the HBI, FC and ESR values can be used to monitor CD patients after ileocolic resection, and prompt endoscopic evaluation should be performed in those with HBI > 4 points, FC values ≥ 150 µg/g and/or ESR values > 12 mm.

Introduction

Capsule panendoscopy is increasingly used in Crohn's disease (CD), particularly in patients with extensive small bowel and colonic involvement. It offers a non-invasive, one-step evaluation of both segments, making it appealing for disease monitoring and treatment response. However, there is a need for validated scoring systems that objectively assess inflammatory activity in both the small bowel and the colon.

Aims & Methods

The aim of this study was to externally validate the Eliakim Score (Elk-S), developed to assess mucosal inflammation in CD by capsule panendoscopy. Patients referred for PillCam™ Crohn's examination at our institution were selected, and procedure data were collected retrospectively to calculate the Elk-S.

Results

A total of 72 patients were included, 62.5% female, with a mean age of 42±15 years. In 52 (72.2%) individuals, the indication for the procedure was suspected CD. Among them, the diagnosis was rejected in 38 cases, while in 14 cases, the diagnosis was established. There was a significant difference in mean Elk-S between the two groups (5.3±1.5 vs. 21.8±5.3, respectively; p<0.001). Capsule panendoscopy was used to evaluate inflammatory activity in 20 (27.8%) patients with CD. Treatment remained unchanged in 10 cases, while therapy was intensified in 10 patients, and there was a significant difference in mean Elk-S between the two groups (2.2±0.5 vs. 17.1±2, respectively; p<0.001). The Elk-S demonstrated an area under the ROC curve of 0.979 for the diagnosis of CD and 0.875 for predicting therapeutic escalation. An Elk-S ≥ 7 (Table 1) had a Sensitivity, Specificity, Negative Predictive Value, and Positive Predictive Value of 100%, 89.5%, 100%, 77.8%, respectively, for the diagnosis of CD. To determine the need for therapeutic intensification in patients with established CD, the same cut-off value showed a Sensitivity, Specificity, Negative Predictive Value, and Positive Predictive Value of 90%, 70%, 87.5%, 75%, respectively.

Conclusion

The Elk-S exhibited high accuracy in establishing the diagnosis of CD and was equally useful in predicting the need for therapeutic intensification in cases of established CD. The present study represents the first external validation of the Elk-S, demonstrating its effectiveness for assessing inflammatory activity via capsule panendoscopy of both the small bowel and colon.

References

Eliakim R, Yablecovitch D, Lahat A, et al. A novel PillCam Crohn’s capsule score (Eliakim score) for quantification of mucosal inflammation in Crohn’s disease. United Eur Gastroenterol J. 2020;8(5):544-551. doi:10.1177/2050640620913368