P286 Ustekinumab for Crohn’s Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study

Abstract Background Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin (IL)-12 and IL-23. It is registered for the treatment of Crohn’s disease (CD) and ulcerative colitis. We assessed the two-year efficacy and safety of ustekinumab in a real world, prospective cohort of CD patients. Methods CD patients who started ustekinumab in regular care were prospectively enrolled in the nationwide Initiative on Crohn and Colitis Registry. At week 0, 12, 24, 52 and 104, clinical remission (HBI ≤ 4 points), biochemical remission (fecal calprotectin (FC) ≤200 μg/g and/or CRP ≤5 mg/L), peri-anal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. Patients starting therapy less than two years ago were excluded for the current evaluation. The primary outcome was corticosteroid-free clinical remission at week 104. Results In total, 252 CD patient with at least two years of follow up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission at week 12, 24, 52 and 104 was 32.3% (81/251), 41.4% (104/251), 39% (97/249) and 34.0% (84/247), respectively. Of the 97 patients in corticosteroid free clinical remission at week 52, 58 (59.8%) were still in corticosteroid-free clinical remission at week 104. In patients with combined clinical and biochemical disease activity at baseline (n=122), the corticosteroid-free clinical remission rates were 23.8% (29/122), 35.2% (43/122), 40.0% (48/120) and 32.8% (39/119) at week 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks was 64.3% and 54.8%, respectively. There were no predictive factors associated with corticosteroid-free clinical remission at week 104 on univariate and multivariate analysis. Most common adverse events were headache, skin reaction and musculoskeletal complaints. Two patients stopped ustekinumab due to an infection after 8 and 30 weeks of treatment (mild fever syndrome and moderate upper airway infection, respectively). The main reason for discontinuing treatment after 52 weeks was loss of response (66.7%). Conclusion Ustekinumab was effective and relatively safe in our real world, prospective cohort of CD patients. After 104 weeks of ustekinumab treatment, one third of patients were in corticosteroid-free clinical remission.

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P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.187 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S75-S75

Author(s):

Scott D Lee ◽

Anand Singla ◽

Caitlin Kerwin ◽

Kindra Clark-Snustad

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Events ◽

Real World ◽

Clinical Remission ◽

Mucosal Healing ◽

Clinical Disease ◽

Endoscopic Remission ◽

Starting Dose

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with >3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.

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P583 Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn’s disease: results from a large Italian cohort study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.704 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S536-S537

Author(s):

G Mocci ◽

A Cuomo ◽

L Allegretta ◽

G Aragona ◽

R Colucci ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Remission ◽

Large Population ◽

Real Life ◽

Previous Treatment ◽

Fecal Calprotectin ◽

Concomitant Treatment ◽

Efficacy And Safety

Abstract Background Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn’s Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics Methods 194 CD patients (108 males and 86 females, mean age 48 years (range 38–58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients Results At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as thirdline therapy (after both anti-TNFα and vedolizumab), FC >200 μg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment Conclusion Ustekinumab seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

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Short and Long-Term Effectiveness of Ustekinumab in Patients with Crohn’s Disease: Real-World Data from a German IBD Cohort

Journal of Clinical Medicine ◽

10.3390/jcm8122140 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2140 ◽

Cited By ~ 4

Author(s):

Alica Kubesch ◽

Laurenz Rueter ◽

Karima Farrag ◽

Thomas Krause ◽

Klaus Stienecker ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Real World ◽

Treatment Options ◽

Fecal Calprotectin ◽

Real World Data ◽

Free Response ◽

Short And Long Term

Background and Aims: The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn’s disease (CD). Due to the recent approval, real-world German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods: Patients with CD receiving UST treatment in three hospitals and two outpatient centers were included and retrospectively analyzed. Rates for short- and long-term remission and response were analyzed with the help of clinical (Harvey–Bradshaw Index (HBI)) and biochemical (C-reactive protein (CRP), Fecal calprotectin (fCal)) parameters for disease activity. Results: Data from 180 patients were evaluated. One-hundred-and-six patients had a follow-up of at least eight weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin antibodies. The median follow-up was 49.1 weeks (95% CI 42.03-56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 48 (51.6%) responded to UST, and 25 patients (26.9%) were in remission. Steroid-free response and remission at week eight was achieved by 30.1% and 19.3% of patients, respectively. At week 48, 37.6% showed steroid-free response to UST, and 20.4% of the initial patient population was in steroid-free remission. Conclusion: Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment-exposed patients.

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Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz042 ◽

2019 ◽

Vol 13 (9) ◽

pp. 1111-1120 ◽

Cited By ~ 9

Author(s):

N Plevris ◽

C S Chuah ◽

R M Allen ◽

I D Arnott ◽

P N Brennan ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Real World ◽

Bowel Disease ◽

Clinical Remission ◽

Mucosal Healing ◽

Inflammatory Bowel

Abstract Background & Aims Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn’s disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. Methods This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn’s disease with objective evidence of active inflammation at baseline (Harvey–Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan–Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. Results Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn’s disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26–52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn’s disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. Conclusions Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn’s disease.

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Ustekinumab for Crohn’s Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz119 ◽

2019 ◽

Vol 14 (1) ◽

pp. 33-45 ◽

Cited By ~ 33

Author(s):

Vince B C Biemans ◽

Andrea E van der Meulen - de Jong ◽

Christine J van der Woude ◽

Mark Löwenberg ◽

Gerard Dijkstra ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Anal Fistula ◽

Clinical Remission ◽

Real World Data ◽

Effective Treatment Option ◽

Faecal Calprotectin ◽

Reactive Protein ◽

Regular Care

Abstract Background and Aims Ustekinumab is approved for the treatment of Crohn’s disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice. Methods We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index [HBI]), biochemical (C-reactive protein [CRP] and faecal calprotectin [FCP]), extra-intestinal manifestations and, peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52. The primary outcome was corticosteroid-free clinical remission. Results In total, 221 CD patients were included (98.6% anti-tumour necrosis factor [TNF] and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks [interquartile range 49.3–58.4]. Corticosteroid-free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate [20.0% vs 42.6%, p = 0.01], but comparable corticosteroid-free clinical remission at week 52 (46.3% [q8w] vs 34.6% [q12w], p = 0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy [combi 40.6% vs mono 36.0%, p = 0.64]. At baseline, 28 patients had active peri-anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections [3.5 per 100 patient-years], with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 [33.9%] patients mainly due to lack of response. Conclusion Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies.

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P575 Real-world effectiveness and safety of ustekinumab for the treatment of refractory Crohn’s disease: The Scottish ustekinumab cohort

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.703 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S484-S484

Author(s):

N PLEVRIS ◽

A Robertson ◽

J Fulforth ◽

R Hall ◽

I Campbell ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Real World ◽

Clinical Remission ◽

Mucosal Healing ◽

Mucosal Inflammation ◽

Physician Global Assessment ◽

Serious Adverse Events ◽

Objective Evidence

Abstract Background Ustekinumab (UST) is an anti-IL12/23 biologic licensed for the treatment of moderate to severe Crohn’s disease (CD). The aims of this study were to establish the long-term real-world effectiveness and safety of UST for the treatment of CD in a large UK cohort. Methods This was a multicentre retrospective cohort study , including 7 NHS health-boards in Scotland. Patients treated with UST between November 2015 and June 2019 were identified. Inclusion criteria included: a diagnosis of CD; active symptoms attributed to CD with objective evidence of mucosal inflammation (CRP >5mg/l or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/ MRI); and completion of induction with a minimum of 8 weeks follow-up. Clinical assessments were performed based on physician global assessment (response was defined as ≥50% reduction in CD-related symptoms and remission defined as complete resolution of all CD-related symptoms). Mucosal healing was defined as the absence of ulceration/erosions on ileo-colonoscopy or no inflammation on MRI if ileo-colonoscopy was not possible (eg. B2 disease). Deep remission was defined as clinical remission plus mucosal healing. Rates of serious adverse events (discontinuation of UST, hospitalisation or death) during follow-up were described quantitively. Results A total of 207 patients (43% male; median age 39.2 years, IQR 28.9–51.4; median disease duration 10.0 years, IQR 5.7–16.6) with a median follow-up of 34.6 weeks (IQR 16.9–52.1) were included. The majority of patients had ileocolonic disease (L1, 19.3%; L2, 23.7%; L3, 57%) and an inflammatory phenotype (B1, 43.0%; B2, 41.1%; B3, 15.9%). A total of 98.6% of patients had previously been exposed to a biologic and 55.1 % had undergone previous surgery. Seventy-one per cent of patients received Q8 maintenance dosing, whilst 25.6% and 42.0% of patients were also receiving an immunomodulator (IMM) and steroids at initiation, respectively. At week 8, clinical response and remission rates were 51.7% and 5.8%, respectively. Twelve-month cumulative rates of clinical remission, mucosal healing (n = 116) and deep remission (n = 116) were 29.8%, 35.3% and 17.9%, respectively (Figure 1). During 155 patient-years of follow-up (PYF), 11 patients experienced a serious adverse event (7.1 per 100 PYF). Conclusion We have shown in a large real-world cohort of complex, treatment-refractory CD patients that UST is a safe and effective treatment option.

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P084 DEEP REMISSION WITH DOUBLE BIOLOGIC THERAPY: A SUCCESSFUL CASE OF COMBINATION USTEKINUMAB AND VEDOLIZUMAB FOR SEVERE REFRACTORY CROHN’S DISEASE

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.182 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S72-S72

Author(s):

Ahmed Elmoursi ◽

Courtney Perry ◽

Terrence Barrett

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Combination Therapy ◽

Clinical Remission ◽

Biologic Therapy ◽

Case Reports ◽

Sigmoid Resection ◽

Safety And Efficacy ◽

Ileal Stricture

Abstract Background Stricturing Crohn’s disease (CD) constitutes a severe phenotype often associated with a high degree of morbidity (3). Surgical resection is first-line therapy for symptomatic strictures, but most patients relapse without subsequent medical therapy (4–5). Biologics are the mainstay for inducing and maintaining remission, but some cases are refractory despite maximum dosage of therapy. Reports of dual biological therapy (DBT) in refractory, stricturing CD are sparse, and prior case reports document only clinical remission (1). To contribute further knowledge regarding the use of DBT in stricturing CD, we present the case of a refractory CD patient who achieved deep remission with ustekinumab and vedolizumab. Case Presentation A 35 year old non-smoking, Caucasian male was referred to our clinic in 2014 for refractory CD complicated by multiple strictures. Prior to establishing care with us, he received two jejunal resections and a sigmoid resection. Previously failed therapies included azathioprine with infliximab, adalimumab, and certolizumab. He continued to progress under our care despite combination methotrexate/certolizumab, as well as methotrexate/golimumab. He underwent proctocolectomy with end ileostomy in 2015 and initiated vedolizumab q8weeks post-operatively. He reoccurred in 2018, when he presented with an ulcerated ileal stricture. He was switched from vedolizumab to ustekinumab q8weeks and placed on prednisone, but continued to progress, developing significant hematochezia requiring hospitalization and blood transfusions. Ileoscopy performed during hospital admission confirmed severe, ulcerating disease in the ileum with stricture. Ustekinumab dosing was increased to q4weeks, azathioprine was initiated, and he underwent stricturoplasty. Follow-up ileoscopy three months later revealed two ulcers in the neo- TI (Figure 1). Vedolizumab q8weeks was initiated in addition to ustekinumab q4weeks and azathioprine 125mg. After four months on this regimen the patient felt better, but follow-up ileoscopy showed two persistent ulcers in the neo-TI. Vedolizumab dosing interval was increased to q4weeks. After four months, subsequent ileoscopy demonstrated normal neo-TI (Figure 2). Histologic evaluation of biopsies confirmed deep remission of crohn’s disease. No adverse side effects have occurred with maximum doses of both ustekinumab and vedolizumab combination therapy. Discussion This case supports both the safety and efficacy of ustekinumab and vedolizumab dual biologic therapy for treatment of severe, refractory Crohn’s disease. While there are reports of DBT inducing clinical remission, this case supports efficacy for vedolizumab and ustekinumab combination therapy to induce deep histologic remission. Large practical clinical trials are needed to better investigate the safety and efficacy of DBT with vedolizumab and ustekinumab, but our case suggests this combination may be a safe and efficacious therapy for refractory CD patients.

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P346 Single-centre experience of ustekinumab: Therapeutic drug monitoring in Crohn’s disease patients

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.475 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S331-S333

Author(s):

C Liefferinckx ◽

M Fassin ◽

D Thomas ◽

C Minsart ◽

A Cremer ◽

...

Keyword(s):

Crohn’S Disease ◽

Therapeutic Drug Monitoring ◽

Crohn's Disease ◽

Median Time ◽

Real World ◽

Drug Monitoring ◽

Drug Exposure ◽

Therapeutic Drug ◽

Loss Of Response

Abstract Background Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences. Methods This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay Results Demographic and baseline data of our population are presented in Table 1. The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1). Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p < 0.001). ADA were undetectable in all the measured samples in maintenance. Conclusion This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.

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A Nomogram Combining Fecal Calprotectin Levels and Plasma Cytokine Profiles for Individual Prediction of Postoperative Crohn’s Disease Recurrence

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz053 ◽

2019 ◽

Vol 25 (10) ◽

pp. 1681-1691 ◽

Cited By ~ 8

Author(s):

Elena Cerrillo ◽

Inés Moret ◽

Marisa Iborra ◽

José Pamies ◽

David Hervás ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Prognostic Index ◽

Predictive Biomarkers ◽

Fecal Calprotectin ◽

Clinical Activity ◽

Predictive Tool ◽

Plasma Cytokine ◽

Ifn Γ

Abstract Background The aims of this study were to characterize the immune response profile in patients with Crohn’s disease (CD) and early postoperative recurrence (POR), to identify predictive biomarkers, and to develop a noninvasive predictive tool for individual estimation of POR risk. Methods Sixty-one patients who had undergone ileocolonic resection for CD were prospectively included and followed up for 24 months. Fecal calprotectin (FC), analytical parameters, and plasma cytokines were obtained before surgery and at various time points during postoperative follow-up. Morphological recurrence was assessed by ileocolonoscopy or magnetic resonance enterography within 6–12 months after surgery. Clinical activity was scored using the Harvey-Bradshaw Index. Results Twenty-seven patients (44.3%) had morphological recurrence during follow-up. Fecal calprotectin values were significantly associated with POR risk over time. The receiver operating characteristic curve for FC provided an area under the curve (AUC) of 0.88 (95% confidence interval, 0.75–0.96), and morphological recurrence was best predicted by FC ≥160 μg/g at 6 months after surgery (85% sensitivity, 70% specificity, 26% predictive positive value, 98% negative predictive value [NPV]). The plasma cytokine profile showed higher presurgery interleukin (IL)-13 plasma levels and higher IL-6 and interferon (IFN)-γ levels at 6 months after surgery in patients with POR compared with patients without recurrence. The combination of FC, IL-6, and IFN-γ values at 6 months gave an AUC of 0.90 for predicting an early recurrence. Conclusions FC values <160 μg/g at 6 months have a high NPV to rule out early lesions. Combined values of FC, IL-6, and IFN-γ levels at 6 months postsurgery constitute a prognostic index with a high predictive capacity to assess the risk of early POR.

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