scholarly journals Combination Ciprofloxacin and Metronidazole for Active Crohn’s Disease

1998 ◽  
Vol 12 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Susan L Greenbloom ◽  
A Hillary Steinhart ◽  
Gordon R Greenberg
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Intestinal Bacteria ◽  
Colonic Disease ◽  
Efficacy And Safety ◽  
Index Reduction ◽  
Ileal Disease

Recent experimental evidence underscores the contribution of intestinal bacteria to the inflammatory process of Crohn's disease. This open study examined the efficacy and safety of combination ciprofloxacin and metronidazole for patients with active Crohn's disease of the ileum and/or colon. Seventy-two patients with active Crohn's disease of the ileum (n=27), ileocolon (n=22) or colon (n=23) were treated with ciprofloxacin 500 mg bid and metronidazole 250 mg tid for a mean of 10 weeks. Clinical remission was defined as a Harvey-Bradshaw index of three points or less; an index reduction of at least three points indicated a clinical response. Clinical remission was observed in 49 patients (68%), and 55 patients (76%) showed a clinical response. A clinical response was noted in 29 of 43 patients (67%) who were not taking concurrent prednisone treatment and in 26 of 29 patients (90%) receiving prednisone (mean dose of 15 mg/day). A clinical response also occurred in a greater proportion of patients with colonic disease, with or without ileal involvement (84%), compared with patients with ileal disease alone (64%), and in patients without resection (86%) compared with those with previous resection (61%). Five patients discontinued antibiotics because of adverse events. After a mean follow-up of nine months, clinical remission was maintained in 26 patients off treatment and in 12 patients who continued antibiotic therapy. Ciprofloxacin in combination with metronidazole is well tolerated and appears to play a beneficial role in achieving clinical remission for patients with active Crohn's disease, particularly when there is involvement of the colon.

scholarly journals 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

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.

scholarly journals A229 USTEKINUMAB FOR THE TREATMENT OF REFRACTORY PEDIATRIC CROHN’S DISEASE: A SINGLE CENTRE EXPERIENCE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 104-106
Author(s):  
A Cohen ◽  
A Sant’Anna ◽  
N Ahmed
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
The Other ◽  
Secondary Loss ◽  
Loss Of Response

Abstract Background Despite the well-established efficacy of Tumor Necrosis Factor (TNF) antagonists as treatment options for Crohn’s Disease, many pediatric patients need a change in therapy due to adverse events, as well as primary and secondary loss of response, highlighting the necessity for medications with a different mechanism of action. Ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, has been approved to treat psoriatic arthritis, plaque psoriasis, and adults with Crohn’s disease. While utekinumab has been shown to be effective in inducing clinical remission in adults with Crohn’s disease refractory to anti-TNF agents, minimal data exists in the pediatric population. Aims We retrospectively describe 11 pediatric patients who received ustekinumab at the Montreal Children’s Hospital with the goal of assessing its efficacy in inducing clinical, biochemical, and endoscopic remission. Methods We abstracted baseline data, prior treatment and response, indications for starting ustekinumab, clinical response, endoscopic data, and laboratory parameters pre- and post- therapy. Clinical response was defined as decrease in abbrPCDAI (Pediatric Crohn’s Disease Activity Index) score. Results Patients ranged in age from 12–17 years old upon initiation of treatment with ustekinumab and had all previously failed either one (N=8) or both (N=3) anti-TNF therapies. Follow-up ranged from 6 to 22 months. We examined three indices of response to ustekinumab: symptomatic improvement, biomarker normalization, and endoscopic changes. Five of eleven patients demonstrated a clinical response – two maintained clinical remission across available follow-up data, while the remaining three experienced a secondary loss of response. The other six patients studied were primary non-responders. Two of these patients had normal abbrPCDAI scores upon initiation of ustekinumab and terminated therapy due to persistent stricturing disease. The other four non-responders either remained unwell or demonstrated clinical worsening, as measured by the abbrPCDAI. Of the clinical responders, 3/5 had elevated CRP values prior to initiating ustekinumab therapy, all of which normalized within one month of clinical improvement. Endoscopic data both pre- and post- ustekinumab was available in two responders and two non-responders, with endoscopic improvement seen in both of the responders and in one of the two non-responders. Conclusions These results demonstrate that ustekinumab has the potential ability to induce not only clinical and biochemical remission, but also endoscopic improvement, in the pediatric population. An area of concern is the fact that only one patient maintained remission for longer than one year. Future research should focus on maximizing and lengthening the effect of ustekinumab, as well as determining factors that influence response to therapy. Funding Agencies None

P697 Efficacy and safety of ustekinumab in Crohn’s disease: A real-world study from Australia

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S564-S565
Author(s):  
P Kakkadasam Ramaswamy ◽  
H Moattar ◽  
E Sawyer ◽  
J Edwards ◽  
D Shukla
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Real World ◽  
Clinical Remission ◽  
Efficacy And Safety ◽  
Clinical Endpoints ◽  
Single Centre Study ◽  
Paradoxical Worsening ◽  
Secondary Endpoints

Abstract Background Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved in Australia for the treatment of adults with moderate to severe Crohn’s disease (CD) in 2017. The aim of this retrospective single centre study was to study the efficacy and safety of UST in CD in a real world cohort. Methods Patients with CD who began UST therapy between June 2017 and July 2019 were included. UST induction was given as an infusion (6 mg/kg) at week 0 followed by 90 mg subcutaneous injection (SC) at week 8 and 90 mg SC every 8 weeks as maintenance. Primary endpoint (PE) was steroid free clinical remission or steroid free clinical response at week 24. Secondary endpoints (SE) were: endoscopic response or remission, radiological response or remission, biochemical response (CRP < 5 mg/L or Calprotectin <150 μg/g), clinical response or remission at week 52. Results Seventy-six patients with CD were included in the study. 64.5% failed ≥1 anti-TNF and 13.1% failed anti-TNF and vedolizumab; 26(34.2%) patients were biologic-naïve. Median follow-up was 61 weeks. Ten patients (13.1%) discontinued UST, and the median time to discontinuation was 48 weeks; eight patients due to loss of response, one patient due to paradoxical worsening of arthralgia, one patient chose to stop treatment. Six patients underwent surgery whilst on UST. At week 12, 48 (63.1%) of patients achieved steroid free clinical remission or response [19/26 (73%) Anti-TNF naive and 29/49 (59%) anti-TNF exposed]; of these patients, 16/19 (84%) in the anti-TNF naive group and 19/29(65.5%) in the anti-TNF exposed group achieved PE. Forty-seven (61.8%) patients achieved PE. At 52 weeks, 68.2% (30/44), 67.5% (27/40), 56.1% (23/41), 69% (29/42) achieved endoscopic, radiological, biochemical and clinical endpoints respectively. Achieving steroid free clinical response or remission at week 12 was associated with achieving PE (79% vs. 42.8%, OR 3.6, p 0.01) and clinical SE (83.3 vs. 58.3%, p 0.001). Patients with B2/3 vs. B1(54% vs. 82%, p 0.09), ≥2 biological failure (72% vs. 33%, p 0.09), CRP < 6 baseline (55 % vs. 67.5%, p 0.3) were less likely to attain PE. Conclusion In a real-world cohort, UST appears efficacious and safe in medium and long term, with modest clinical, biochemical, radiological and endoscopic outcomes. Patients who achieve steroid-free clinical remission or response at 12 weeks are more likely to be in clinical remission or response at 24 and 52 weeks.

scholarly journals P717 Ustekinumab in Crohn’s disease: Real-world outcomes from the Sicilian Network for inflammatory bowel diseases (SN-IBD):–Preliminary results

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S578-S578
Author(s):  
A Viola ◽  
G Fiocco ◽  
A Alibrandi ◽  
F S Macaluso ◽  
M Cappello ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Demographic Data ◽  
Real Life ◽  
Primary Study ◽  
Clinical Activity ◽  
Secondary Failure

Abstract Background Ustekinumab is approved in Europe for the treatment of moderate-to-severe Crohn’s disease (CD) since 2016. Italian real-life data on efficacy and safety are scarce. The aim of this study was to assess effectiveness, safety and usage of Ustekinumab in an Italian cohort of patients. Methods Data of patients with moderate-to-severe CD who started Ustekinumab in Sicily were extracted from the database of the SN-IBD. Demographic data, disease-related data (disease duration, location, clinical activity) and previous therapies with biologics were collected. The primary study endpoints were steroid-free clinical remission and steroid-free clinical response at week 12, 24 and 52 on Ustekinumab therapy. Secondary study endpoints were: treatment persistence at 24 weeks, safety, and biochemical response (reduction of CRP). Results One hundred thirteen patients started Ustekinumab in Sicily. We performed a preliminary analysis only on patients who reached at least 24 weeks of follow-up. Ninety-three patients (M = 53%; mean age 45 ± 14.9 years) were included. At week 24, 38 patients (41%) achieved steroid-free clinical remission, 56 patients (60%) clinical response. From baseline to the end of follow-up there was a significant reduction of steroid use (41% vs. 21%, p = 0.038) and of mean HBI score (6.5 ± 4.4 vs. 4.8 ± 4.1; p < 0.001). No significant CRP changes were recorded during follow-up. Twelve patients (11%) discontinued therapy due to primary failure (3 patients), secondary failure (5 patients), adverse events (3 patients) and 1 patient was lost to follow-up. Kaplan–Meier survival analysis showed a persistence on therapy with Ustekinumab of 89% of patients after 24 weeks (Figure 1). Conclusion Preliminary data from our real-life cohort of treatment-refractory CD patients suggest a satisfactory effectiveness and a good safety profile of Ustekinumab.

scholarly journals P389 Efficacy and safety of ustekinumab in patients with Crohn’s disease refractory to anti-tumour necrosis factor: real clinical practice

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S400-S401
Author(s):  
R M Saiz Chumillas ◽  
L Alba Hernández ◽  
I Chivato Martín-Falquina ◽  
E Badia Aranda ◽  
M L Arias García ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Real Life ◽  
Corticosteroid Treatment ◽  
Faecal Calprotectin ◽  
Biochemical Remission

Abstract Background The efficacy of ustekinumab in patients with Crohn’s disease (CD) refractory to anti-TNF is worse than in anti-TNF naïve patients. Methods Retrospective study of patients with CD refractory or intolerant to TNF initiating ustekinumab between January 2013 and March 2020, with a minimum follow-up of 12 months, and without corticosteroid treatment. Our aim was evaluated clinical response (reduction of CDAI >100), clinical remission (CDAI <150) and biochemical remission (CDAI <100 and CRP <1 mg/L and faecal calprotectin <100 µg/g) in short and long term. Results A total of 49 patients with a medium follow-up of 28 months (IQR:13-37) were included. Patients baseline characteristics are reflected in Table 1. In 20% patients the induction was made subcutaneous (90 mg/week for 4 weeks). At week 52, clinical response, clinical remission and biochemical remission was 93%, 82% and 54% respectively (Figure 1). In the long term (3 years), 62% had clinical response, 52% remained in clinical remission, and 48% showed biochemical remission. 1/3 of patients needed intensification every year. Ustekinumab treatment discontinuation was observed in 13 patients (27%) mainly due to lack of response (6[12%]: primary, 7[14%]: secondary). No serious adverse effects have been reported. Conclusion About 50% of the patients are in clinical and biochemical remission at week 152 in a real-life cohort of anti-TNF-exposed CD patients. With a harder remission definition including biochemical parameters, our results in real life are similar to pivotal studies at week 152. Nevertheless, at week 52 our remission rates were higher.

scholarly journals P559 Efficacy of Ustekinumab in the treatment of patients with Crohn’s disease with failure to previous conventional or biologic therapy: an observational real-life study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S522-S523
Author(s):  
A Miranda ◽  
A Cuomo ◽  
S Camera ◽  
C Ciacci ◽  
F R De Filippo ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Biologic Therapy ◽  
Real Life ◽  
Mucosal Healing ◽  
Endoscopic Evaluation ◽  
Life Study

Abstract Background Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn’s disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. Methods The study was performed on 92 subjects (47 males; 45 females; mean age: 42 (17–78) from six medical centers in Campania, Italy, with confirmed diagnosis of moderate to severe Crohn’s disease and no neoplasia. In all patients diagnosis of CD had been reached to years earlier. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy.The administration of UST was as follows: IV infusion at week 0 (3 vials of 130 mg each if body weight of 55–85 kg; 2 vials of130 mg each if body weight < 55 kg) and subsequent SC injections (90 mg) q8w thereafter. At enrollment, all subjects underwent colonoscopy and were divided into groups according to endoscopic evaluation: 5 (5.4%) patients had erosions; 24 (26.1%) inflammation; 63 (68.5%) ulcers. Based on the CDAI value, 52 (56.5%) patients had a CDAI of 180–220, 35 (38%) had a CDAI of 220–450, and 5 (5.4%) had a CDAI >450. All patients underwent endoscopic examination and bowel MRI or ultrasonography at baseline and at week 52 to evaluate mucosal and transmural healing. Clinical response was defined as a reduction of CDAI by at least 100 points; clinical remission when CDAI was lower than 150. Clinical response and remission were evaluated at baseline and on 5 different occasions throughout a 12 months follow-up. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Results Seventeen patients interrupted therapy while 75 patients continued follow-up until the fifth visit. Clinical response at week 52 was achieved in 38 (50,5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. Fifteen patients (20%) did not show any change during endoscopic evaluation at follow-up. All patients showing mucosal healing also showed transmural healing, as assessed by ultrasonography or MRI. No major TRAEs were observed during treatment. Conclusion In this multi-center, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

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

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.

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

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.

scholarly journals OP26 Risankizumab induces early clinical remission and response in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S026-S027
Author(s):  
S W Schreiber ◽  
M Ferrante ◽  
R Panaccione ◽  
J F Colombel ◽  
T Hisamatsu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Activity Index ◽  
Unmet Need ◽  
Inadequate Response ◽  
Biologic Treatment ◽  
Double Blind

Abstract Background Present therapies leave an unmet need for early and effective treatment for patients with Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin-23, was evaluated as an induction therapy to induce early clinical remission and response in patients with moderate-to-severe CD in two double-blind, randomized, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]). Methods Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES-CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE), or biologic treatment only (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous RZB 600 mg, RZB 1200 mg, or PBO as induction therapy at weeks 0, 4, and 8. Clinical remission (per either CDAI or a composite of SF and AP criteria), clinical response (per CDAI criterion), and enhanced clinical response (per a composite of SF and AP criteria) were evaluated at weeks 4, 8, and 12 (endpoints defined in Figure 1 footnotes). Safety was assessed throughout the studies. Results A total of 1419 patients from ADVANCE (N = 850) and MOTIVATE (N = 569) respectively, were randomised and included in the intention-to-treat population. In both studies, starting at week 4 (the first prespecified measurement), greater proportions of RZB 600 mg or RZB 1200 mg- vs PBO-treated patients achieved clinical remission per either CDAI (P = .01/P < .05) or SF/AP criteria (P < .01/P < .01), clinical response per CDAI criterion (P = .001/P < .01), and enhanced clinical response per SF/AP criteria (P < .01/P = .14) (Figure 1). For both RZB 600 mg and RZB 1200 mg, the efficacy and treatment effect increased through week 12 (P ≤ .001/P ≤ .001) (Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2 Conclusion Induction therapy with both RZB 600 mg and 1200 mg intravenous resulted in significantly greater clinical remission and response vs PBO as early as week 4 and sustained through week 12 in patients with moderate-to-severe CD who had inadequate response or intolerance to conventional and/or biologic treatment. References

scholarly journals P160 A novel PillCam Crohn’s capsule score (Eliakim score) for quantification of mucosal inflammation in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S218-S219
Author(s):  
R Eliakim ◽  
D Yablecovitch ◽  
A Lahat ◽  
B Ungar ◽  
E Shachar ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Colonic Disease ◽  
Study Cohort ◽  
The Novel ◽  
Colonic Preparation ◽  
Pearson's R ◽  
Pearson’S R

Abstract Background Capsule endoscopy (CE) is an important modality for monitoring of Crohn’s disease (CD). We recently established that small bowel (SB) inflammation on CE quantified by a Lewis score >350 accurately predicts risk of relapse within 2 years in CD patients in clinical remission. Recently, a novel pan-enteric capsule (PillCam Crohn’s (PCCE), Medtronic, USA) was approved for use. However, no quantitative index for pan-enteric PCCE is currently available. The current study was undertaken as a sub-study of a prospective randomised controlled CURE-CD trial aiming to optimise treatment of CD patients in remission using a PCCE- based treat-to-target approach; the aim of this ancillary study was to compare the correlation and reliability of the novel PCCE inflamatory score (Eliakim score) with the Lewis score as performed by 2 independent experienced CE readers. Methods The study cohort includes CD patients in clinical remission (CDAI<150). The patients were prospectively enrolled and underwent patency capsule evaluation; if excreted within 30 h, PCCE was performed following bowel preparation. PCCE was repeated every 6 months; if no colonic disease was detected on first PCCE, subsequent examinations were performed without colonic preparation. Each PCCE was independently reviewed by 2 experienced readers (RE (reader 1);UK (reader 2)). All studies were scored using the Lewis score and Eliakim score (comprised of a sum of scores for most common and most severe lesions multiplied by percentage of involvement per bowel segment (3 for small bowel and 2 for colon) with an additional stricture score). Pearson’s and Spearman’ correlation, Cohen’s kappa and inter-rater reliability coefficient (IRC) between the scores and the readers were calculated as appropriate. Results Forty PCCE exams were included. The median LS was 225 for both readers (interquartile range (IQR)—157–815 for reader 1, 33- 1125 for reader 2). Both readers identified significant SB inflammation (LS>350) in 17/40 (42.5%) of the patients with strong agreement between the readers (Spearman’s r = 0.87, p < 0.0001). The median PCCE score was 6 (4–14.75) and 4 (2–14.75) for reader 1 and 2, respectively. There was a high IRC between the two readers for LS (0.88, p < 0.0001 for absolute agreement) and PCCE score (0.91, p < 0.0001). For the small bowel, the correlation between LS and PCCE was moderate for reader 1 (Pearson’s r = 0.72, p < 0.0001 and strong for reader 2 Pearson’s r = 0.84, p < 0.0001). Conclusion There is a need for a quantitative pan-enteric score for the novel Pillcam Crohns capsule. The presently proposed score, while mandating further clinical validation, has strong inter-reader reliability and moderate-to-strong correlation with the validated small bowel capsule score (LS)

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