Identification of Target Golimumab Levels in Maintenance Therapy of Crohn’s Disease and Ulcerative Colitis Associated With Mucosal Healing

2019 ◽  
Vol 26 (5) ◽  
pp. 766-773 ◽  
Author(s):  
Karen Boland ◽  
Tomer Greener ◽  
Boyko Kabakchiev ◽  
Joanne Stempak ◽  
Jenna Tessolini ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Operating Characteristic ◽  
Mucosal Healing ◽  
Clinical Practices ◽  
Target Drug ◽  
Endoscopic Remission ◽  
Trough Levels ◽  
Selection Of

Abstract Introduction Golimumab is approved as a therapy for ulcerative colitis (UC) patients. Recent data also demonstrate efficacy in Crohn’s disease (CD); however, little is known about target drug levels to achieve endoscopic remission. Methods We performed a retrospective analysis of IBD patients on maintenance golimumab. Median trough levels were compared using Kruskal-Wallis test, and logistic regression was used to construct a probabilistic model to determine sensitivity and specificity of levels predicting mucosal healing. Results Fifty-eight patients on maintenance golimumab were included (n = 39 CD, n = 19 UC/IBD-unclassified [IBDU]). Forty percent (n = 23) were cotreated with an immunomodulator, 95% (n = 55) of patients were anti-TNF experienced, and 15.5% (n = 9) had 3 or more prior biologic therapies. Forty-four percent of patients achieved mucosal healing with endoscopic response in a further 26% of patients. Clinical remission was recorded in 41% of patients, and 82% had clinical response. Patients were treated with doses generally higher than the approved maintenance dose. In CD patients, median golimumab trough levels were higher in patients with mucosal healing (8.8 μg/mL vs 5.08 μg/mL, P = 0.03). After calculation of a receiver operating characteristic (ROC) curve for mucosal healing vs nonresponse, a trough level >8 μg/mL was associated with mucosal healing, with 67% sensitivity, 88% specificity, and a likelihood ratio of 3:4. Conclusion Treatment with golimumab was associated with mucosal healing in 44% of all IBD patients. Higher golimumab levels were associated with mucosal healing in CD. These findings support the need for prospective studies to determine target golimumab levels in IBD, which may impact current clinical practices in relation to selection of maintenance dosing.

scholarly journals P302 Diagnostic accuracy of a serum-based biomarker panel for endoscopic activity in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S304-S304
Author(s):  
A HOLMER ◽  
B Boland ◽  
S Singh ◽  
H Le ◽  
J Neill ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Diagnostic Accuracy ◽  
Operating Characteristic ◽  
Mucosal Inflammation ◽  
Serum Samples ◽  
Receiver Operating Characteristic Curves ◽  
Biomarker Panel ◽  
Endoscopic Remission

Abstract Background The endoscopic healing index (EHI, Monitr, Prometheus Biosciences, San Diego, CA) is a serum-based biomarker panel available for identifying mucosal inflammation in Crohn’s disease.[1] We aimed to study its performance for identifying mucosal inflammation in ulcerative colitis. Methods EHI was analysed on serum samples paired with endoscopies from adult patients (≥18 years) participating in a prospective biobank (June 2014 to December 2017). Area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of EHI for endoscopic improvement (EI; Mayo endoscopic sub-score [MES] 0–1) and endoscopic remission (ER; MES 0). Sensitivity for EHI was calculated using a cut-off previously identified for Crohn’s disease which optimised performance for ruling out endoscopic activity (20 points). Alternative cut-offs were explored. Results A total of 114 patients were included, with an overall prevalence of 56% and 44% for EI and ER. The AUROC was 0.79 (95% CI 0.70–0.87) for EI and 0.70 (95% CI 0.61–0.80) for ER. A cut-off of 20 points had a sensitivity of 94% (95% CI 83–99%) for ruling out moderate to severe (MES 2–3) endoscopic activity, and a sensitivity of 84% (95% CI 72–92%) for ruling out mild to severe (MES 1–3) endoscopic activity. A cut off of 40 points or higher had > 90% specificity for ruling in moderate to severe (MES 2–3) or mild to severe (MES 1–3) endoscopic activity. (Table 1) Conclusion EHI has favourable accuracy in identifying the presence of mucosal inflammation in patients with ulcerative colitis. Although it was not developed and validated for ulcerative colitis, further validation is warranted. Reference

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.

Multiparametric Evaluation Predicts Different Mid-Term Outcomes in Crohn’s Disease

2018 ◽  
Vol 36 (3) ◽  
pp. 184-193 ◽  
Author(s):  
Lucrezia Laterza ◽  
Anna Chiara Piscaglia ◽  
Laura Maria Minordi ◽  
Iolanda Scoleri ◽  
Luigi Larosa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Mucosal Healing ◽  
Hospitalization Rate ◽  
Clinical Activity ◽  
Ct Enterography ◽  
Complementary Information ◽  
Endoscopic Remission ◽  
Rutgeerts Score

Aim: To evaluate if a single and/or combined (clinical, endoscopic and radiological) assessment could predict clinical outcomes in Crohn’s disease (CD). Methods: We prospectively evaluated 57 CD cases who underwent both a colonoscopy and a CT-enterography (CTE). Harvey-Bradshaw Index (HBi), SES-CD (and/or Rutgeerts score) and the radiological disease activity were defined to stratify patients according to clinical, endoscopic and radiological disease activity respectively. Hospitalizations, surgery, therapeutic changes and deaths were evaluated up to 36 months (time 1) for 53 patients. Results: CTE and endoscopy agreed in stratifying disease activity in 47% of cases (k = –0.05; p = 0.694), CTE and HBi in 35% (k = 0.09; p = 0.08), endoscopy and HBi in 39% (k = 0.13; p = 0.03). Taken together, CTE, endoscopy and HBi agreed only in 18% of cases (k = 0.01; p = 0.41). Among the 11 cases with mucosal healing, only 3 (27%) showed transmural healing. Patients with endoscopic activity needed significantly more changes of therapy compared to patients with endoscopic remission (p = 0.02). Patients with higher transmural or clinical activity at baseline required significantly more hospitalizations (p < 0.01). Hospitalization rate decreases with an increase in the number of parameters indicating remissions at baseline (p = 0.04). Conclusions: Clinical, endoscopic and radiological assessments offer complementary information and could predict different mid-term outcomes in CD.

scholarly journals S31 Mucosal healing in Crohn's disease is associated with high infliximab trough levels

2010 ◽  
Vol 4 (1) ◽  
pp. 30-31 ◽  
Author(s):  
W. Van Moerkercke ◽  
G. Compernolle ◽  
C. Ackaert ◽  
A. Gils ◽  
S. Vermeire ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Healing ◽  
Trough Levels

Letter: mucosal healing in ulcerative colitis - higher relevance than in Crohn's disease? Authors' reply

2013 ◽  
Vol 38 (2) ◽  
pp. 208-208
Author(s):  
D. Laharie ◽  
J. Filippi ◽  
X. Roblin ◽  
S. Nancey ◽  
L. Peyrin-Biroulet
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Healing

Mo1880 Mucosal Healing and Dysplasia Surveillance in a Large Referral Center Cohort of Patients With Crohn's Disease and Ulcerative Colitis Treated With Vedolizumab

2016 ◽  
Vol 150 (4) ◽  
pp. S804 ◽  
Author(s):  
Maja Noman ◽  
Marc Ferrante ◽  
Raf Bisschops ◽  
Gert De Hertogh ◽  
Karolien Van den Broeck ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Healing ◽  
Referral Center

Serum Adalimumab Trough Levels Required for Endoscopic Mucosal Healing during Maintenance Therapy of Crohn's Disease

2017 ◽  
Vol 152 (5) ◽  
pp. S393 ◽  
Author(s):  
Hirotsugu Imaeda ◽  
Kyohei Nishino ◽  
Masashi Ohno ◽  
Atsushi Nishida ◽  
Mitsushige Sugimoto ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Maintenance Therapy ◽  
Mucosal Healing ◽  
Trough Levels ◽  
Therapy Of Crohn's Disease

scholarly journals P417 Long-term deep remission after adalimumab discontinuation in Crohn’s disease patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S423-S423
Author(s):  
L Melotti ◽  
F Rizzello ◽  
C Calabrese ◽  
N Dussias ◽  
P Gionchetti
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Healing ◽  
Treatment Withdrawal ◽  
Biologic Agent ◽  
Drug Discontinuation ◽  
Endoscopic Remission ◽  
Observational Cohort

Abstract Background Adalimumab is a safe and effective drug in treatment of Crohn’s Disease (CD). Current literature is not definitive regarding an exact timing for treatment withdrawal and disease relapses after drug discontinuation. Methods We conducted a single-centre, retrospective, observational cohort study involving patients affected by Crohn’s Disease (CD) treated with adalimumab. Of 575 patients treated with adalimumab for CD, 149 patients suspended treatment for stable deep remission (clinical steroid-free, biochemical, endoscopic remission defined as mucosal healing). Of these, 126 have a minimum follow up of 4 years, the other 23 where lost or finished the follow-up. Patients were assessed clinically, laboratoristically and endoscopically for 4 years. Relapse was defined as clinical (HBI &gt; 4) and biochemical (PCR &gt; 0.5 mg/dL). Results Of the 126 patients with 4 years follow-up, 64 (51%) maintained deep remission during the 4 year follow-up period. Of these, 38 (59%) were on exit-therapy with thiopurines. Twenty-seven patients (18%) had relapsed by year 1, 24 (18%) by year 2, 8 (6%) by year 3, and 1 (0.8%) by year 4. Relapses needed surgical therapy in 9 (15%) cases, whereas 36 (60%) were retreated with adalimumab and 4 (7%) with another biologic agent. The remaining 11 patients (18%) were treated only with a course of steroids. Conclusion Patients who suspend treatment with adalimumab for stable deep remission maintain remission in the long term in approximately half of cases. The majority of relapses occur in the first 24 months after discontinuation.

scholarly journals Levels of Biosimilar Infliximab during and after Induction Treatment in Crohn’s Disease and Ulcerative Colitis—A Prospective Polish Population Study

2021 ◽  
Vol 10 (22) ◽  
pp. 5311
Author(s):  
Anna Pękala ◽  
Rafał Filip
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Therapeutic Drug ◽  
Induction Phase ◽  
Drug Levels ◽  
Trough Levels

Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13). Results: A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment. Conclusions: Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase.

scholarly journals Diagnosis and Outcome of Oesophageal Crohn’s Disease

2019 ◽  
Vol 14 (5) ◽  
pp. 624-629
Author(s):  
Rita Vale Rodrigues ◽  
Margaret Sladek ◽  
Konstantinos Katsanos ◽  
C Janneke van der Woude ◽  
Juan Wei ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Case Reports ◽  
Case Series ◽  
Disease Diagnosis ◽  
Mucosal Healing ◽  
Case Report Form ◽  
Endoscopic Remission ◽  
Mean Time

Abstract Background and Aims Crohn’s disease [CD] can involve any part of the gastrointestinal tract. We aimed to characterize the clinical, endoscopic and histological features and treatment outcomes of CD patients with oesophageal involvement. Methods We collected cases through a retrospective multicentre European Crohn’s and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. Results A total of 40 patients were reported (22 males, mean [±SD, range] age at oesophageal CD diagnosis: 25 [±13.3, 10–71] years and mean time of follow-up: 67 [±68.1, 3–240] months). Oesophageal involvement was established at CD diagnosis in 26 patients [65%] and during follow-up in 14. CD was exclusively located in the oesophagus in two patients. Thirteen patients [32.2%] were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in five patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors [PPIs] were administered in 37 patients [92.5%]. Three patients underwent endoscopic dilatation for symptomatic strictures but none underwent oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients [82.5%] after a mean time of 7 [±5.6, 1–18] months. Follow-up endoscopy was performed in 29/40 patients and 26/29 [89.7%] achieved mucosal healing. Conclusion In this case series the endoscopic and histological characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing inflammatory bowel disease-related therapy occurring in two-thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients.

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