Relationship between Serum Adalimumab Levels and Clinical Outcome in the Treatment of Inflammatory Bowel Disease

Background: Adalimumab (ADA) is an anti-tumor necrosis factor agent that has been shown to be effective in inducing and maintaining remission in adult patients with inflammatory bowel disease. The relationship between the ADA trough levels and clinical efficacy has been demonstrated, but there is variability in the definition of the most suitable range for its clinical applicability. Summary: A review of published studies during the last 5 years on ADA serum levels and its relationship with the clinical outcome was performed. The studies selected included 7 observational studies, a systematic review, a meta-analysis and a post hoc analysis of a clinical trial. The reported ADA levels that discriminate patients in clinical remission from those with active disease range from 4.5 to 8 µg/mL. This therapeutic range varies when considering endoscopic remission (7.5 to >13.9 µg/mL). Although the sample of patients with ulcerative colitis is small, a tendency to reach higher levels of ADA is observed in both clinical and endoscopic remission. Key Messages: The optimal therapeutic cut-off point of serum ADA levels ranges from 4.5–5 to 12 µg/mL, where ADA levels are associated with an adequate clinical monitoring of the disease during maintenance therapy. These ranges vary according to the target, suggesting levels of 4.8 µg/mL as the cut-off for clinical remission and levels ≥7.5 µg/mL for mucosal healing/endoscopic response. Controlled prospective studies are required to determine the optimal therapeutic interval of ADA serum levels both as induction and as maintenance therapy.

Download Full-text

Relapse From Deep Remission After Therapeutic De-escalation in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa087 ◽

2020 ◽

Vol 14 (10) ◽

pp. 1413-1423

Author(s):

Bing Zhang ◽

Alakh Gulati ◽

Omeed Alipour ◽

Ling Shao

Keyword(s):

Systematic Review ◽

Inflammatory Bowel Disease ◽

Relapse Rate ◽

Bowel Disease ◽

Meta Analysis ◽

Severe Disease ◽

Mucosal Healing ◽

Endoscopic Remission ◽

Inflammatory Bowel ◽

Relapse Rates

Abstract Background and Aims We conducted a systematic review and meta-analysis evaluating the relapse rate after therapeutic de-escalation in inflammatory bowel disease [IBD] patients who achieved deep remission [DR]. Methods We searched MEDLINE, EMBASE, and major gastroenterology conferences up to July 2019 for studies reporting relapse in adult patients with DR who subsequently underwent therapeutic de-escalation. Eligible studies defined DR as at least a combination of clinical remission and mucosal healing/endoscopic remission. The primary outcome was cumulative 1-year and 2-year relapse rates after therapeutic de-escalation. Secondary outcomes were relapse rates in ulcerative colitis [UC] and Crohn’s disease [CD], relapse after anti-tumour necrosis factor-α [anti-TNFα] de-escalation, and the rate of disease response recapture following re-escalation. Results Thirteen studies encompassing 837 patients were identified. The cumulative relapse rate after therapeutic de-escalation was 28.7% within 1 year [12 studies], and 38.4% within 2 years [eight studies]. Relapse rates within 1 year and 2 years were comparable between UC [five studies; 25.4% and 37.4%] and CD [seven studies; 34.1% and 39.9%]. Ten studies reported de-escalation of anti-TNFα, of which 29.8% patients relapsed within 1 year and 41.4% within 2 years. Response recapture following re-escalation [eight studies] was 75.4%. Conclusions Despite achieving deep remission, therapeutic de-escalation in this patient population is associated with significant relapse risk within 1 year and 2 years. This risk is more pronounced in patients requiring anti-TNFα for management, likely because of more severe disease. Similar rates of relapse were reported among UC and CD within these time periods. These findings suggest that combined clinical and endoscopic remission should not be an impetus to consider therapeutic de-escalation.

Download Full-text

Association of trough vedolizumab levels with clinical, biological and endoscopic outcomes during maintenance therapy in inflammatory bowel disease

Frontline Gastroenterology ◽

10.1136/flgastro-2019-101197 ◽

2019 ◽

Vol 11 (2) ◽

pp. 117-123 ◽

Cited By ~ 2

Author(s):

Nikolas Plevris ◽

Philip W Jenkinson ◽

Cher S Chuah ◽

Mathew Lyons ◽

Lynne M Merchant ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Maintenance Therapy ◽

Bowel Disease ◽

Clinical Remission ◽

Clinical Activity ◽

Faecal Calprotectin ◽

Cross Sectional ◽

Mayo Score ◽

Endoscopic Remission ◽

Inflammatory Bowel

ObjectiveTo establish the relationship between trough vedolizumab levels and outcomes during maintenance therapy.DesignCross-sectional service evaluation was performed on patients with inflammatory bowel disease (IBD) receiving maintenance vedolizumab therapy (minimum of 12 weeks following induction). Prior to infusion, data on clinical activity (Harvey-Bradshaw Index or partial Mayo score), trough C-reactive protein (CRP)/vedolizumab levels and faecal calprotectin were collected. Endoscopic data (±8 weeks from vedolizumab level testing) were obtained by review of medical records. Vedolizumab levels were processed using the Immundiagnostik monitor ELISA.SettingThe Edinburgh IBD Unit, Western General Hospital (tertiary IBD referral centre).PatientsSeventy-three patients (30 ulcerative colitis and 43 Crohn’s disease) were identified who fulfilled inclusion criteria and had vedolizumab levels matched with clinical activity scores, CRP and faecal calprotectin. Of these, 40 patients also had matched endoscopic data.Main outcome measuresThe association of trough vedolizumab levels with clinical remission (Harvey-Bradshaw Index <5 or partial Mayo <2), biologic remission (faecal calprotectin <250 µg/g+CRP <5 mg/L) and endoscopic remission (Mayo score 0/no inflammation and ulceration on colonoscopy).ResultsThe median trough vedolizumab levels were similar between patients in and not in clinical remission (10.6 vs 9.9 µg/mL, p=0.54); biologic remission (10.6 vs 9.8 µg/mL, p=0.35) and endoscopic remission (8.1 vs 10.2 µg/mL, p=0.21). Quartile analysis revealed no significant increase in the proportion of patients in clinical remission, biologic remission or endoscopic remission with increasing trough vedolizumab levels (p<0.05).ConclusionsIn this cohort, trough vedolizumab levels were not associated with clinical, biological or endoscopic outcomes during maintenance therapy.

Download Full-text

P424 Association between infliximab trough levels, clinical remission, mucosal healing and quality of life in patients with inflammatory bowel disease on maintenance therapy

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx002.549 ◽

2017 ◽

Vol 11 (suppl_1) ◽

pp. S292-S292

Author(s):

R.S. Parra ◽

M.R. Feitosa ◽

O. Féres ◽

J.J.R.d. Rocha

Keyword(s):

Quality Of Life ◽

Inflammatory Bowel Disease ◽

Maintenance Therapy ◽

Bowel Disease ◽

Clinical Remission ◽

Mucosal Healing ◽

Inflammatory Bowel ◽

Trough Levels

Download Full-text

Infliximab Trough Levels and Quality of Life in Patients with Inflammatory Bowel Disease in Maintenance Therapy

Gastroenterology Research and Practice ◽

10.1155/2018/1952086 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Rogério S. Parra ◽

Marley R. Feitosa ◽

Letícia C. H. Ribeiro ◽

Lais A. Castro ◽

José J. R. Rocha ◽

...

Keyword(s):

Quality Of Life ◽

Inflammatory Bowel Disease ◽

Maintenance Therapy ◽

Bowel Disease ◽

Clinical Remission ◽

Mucosal Healing ◽

Mayo Score ◽

Inflammatory Bowel ◽

Trough Levels

Objective. Investigate the association between infliximab trough levels and quality of life in inflammatory bowel disease patients in maintenance therapy. Methods. We carried out a transversal study with inflammatory bowel disease patients in infliximab maintenance therapy. Infliximab trough levels were determined using a quantitative rapid test. Disease activity indices (partial Mayo Score and Harvey-Bradshaw Index) and endoscopic scores (endoscopic Mayo Score or Simple Endoscopic Score in Crohn’s disease) were obtained. Quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). Results. Seventy-one consecutive subjects were included in the study (55 with Crohn’s disease and 16 with ulcerative colitis). Drug levels were considered satisfactory (≥3 μg/mL) in 28 patients (39.4%) and unsatisfactory (<3 μg/mL) in 43 (60.6%). Satisfactory trough levels were associated with higher rates of clinical remission and mucosal healing. Higher trough levels were also associated with improved IBDQ scores, particularly regarding bowel symptoms, systemic function, and social function. Conclusion. Satisfactory trough levels of infliximab were associated with higher rates of clinical remission, mucosal healing, and improved quality of life in inflammatory bowel disease patients on maintenance therapy.

Download Full-text

Optimal Range of Fecal Calprotectin for Predicting Mucosal Healing in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Visceral Medicine ◽

10.1159/000514196 ◽

2021 ◽

pp. 1-11

Author(s):

Bing-Jie Xiang ◽

Min Jiang ◽

Ming-Jun Sun ◽

Cong Dai

Keyword(s):

Inflammatory Bowel Disease ◽

Diagnostic Accuracy ◽

Likelihood Ratio ◽

Sensitivity And Specificity ◽

Bowel Disease ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

Inflammatory Bowel

Objective: Fecal calprotectin (FC) is a promising marker for assessment of inflammatory bowel disease (IBD) activity. However, the utility of FC for predicting mucosal healing (MH) of IBD patients has yet to be clearly demonstrated. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of FC in predicting MH of IBD patients. Methods: We systematically searched the databases for studies from inception to April 2020 that evaluated MH in IBD. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Results: Sixteen studies comprising 1,682 ulcerative colitis (UC) patients and 4 studies comprising 221 Crohn’s disease (CD) patients were included. The best performance of FC for predicting MH in UC was at cut-off range of 60–75 μg/g with area under the curve (AUC) of 0.88 and pooled sensitivity and specificity of 0.87 and 0.79, respectively. The pooled sensitivity and specificity values of cutoff range 180–250 μg/g for predicting MH in CD were 0.67 and 0.76, respectively. The AUC of 0.79 also revealed improved discrimination for identifying MH in CD with FC concentration. Conclusion: Our meta-analysis has found that FC is a simple, reliable noninvasive marker for predicting MH in IBD patients. FC cutoff range 60–75 μg/g appears to have the best overall accuracy in UC patients.

Download Full-text

PA.147 PROLONGED SCHEDULED THERAPY WITH INFLIXIMAB IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: EVALUATION OF CLINICAL REMISSION AND MUCOSAL HEALING

Digestive and Liver Disease ◽

10.1016/s1590-8658(08)60342-4 ◽

2008 ◽

Vol 40 ◽

pp. S128-S129

Author(s):

L. Grossi ◽

M. Spezzaferro ◽

L.F. Sacco ◽

M.E. Serio ◽

M. Amitrano ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Clinical Remission ◽

Mucosal Healing ◽

Inflammatory Bowel

Download Full-text

P837 Changes in the intestinal microbiota of patients with inflammatory bowel disease during an 8-week infliximab infusion cycle

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.965 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S649-S649

Author(s):

G Seong ◽

J H Song ◽

J Shin ◽

S M Kong ◽

E R Kim ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Species Richness ◽

Maintenance Therapy ◽

Intestinal Microbiota ◽

Bowel Disease ◽

Clinical Remission ◽

Microbial Composition ◽

Infliximab Infusion ◽

Faecal Samples ◽

Inflammatory Bowel

Abstract Background This study investigated changes in the intestinal microbiota during 8-week infliximab maintenance therapy in inflammatory bowel disease (IBD) patients with clinical remission. Microbial compositional differences were analysed according to the trough level of infliximab (TLI) and mucosal healing (MH) status. Methods 16S rRNA gene-based microbiome profiling was performed on 10 and 74 faecal samples from 10 healthy volunteers and 40 adult IBD patients, respectively. All enrolled IBD patients were in clinical remission during infliximab maintenance therapy. To identify changes in the intestinal microbiota, faecal sampling occurred at 1–2 weeks (1W) and 7–8 weeks (7W) after infliximab infusion. TLI was measured by ELISA at 8 weeks immediately before the subsequent infusion; MH was evaluated by endoscopy within 3 months. Results No significant differences were found in microbial composition, species richness, and diversity indices between 1W and 7W samples or in microbial composition and diversity between healthy volunteer and 1W or 7W samples. However, 7W faecal samples from the patients with TLI≥5 μg/ml showed increased species richness compared with TLI<5 μg/ml, and patients with MH showed increased species diversity compared with non-MH. Beta-diversity analysis showed clustering between samples in the MH and non-MH groups. LefSe analysis identified differential expression of Faecalibacterium prausnitzii group between TLI < 5 μg/ml and TLI ≥ 5 μg/ml and MH and non-MH groups. Conclusion There were no significant changes in the intestinal microbiota during an 8-week infliximab infusion cycle in IBD patients with clinical remission; however, microbial composition, species richness, and diversity were associated with TLI and MH status.

Download Full-text

P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.507 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S355-S355

Author(s):

M I Calvo Moya ◽

I Omella Usieto ◽

M I Vera Mendoza ◽

V Matallana Royo ◽

I Gonzalez Partida ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Practice ◽

Bowel Disease ◽

Clinical Remission ◽

Real Life ◽

Mucosal Healing ◽

Surveillance Colonoscopy ◽

Previously Treated ◽

Inflammatory Bowel

Abstract Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score <2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) <4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was deﬁned by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was deﬁned by a decrease of SES-CD of 50% or Rutgeerts index <i2 with at least 1 point of decease compared with baseline. Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

Download Full-text