Editorial: predicting response to treatment in children with Crohn's disease

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.

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ASSESSMENT OF THE RESPONSE OF PATIENTS WITH CROHN'S DISEASE TO BIOLOGICAL THERAPY USING NEW NON-INVASIVE MARKERS: lactoferrin and calprotectin

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032013000200022 ◽

2013 ◽

Vol 50 (2) ◽

pp. 130-137 ◽

Cited By ~ 3

Author(s):

Islaine Martins NOGUEIRA ◽

Sender Jankiel MISZPUTEN ◽

Orlando AMBROGINI Jr. ◽

Ricardo ARTIGIANI-NETO ◽

Cláudia Teresa CARVENTE ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Biological Therapy ◽

Activity Index ◽

Maintenance Phase ◽

Disease Activity Index ◽

Inflammatory Activity ◽

Response To Treatment ◽

Significant Difference ◽

Fecal Markers

Context The use of fecal markers to monitor Crohn's disease is crucial for assessing the response to treatment. Objective To assess the inflammatory activity of Crohn's disease by comparing fecal markers (calprotectin and lactoferrin), colonoscopy combined with biopsy, and the Crohn's disease activity index (CDAI), as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance. Methods Seventeen patients were included who had been previously diagnosed with Crohn's disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin) tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8), and after maintenance (week 32). Results The calprotectin levels exhibited significant reductions (P = 0.04) between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P = 0.036), and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P<0.01). Conclusion Calprotectin and lactoferrin are not useful for monitoring inflammatory activity in Crohn's disease patients who are subjected to biological therapy.

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Adalimumab Therapy Improves Intestinal Dysbiosis in Crohn's Disease

Journal of Clinical Medicine ◽

10.3390/jcm8101646 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1646 ◽

Cited By ~ 16

Author(s):

Davide Giuseppe Ribaldone ◽

Gian Paolo Caviglia ◽

Amina Abdulle ◽

Rinaldo Pellicano ◽

Maria Chiara Ditto ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiota ◽

Response To Treatment ◽

Biologic Drugs ◽

Therapeutic Success ◽

Bacterial Phyla ◽

Reactive Protein ◽

Adalimumab Therapy ◽

A Prospective Study

The response to treatment with biologic drugs, in patients with Crohn’s disease, could be associated with changes in gut microbiota composition. The aim of our study was to analyse the modification of microbiota during adalimumab therapy in patients with Crohn’s disease. We performed a prospective study in patients with Crohn’s disease analysing gut microbiota before start of adalimumab therapy (T0) and after six months of therapy (T1). Among the 20 included patients, the phylum Proteobacteria fell from 15.7 ± 3.5% at T0 to 10.3 ± 3.4% at T1 (p = 0.038). Furthermore, the trend in relation to therapeutic success was analysed. Regarding bacterial phyla, Proteobacteria decreased in patients in whom therapeutic success was obtained, passing from a value of 15.8% (± 4.6%) to 6.8 ± 3.1% (p = 0.049), while in non-responder patients, percentages did not change (T0 = 15.6 ± 5.7%, T1 = 16.8 ± 7.6%, p = 0.890). Regarding the Lachnospiraceae family, in patients with normalization of C reactive protein six 6 months of adalimumab therapy, it increased from 16.6 ± 3.1% at T0 to 23.9 ± 2.6% at T1 (p = 0.049). In conclusion, in patients who respond to Adalimumab therapy by decreasing inflammation, there is a trend of intestinal eubiosis being restored.

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A Pilot Study of Positron Emission Tomography: Computed Tomography Scans as Predictors of Non-response to Treatment With Anti-TNF Agents in Patients With Small Bowel Crohn’s Disease

The American Journal of Gastroenterology ◽

10.14309/00000434-201410002-00396 ◽

2014 ◽

Vol 109 ◽

pp. S120

Author(s):

Arun Swaminath ◽

Masanori Ichise ◽

Katherine Lameka ◽

Michael Kulon

Keyword(s):

Computed Tomography ◽

Positron Emission Tomography ◽

Crohn’S Disease ◽

Pilot Study ◽

Small Bowel ◽

Crohn's Disease ◽

Emission Tomography ◽

Response To Treatment ◽

Positron Emission ◽

Computed Tomography Scans

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NOD2 Polymorphism Predicts Response to Treatment in Crohn’s Disease—First Steps to a Personalized Therapy

Digestive Diseases and Sciences ◽

10.1007/s10620-011-1977-3 ◽

2011 ◽

Vol 57 (4) ◽

pp. 879-886 ◽

Cited By ~ 23

Author(s):

Jan Hendrik Niess ◽

Jochen Klaus ◽

Johannes Stephani ◽

Carolin Pflüger ◽

Nadine Degenkolb ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Personalized Therapy ◽

Response To Treatment ◽

Nod2 Polymorphism

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Efficacy and tolerability of certolizumab pegol in Crohn's disease in clinical practice

Terapevticheskii arkhiv ◽

10.26442/terarkh201890674-80 ◽

2018 ◽

Vol 90 (6) ◽

pp. 74-80 ◽

Cited By ~ 1

Author(s):

O V Knyazev ◽

A V Kagramanova ◽

A A Lishchinskaya ◽

N G Samsonova ◽

N V Orlova ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Dose Escalation ◽

Certolizumab Pegol ◽

Response To Therapy ◽

Response To Treatment ◽

Predictors Of Response ◽

Tnf Α ◽

Previously Treated

Aim. To assess the efficacy and tolerance of certolizumab pegol (CP) in patients with Crohn's disease (CD) treated in the Department of inflammatory bowel diseases of the A.S. Loginov Moscow Clinical Research Center and to determine the predictors of response to therapy. Materials and methods. All patients with CD who had received the treatment of CP were observed prospectively for at least 6 months or until the date of discontinuation of the drug. The effectiveness of the study was assessed response to therapy by the 6th week, maintaining the clinical response (6th and 26th weeks), the dynamics of endoscopic parameters by the 10th and 54th week of therapy, long-term maintenance of remission, healing fistula. Used univariant and multivariate analyses of predictors of response to treatment. Results and discussion. The study included 39 patients: 12 (30.7%) men and 27 (69.3%) female, the average duration of observation was 104 weeks. The interdepartmental range was in the range from 28 to 158 weeks. Clinical improvement occurred in 38 out of 39 (97.4 %) patients with CD. Comparative analysis of response to treatment with CP have bionaive patients previously treated with another inhibitor of TNF-α. In the group of bionaive response to therapy in a month, 6 months and at the end of the observation period occurred at 100.0%, 95.0% and 95.0%, respectively. In the group of patients previously treated with GSI, the response rate was about 94.4 %, 88.9 % and 77.7% week 54 endoscopic response and endoscopic remission was maintained in 46,2% and 30,1% patients, complete healing of the mucosa on the background of maintenance therapy, CP, was preserved in 20.5% of patients with Crohn's disease. In the group of patients with perianal lesions (n=13) complete closure of all fistulas was observed in 5 (38.6 %) patients, partial response was observed in 4 patients (30,7%) patients, in 4 (30.7 %) closure of fistulas occurred. The frequency of adverse events was 0 cases (0.0%). The dose escalation was required in 3 patients (7,7%) patients with CD. Dose escalation in our study required patients with high initial CDAI and previous inefficiencies of the other two inhibitors of TNF-α. Reliable predictors of secondary loss of response and need for dose escalation of the drug has been the continued level of CRP >5 mg/l after 2 weeks initiation of therapy CP and smoking. Conclusion. The obtained results demonstrate the efficacy and tolerability profile of CP appropriate for long-term CD therapy in real clinical practice.

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Surgical Treatment of Perianal Fistulizing Crohn’s Disease: From Lay-Open to Cell-Based Therapy—An Overview

The Scientific World JOURNAL ◽

10.1155/2014/146281 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Gianluca Pellino ◽

Francesco Selvaggi

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Treatment Success ◽

Combined Treatment ◽

Scoring Systems ◽

Response To Treatment ◽

Treatment Modalities ◽

Definitive Treatment ◽

Collaborative Management ◽

Cell Based Therapy

Background. Perianal Crohn’s disease (CD) can be challenging. Despite the high incidence of fistulizing CD, literature lacks clear guidelines. Several medical, surgical, and combined treatment modalities have been proposed, but evidences are scarce.Methods. We searched the literature to assess the facets of perianal CD, with particular focus on complex fistulae. Disease epidemiology, classification, diagnosis, activity scoring systems, and medical-surgical treatments were assessed.Results. Perianal fistulizing CD is common, frequently associated with upper gastrointestinal and colorectal CD. Complex fistulas often require repeated treatments. Continence is a major concern when dealing with repeated procedures. A prudent pathway is to resolve active sepsis and to limit damages, delaying a definitive treatment to the time when acute phase has been controlled. The improved diagnostic techniques allow better preoperative planning and are useful in monitoring the response to treatment. Besides newer devices, cell-based treatments are promising tools which have recently enriched the treatment portfolio. However, the need for proctectomy is still disturbingly high in CD patients with complex perianal fistulae.Conclusions. Perianal CD can impair quality of life and lead to need for proctectomy. A staged approach is reasonable. Treatment success can be improved by multimodal treatment and collaborative management by experienced gastroenterologists and surgeons.

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