Proactive adalimumab trough measurement is associated with improved treatment outcomes in children with Crohn’s Disease: The PAILOT randomised controlled trial

Amit Assa © ECCO

Loss of response (LOR) during anti-TNF treatment for Crohn's Disease (CD) is commonly approached through the measurement of trough concentration (TC) and anti-drug antibodies, with subsequent modification of treatment (reactive therapeutic drug measurement, TDM). It is appealing to speculate that tailored treatment based on routine TC and antibody measurements (proactive TDM) may assist in sustaining adequate drug levels and thus in improving efficacy and preventing the evolution of anti-drug antibodies. Nevertheless, two randomised controlled trials, the TAXIT [1] and the TAILORIX [2], have failed to demonstrate superiority of level-based over clinically based adjustment of infliximab treatment. To date, there are no prospective studies comparing proactive vs reactive TDM in paediatric CD nor are there any studies evaluating the proactive approach among adults or children treated with adalimumab. Hence, we aimed to investigate the effect of proactive drug monitoring-based treatment, in comparison with clinical and biologic-based monitoring of disease activity in children with CD treated with adalimumab.

John Mansfield © ECCO

The ECCO Clinical Research Committee (ClinCom) organises The School for Clinical Trialists as a half-day workshop at the ECCO Congress. This year the topics covered were: The Evolution of Trial Design and How to Optimise Recruitment to Clinical Trials. 

Krisztina Gecse © ECCO

It was our pleasure to welcome three new members, Laurent Beaugerie, Peter Bossuyt and Shaji Sebastian, onto the Clinical Research Committee of ECCO at the ECCO’19 Copenhagen Congress.

John Mansfield © ECCO

ClinCom is pleased to present the 3rd School for Clinical Trialists: Clinical Trial Evolution and Recruitment in IBD, on Wednesday, March 6, 2019, 08:00-11:30.

ClinCom exists as an ECCO Committee to further develop and encourage clinical trial activity in IBD within ECCO. This, the 3^rd School for Clinical Trialists, will give clinicians, nurses, research coordinators and all those interested in clinical trials a state-of-the-art view of the evolution of clinical trial design and practical aspects of the key problem of how to optimise trial recruitment.

An interview with María Chaparro

Javier P. Gisbert: Investigator-initiated studies (IIS) are clinical studies initiated and managed by non-pharmaceutical company researchers, including individual investigators, institutions, collaborative study groups and cooperative groups. The researcher is responsible for the legal and regulatory responsibilities of the trial sponsor for the conduct and management of the study as defined by all applicable laws and regulations. Your group at La Princesa Hospital (Madrid, Spain) has remarkable experience in this type of study. What attracts you most to such studies?

The PANTS study

Nicholas Kennedy © ECCO

Use of the anti-TNF alpha monoclonal antibodies infliximab and adalimumab has transformed the management of patients with refractory Crohn’s Disease. However, clinicians and patients are all too aware that anti-TNF treatment failure is common: 10%–40% of patients fail to respond to induction therapy (referred to as primary non-response: PNR), up to 40% of patients suffer secondary loss of response in the first year of therapy and approximately 10% suffer an adverse drug reaction that curtails treatment.

In faecal microbiota transplantation (FMT) for Ulcerative Colitis, Fusobacterium is associated with lack of remission, while metabolic shifts to starch degradation and short chain fatty acid production are associated with remission (FOCUS study)

Sudarshan Paramsothy © ECCO

The randomised controlled FOCUS study [1], along with other trials [2–4], suggests that FMT is effective in the treatment of patients with active Ulcerative Colitis (UC). However, the underlying microbial basis and predictors of therapeutic outcome in UC are largely unknown. We therefore performed in-depth microbial analyses on the samples collected during the FOCUS study to help identify bacterial taxonomic and functional changes associated with FMT in UC, particularly those predictive of therapeutic success or failure.

John Mansfield © ECCO

The 6^th ClinCom Workshop focussed on two current themes in IBD research: Evolving endpoints in clinical trials and comparative effectiveness research (CER).

Laurent Peyrin-Biroulet (Nancy, France) described the drivers that have led to the move from Crohn’s Disease Activity Index (CDAI) and Mayo scores to patient-reported outcomes (PROs) that just record clinical symptoms. The ultimate therapeutic goal is not only to reduce symptoms but also to return the patient to a normal life without disability. For Ulcerative Colitis (UC) the PRO uses rectal bleeding and stool frequency scores from the Mayo score, while for Crohn’s Disease (CD) abdominal pain and stool frequency scores are used. Many clinical trials also aim to show resolution of mucosal inflammation so endoscopic scores are frequently being used as co-primary endpoints with symptom scores. Some problems with PROs remain to be settled, especially the cut-off values for active disease, response and remission, and also the variability of patients’ assessment of loose stools and rectal bleeding.

Marc Ferrante  ©  ECCO

Following the success of the previous workshops, the Clinical Research Committee (ClinCom) of ECCO will run a sixth workshop in 2018.

During past years, endpoints in clinical trials for patients with Inflammatory Bowel Disease (IBD) have evolved substantially. Initially we mainly aimed for clinical remission, but it has become obvious that this is certainly insufficient to alter the natural history of the disease.