Real World Effectiveness of Ustekinumab in Induction and Maintenance Therapy for Crohn´s Disease

Study Overview
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Brief Summary
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RUN-CD is an investigator initiated Non interventional Trial on biologics in Crohn´s Disease (CD) patients in Germany with a prospective documentation of effectiveness in induction and maintenance therapy of biologics, especially of Ustekinumab, with a special interest on predictors of long-term responses and favorable disease outcome and documentation of severe side effects caused by the therapy with biologics.

Detailed Description
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The effectiveness and safety of induction and maintenance therapy of Ustekinumab and other biologics will be assessed in different relevant subgroups of Crohn's Disease patients. To this end, different confounders have to be considered. Patients followed-up for several years will likely receive changing treatments. These changes have to be taken into account. Furthermore, the decision to prescribe, to stop or to continue a treatment depends on the availability of treatment options and experiences with these alternatives: Confounding by indication will be taken into account Patient characteristics which likely influence the risk of developing a particular endpoint will be taken into account The possible influence of co-medication will be considered Changing risks over time will be considered Power considerations needs to be conducted prior to the comparison of incidence rates Appropriate statistical methods will be applied to deal with these challenges The principles described above will be followed in a similar manner for the analysis of effectiveness and safety endpoints. An appropriate power analysis will be performed before each sub-analysis.

Official Title
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Real World Effectiveness of Ustekinumab in Induction and Maintenance Therapy for Crohn´s Disease in Conjunction With Long-term Outcome

Conditions
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Crohn Disease

Intervention / Treatment
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* Biological: Stelara, Remicade, Entyvio, Humira, Remsima, Flixabi, Inflectra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD-patients aged 18-80 years at enrollment written informed consent is given Exclusion Criteria: planned surgical intervention malignant disease in history lack of adequate documentation possibilities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1a<br>CD-patients (age at enrollment: 18-80 years) receiving a newly introduced Ustekinumab therapy (n=150). A prior therapy with biologics is not allowed. | |
| Group 1b<br>CD-patients (age at enrollment: 18-80 years) receiving a newly introduced Ustekinumab therapy (n=150). A prior therapy with 1 biologics is allowed | |
| Group 2<br>CD-patients (age at enrollment: 18-80 years) receiving a newly introduced Ustekinumab therapy (n=150). A prior therapy with ≥2 biologic is allowed. | Biological: Stelara, Remicade, Entyvio, Humira, Remsima, Flixabi, Inflectra<br>* The data of Crohn´s Disease (CD)-patients on Ustekinumab will be compared in an explorative analysis with CD-patients on other Biologics.<br>|
| Group 3a<br>CD-patients (age at enrollment: 18-80 years) receiving a newly introduced biologics therapy other than Ustekinumab (n=150). A prior therapy with biologic is not allowed. | |
| Group 3b<br>CD-patients (age at enrollment: 18-80 years) receiving a newly introduced biologics therapy other than Ustekinumab (n=150). A prior therapy with 1 biologic is allowed. | |
| Group 4<br>CD-patients (age at enrollment: 18-80 years) receiving a newly introduced biologics therapy other than Ustekinumab (n=150). A prior therapy with ≥2 biologics is allowed. | Biological: Stelara, Remicade, Entyvio, Humira, Remsima, Flixabi, Inflectra<br>* The data of Crohn´s Disease (CD)-patients on Ustekinumab will be compared in an explorative analysis with CD-patients on other Biologics.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of induction therapy in CD-patients treated with Ustekinumab. | clinical remission HBI ≤ 4 at week 16 | Week 0 till 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of induction therapy at week 8 in CD-patients treated with Ustekinumab vs. anti-TNF/Vedolizumab. | clinical remission HBI ≤ 4 at week 8 | Week 0 till 8 | 
| Effectiveness of maintenance therapy up to 3 years in CD-patients treated with Ustekinumab vs. anti-TNF/Vedolizumab. | clinical remission HBI ≤ 4 at year 3 | Week 0 till year 3 | 
| Effectiveness of Ustekinumab in different subpopulations | e.g. based on prior biologics therapy or clinical parameters/phenotype at baseline in comparison with the other biologics-group. or clinical parameters/phenotype at baseline in comparison with the other biologics-group. | Week 0 till year 3 | 
| Measurement of disease activity with HBI | HBI= Harvey-Bradshaw-Index (e.g. steroids), co-morbidities and adverse events. | Week 0 till year 3 | 
| Measurement of Quality of Life with EQ-5D questionnaire | EQ-5D™ is a standardised instrument for use as a measure of health outcome | Week 0 till year 3 | 
| Measurement of disease activity with CDAI | CDAI = Crohn's Disease Activity Index | Week 0 till week 16 |