Patients with Crohn disease or Ulcerative Colitis which need biotherapy (antibody against TNF-a)
Conditions
Interventions
Trade Name: Remsima
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Other descriptive name: Remsima
Concentration unit:
Sponsors
CUB- Hopital Erasme
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age > 18 years Moderate-to-severe CD (HBI=8) with endoscopically visible ulcers or moderate-to-severe and severe UC (Mayo Score =6) and Mayo endoscopic subscore >1 (APPENDIX 1-2-3) (a patient with active disease without CRP can be included) Patients must be starting on infliximab (Remicade (MSD) or CT-P13: Remsima (Mundipharma) or Inflectra (Hospira)) in accordance with national reimbursement criteria or a washout period of 8 weeks will be observed before starting any new anti-TNF therapy after vedolizumab and 4 weeks after adalimumab before starting infliximab Patients may be naïve to thiopurines or have failed therapy with 1 thiopurine; in which case AZA or 6MP will be either continued or stopped: The dose must remain stable 4 weeks before beginning the study. Patients previously intolerant to Azathioprine or 6-MP can start with the other thiopurine or with Methotrexate (MTX) per investigators discretion. Patient intolerant to standard doses of AZA or 6-MP can start at a lower dose or AZA or 6MP can be stopped per investigators discretion. However, if the immunomodulator is continued or introduced during screening period, the dose should remain stable for the duration of the trial, except if intolerance leading to discontinuation. Patients failing MTX can continue on MTX with infliximab Ongoing steroids are allowed if dose was stable 2 weeks before beginning the study with a maximum of prednisone 16 mg/d or budesonide 9 mg/day and should be tapered in 2 weeks. Patients who consent to receive Infliximab 5 mg/kg at week 0, 2 and 6 and further on every 8 weeks in conjunction with their current Azathioprine, 6-MP or MTX Women must have a contraceptive method Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Absence of endoscopically visible ulcers Ongoing steroid therapy at doses > 16 mg/d prednisolone or equivalent Ongoing infections Previous use of IFX Prior use of biologic therapies excepted if a washout period of 8 weeks is respected Serious other diseases including cancer in the 5 years prior to inclusion excluding non-melanoma skin cancer Indication for immediate surgery Critical gastrointestinal stricture with obstructive symptoms and/or presence of abscess. Pregnant or breast-feeding woman. Positive fecal culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools Active tuberculosis. Positive tuberculosis screen per local guidelines Untreated latent tuberculosis, latent TB is allowed if treated for at least 6 months Patients with moderate or severe heart failure Patients with multiple sclerosis or lupus disease Patients with a history of hypersensitivity to infliximab, or to any of the excipients HIV, HBV, HCV viral infection (except the presence of positive anti-HBs antibodies) with serology not older than 3 months Azathioprine or 6-MP in combination with allopurinol or with other myelotoxic therapy (a washout period of 7 days is required for allopurinol or other myelotoxic therapy) Non-compliant subjects Participation in another therapeutic study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of the inter-individual variability of the pharmacokinetics of infliximab level and antibodies to infliximab during induction treatment and correlation with clinical response at W14 and W30;Secondary Objective: Proportion of patients in steroid-free remission at W10-14 w/o normal CRP and/or fecal calprotectin levels Sustained steroid-free clinical response at W30 w/o normal CRP and/or fecal calprotectin levels and mucosal healing Sustained steroid-free clinical remission at W30 w/o normal CRP and/or fecal calprotectin levels Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with clinical response or remission, and/or normal CRP and/or normal fecal calprotectin levels at W14 and 30 Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels > 3 µg/ml at W14 and W30 without need for optimization Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels in third and fourth quartile at W14 and W30 ;Primary end point(s): Evaluation of the inter-individual variability of the pharmacokinetics of infliximab level and antibodies to infliximab during induction treatment and correlation with clinical response at W14 and W30;Timepoint(s) of evaluation of this end point: The timepoints of evaluation for the primary endpoint will be done at the end of induction treatment (at 6 weeks) The correlation between induction treatment and clinical response will be done at W14 and W30 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of patients in steroid-free remission at W10-14 w/o normal CRP and/or fecal calprotectin levels Sustained steroid-free clinical response at W30 w/o normal CRP and/or fecal calprotectin levels and mucosal healing Sustained steroid-free clinical remission at W30 w/o normal CRP and/or fecal calprotectin levels Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with clinical response or remission, and/or normal CRP and/or normal fecal calprotectin levels at W14 and 30 Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels > 3 µg/ml at W14 and W30 without need for optimization Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels in third and fourth quartile at W14 and W30 ;Timepoint(s) of evaluation of this end point: The timepoints of evaluation for the secondary endpoints will be done at: - W10-14 for the first - W14 and W30 for the other secondary endpoints | — |
Countries
Belgium
Contacts
Public ContactLiefferinckx
CUB- Hopital Erasme
Outcome results
None listed