Salvage Therapy With High/Low Methotrexate for Loss of Response to Infliximab Dose Escalation
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|ClinicalTrials.gov Identifier: NCT02269358|
Recruitment Status : Completed
First Posted : October 21, 2014
Last Update Posted : October 18, 2018
The goal of the present study is to evaluate if addition of methotrexate can restore remission after loss of response to infliximab after dose escalation.
another goal is to evaluate if low dose methotrexate can maintain remission achieved by regular dose methotrexate by 6 months.
|Condition or disease||Intervention/treatment||Phase|
|Crohn's Disease||Drug: METHOTREXATE||Phase 4|
Background: IFX mono-therapy became the method of choice for treatment in pediatric CD, though this strategy has been called into question due to frequent loss of response to IFX requiring dose escalation of IFX or decreased intervals of IFX( up to 40% during the first year) (1). This loss of response has been attributed to development of ATIs and low trough levels of IFX, which can develop after the first infusions. This loss of response will often occur in patients with prior azathioprine exposure (2,3,4).
Currently , the first step during loss of response to infliximab in children is dose escalation either by decreasing the interval between infusions or doubling the dose. However, patients with persistent antibodies or high titers are likely to fail even with dose escalation. The Sonic trial clearly demonstrated that combination therapy with a thiopurine may be more effective than Anti TNF alpha monotherapy (2). Ben Horin et al demonstrated that antidrug antibodies can be reversed and improved anti TNF trough levels obtained by adding an immunomodulator to failed monotherapy due to an antidrug antibody (3).
We have previously shown that in patients with a previous loss of response to two biologics leading to cessation of both biologics can respond to reinduction with adalimumab and methotrexate . Among 12 patients (10 children and two adults) , 6 obtained complete remission. We subsequently lowered the does in several patients without loss of response, and tried stopping methotrexate in 3 patients. All 3 patients relapsed within months of complete cessation of methorexate.In this previous study we took two separate actions that restored response, re-induction and methotrexate therapy. In the current proposal we will take patients that are on escalated therapy and just add methotrexate, in order to evaluate if adding methotrexate once weekly can restore response after loss of response to infliximab after failed dose escalation.It is important to note that methotrexate does not increase the risk of malignancy as co-therapy as far as we know.
Methods: It is a prospective open label phase 4, non randomized uncontrolled study in a small cohort of patients to evaluate if addition of methotrexate can restore remission after loss of response to infliximab after dose escalation in paediatric patients.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 4, Open Lable Non Randomized un Controlled Study. Salvage Therapy With High/Low Methotrexate for Loss of Response to Infliximab Dose Escalation|
|Study Start Date :||July 2015|
|Actual Primary Completion Date :||October 9, 2018|
|Actual Study Completion Date :||October 9, 2018|
Experimental: Addition of methotrexate
Addition SC methotrexate at 15 mg/m2, not to exceed 25 mg/m2 . Patients in remission after 4 weeks will reduce their dose by halve. patients not in remission will continue the full dose until 12 weeks.
Infliximab therapy after escalation. SC methotrexate at 15 mg/m2 , not to exceed 25 mg/m2 per week for 4 weeks. Patients in remission after 4 weeks reduce their dose by halve. patients not in remission will continue the full dose until 12 weeks.
- remission [ Time Frame: at 12 weeks ]remission without additional therapy.
- Remission [ Time Frame: 6 months ]
- Trough levels [ Time Frame: week 12 ]
- ATIs [ Time Frame: week 12 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02269358
|The E. Wolfson.Medical Center|
|Holon, Israel, 58100|
|Study Chair:||Arie Levine, MD||Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson MC, Tel-Aviv University, Holon, Israel|