Contributions
Abstract: EP1617
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Natalizumab is an efficacious drug in the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite the knowledge of a large variation in pharmacokinetics and patient characteristics, every patient receives the same treatment regimen of 300mg intravenously administered natalizumab every four weeks. We believe that a natalizumab concentration based treatment schedule may result in fewer hospital visits and lower costs, without decreasing drug efficacy.
Objective: To prove that extending dose intervals guided by serum concentrations of natalizumab will not result in radiological and clinical disease activity in completely stable RRMS patients treated with natalizumab.
Study design: A prospective multicentre, single arm trial.
Study population: Adult patients with RRMS with no evident disease activity during the last 12 months of natalizumab infusions with a minimum treatment duration of 12 months. Only patients with natalizumab trough concentrations of ≥15µg/ml can enter the study.
Intervention: Before subsequent natalizumab infusions, serum natalizumab concentrations will be evaluated. If the concentration exceeds 15µg/ml the dose interval will be extended with one week to a maximum of eight weeks. If serum concentration falls between 10-15µg/ml patients will remain on their current schedule. If serum concentration drops below 10µg/ml the infusion schedule will be put back with one week with a minimum of a four week interval.
Patients will undergo 3 monthly brain MRI's with gadolinium and 3 monthly neurological testing, i.e. expanded disability status scale (EDSS). Furthermore, at baseline and at 12 months, patients will complete questionnaires including Short form-36 and Multiple Sclerosis Impact Scale-29.
Main study parameters/endpoints: The primary endpoint is the number of patients developing gadolinium enhancing lesions on brain MRI. Secondary endpoints are new or enlarging T2 lesions on brain MRI, clinical relapses, progression on EDSS and changes of subjective health measured with the questionnaires.
Preliminary trial results: The first patient was included in November 2016. So far, 30 patients have been included and >50% of patients are treated with an interval ≥6 weeks. MRI follow-up showed no gadolinium enhancing lesions in included patients. Furthermore, no new/enlarging T2 lesions were found at MRI follow-up and no patient experienced a clinical relapse so far.
Disclosure:
Z.L.E. van Kempen has nothing to disclose.
D. Doesburg has nothing to disclose.
N.F. Kalkers has received speaker and consulting fees from Biogen, TEVA, Genzyme and Novartis.
J.P. Mostert has accepted speaker and consulting fees from Merck-Serono, Biogen, TEVA, Genzyme and Novartis.
E.L.J. Hoogervorst has received speaker and consulting fees from Merck-Serono, Biogen, TEVA, Genzyme and Novartis.
R.Q. Hintzen received honoraria for serving on advisory boards for Biogen Idec, Roche and Sanofi. He participated in trials with Biogen Idec, Merck-Serono, Roche, Genzyme and Novartis.
H.C. Weinstein has nothing to disclose.
M.P. Wattjes has received speaking and consultancy fees from Genzyme, Biogen, Novartis, Roche.
B.M.J. Uitdehaag has received personal compensation for consulting from Biogen, Genzyme, Merck Serono, Novartis, Roche en TEVA.
T. Rispens has received speaking fees from Pfizer and AbbVie, and Regeneron, and consulting fees and a research grant from Genmab.
J. Killestein has received speaker and consulting fees from Merck-Serono, Biogen, TEVA, Genzyme, Roche and Novartis.
Abstract: EP1617
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Natalizumab is an efficacious drug in the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite the knowledge of a large variation in pharmacokinetics and patient characteristics, every patient receives the same treatment regimen of 300mg intravenously administered natalizumab every four weeks. We believe that a natalizumab concentration based treatment schedule may result in fewer hospital visits and lower costs, without decreasing drug efficacy.
Objective: To prove that extending dose intervals guided by serum concentrations of natalizumab will not result in radiological and clinical disease activity in completely stable RRMS patients treated with natalizumab.
Study design: A prospective multicentre, single arm trial.
Study population: Adult patients with RRMS with no evident disease activity during the last 12 months of natalizumab infusions with a minimum treatment duration of 12 months. Only patients with natalizumab trough concentrations of ≥15µg/ml can enter the study.
Intervention: Before subsequent natalizumab infusions, serum natalizumab concentrations will be evaluated. If the concentration exceeds 15µg/ml the dose interval will be extended with one week to a maximum of eight weeks. If serum concentration falls between 10-15µg/ml patients will remain on their current schedule. If serum concentration drops below 10µg/ml the infusion schedule will be put back with one week with a minimum of a four week interval.
Patients will undergo 3 monthly brain MRI's with gadolinium and 3 monthly neurological testing, i.e. expanded disability status scale (EDSS). Furthermore, at baseline and at 12 months, patients will complete questionnaires including Short form-36 and Multiple Sclerosis Impact Scale-29.
Main study parameters/endpoints: The primary endpoint is the number of patients developing gadolinium enhancing lesions on brain MRI. Secondary endpoints are new or enlarging T2 lesions on brain MRI, clinical relapses, progression on EDSS and changes of subjective health measured with the questionnaires.
Preliminary trial results: The first patient was included in November 2016. So far, 30 patients have been included and >50% of patients are treated with an interval ≥6 weeks. MRI follow-up showed no gadolinium enhancing lesions in included patients. Furthermore, no new/enlarging T2 lesions were found at MRI follow-up and no patient experienced a clinical relapse so far.
Disclosure:
Z.L.E. van Kempen has nothing to disclose.
D. Doesburg has nothing to disclose.
N.F. Kalkers has received speaker and consulting fees from Biogen, TEVA, Genzyme and Novartis.
J.P. Mostert has accepted speaker and consulting fees from Merck-Serono, Biogen, TEVA, Genzyme and Novartis.
E.L.J. Hoogervorst has received speaker and consulting fees from Merck-Serono, Biogen, TEVA, Genzyme and Novartis.
R.Q. Hintzen received honoraria for serving on advisory boards for Biogen Idec, Roche and Sanofi. He participated in trials with Biogen Idec, Merck-Serono, Roche, Genzyme and Novartis.
H.C. Weinstein has nothing to disclose.
M.P. Wattjes has received speaking and consultancy fees from Genzyme, Biogen, Novartis, Roche.
B.M.J. Uitdehaag has received personal compensation for consulting from Biogen, Genzyme, Merck Serono, Novartis, Roche en TEVA.
T. Rispens has received speaking fees from Pfizer and AbbVie, and Regeneron, and consulting fees and a research grant from Genmab.
J. Killestein has received speaker and consulting fees from Merck-Serono, Biogen, TEVA, Genzyme, Roche and Novartis.