Abstract Details

Title Subcutaneous natalizumab 300mg every 4 weeks is comparable to standard intravenous dosing in REFINE: a study exploring the safety, tolerability, and efficacy of multiple natalizumab treatment regimens in patients with relapsing multiple sclerosis

Topic Multiple Sclerosis

Presentation(s) (-)

Poster/Presentation
Number 009

Objective

Background In RRMS patients, natalizumab 300mg intravenously (IV) every 4 weeks (q4wk) significantly reduces clinical and MRI activity. The benefit/risk profiles of other dosing/administration regimens are poorly understood.

Design/Methods REFINE was a parallel-group exploratory study of 290 clinically stable RRMS patients previously treated with natalizumab for >=12 months who were randomized to 1 of 6 natalizumab regimens over 60 weeks: 300mg IV or subcutaneously (SC) q4wk, 300mg IV or SC every 12 weeks (q12wk), 150mg IV or SC q12wk. Patients and study staff were blinded to dose/frequency but not to administration route; all patients received natalizumab or placebo q4wk.

Results All q12wk dosing arms were closed early because of increased MRI activity (gadolinium-enhancing and new/newly enlarging T2 lesions). The mean cumulative number of combined unique active lesions on brain MRI (primary endpoint) was 0.23/0.02 for 300mg IV/SC q4wk, 3.84/3.08 for 300mg IV/SC q12wk, and 6.09/6.44 for 150mg IV/SC q12wk. Annualized relapse rates were 0.07/0.08 for 300mg IV/SC q4wk, 0.20/0.30 for 300mg IV/SC q12wk, and 0.47/0.18 for 150mg IV/SC q12wk. Time to first relapse and time to first MRI meeting rescue criteria were comparable in the 300mg IV and SC q4wk arms, as were trough natalizumab concentration and trough alpha4-integrin saturation. Anti-natalizumab antibodies were absent in the 300mg IV and SC q4wk arms; persistent antibodies were detected in two patients receiving natalizumab IV q12wk. Adverse events were consistent with natalizumab’s known safety profile.

Conclusions Administration of natalizumab q12wk was associated with increased MRI activity, leading to early closures of the q12wk study arms. Natalizumab 300mg SC q4wk was comparable to standard 300mg IV q4wk dosing with respect to clinical/MRI efficacy, pharmacokinetics/pharmacodynamics, immunogenicity, and safety.

Authors/Disclosures
Maria Trojano (Policlinico - Bari)	Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi_Genzyme. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi-Genzyme. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Maria Trojano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen.
	No disclosure on file
	No disclosure on file
Catherine Lubetzki (Hopital De La Salpetriere)	Catherine Lubetzki has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE. Catherine Lubetzki has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MERCK SERONO. Catherine Lubetzki has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for REWIND.
	No disclosure on file
Karleyton Evans, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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