Contributions
Abstract: P587
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: Some clinicians in Italy extended the dose of natalizumab infusions after 24 doses,with the hypothesis of reducing PML risk; this idea was supported by recent reports.
Objective:To make this strategy feasible, it is necessary to ascertain the therapeutic durability of the extended dosing strategy.
Aim: To evaluate the non-inferiority in controlling disease activity of an extended interval dosing (EID) of natalizumab.
Methods: Patients who received natalizumab for at least 24 weeks in 14 Italian centers were included in the analysis. Patients were grouped in 2 categories according to the mean number of weeks between doses (< =5.5 weeks, standard interval dosing (SID);>5.5 weeks, EID). Only the dose intervals before the first relapse was used to estimate the mean intervals between doses, to minimize the bias associated to a possible return to SID in patients under EID after they experienced a relapse. The non-inferiority of EID vs SID was a priori defined as satisfied if the upper limit of the 95%CI of the annualized relapse rate (ARR) in the EID group did not exceed the mean ARR of the SID group by 0.02 relapse/year. Baseline characteristics were comparedbetween groups by aMann Whitney U test. ARR during follow up was estimated and compared between groups by a multivariate Poisson regression model.
Results: 341 patientswere included in this analysis. The median interval between doses was 4.9 weeks (range 3.7-8.4), with a clear bimodal distribution (modes at 4 and 6 weeks) associated with individual centers strategies (the median was 4.5 weeks in 220 patients from 12 centers and 6.2 in 121 patients from 2 centers). 221 patients were in the SID (median dose interval=4.5 weeks) and 120 in the EID group (median dose interval=6.3 weeks). The ARRduring follow up adjusting for all the baseline variables (age, disease duration, relapses in 2 years pre-natalizumab start, EDSS, number of previous treatments) was 0.042 (95%CI=0.026-0.067) in the SID group, and it was 0.007 (95%CI=0.002-0.028) in the EID group. The non-inferiority of EID vs SID was satisfied.
Conclusions: In this cohort there is no evidence of a reduced efficacy of natalizumab by extending the intervals between doses from a median of 4.5 to a median of 6.3 weeks. This observation confirms previous results and together with the emerging evidence of a reduced risk of PML associated to an EID supports the need of a randomized study to change the standard of the natalizumab dosing schedule.
Disclosure: M.Clerico: received personal compensations for advisory boards, public speaking, editorial commitments or travel grants from Biogen Idec, Merck Serono, Fondazione Serono, Novartis,Pomona, Sanofi-Genzyme and Teva.
A. Signori: received teaching honoraria from Novartis
C. Cordioli: received advisory board and/or speaker honoraria from Novartis, TEVA, Biogen, Merck Serono, Genzyme
S. De Mercanti: nothing to disclose
E. Signoriello: received travel funding and speaker honoraria from Biogen, Novartis, Sanofi Genzyme, Bayer, Teva
G. Lus: received travel funding, research support, speaker honoraria from Biogen, Novartis, Sanofi Genzyme, Bayer, Teva, Almirall, Allergan, Ipsen
G.T. Maniscalco: has served on advisory boards and/or received travel grants and speaker honoraria from Almirall, Biogen, Merck Serono, Novartis and Teva
E. Curti: has served on scientific advisory boards for Merck Serono and has received funding for travel from Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Roche
L. Lorefice: received speaker fee from Teva and serves on scientific advisory boards for Merck Serono
E. Cocco: have received honoraria for consultancy or speaking from Bayer, Biogen, Novartis, Sanofi, Genzyme, Serono and Teva.
V. Nociti: has served on scientific advisory boards for Biogen, Teva, Sanofi-Genzyme and Merck Serono and has received travel grants and/or speaker honoraria from MerckSerono, Teva, Biogen, Sanofi-Genzyme Roche and Novartis
M. Mirabella: received honoraria for scientific advisory board, consulting and/or speaking fees, research support or travel grants from Almirall, Bayer Schering, Biogen, CSL Behring, Sanofi-Genzyme, Merck Serono, Novartis, Teva, Ultragenix; principal investigator in clinical trials for Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva, Ultragenix
D. Baroncini: eceived travel grants from Genzyme, Merck and Biogen for participation at national and international congresses; he received speaking honoraria from Sanofi and Novartis, and personal compensation from Almirall for scientific publication
D. Landi: received travel funding from Biogen, Merck Serono, Sanofi-Genzyme, Teva, honoraria for speaking from Sanofi-Genzyme, Teva, Biogen and consultation fees from Merck Serono, Teva, Roche. She is currently subinvestigator in clinical trials being conducted for Biogen, Novartis, Roche, Celgene
G. Mataluni: nothing to disclose
M. Petruzzo: nothing to diclose
R. Lanzillo: received personal compensation from Merck Serono, Biogen, Novartis, Almirall, Genzyme, and TEVA for public speaking, editorial work and advisory boards
I. Gandoglia: received funding for travel from Biogen, Novartis, Genzyme, Merk Serono and honoraria from Almirall and Genzyme
A. Laroni: received consulting honoraria and/or speaker fees from Novartis, Genzyme, Biogen, Sanofi, Merck Serono, and Teva and received research support from Biogen
R. Frangiamore: received travel founding from Biogen, Merck Seono, Sanofi-Genzyme, Teva to take part in conferences and scientific events
A. Sartori: received funding for travel and/or speaker honoraria from Novartis, Teva, Merk, Genzyme, Almirall, Roche
P. Cavalla: has served on advisory boards and/or has received travel grants and/or speaker honoraria from Merck Serono, Teva Italia, Biogen, Almirall, Novartis, Sanofi-Genzyme
G. Costantini: nothing to disclose
M.P. Sormani: received personal compensation for consulting services and for speaking activities from Merck Serono, Teva, Novartis, Roche, Genzyme and Biogen
R. Capra: received lecture fees and/or travel grants from Novartis, Biogen, Celgene, Novartis, TEVA, Genzyme and Sanofi-Aventis
Abstract: P587
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: Some clinicians in Italy extended the dose of natalizumab infusions after 24 doses,with the hypothesis of reducing PML risk; this idea was supported by recent reports.
Objective:To make this strategy feasible, it is necessary to ascertain the therapeutic durability of the extended dosing strategy.
Aim: To evaluate the non-inferiority in controlling disease activity of an extended interval dosing (EID) of natalizumab.
Methods: Patients who received natalizumab for at least 24 weeks in 14 Italian centers were included in the analysis. Patients were grouped in 2 categories according to the mean number of weeks between doses (< =5.5 weeks, standard interval dosing (SID);>5.5 weeks, EID). Only the dose intervals before the first relapse was used to estimate the mean intervals between doses, to minimize the bias associated to a possible return to SID in patients under EID after they experienced a relapse. The non-inferiority of EID vs SID was a priori defined as satisfied if the upper limit of the 95%CI of the annualized relapse rate (ARR) in the EID group did not exceed the mean ARR of the SID group by 0.02 relapse/year. Baseline characteristics were comparedbetween groups by aMann Whitney U test. ARR during follow up was estimated and compared between groups by a multivariate Poisson regression model.
Results: 341 patientswere included in this analysis. The median interval between doses was 4.9 weeks (range 3.7-8.4), with a clear bimodal distribution (modes at 4 and 6 weeks) associated with individual centers strategies (the median was 4.5 weeks in 220 patients from 12 centers and 6.2 in 121 patients from 2 centers). 221 patients were in the SID (median dose interval=4.5 weeks) and 120 in the EID group (median dose interval=6.3 weeks). The ARRduring follow up adjusting for all the baseline variables (age, disease duration, relapses in 2 years pre-natalizumab start, EDSS, number of previous treatments) was 0.042 (95%CI=0.026-0.067) in the SID group, and it was 0.007 (95%CI=0.002-0.028) in the EID group. The non-inferiority of EID vs SID was satisfied.
Conclusions: In this cohort there is no evidence of a reduced efficacy of natalizumab by extending the intervals between doses from a median of 4.5 to a median of 6.3 weeks. This observation confirms previous results and together with the emerging evidence of a reduced risk of PML associated to an EID supports the need of a randomized study to change the standard of the natalizumab dosing schedule.
Disclosure: M.Clerico: received personal compensations for advisory boards, public speaking, editorial commitments or travel grants from Biogen Idec, Merck Serono, Fondazione Serono, Novartis,Pomona, Sanofi-Genzyme and Teva.
A. Signori: received teaching honoraria from Novartis
C. Cordioli: received advisory board and/or speaker honoraria from Novartis, TEVA, Biogen, Merck Serono, Genzyme
S. De Mercanti: nothing to disclose
E. Signoriello: received travel funding and speaker honoraria from Biogen, Novartis, Sanofi Genzyme, Bayer, Teva
G. Lus: received travel funding, research support, speaker honoraria from Biogen, Novartis, Sanofi Genzyme, Bayer, Teva, Almirall, Allergan, Ipsen
G.T. Maniscalco: has served on advisory boards and/or received travel grants and speaker honoraria from Almirall, Biogen, Merck Serono, Novartis and Teva
E. Curti: has served on scientific advisory boards for Merck Serono and has received funding for travel from Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Roche
L. Lorefice: received speaker fee from Teva and serves on scientific advisory boards for Merck Serono
E. Cocco: have received honoraria for consultancy or speaking from Bayer, Biogen, Novartis, Sanofi, Genzyme, Serono and Teva.
V. Nociti: has served on scientific advisory boards for Biogen, Teva, Sanofi-Genzyme and Merck Serono and has received travel grants and/or speaker honoraria from MerckSerono, Teva, Biogen, Sanofi-Genzyme Roche and Novartis
M. Mirabella: received honoraria for scientific advisory board, consulting and/or speaking fees, research support or travel grants from Almirall, Bayer Schering, Biogen, CSL Behring, Sanofi-Genzyme, Merck Serono, Novartis, Teva, Ultragenix; principal investigator in clinical trials for Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva, Ultragenix
D. Baroncini: eceived travel grants from Genzyme, Merck and Biogen for participation at national and international congresses; he received speaking honoraria from Sanofi and Novartis, and personal compensation from Almirall for scientific publication
D. Landi: received travel funding from Biogen, Merck Serono, Sanofi-Genzyme, Teva, honoraria for speaking from Sanofi-Genzyme, Teva, Biogen and consultation fees from Merck Serono, Teva, Roche. She is currently subinvestigator in clinical trials being conducted for Biogen, Novartis, Roche, Celgene
G. Mataluni: nothing to disclose
M. Petruzzo: nothing to diclose
R. Lanzillo: received personal compensation from Merck Serono, Biogen, Novartis, Almirall, Genzyme, and TEVA for public speaking, editorial work and advisory boards
I. Gandoglia: received funding for travel from Biogen, Novartis, Genzyme, Merk Serono and honoraria from Almirall and Genzyme
A. Laroni: received consulting honoraria and/or speaker fees from Novartis, Genzyme, Biogen, Sanofi, Merck Serono, and Teva and received research support from Biogen
R. Frangiamore: received travel founding from Biogen, Merck Seono, Sanofi-Genzyme, Teva to take part in conferences and scientific events
A. Sartori: received funding for travel and/or speaker honoraria from Novartis, Teva, Merk, Genzyme, Almirall, Roche
P. Cavalla: has served on advisory boards and/or has received travel grants and/or speaker honoraria from Merck Serono, Teva Italia, Biogen, Almirall, Novartis, Sanofi-Genzyme
G. Costantini: nothing to disclose
M.P. Sormani: received personal compensation for consulting services and for speaking activities from Merck Serono, Teva, Novartis, Roche, Genzyme and Biogen
R. Capra: received lecture fees and/or travel grants from Novartis, Biogen, Celgene, Novartis, TEVA, Genzyme and Sanofi-Aventis