Contributions
Abstract: P877
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Objective: Natalizumab (NTZ), a monoclonal antibody, has a clear effect on disease activity in relapsing remitting MS (RRMS). However, many neurologists prescribing NTZ are aware of a notable part of patients reporting an increase of symptoms at the end of the NTZ cycle. Patients might mention the NTZ is wearing-off and they are in 'need' of their next NTZ infusion.
The objective of this study is to evaluate the prevalence of the wearing-off effect and to study possible associations with pharmacokinetic/dynamic measurements and patient characteristics. Furthermore, this study compares the wearing-off effect in patients with a standard 4-week treatment interval and extended interval of 5-8 weeks.
Methods: This prospective mono-center cohort study included adult RRMS patients with a minimum of six consecutive NTZ infusions. Patients were asked to fill in three questionnaires; the Multiple Sclerosis Impact Scale (MSIS-29), the Short Form Health Survey (SF-36) and a general questionnaire. Before NTZ infusion, blood was taken to assess NTZ concentration and alpha 4-integrin receptor saturation.
Results: Ninety-three patients were included in this study. Of all patients, 54% had ever experienced the wearing-off effect during treatment and 32% experienced a current wearing-off effect at time of sampling. The current wearing-off effect was associated with a significant increase of quality of life on the MSIS-29 and SF-36 one week after NTZ infusion. The current experience of a wearing-off effect was not associated with NTZ concentration (p=0.17) or NTZ alpha 4-integrin receptor saturation (preliminary data). Median NTZ concentration in the standard interval (SI) group (n=62) was significantly higher than the extended interval (EI) group (n=31) (p< 0.001). However, the reported current experience of a wearing-off effect was higher in the SI group (39%) than in the EI group (19%) (p=0.060). The duration of the wearing-off symptoms was comparable between the SI and EI groups. The wearing-off effect was not associated with the number of NTZ infusions, disease duration, age or sex.
Conclusion: The wearing-off effect is a frequent reported phenomenon but is not associated with NTZ concentration or NTZ receptor saturation and most likely does not reflect a non-optimal pharmacokinetic/dynamic state. We did not find risk factors predicting the wearing-off effect and extended treatment intervals do not result in a higher prevalence or longer duration of the wearing-off effect.
Disclosure: Z.L.E. van Kempen: nothing to disclose
D. Doesburg: nothing to disclose
I. Dekker: received speaking honoraria from Roche, receives funding from the Dutch MS Society, grant number 14-358e
B. Lissenberg-Witte: nothing to disclose
A. de Vries: nothing to disclose
I. Claessen: nothing to disclose
A. ten Brinke: nothing to disclose
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: P877
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Objective: Natalizumab (NTZ), a monoclonal antibody, has a clear effect on disease activity in relapsing remitting MS (RRMS). However, many neurologists prescribing NTZ are aware of a notable part of patients reporting an increase of symptoms at the end of the NTZ cycle. Patients might mention the NTZ is wearing-off and they are in 'need' of their next NTZ infusion.
The objective of this study is to evaluate the prevalence of the wearing-off effect and to study possible associations with pharmacokinetic/dynamic measurements and patient characteristics. Furthermore, this study compares the wearing-off effect in patients with a standard 4-week treatment interval and extended interval of 5-8 weeks.
Methods: This prospective mono-center cohort study included adult RRMS patients with a minimum of six consecutive NTZ infusions. Patients were asked to fill in three questionnaires; the Multiple Sclerosis Impact Scale (MSIS-29), the Short Form Health Survey (SF-36) and a general questionnaire. Before NTZ infusion, blood was taken to assess NTZ concentration and alpha 4-integrin receptor saturation.
Results: Ninety-three patients were included in this study. Of all patients, 54% had ever experienced the wearing-off effect during treatment and 32% experienced a current wearing-off effect at time of sampling. The current wearing-off effect was associated with a significant increase of quality of life on the MSIS-29 and SF-36 one week after NTZ infusion. The current experience of a wearing-off effect was not associated with NTZ concentration (p=0.17) or NTZ alpha 4-integrin receptor saturation (preliminary data). Median NTZ concentration in the standard interval (SI) group (n=62) was significantly higher than the extended interval (EI) group (n=31) (p< 0.001). However, the reported current experience of a wearing-off effect was higher in the SI group (39%) than in the EI group (19%) (p=0.060). The duration of the wearing-off symptoms was comparable between the SI and EI groups. The wearing-off effect was not associated with the number of NTZ infusions, disease duration, age or sex.
Conclusion: The wearing-off effect is a frequent reported phenomenon but is not associated with NTZ concentration or NTZ receptor saturation and most likely does not reflect a non-optimal pharmacokinetic/dynamic state. We did not find risk factors predicting the wearing-off effect and extended treatment intervals do not result in a higher prevalence or longer duration of the wearing-off effect.
Disclosure: Z.L.E. van Kempen: nothing to disclose
D. Doesburg: nothing to disclose
I. Dekker: received speaking honoraria from Roche, receives funding from the Dutch MS Society, grant number 14-358e
B. Lissenberg-Witte: nothing to disclose
A. de Vries: nothing to disclose
I. Claessen: nothing to disclose
A. ten Brinke: nothing to disclose
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