Highlights
- •The rebound phenomenon, a period of increased disease activity, following natalizumab discontinuation is recognised but its incidence has not been well documented.
- •Using two different treatment schedules of intravenous methylprednisolone, we observed disease activity following natalizumab discontinuation.
- •The incidence of rebound was 10%, lower than previously observed.
- •Rebound, in our study population, occurred in younger patients.
- •Treatment with intravenous methylprednisolone may reduce the incidence and severity of the rebound phenomenon.
Abstract
Background
Natalizumab (NTZ) is a disease-modifying treatment (DMT) in multiple sclerosis (MS)
whose discontinuation can produce a “rebound effect”, consisting of severe clinical
deterioration and/or evidence of disease reactivation on magnetic resonance imaging
(MRI).
Objective
To analyze the efficacy of two treatment schedules with intravenous methylprednisolone
(IVMP) administered during the washout period of natalizumab (i.e., before starting
another DMT) in preventing the rebound phenomenon.
Methods
Five-year retrospective study of NTZ withdrawals after at least 24 uninterrupted doses.
Two IVMP schedules were tested. In schedule 1 (3-month washout), 1, 2, and 3 g of
IVMP were administered on the first, second, and third month respectively. In schedule
2 (2-month washout), 1 and 2 g of IVMP were administered on the first and second month
respectively. A new DMT was started 10 days after the end of each schedule. Rebound
was defined as at least one clinical relapse plus rebound activity on MRI (>5 gadolinium-enhanced
lesions and a number of new/T2-enhanced and/or gadolinium-enhanced lesions greater
than before initiation of NTZ) during washout or at 6 months after new DMT initiation
(6M-DMT). Clinical and MRI evaluations were performed at 3, 6, 12, and 24 months after
initiation of the new DMT.
Results
Fifty patients (68% women) were included, with a mean (SD) age of 37.76 (10.88) years
and pre-NTZ annualized relapse rate (ARR) of 1.78 (1.04). During NTZ therapy, mean
Expanded Disability Status Scale (EDSS) score was 3.7 (1.73) and ARR was 0.23 (0.39).
The ARR (mean of both schedules) was 0.1 (0.71) during washout and 0.32 (0.84) at
6M-DMT. Rebound was observed in 10% of cases (n = 5), with no significant clinical or radiological differences (p>0.05) between the two IVMP schedules. Rebound was observed in younger patients and
was associated with new MRI lesions and higher ARR at 3M-DMT and 6M-DMT respectively,
with no difference in EDSS after 2 years of follow-up. Neither the ARR before NTZ
initiation nor the choice of new DMT after NTZ discontinuation was associated with
development of rebound effect.
Conclusions
Both IVMP schedules were well tolerated during NTZ washout and rebound was observed
in only 10% of cases. In our experience, administration of IVMP during NTZ washout
could reduce the possibility of a rebound effect.
Keywords
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Article info
Publication history
Published online: June 19, 2020
Accepted:
June 16,
2020
Received in revised form:
June 3,
2020
Received:
April 21,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
