Highlights
- •Alemtuzumab demonstrated high efficacy in several clinical studies.
- •Data about use of alemtuzumab in real clinical practice are scarce.
- •Effectiveness and safety of alemtuzumab in a real-world cohort is investigated.
- •Alemtuzumab was effective and safe in a real word setting.
Abstract
Background
Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis
(RRMS), but in recent years safety-related concerns had emerged due to description
of novel serious side effects not registered in CARE-MS I and CARE-MS II phase 3 studies,
nor in TOPAZ extension study. Data about alemtuzumab use in real clinical practice
are limited and based mainly on retrospective studies with small sample sizes. Therefore,
more information about effectiveness and safety of alemtuzumab in this context is
needed.
Methods
A multicenter observational prospective study to investigate effectivity and safety
of alemtuzumab in a real-world setting was performed. Primary endpoints were the change
in annualized relapse rate (ARR), and in disability measured by EDSS score. Secondary
endpoints were the cumulative probability of confirmed 6-month disability improvement
and worsening. Disability worsening and disability improvement were considered when
the EDSS score was increased or decreased, respectively, in 1 point if baseline EDSS
score was <5.0, or in 0.5 point if baseline EDSS score was ≥5.5, confirmed over 6
months. Other secondary endpoint was the proportion of patients who achieved NEDA-3
status (absence of clinical relapses, disability EDSS progression, and MRI disease
activity as depicted by new/enlarging T2 lesions or Gadolinium enhancing T1 lesions).
Adverse events also were recorded.
Results
A total of 195 RRMS patients (70% female) who started alemtuzumab treatment were included.
Mean of follow-up was 2.38 years. Alemtuzumab significantly reduced the annualized
relapse rate from baseline with risk reductions of 86%, 83.5%, and 84%, at 12, 24,
and 36 months of follow-up respectively (Friedman test, p-value < 0.05 for all comparisons).
Alemtuzumab also significantly reduced EDSS score over one and two years after starting
alemtuzumab treatment (Friedman test, p-value<0.001 for both comparisons). A high
proportion of patients presented confirmed 6-month stability or disability improvement
(92%, 82%, and 79%, over 1, 2 and 3 years of follow-up respectively). The proportion
of patients who retained NEDA-3 status at 12, 24 and 36 months were 61%, 49%, and
42%, respectively. Baseline characteristics associated with a lower probability of
achieving NEDA-3 were younger age, sex female, high ARR, elevated number of previous
treatments, and switch from a second line therapy. Infusion related reactions were
the most frequent adverse event observed. The most common infections were urinary
tract infections (50%), and upper respiratory tract infections (19%) over the 3 years
of follow- up. Secondary thyroid autoimmunity was developed in 18.5% of patients.
Conclusion
Alemtuzumab has demonstrated in real clinical practice high effectiveness in controlling
multiple sclerosis activity, and no unexpected adverse events were observed.
Keywords
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Article info
Publication history
Published online: May 12, 2023
Accepted:
May 10,
2023
Received in revised form:
April 23,
2023
Received:
November 23,
2022
Identification
Copyright
© 2023 Elsevier B.V. All rights reserved.
