Author Of 2 Presentations
P0306 - Cardiovascular monitoring during alemtuzumab infusion in Multiple Sclerosis patients (ID 1880)
Abstract
Background
Alemtuzumab (AL) is a monoclonal antibody approved for Relapsing Remitting Multiple Sclerosis (RRMS). Infusion adverse events (AEs) are common during AL administration. AL administration protocol was revised in 2019 by regulatory agencies due to serious cardiovascular (CV) AEs. The new recommendations included at least hourly measurement of vital signs (VS) during infusion, daily electrocardiogram (EKG) before infusion, and contraindication in patients with previous CV comorbidities.
Objectives
To describe changes in VS and EKGs recordings in a cohort of RRMS patients during the first AL cycle treated at the same MS Center.
Methods
Since 2015, when AL was approved for MS in Italy, we consecutively monitored our patients for VS before and every 30 minutes during AL administration lasting at least 5 hours; EKGs were recorded daily before premedication. Methylprednisolone, chlorphenamine, acetaminophen, were given as premedication with ranitidine or omeprazole. We collected heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) after premedication, before AL infusion and every 60 minutes thereafter up to hospital discharge. Bradycardia was defined as HR<60 bpm or HR<20% if patient had bradycardia at day 1 admission. HR<45 bpm was the cut-off for clinically relevant bradycardia. Data about clinical history, comorbidities, and concomitant medications were collected.
Results
From June 2015 to November 2019, 47 (31 female) RRMS patients received the first AL course. At baseline mean age was 20.1(±8.1) years, disease duration 5.5(±5.5) years and EDSS 2 (0-4.5). 4 patients had CV comorbidities (2 hypertension, 2 premature ventricular contraction). A total of 153 EKGs were analyzed. We observed 30 non-specific repolarization abnormalities and 18 inverted T waves. Bradycardia was reported in 24 EKGs (20/24 at day 4 and 5). Bradycardia was recorded in 45/229 infusions. 24 patients showed at least 1 episode of bradycardia, 16/47 had clinically relevant bradycardia. SBP showed an increasing trend starting from the third day, but still within normal limits.
Conclusions
Our data support the need for accurate monitoring of AL infusion. AL administration was rarely associated with clinically relevant CV. Nevertheless, bradycardia was frequently recorded even though usually asymptomatic. Careful monitoring should be continued for the whole protocol of AL infusion since CV events can be observed independently from the expected early infusion-related reactions likely associated to cytokine release.
P0883 - MRI activity and extended interval of Natalizumab dosing: a multicenter Italian study (ID 1269)
- M. Clerico
- S. De Mercanti
- A. Signori
- M. Iudicello
- C. Cordioli
- E. Signoriello
- G. Lus
- S. Bonavita
- L. Lavorgna
- G. Maniscalco
- E. Curti
- L. Lorefice
- E. Cocco
- V. Nociti
- M. Mirabella
- D. Baroncini
- G. Mataluni
- D. Landi
- M. Petruzzo
- R. Lanzillo
- I. Gandoglia
- A. Laroni
- R. Frangiamore
- A. Sartori
- P. Cavalla
- G. Costantini
- M. Sormani
- R. Capra
Abstract
Background
Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML) without efficacy reduction.
Objectives
To evaluate the non-inferiority of the efficacy of an extended interval dosing (EID) regimen compared with the standard interval dosing (SID) of natalizumab regarding the multiple sclerosis (MS) MRI activity.
Methods
It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and eight patients were enrolled. Median dose interval (MDI) following 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks).
Results
Two hundred and sixteen patients were in the SID group (MDI = 4.4 weeks) and 144 in the EID group (MDI 6 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 2.98% (95% CI: 0.56-5.40) vs 3.32% (95% CI: 0.00-6.65%) [p=0.88] and 6.65% (95% CI: 3.02-10.29) vs 5.67% (95% CI: 1.76-9.58%) [p=0.73]. The EID regimen does not increase the occurrence of MRI activity after 6 and 12 months.
Conclusions
There is no evidence of a reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation confirms previous clinical results and together with the increasing evidence of a reduced risk of PML associated to an EID regimen, supports the need of a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, in order to better manage JCV-positive patients after 24 doses of natalizumab.