scholarly journals Fingolimod initiation in multiple sclerosis patients is associated with potential beneficial cardiovascular autonomic effects

2017 ◽  
Vol 10 (4) ◽  
pp. 191-209 ◽  
Author(s):  
Max J. Hilz ◽  
Ruihao Wang ◽  
Carmen de Rojas Leal ◽  
Mao Liu ◽  
Francesca Canavese ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Time Course ◽  
Low Frequency ◽  
Autonomic Modulation ◽  
Autonomic Changes ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: Fingolimod slows heart rate (HR) due to vagomimetic effects and might cause additional cardiovascular autonomic changes. While the time course of HR changes is well described, the extent and course of cardiovascular autonomic changes upon fingolimod initiation has not yet been evaluated. This study, therefore, intended to assess cardiovascular autonomic changes during the first 6 h after fingolimod initiation. Methods: In 21 patients with relapsing-remitting multiple sclerosis (RRMS), we recorded respiration (RESP), electrocardiographic RR interval (RRI), systolic and diastolic blood pressure (BPsys, BPdia) at rest, before and 0.5, 1, 2, 3, 4, 5, and 6 h after fingolimod initiation. We calculated parameters of total autonomic modulation [RRI standard deviation (RRI-SD), RRI coefficient of variation (RRI-CV), RRI-total powers], mainly sympathetic cardiac modulation [RRI low frequency (LF) powers], sympathetic BP modulation (BPsys-LF powers), parasympathetic modulation [square root of the mean squared difference of successive RRIs (RMSSD), RRI high frequency (HF) powers], sympatho-vagal cardiac balance (RRI-LF/HF ratios), and baroreflex sensitivity (BRS). We compared parameters between the eight measurements [analysis of variance (ANOVA) or Friedman test with post-hoc analysis; significance: p < 0.05]. Results: After fingolimod initiation, RESP, BPsys, and BPsys-LF powers remained unchanged while RRIs, RRI-CV, RRI-SD, RRI-total powers, RRI-LF powers, RMSSD, RRI-HF powers, and BRS increased after 1 h and rose to peak values occurring after 5, 1, 2, 2, 1, 4, 4, and 4 h, respectively. After 3 h, BPdia had decreased significantly and was lowest after 5 h. RRI-LF/HF ratios decreased to a nadir after 4 h. Conclusions: The increases in parasympathetic and overall cardiac autonomic modulation and in BRS seen with fingolimod initiation are theoretically beneficial for the MS patient’s cardiovascular system. However, long-term studies must show whether these effects persist or are attenuated (e.g. due to S1P1 receptor down-regulation upon continued fingolimod therapy).

Interferon beta-1a long-term therapy related to pulmonary arterial hypertension in multiple sclerosis patients

2016 ◽  
Vol 22 (11) ◽  
pp. 1495-1498 ◽  
Author(s):  
Anthony Fok ◽  
Trevor Williams ◽  
Catriona A McLean ◽  
Ernest Butler
Keyword(s):  
Multiple Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Term Therapy ◽  
Relapsing Remitting ◽  
Pulmonary Arterial ◽  
Multiple Sclerosis Patients ◽  
Long Term Therapy ◽  
Relapsing Remitting Multiple Sclerosis

We report two patients with relapsing remitting multiple sclerosis (RRMS) on interferon (IFN) beta-1a treatment for more than 7 years who developed pulmonary arterial hypertension (PAH). Patient 1 developed severe PAH requiring lung transplantation. Histology showed typical proliferative lesions including plexiform lesions consistent with PAH. Patient 2 ceased IFN beta-1a, and their symptoms stabilised. Both cases highlight IFN beta-1a treatment as a potential risk factor for PAH. PAH needs to be considered as a diagnosis in patients on long-term IFN beta-1a treatment who develop new-onset respiratory symptoms.

scholarly journals Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing–remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study

2016 ◽  
Vol 23 (6) ◽  
pp. 818-829 ◽  
Author(s):  
Omar Khan ◽  
Peter Rieckmann ◽  
Alexey Boyko ◽  
Krzysztof Selmaj ◽  
Natalia Ashtamker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Gray Matter Volume ◽  
Low Frequency ◽  
Open Label ◽  
Treatment Benefit ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: The 1-year placebo-controlled (PC) phase of the Glatiramer Acetate Low-Frequency Administration (GALA) study showed that glatiramer acetate 40 mg/mL three times weekly (GA40) significantly reduced annualized relapse rate (ARR) and magnetic resonance imaging (MRI) activity in patients with relapsing–remitting multiple sclerosis. Patients completing the PC phase were invited to an open-label (OL) extension. Objective: To evaluate the effects of early start (ES) and delayed start (DS) of GA40 over 3 years. Methods: A total of 97.2% of patients completing the PC phase received GA40 in the OL extension. ES ( n = 943) patients received GA40 throughout; DS ( n = 461) patients received placebo during the PC phase and GA40 during the OL phase. Relapse, MRI, disease progression, and safety were evaluated. Results: A total of 1041 patients completed 3 years of follow-up. During the OL phase, ES and DS patients showed comparable ARRs (0.20–0.22) and similar numbers of gadolinium-enhancing T1 ( p = 0.49) and new or enlarging T2 lesions ( p = 0.51) at Year 3. ES patients showed significantly smaller changes in gray matter volume than DS patients from Months 12 to 36 (mean difference, 0.371%; p = 0.015), with similar trend in whole-brain volume ( p = 0.080). Adverse events were mild, consistent with the well-established glatiramer acetate (GA) safety profile. Conclusion: GA40 conferred treatment benefit over 3 years: sustained low ARR and lesion activity and favorable safety.

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