Time of interferon-β 1a injection and duration of treatment affect clinical side effects and acute changes of plasma hormone and cytokine levels in multiple sclerosis patients

Kümpfel, Tania; Schwan, Michaela; Pollmächer, T.; Yassouridis, Alexander; Uhr, Manfred; Trenkwalder, C.; Weber, Frank

doi:10.1177/1352458507078685

Cited by 13 publications

(10 citation statements)

References 23 publications

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“…Since its introduction as an established therapy for relapsing-remitting MS, IFN-β has been known to affect sleep continuity, at least in the early phase of therapy, 9 although objective evidence of sleep disruption with chronic use is still lacking. Moreover, it has recently been suggested that fatigue may be linked to direct or indirect effects of IFN-β on the central nervous system (CNS), particularly via activation of corticotropin-releasing hormone synthesis and adrenocorticotropic axis function, and its effects on interleukin (IL)-1 and IL-6 production.…”

Section: Ifn-βmentioning

confidence: 99%

The impact of drugs for multiple sclerosis on sleep

et al. 2016

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Abstract:Although there is a growing literature on the presence of sleep disorders in multiple sclerosis (MS), few studies have specifically addressed the impact of drugs on sleep of these patients. Moreover, even when sleep is considered, quantitative assessment by standardized questionnaires or polysomnography is lacking. The studies that have been done highlight that interferon-beta and some symptomatic medications may affect sleep, thus contributing to fatigue, depression, and poor quality of life; conversely, natalizumab and cannabinoids may improve sleep. Common limitations of the literature reviewed here are small sample size, selection bias, and often a lack of objective outcome measures. Clinicians need to remember to ask about sleep in all MS patients and intervene when appropriate. A systematic approach that takes sleep into account is recommended to enhance recognition and appropriate management of sleep disruption, including disorders related to medication. Consideration of the impact on sleep should also be part of the design of trials of new therapies. Tables 1 and 2, both disease-modifying drugs and common symptomatic medications for MS may interfere with sleep. 33 Keywords MethylprednisoloneAs known, insomnia and other sleep changes, such as decreased REM sleep, are common side effects of steroid treatment, even after only a few days of administration. 34 A randomized, placebo-controlled trial of oral methylprednisolone given in pulses every 4 weeks as an add-on therapy to IFN-β-1a for the treatment of relapsing-remitting MS was carried out. 6 The authors found that steroid intake led to a significant reduction in relapse rate; however, insomnia was one of the most frequent adverse event recorded (~25% of patients). 6 As in the general population, the clinician must consider this co-morbid cause of insomnia and encourage lifestyle changes (such as proper sleep hygiene), cognitive behavioral therapy (CBT), and pharmacological intervention if needed. 35 A very recent prospective multicenter observational study evaluated through self-report questionnaires the frequency, severity, and impact on activities of daily living of adverse effects of high-dose intravenous methylprednisolone in relapsing-remitting MS patients with a relapse. The authors observed that sleep disturbance (not better specified) was among the most common adverse events experienced by the patients (44% of 59), especially in those with high disease impact or high disability. 8Nevertheless, although most clinicians warn patients about the steroid-related effects on sleep, an actigraphy study evaluating the short-term tolerance of 5-day regimen of intravenous methylprednisolone demonstrated high sleep efficiency, which is discrepant with the complaints reported by the patients. The authors conclude that sleep efficiency was not disturbed by methylprednisolone in patients, whether used for a clinically isolated syndrome (CIS), MS relapse, or sub-acute disease progression. 7 IFN-βSince its introduction as an established therapy for re...

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Section: Ifn-βmentioning

confidence: 99%

The impact of drugs for multiple sclerosis on sleep

et al. 2016

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“…A study comparing the time course of plasma hormone and cytokine levels and the severity of side effects in RRMS patients injecting IFNβ in the morning or in the evening found that IFNβ administration in the evening resulted in a more rapid increase in IL-6 plasma levels and temperature and was associated with more severe symptoms compared with morning administration [22]. In a more recent study, the change of the IFNβ injection time from evening to morning improved flu-like symptoms and sleep in a substantial proportion of the study cohort consisting of RRMS patients with persistent IFNβ-related FLS [23].…”

Section: Discussionmentioning

confidence: 99%

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study

et al. 2017

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BackgroundFlu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS.MethodsWe conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1) 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2) first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)] after 4 weeks of treatment within each sequence.ResultsForty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference –0.15; 95% confidence interval: from –0.74 to 0.44; p = 0.6029). The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile.ConclusionsThe addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFNβ-induced FLS.Trial registrationEudraCT 2013-001055-12.

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“…In a study examining the effects of time of injection on clinical response, IFN-b injection in the evening led to more intense clinical side effects compared to morning group, suggesting that tolerability and effectiveness of IFN-b therapy may be optimized by adjusting time of drug delivery [16]. Similarly, it has been suggested that steroids treatment, specifically GC, commonly used to counteract the acute MS relapse, might benefit from application of a chronomodulated therapy to provide increased drug effectiveness without increasing dose.…”

mentioning

confidence: 96%