Multiple sclerosis associated fatigue during natalizumab treatment

https://doi.org/10.1016/j.jns.2009.06.004Get rights and content

Abstract

Objective

To assess multiple sclerosis (MS) associated fatigue after the first 6 months of natalizumab treatment.

Methods

Prospective, open-label, uncontrolled study. Fatigue was measured before treatment initiation and at month 6 with the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS) in 42 patients. Subjective impression of well-being was assessed with a visual analogue scale (1–10).

Results

42 patients were followed (mean age 35.1 years, 60% female, mean EDSS 3.7). The mean total MFIS were 45.8 (17.5) at baseline and decreased to 40.1 (18.0) (p < 0.01) at month 6. Mean scores on the VAS for subjective impression of well-being increased from 5.5 (1.9) to 6.1 (2.1) at month 6 (p < 0.01). Pre-treatment annual relapse rate decreased from 2.2 to 0.2, gadolinium enhancing lesions were reduced by 96% with natalizumab. There was no correlation of gadolineum enhancing lesions and fatigue scores.

Conclusion

Fatigue and well-being improved after treatment initiation with natalizumab. A randomized controlled trial is necessary to come to definite conclusions as to a potential effect of natalizumab on fatigue in MS.

Introduction

Fatigue is one of the most common and most disabling symptoms of multiple sclerosis (MS) associated with an impaired quality of life [1], [2], [3], [4]. Despite its relevance, little is known about the underlying cause. Several pharmacological and non-pharmacological treatment approaches have been investigated, but evidence regarding their effectiveness is restricted [5], [6]. It was suggested that fatigue could be caused by peripheral or central inflammation [7], [8], [9]. Interferon-beta preparations and glatiramer acetate are the most frequently used agents in the treatment of relapsing remitting MS. Despite the fact that all disease modifying MS therapies (DMT) successfully reduce inflammatory disease activity, fatigue is still a major concern for most MS patients [10]. However, the course of fatigue was not studied in randomized, prospective trials of DMT (interferon-beta preparations, glatiramer acetate) and an impact of these agents on fatigue is unclear [11], [12], [13], [14]. Since fatigue may interfere with activities of daily living already in stages of MS when physical disability is not a major concern, alleviation of fatigue represents an important benefit and could result in improved quality of life.

Natalizumab – a monoclonal antibody against Very-Late-Activation-Antigene 4 – reduces leukocyte migration across the blood brain barrier (BBB) [15]. Natalizumab treatment resulted in a substantial reduction of both clinical and MRI signs of central inflammatory activity [15]. Expert statements and also the European Medicines Agency (EMEA) approval recommended the use of natalizumab after failure of previous disease modifying therapies (DMT) or in highly active MS due to safety concerns [16], [17]. Aside from the beneficial effects on disease activity, patients treated with natalizumab experienced improved QoL [18]. There are no reports on the impact of glatiramer acetate or mitoxantrone on QoL in patients with MS and results for IFN-beta preparations were controversial in several phase IV studies [19], [20], [21], [22].

We hypothesised that natalizumab has the potential to reduce MS associated fatigue due to its potent effect on CNS inflammation.

Section snippets

Population and study design

Natalizumab was approved in July 2006 in Germany. All relapsing remitting MS patients (> 18 years) initiating treatment with natalizumab according to the European Medicines Agency approval at our center were asked to fill in questionnaires for screening of fatigue according to a pre-defined protocol as part of the clinical routine. IFN-beta or glatiramer acetate was stopped 1–2 weeks and immunosuppressants were stopped > 3 months before treatment with natalizumab. No patient was treated with

Results

Forty-two patients were included (all patients initiating natalizumab 300 mg i.v. every 4 weeks during the inclusion period participated). Baseline characteristics are given in Table 1. No patient discontinued treatment within the observational period.

Patient characteristics and baseline data are given in Table 1.

Discussion

This prospective study demonstrated that MS fatigue in patients with highly active MS may improve during natalizumab treatment. Improvement was consistently found on all fatigue outcome measures. Secondly, the reduction of clinical and MRI activity in our study is in line with the results from the pivotal trial [15]. Baseline fatigue levels were uninfluenced by clinical parameters indicating that we examined a common construct of MS fatigue [23], [24].

Disclosures

NP has received honoraria, personal compensation for consultation, speaking honoraria and research grants/compensation for study conduction from Bayer Schering, Biogen Idec, Glaxo SmithKline, Merck Serono, Sanofi Aventis and TEVA. OY has nothing to disclose. BT has received honoraria, personal compensation for consultation, speaking honoraria from Bayer Schering, Biogen Idec, Merck Serono, Sanofi Aventis. HCD received honoraria for participation in clinical trials, contribution to advisory

Acknowledgements

This work was in part supported by Biogen Idec GmbH, Germany. The funder had no role in the trial design, data collection, or preparation of the manuscript. We are grateful to E. Igwe and S. Woods for data management.

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