Oral dexamethasone pulse therapy versus daily prednisolone in sub-acute onset myositis, a randomised clinical trial

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Abstract

To determine if high-dose pulsed dexamethasone is more effective and safer than daily high-dose prednisolone in treatment-naive adult patients with inflammatory myopathies (sporadic inclusion body myositis excluded) we performed a multicenter, double-blind randomised controlled clinical trial with 18 months follow-up.

Sixty-two patients were randomised into 28-day cycles of oral high-dose dexamethasone or daily high-dose prednisolone. Primary outcome measures included (1) seven point composite score of six clinically relevant outcomes and (2) (time-to) remission and (time-to) relapse.

No difference between both treatment groups on the composite score was found. Side-effects occurred significantly less frequently in the dexamethasone group. Median time to relapse was 60 (2.9) weeks in the prednisolone and 44 (4.7) weeks in the dexamethasone group (log-rank test p = 0.03).

In conclusion, pulsed high-dose oral dexamethasone is not superior to daily prednisolone as first-line treatment of idiopathic inflammatory myopathies, but is a good alternative by causing substantially fewer side-effects.

Introduction

Dermatomyositis, polymyositis, and non-specific myositis are immune-mediated myopathies and have an estimated prevalence of one per 100,000 population. These disorders are characterised by sub-acute-onset, progressive muscle weakness and inflammation in the skeletal muscle. They often cause severe chronic disability, and may be complicated by life-threatening impairment of swallowing and lung function [1]. First-line treatment consists of a 4 week course of high-dose daily oral prednisone (1–1.5 mg/kg/day), followed by slow tapering to prevent relapses, although this has never been investigated in a placebo-controlled trial [2]. This long-term treatment with corticosteroids is often complicated by debilitating side effects such as diabetes mellitus, hypertension, mood changes, weight gain, gastric symptoms and osteoporosis. To perform a placebo-controlled trial would nowadays be considered unethical. Other immunosuppressive drugs can be used as add-on medication but are usually not as effective, stressing the need for alternative first-line treatment strategies with fewer side effects [3]. Oral dexamethasone is seven times more potent than prednisone and pulsed schemes have been successfully used in other autoimmune diseases as an alternative to prednisone [4], [5], [6], [7], [8], [9], [10], [11]. Dexamethasone was well tolerated with fewer side effects than prednisone. Previously, we performed a small open-label study with pulsed dexamethasone as initial first-line treatment on patients with idiopathic inflammatory myopathies, sporadic inclusion body myositis (sIBM) excluded, who showed a quick improvement without severe side effects [12]. Based on these promising results we initiated a clinical trial to investigate whether high-dose pulsed oral dexamethasone is more effective and safer than daily high-dose prednisolone as first-line treatment in newly diagnosed adult patients with myositis.

Section snippets

Methods

We performed a multicentre, double-blind, randomised trial with 18 months follow-up. Patients’ consent was obtained according to the Declaration of Helsinki. The study protocol was approved by the medical ethics committees of all participating hospitals. Written informed consent was obtained from all patients before study entry. The Data Safety Monitoring Board comprised an independent neurologist, a biostatistician and a clinical epidemiologist who monitored possibly unfavourable events and the

Characteristics of the patients

Of the 162 patients screened between July 2001 and February 2007, 62 were randomised (Fig. 1): 32 in the prednisolone group and 30 in the dexamethasone group. None of the patients met the criteria for polymyositis [15]. All patients diagnosed with dermatomyositis had one or more characteristic skin abnormalities. Baseline characteristics of the study population are described in Table 1. The two groups were comparable regarding their demographic and clinical features.

A total of 38 (61%) patients

Discussion

This is the first long-term RCT comparing first-line treatment of idiopathic inflammatory myopathies, sporadic inclusion body myositis excluded. No statistically significant difference in the primary composite outcome scores of dexamethasone-treated or prednisolone-treated patients was found. However, a more favourable side-effect profile was observed in dexamethasone-treated patients, probably by the intermittent administration. This was most conspicuous with regard to the occurrence of

Funding

This work was supported by a Grant from the Prinses Beatrix Fonds (The Hague), Grant No. MAR02-0107.

Acknowledgment

We thank: all patients for participating in the study; Data and Safety Monitoring Board: P.A. van Doorn (Erasmus Medical Center, Rotterdam), A. Algra (University Medical Center, Utrecht), I. van der Tweel (University Medical Center, Utrecht); Steering Committee: J.W.J. Bijlsma (University Medical Center, Utrecht), J.H.J. Wokke (University Medical Center, Utrecht), B.G.M. van Engelen (University Medical Center St. Radboud, Nijmegen), F.H.J. van den Hoogen (University Medical Center St. Radboud,

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    1

    Present address: Flevoziekenhuis, Almere, The Netherlands.

    2

    These authors contributed equally to this work.

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