ArticlesPrednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial
Introduction
Juvenile dermatomyositis is a chronic disease that, similar to its adult equivalent, primarily affects skin and muscles. Despite improved disease outcomes with treatment strategies used over the past few decades, juvenile dermatomyositis is still associated with significant morbidity and mortality.1, 2, 3
Treatment of dermatomyositis for both children and adults is based on anecdotal evidence from case reports and retrospective studies, because very few randomised controlled trials have been done.4 Clinical consensus is that corticosteroids represent the first-line treatment of choice for juvenile dermatomyositis. In steroid-resistant or steroid-dependent cases, an immunosuppressive drug is added as a steroid-sparing agent. The choice of the immunosuppressive agent relies mostly on the experience of the clinician and varies widely between countries.5, 6
The two most common immunosuppressants used in the treatment of juvenile dermatomyositis are methotrexate and ciclosporin.5, 6 However, a more aggressive therapeutic approach has been suggested, combining steroids and an immunosuppressive drug at disease onset, that could result in a better outcome.7, 8, 9 Yet, a Cochrane review4 has highlighted the paucity of randomised clinical trials, in both adults and children, assessing efficacy and safety of immunosuppressants in inflammatory myositis, concluding that evidence is inadequate to decide whether immunosuppressive agents are beneficial in dermatomyositis.
We did a randomised trial to establish whether, in patients with newly diagnosed juvenile dermatomyositis, combined treatment with prednisone and either methotrexate or ciclosporin has a safety and efficacy profile that is superior to prednisone monotherapy. Here, we present results after at least 2 years of treatment (induction and maintenance phases). The trial is ongoing in the extension phase (up to 5 years of treatment).
Section snippets
Patients
We did an international, multicentre, randomised, open-label, superiority trial at 54 centres in 22 countries that were part of the Paediatric Rheumatology International Trials Organisation (PRINTO).10 We enrolled children aged 18 years or younger with newly diagnosed and untreated probable or definite juvenile dermatomyositis, as per Bohan and Peter criteria (appendix p 4).11, 12 We allowed previous treatment with prednisone if the daily dose was greater than 1 mg/kg for no more than 1 month.
Results
Between May 31, 2006, and Nov 12, 2010, 151 patients were screened for eligibility to our trial. 12 did not meet inclusion criteria; therefore, 139 were enrolled and randomly allocated to study treatment (figure 1). 47 patients were assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised to prednisone plus methotrexate. Baseline characteristics are shown in table 1. No child had previously received ciclosporin or methotrexate. 67 children had treatment
Discussion
Our findings suggest that combination treatment with prednisone plus either ciclosporin or methotrexate is superior to prednisone monotherapy in patients with juvenile dermatomyositis, at 6 months and after at least 24 months of treatment. Both time to clinical remission (clinically inactive disease persisting for at least 6 continuous months) and time to clinically inactive disease favoured the combination of prednisone plus methotrexate over the combination of prednisone plus ciclosporin or
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Contributed equally
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For a full list of investigators, see appendix (pp 1–3)