Dermatomyositis: Triple therapy with tacrolimus beats cyclosporin regimen

Retrospective data on patients with anti-MDA5-positive dermatomyositis and interstitial lung disease (ILD) was used to evaluate tacrolimus- versus cyclosporin-based triple therapies. The results showed a significant difference in the composite endpoint of death or long-term domiciliary oxygen therapy (LTOT) with no events on tacrolimus versus 4 events on cyclosporin.

“Anti-MDA5-positive dermatomyositis is associated with classic skin rash, mild muscular manifestation, and ILD. Up to 50% of patients with ILD and anti-MDA5-positive dermatomyositis die within 6 months after diagnosis despite treatment including high-dose corticosteroids,” Prof. Yasuhiro Katsumata (Tokyo Women’s Medical University, Japan) stated [1]. He presented a single-centre retrospective cohort study that compared a tacrolimus-based with a cyclosporin-based triple combination therapy for newly diagnosed anti-MDA5-positive dermatomyositis with ILD.

The analysis included 24 patients who were treated between 2013 and 2022. The participants had a mean age of approximately 52 years and about 70% were women. Overall, the baseline characteristics and clinical manifestations did not differ significantly between the 2 groups. Until 2016, 10 patients received therapy with cyclosporin, high-dose corticosteroids, and intravenous cyclophosphamide (IVCY) individualised by their attending physicians. As of 2017, 14 patients were treated with a pre-specified regimen of tacrolimus at trough levels of 10–12 ng/mL plus IV cyclophosphamide and high-dose corticosteroids. The primary composite outcome was defined as death or LTOT at 1 year.

At 12 months, death or requirement of LTOT did not happen to any participants in the tacrolimus group, but to 4 participants in the cyclosporin group, corresponding to a 40%-point difference (P=0.002). Death at 6 months, a secondary endpoint, was not statistically different between the groups. “Time-to-event analysis demonstrated that the tacrolimus group had a better composite outcome compared with the cyclosporin group,” Prof. Katsumata added.

The corticosteroid dosages of the surviving participants at 6 and 12 months were found lower on the tacrolimus regimen (P=0.046 and P=0.086). Also, larger cumulative doses and a higher total number of cyclophosphamide cycles were observed in the tacrolimus arm (P<0.001 for both comparisons). In terms of safety, a reactivation of the cytomegalovirus was reported in 40% of those on the tacrolimus and in 80% on the cyclosporin regimen.

“The predefined triple combination therapy with high-dose corticosteroids, tacrolimus, and cyclophosphamide demonstrated a better composite outcome than cyclosporin-based triple combination therapy and was well-tolerated in patients with anti-MDA5-positive dermatomyositis-associated ILD,” Prof. Katsumata summarised. He further acknowledged that reduced doses of corticosteroids and more intensive use of cyclophosphamide may have contributed to the superior outcomes on tacrolimus. Given reports of increasing rates of MDA5 disease around the globe, these findings may be of considerable relevance to managing this potentially rapidly progressive disease [2].

1. Yamada R, et al. Comparison of outcome between tacrolimus-based and cyclosporin-based triple-combination therapy in interstitial lung disease with anti-MDA5-positive dermatomyositis: a single-center case-control study. OP0095, EULAR 2024 Congress, 12–15 June, Vienna, Austria.
2. David P, et al. EBioMedicine. 2024:104:105136.

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Posted on 29 July 2024