# Tacrolimus Trough Concentration‐Escalating Bipartite Therapy (Glucocorticoids Combined With Tacrolimus) for Refractory MDA5 Antibody‐Positive Clinically Amyopathic Dermatomyositis With Rapidly Progressive Interstitial Pneumonia

## TL;DR

This study shows that combining glucocorticoids and tacrolimus can help treat a rare and severe autoimmune disease with lung complications, though it requires careful monitoring.

## Contribution

The novel approach of using tacrolimus trough concentration-escalating bipartite therapy for a specific subset of dermatomyositis patients is evaluated.

## Key findings

- 16 out of 19 patients showed improved lung function and reduced inflammation markers after treatment.
- One patient developed tacrolimus-induced renal impairment, which resolved after adjusting the drug concentration.
- Combination therapy was effective but required individualized tacrolimus dosing to avoid complications.

## Abstract

This study aimed to determine the outcomes of patients that have refractory anti‐melanoma differentiation‐associated gene 5 (MDA5) antibody‐positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonia treated with tacrolimus trough concentration‐escalating bipartite therapy (glucocorticoids combined with tacrolimus).

We retrospectively enrolled 19 patients that had refractory anti‐MDA5 antibody‐positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonitis who were unable to achieve disease control on intensive combination immunosuppressive therapy with glucocorticoids and immunosuppressive agents. They were treated with tacrolimus trough concentration‐escalating bimodal therapy. Patients receiving tacrolimus trough concentration‐escalating dual therapy were selected based on poor prognostic factors and refractoriness to the initial immunosuppressive therapy.

The 19 patients included in the study were treated with tacrolimus trough concentration‐escalating bipartite therapy (glucocorticoids combined with tacrolimus) immediately after diagnosis of refractory anti‐melanoma differentiation‐associated gene 5 (MDA5) antibody‐positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonia. Following 17 months of treatment and subsequent follow‐up, 16 patients displayed decreased ferritin and lactate dehydrogenase levels and improved oxygenation index and high‐resolution lung computed tomography findings. Two patients died, and one patient (case 9) developed renal impairment on Day 14 of treatment. Renal damage occurred when the tacrolimus trough concentration was 15.68 ng/mL. After lowering the tacrolimus trough concentration, the patient′s renal function gradually normalized. However, because of the addition of cyclophosphamide due to disease activity, the patient did not experience the full efficacy of the two‐combination therapy. Tacrolimus‐associated renal impairment and viral and fungal infections occurred in some patients treated with bimodal therapy, but it did not have serious consequences.

For patients with refractory anti‐MDA5 antibody‐positive clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia, the combination of glucocorticoids and tacrolimus is a potentially effective treatment regimen. However, there is considerable individual variation in the optimal trough concentration of tacrolimus.