Op0095 Comparison of Outcome Between Tacrolimus-Based and Ciclosporin-Based Triple-Combination Therapy in Interstitial Lung Disease With Anti-Mda5-Positive Dermatomyositis: A Single-Center Case-Control Study

Background: Anti-MDA5 antibody is associated with dermatomyositis (DM) with interstitial lung disease (ILD). Up to 50% of ILD patients with anti-MDA5-positive DM die within 6 months after diagnosis despite treatment including high-dose glucocorticoids (GCs). A prospective single-arm study demonstrated that the ILD patients with anti-MDA5-positive DM treated with triple-combination therapy (high-dose GCs, tacrolimus, and intravenous cyclophosphamide [IVCY]) were accompanied with higher 6-month survival rates than historical controls who received only GCs or sequential combination therapy [1]. However, a cluster analysis using a large-scale multicenter retrospective cohort failed to show survival benefits of triple-combination therapy (GCs, tacrolimus/ciclosporin, and IVCY) over dual-combination therapy or GC monotherapy [2]. Objectives: We aimed to retrospectively investigate the outcomes of the predefined tacrolimus-based triple-combination therapy in newly diagnosed ILD with anti-MDA5-positive DM comparing to those of ciclosporin-based triple-combination therapy in historical controls. Methods: Clinical data of consecutive newly diagnosed anti-MDA5-positive DM-associated ILD patients in our hospital from 2013 to 2022 were enrolled. Among these, recent patients (2017–2022; tacrolimus group) were treated according to a protocol including high-dose GCs, tacrolimus (target blood trough level of 10–12 ng/mL), and IVCY (10–15 cycles) [1]. Earlier patients (2013–2016; ciclosporin group) were treated with high-dose GCs, ciclosporin, and IVCY where the GC and IVCY regimens were individually tailored by treating physicians. The primary outcome was a composite of death from any cause or a requirement for long-term domiciliary oxygen therapy (LTOT) within 12 months after GC initiation. The secondary outcomes were the 6-month survival rate, mean GC dosage at 6-month, and incidence of cytomegalovirus reactivation. Observation periods were 12 months and censored if each event occurred. Results: In a total of 24 anti-MDA5-positive DM-associated ILD patients, 14 and 10 patients were treated with the tacrolimus- based and ciclosporin-based triple-combination therapies, respectively. Backgrounds, such as age, baseline pulmonary function test results, baseline serum ferritin levels, and time from ILD onset to GC initiation, were not significantly different between the 2 groups. None of the tacrolimus group patients died, or required LTOT. In the ciclosporin group, 4/10 (40%) of the patients died (n = 2) or required LTOT (n = 2). Significant difference between the 2 groups in the composite outcome was observed (difference, 40 percentage points; 95% confidence interval [CI], 10 to 70; p = 0.02). Time-to-event analyses indicated the better composite outcome in the tacrolimus group over ciclosporin group (p < 0.01). The 6-month survival rates were not significantly different between the tacrolimus and ciclosporin groups (0% vs. 20%; difference, 20 percentage points; 95% CI, −5 to 45). Among the live patients, mean prednisolone dosages were 18 and 23 mg/day at 6-month in the tacrolimus and ciclosporin groups, respectively (mean difference, 5.4 mg/day; 95% CI, 0.1 to 10.7). Mean total numbers of IVCY cycles were larger in the tacrolimus group than in the ciclosporin group (12 vs. 6; difference, 6; 95% CI, 3 to 9). Cytomegalovirus reactivation was more frequently observed in the ciclosporin group than in the tacrolimus group (8/10 [80%] vs. 5/14 [40%]; difference, 40 percentage points; 95% CI, 9 to 80). Conclusion: The predefined triple-combination therapy with high-dose GCs, tacrolimus, and IVCY demonstrated the better composite outcome than ciclosporin-based triple-combination therapy and well-tolerated in the patients with anti-MDA5-positive DM-associated ILD. Reduced dose of GCs and more intensive use of IVCY may have also contributed to the better outcomes in the tacrolimus group. REFERENCES: [1] Arthritis Rheumatol. 2020;72:488. [2] Front Med. 2022;9:883699. Acknowledgements: NIL. Disclosure of Interests: Risa Yamada: None declared, Yasuhiro Katsumata Asahi Kasei Pharma, Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Sanofi K.K., Masayoshi Harigai AbbVie GK, Ayumi Pharmaceutical Co., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Bristol-Myers Squibb K.K., Kissei Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Teijin Pharma, AbbVie GK, Asahi Kasei Pharma, Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc., Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd.