CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.
However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD,at the of the American College of Rheumatology.
ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.
“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.
The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.
Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.
Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.
When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.
Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.
They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m2 of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.
Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.
Dr. Tsuji reported having no disclosures.
SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), .