Tofacitinib for new-onset adult patients with anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis

Abstract

Objective: We aimed to investigate the efficacy and safety of tofacitinib in adult anti-melanoma differentiation-associated 5 gene (Anti-MDA5) antibody-positive dermatomyositis (DM) patients and evaluate the effects of tofacitinib on peripheral lymphocyte subsets.

Methods: An open-label study was conducted of 15 new-onset, untreated adult patients with anti-MDA5-positive DM for tofacitinib with a dose of 5mg twice per day. The primary outcome was defined by the total improvement score after treatment for 6 months, classified according to the 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) response criteria for adult DM and polymyositis. Secondary outcomes after 6 months treatment comprised the change in predicted forced vital capacity, the percentage of predicted carbon monoxide diffusion capacity, ferritin level and peripheral blood lymphocyte subsets measured by flow cytometry.

Results: Disease responses occurred in 10 patients (71.4%) after 6 months. The median total improvement score was 43.75 (41.875-59.375). Two patients achieved major improvement, seven achieved moderate and one minimal. The serum ferritin level (p = 0.008), DLCO% (p = 0.009) was improved and a marked increase in total lymphocyte cells (p = 0.045) and CD8+ T cells (p = 0.006) was measured after 6 months treatment compared to baseline.

Conclusion: Tofacitinib demonstrates efficacy for new-onset, untreated adult patients with anti-MDA5-positive DM and stimulates proliferation of peripheral lymphocyte subsets (especially total lymphocyte cells and CD8+ T cells) after 6 months treatment. Further studies are warranted to validate the current findings. Key Points • Treatment of anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis is always challenging. • This prospective, open-label clinical trial demonstrates tofacitinib is an effective and safe agent for new-onset adult patients with anti-MDA5-positive DM. • Tofacitinib treatment results in an increase in peripheral lymphocyte numbers, especially CD8+ T cells at 6 months compared with pre-treatment levels.

Keywords: Adult; Anti-MDA5 antibody; Dermatomyositis; Peripheral lymphocyte subsets; Tofacitinib.