OBJECTIVE: To assess the safety and efficacy of treatment with belimumab in patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated withbackground mycophenolate mofetil (MMF). METHODS: In this 52-week, investigator-initiated, single-center, double-blind, placebo-controlled, pilot study, 20 patients with dcSSc recently started on MMF were randomized 1:1 to additionally receive belimumab at 10 mg/kg intravenously or placebo. We assessed safety, efficacy, and differential gene expression. RESULTS: In the belimumab group, the median modified Rodnan skin thickness score (MRSS) decreased from 27 (interquartile range [IQR] 26.5, 31) to 18 (IQR 11, 23) (P = 0.039). In the placebo group, the median MRSS decreased from 28 (IQR 22, 28) to 21 (IQR 14, 25) (P = 0.023). The median change in MRSS was -10 (IQR -13, -9) in the belimumab group and -3.0 (IQR -15, -1) in the placebo group (P = 0.411). There were no significant differences between the groups in the number of adverse events (AEs). A significant decrease in expression of B cell signaling and profibrotic genes and pathways was observed in patients with improved MRSS in the belimumab group but not in the placebo group. CONCLUSION: Patients in both treatment groups experienced significant improvements in MRSS. The median difference was greater in the belimumab group but did not achieve statistical significance in this small pilot study. AEs were similar between the groups. Changes in gene expression were consistent with mechanism of action and showed that clinical response to treatment with belimumab is associated with a significant decrease in profibrotic genes and pathways. Additional studies are needed to determine the role of belimumab in the treatment of dcSSc.
RCT Entities:
OBJECTIVE: To assess the safety and efficacy of treatment with belimumab in patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated with background mycophenolate mofetil (MMF). METHODS: In this 52-week, investigator-initiated, single-center, double-blind, placebo-controlled, pilot study, 20 patients with dcSSc recently started on MMF were randomized 1:1 to additionally receive belimumab at 10 mg/kg intravenously or placebo. We assessed safety, efficacy, and differential gene expression. RESULTS: In the belimumab group, the median modified Rodnan skin thickness score (MRSS) decreased from 27 (interquartile range [IQR] 26.5, 31) to 18 (IQR 11, 23) (P = 0.039). In the placebo group, the median MRSS decreased from 28 (IQR 22, 28) to 21 (IQR 14, 25) (P = 0.023). The median change in MRSS was -10 (IQR -13, -9) in the belimumab group and -3.0 (IQR -15, -1) in the placebo group (P = 0.411). There were no significant differences between the groups in the number of adverse events (AEs). A significant decrease in expression of B cell signaling and profibrotic genes and pathways was observed in patients with improved MRSS in the belimumab group but not in the placebo group. CONCLUSION:Patients in both treatment groups experienced significant improvements in MRSS. The median difference was greater in the belimumab group but did not achieve statistical significance in this small pilot study. AEs were similar between the groups. Changes in gene expression were consistent with mechanism of action and showed that clinical response to treatment with belimumab is associated with a significant decrease in profibrotic genes and pathways. Additional studies are needed to determine the role of belimumab in the treatment of dcSSc.
Authors: R Paul Wilson; Shannon E McGettigan; Van Duc Dang; Anil Kumar; Michael P Cancro; Neda Nikbakht; William Stohl; Gudrun F Debes Journal: J Invest Dermatol Date: 2019-05-30 Impact factor: 8.551
Authors: Christina G Katsiari; Theodora Simopoulou; Ioannis Alexiou; Lazaros I Sakkas Journal: Hum Vaccin Immunother Date: 2018-07-16 Impact factor: 3.452
Authors: Lorinda Chung; Cathie Spino; Richard McLain; Sindhu R Johnson; Christopher P Denton; Jerry A Molitor; Virginia D Steen; Robert Lafyatis; Robert W Simms; Suzanne Kafaja; Tracy M Frech; Vivien Hsu; Robyn T Domsic; Janet E Pope; Jessica K Gordon; Maureen D Mayes; Nora Sandorfi; Faye N Hant; Elana J Bernstein; Soumya Chatterjee; Flavia V Castelino; Ali Ajam; Yannick Allanore; Marco Matucci-Cerinic; Michael L Whitfield; Oliver Distler; Ora Singer; Amber Young; Vivek Nagaraja; David A Fox; Daniel E Furst; Dinesh Khanna Journal: Lancet Rheumatol Date: 2020-10-19
Authors: Dana E Orange; Jessica K Gordon; Kimberly Showalter; Robert Spiera; Cynthia Magro; Phaedra Agius; Viktor Martyanov; Jennifer M Franks; Roshan Sharma; Heather Geiger; Tammara A Wood; Yaxia Zhang; Caryn R Hale; Jackie Finik; Michael L Whitfield Journal: Ann Rheum Dis Date: 2020-10-07 Impact factor: 19.103