Tomonori Ishii1, Yoshiya Tanaka2, Atsushi Kawakami3, Kazuyoshi Saito2, Kunihiro Ichinose3, Hiroshi Fujii4, Yuko Shirota4, Tsuyoshi Shirai4, Yoko Fujita4, Ryu Watanabe4, Shih-Wei Chiu1, Takuhiro Yamaguchi1, Hideo Harigae4. 1. a Department of Clinical Research, Innovation and Education Center , Tohoku University Hospital , Miyagi , Japan. 2. b The First Department of Internal Medicine, School of Medicine , University of Occupational and Environmental Health , Fukuoka , Japan. 3. c Division of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan. 4. d Division of Hematology and Rheumatology , Tohoku University Graduate School of Medicine , Miyagi , Japan.
Abstract
OBJECTIVES: The objective of this study is to evaluate the efficacy and safety of bortezomib for treating systemic lupus erythematosus (SLE), in patients whose disease activity could not be controlled. METHODS:Fourteen SLE patients with persistent disease activity were selected, who required prednisolone doses of >10 mg/d despite concomitant immunosuppressive therapy. Patients were randomly administered either bortezomib or a placebo, eight times. The primary and secondary end-points were a change in anti-dsDNA antibody titer at week 24 and the SLE Responder Index (SRI), respectively. RESULTS: In the bortezomib group, four out of eight patients discontinued the trial; three others failed to complete the minimum protocol treatment due to adverse reactions. The changes in anti-dsDNA antibody titers at week 24 were 4.24% and -1.96%, for the bortezomib and placebo groups, respectively, disconfirming bortezomib's efficacy. In contrast, the corresponding SRI at week 12 was 75% and 40%. CONCLUSIONS: As bortezomib therapy for SLE is associated with many adverse reactions, treatment indications should be selected carefully, and protocols should aim to prevent these occurrences. Although the change in anti-dsDNA antibody titer did not support the efficacy of bortezomib as a treatment for SLE, high SRI in the treatment group suggests bortezomib may utilize mechanisms other than inhibition of anti-dsDNA antibody production.
RCT Entities:
OBJECTIVES: The objective of this study is to evaluate the efficacy and safety of bortezomib for treating systemic lupus erythematosus (SLE), in patients whose disease activity could not be controlled. METHODS: Fourteen SLEpatients with persistent disease activity were selected, who required prednisolone doses of >10 mg/d despite concomitant immunosuppressive therapy. Patients were randomly administered either bortezomib or a placebo, eight times. The primary and secondary end-points were a change in anti-dsDNA antibody titer at week 24 and the SLE Responder Index (SRI), respectively. RESULTS: In the bortezomib group, four out of eight patients discontinued the trial; three others failed to complete the minimum protocol treatment due to adverse reactions. The changes in anti-dsDNA antibody titers at week 24 were 4.24% and -1.96%, for the bortezomib and placebo groups, respectively, disconfirming bortezomib's efficacy. In contrast, the corresponding SRI at week 12 was 75% and 40%. CONCLUSIONS: As bortezomib therapy for SLE is associated with many adverse reactions, treatment indications should be selected carefully, and protocols should aim to prevent these occurrences. Although the change in anti-dsDNA antibody titer did not support the efficacy of bortezomib as a treatment for SLE, high SRI in the treatment group suggests bortezomib may utilize mechanisms other than inhibition of anti-dsDNA antibody production.
Authors: Tomas Walhelm; Iva Gunnarsson; Rebecca Heijke; Dag Leonard; Estelle Trysberg; Per Eriksson; Christopher Sjöwall Journal: Front Immunol Date: 2021-10-01 Impact factor: 7.561