Multicenter double-blind randomized controlled trial to evaluate the effectiveness and safety of bortezomib as a treatment for refractory systemic lupus erythematosus

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.

Keywords:

• Bortezomib
• randomized controlled trial
• systemic lupus erythematosus

Conflict of interest

Tomonori Ishii, has received speaking fees from Astellas and Ono. Yoshiya Tanaka, has received speaking fees from Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly, Sanofi, Janssen, and UCB and has received research grants from Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, MSD, Daiichi-Sankyo, Pfizer, Kyowa-Kirin, Eisai, Ono, Atsushi Kawakami, None, Kazuyoshi Saito, None, Kunihiro Ichinose, None, Hiroshi Fujii, None, Yuko Shirota, None, Tsuyoshi Shirai, None, Yoko Fujita, None, Ryu Watanabe, None, Shih-Wei Chiu, None, Takuhiro Yamaguchi, None, Hideo Harigae, None.

Additional information

Funding

A grant-in-aid was received from the Ministry of Health, Labour and Welfare of Japan.