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

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.Fourteen SLE patients with persistent disease activity were selected, who required prednisolone doses of10 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.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%.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.