Epratuzumab for the treatment of systemic lupus erythematosus

ABSTRACT

Introduction: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. There are three drugs licensed for the treatment of lupus: corticosteroids, hydroxychloroquine and belimumab. Immunosuppressants such as azathioprine, methotrexate and mycophenolate are also used. Despite these treatments there is still considerable morbidity. New treatments are needed for the management of active lupus. Epratuzumab a humanized IgG1 monoclonal antibody that targets CD22 resulting in selective B cell modulation that has been considered a potential treatment for SLE.

Areas covered: Summary of the relevant pathogenesis and disease activity measurements used in SLE patients, current treatments and unmet needs in SLE, pharmacokinetics and pharmacodynamics of epratuzumab therapy, and a summary of the 7 clinical trials that have investigated the efficacy and safety of epratuzumab in SLE.

Expert commentary: It is not clear why trials have failed to demonstrate efficacy but high placebo response rates from optimisation of standard of care and a sub-optimal dosing regimen may have played a role. Post-hoc analysis suggested that there may be subgroups that did respond, such as anti-SSA positive patients with features of Sjogren’s syndrome. Further research is needed to explore this and other potential sub-groups that might respond.

KEYWORDS:

• B cell modulation
• BILAG
• BICLA
• CD22
• disease activity
• epratuzumab
• monoclonal antibody
• lupus
• outcome
• response
• Sjogren’s syndrome
• SLEDAI-2K
• treatment

Declaration of interest

C Gordon received grant funding from UCB for a clinical research observational study unrelated to the work reported here or any pharmaceutical product and has received funding from them for advice on the design and analysis of clinical trials and training in disease activity instruments including (but not limited to) the epratuzumab program. She has had no financial interests in the outcome of these trials but has entered patients into the trials. C Gordon has also provided advice on the design and analysis of trials to EMD Serono, Genentech and Roche, and has taken part in scientific advisory boards for UCB, EMD Serono, and GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. UCB provided a scientific accuracy review at the request of the journal editor. One peer reviewer for this manuscript has received consulting fees, speaking fees, and/or honoraria from Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly, Sanofi, Janssen, UCB and has received research grants from Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, MSD, Daiichi-Sankyo, Pfizer, Kyowa-Kirin, Eisai, Ono. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This article was not funded.