Efficacy, pharmacokinetic and pharmacodynamic profile of belimumab for systemic lupus erythematosus.
BACKGROUND
Systemic lupus erythematosus (SLE) is a severe autoimmune disease and a sizeable proportion of patients remain refractory to currently available immunosuppressive agents. The burden of uncontrolled disease is significant as disease flare and persistent inflammation lead to long-term damage accrual and increased morbidity. Belimumab , a humanized monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS), is the first drug to be approved by the US FDA for the treatment of SLE in 50 years.


METHODS
In this review, we provide an overview of novel therapeutic agents under development for the treatment of SLE, a description of the pharmacodynamic and pharmacokinetic properties of belimumab, evidence of efficacy of belimumab as demonstrated in clinical trials, safety and tolerability data and a summary of ongoing clinical trials of belimumab in SLE. This information was amassed following a comprehensive MEDLINE and Cochrane library search. Ongoing clinical trial information was obtained from ClinicalTrials.gov.


CONCLUSIONS
Two, large Phase III trials have demonstrated the clinical efficacy of belimumab in musculoskeletal, mucocutaneous, haematologic and constitutional features of SLE. Patients with severe disease manifestations such as lupus nephritis and CNS disease were excluded from these trials and hence the role of belimumab in the overall management of SLE has yet to be established. Studies in lupus nephritis are ongoing.
a 1 Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Rheumatology Department , Hills Road, Cambridge CB2 0QQ, UK.
Natasha P
NP
Jordan
b 2 Guy's Hospital, Louise Coote Lupus Unit , 4th Floor Tower Wing, London SE1 9RT, UK +004 420 718 897 56 ; +004 420 718 835 74 ; david.d'cruz@kcl.ac.uk.
David P
DP
D'Cruz
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors; D017277:Drug Approval; D015195:Drug Design; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000503:physiopathology
D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D007166:Immunosuppressive Agents; C511911:belimumab
B-lymphocyte stimulator; belimumab; systemic lupus erythematosus