A phase II, randomized, double‐blind, placebo‐controlled, dose‐ranging study of belimumab in patients with active systemic lupus erythematosus

Wallace, Daniel J.; Stohl, William; Furie, Richard; Lisse, Jeffrey R.; McKay, James D.; Merrill, Joan T.; Petri, Michelle; Ginzler, Ellen M.; Chatham, W. Winn; McCune, W. Joseph; Fernandez, Vivian; Chévrier, Marc; Zhong, Z. John; Freimuth, William W.

doi:10.1002/art.24699

Cited by 521 publications

(478 citation statements)

References 41 publications

Supporting

Mentioning

432

Contrasting

Unclassified

Order By: Relevance

“…Increases in memory B cells (CD20+/CD27+) occurred in the 10 mg/kg group. The mechanism underlying this increase in memory B cells may include release of memory B cells from disrupted lymphoid tissue, inhibition of the return of memory B cells to germinal centers, or the promotion of differentiation of naïve cells to memory B cells, although the latter may be less likely with effective binding of BLyS by belimumab11,12. The serum immunoglobulins (IgA, IgG and IgM) and autoantibodies (anti-dsDNA antibody and ANA) were not consistent and did not follow a trend in all the treatment groups.…”

Section: Discussionmentioning

confidence: 99%

Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

Yamada

Akita

Nakagawa

et al. 2013

Journal of Drug Assessment

View full text Add to dashboard Cite

ObjectivesBelimumab, an anti-B lymphocyte stimulator (BLyS) human monoclonal antibody, was approved in the United States, Canada and European Union for the treatment of the patients with systemic lupus erythematosus (SLE). However, belimumab had not been evaluated in Japanese patients. The objectives of this study were to evaluate the safety and tolerability of belimumab in Japanese patients with SLE, as well as to investigate the pharmacokinetics (PK) and biological activity of belimumab in this population.MethodsA total of 12 Japanese patients were enrolled in a randomized, single-blind, placebo-controlled, dose-ascending design study. A dosing regimen of a single intravenous infusion over 1 hour of belimumab (1 mg/kg and 10 mg/kg) was employed. Patients were followed for 84 days after dosing to assess adverse events, pharmacokinetics, biomarkers and SLE disease activity.Clinical trial registration numberClinicalTrials.gov identifier is NCT01381536.ResultsBelimumab (1 mg/kg and 10 mg/kg) demonstrated a favorable clinical safety and tolerability profile in Japanese patients with SLE. The incidence of adverse events was similar among the two belimumab groups and placebo group. The PK profile of single-dose belimumab was approximately dose proportional, and the long terminal elimination half-life (12.4–15.7 days), low clearance (3.55–4.65 mL/day/kg), and small volume of distribution (76.2–80.1 mL/kg) were consistent with a fully humanized antibody. Effects of belimumab on B cells suggested biological activity effects expected as an inhibitor of BLyS.LimitationThe small sample size and single dose design of this study prevent definitive conclusions regarding the safety, pharmacokinetics or pharmacodynamics of belimumab in a Japanese population being made.ConclusionsThe preliminary safety, PK profile, and observed biological activity of belimumab support further evaluation of its safety and efficacy in Japanese patient with SLE.

show abstract

Section: Discussionmentioning

confidence: 99%

Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

Yamada

Akita

Nakagawa

et al. 2013

Journal of Drug Assessment

View full text Add to dashboard Cite

show abstract

“…Belimumab binds to and inhibits the activity of soluble human B lymphocyte stimulator protein 10. A placebo‐controlled phase II study showed that intravenous (IV) belimumab plus standard therapy was generally well tolerated 11; a good safety profile was maintained over 7 years 12. Two phase III studies, the Study of Belimumab in Subjects with SLE 52‐week (BLISS‐52) and 76‐week (BLISS‐76) trials, demonstrated the safety and efficacy of belimumab in patients with autoantibody‐positive, active SLE 13, 14.…”

mentioning

confidence: 99%

Long‐Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus

Furie

Wallace

Aranow

et al. 2018

Arthritis & Rheumatology

Self Cite

View full text Add to dashboard Cite

ObjectiveWe undertook this US multicenter continuation study (GlaxoSmithKline study BEL112233; ClinicalTrials.gov identifier: NCT00724867) to assess long‐term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) who completed the Study of Belimumab in Subjects with SLE 76‐week trial (ClinicalTrials.gov identifier: NCT00410384).MethodsPatients continued to receive the same belimumab dose plus standard therapy; patients previously receiving placebo received 10 mg/kg belimumab. The primary outcome measure was long‐term safety of belimumab (frequency of adverse events [AEs] and damage assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI], evaluated every 48 weeks [1 study year]). Other assessments included the SLE Responder Index (SRI), flare rates (using the modified SLE Flare Index [SFI]), prednisone use, and B cell levels.ResultsOf 268 patients, 140 completed the study and 128 withdrew. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA–SLEDAI) at baseline was 7.8 ± 3.86. The mean ± SD SDI score increased by 0.4 ± 0.68 from its value at baseline (1.2 ± 1.51). The overall incidence of treatment‐related and serious AEs remained stable or declined through study year 7. An SRI response was achieved by 41.9% and 75.6% of patients at the study year 1 and study year 7 midpoints, respectively. At the study year 7 midpoint, relative to baseline, 78.2% had achieved a ≥4‐point reduction in the SELENA–SLEDAI score, 98.4% had no new British Isles Lupus Assessment Group (BILAG) A organ domain score and no more than 1 new BILAG B organ domain score, 93.7% had no worsening in the physician's global assessment of disease activity, 20.6% had experienced ≥1 severe SFI flare, the mean decrease in prednisone dose was 31.4%, and the median change in CD20+ B cell numbers was −83.2%.ConclusionThese long‐term exposure results confirm the previously observed safety and efficacy profiles of belimumab in patients with SLE.

show abstract

“…This association may be not only a clue to understanding the pathological mechanism of PCNSL but also an aid to developing treatment applications. Belimumab, a B cell stimulator inhibitor, has significantly reduced systemic lupus erythematosus disease activity 18. The agents that modulate the BAFF system molecule may thus be useful in PCNSL treatment.…”

Section: Discussionmentioning

confidence: 99%

CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers

Mizutani

Nakane

Ikeda

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

We used an enzyme‐linked immunosorbent assay to measure pretreatment B cell‐activating factor belonging to the tumour necrosis factor family (BAFF) and transmembrane activator and CAML‐interactor (TACI) levels in CSF and serum collected from patients with primary central nervous system lymphoma (PCNSL) and control groups. The decision tree analysis of CSF TACI and BAFF levels for patients with a PCNSL diagnosis showed 100% sensitivity and 100% specificity when we attempted to differentiate PCNSL from glioblastoma and CNS inflammatory diseases. The combination of CSF TACI and BAFF levels may thus be a novel and useful diagnostic biomarker of PCNSL.

show abstract

A phase II, randomized, double‐blind, placebo‐controlled, dose‐ranging study of belimumab in patients with active systemic lupus erythematosus

Cited by 521 publications

References 41 publications

Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

Long‐Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus

CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers

Contact Info

Product

Resources

About