Background and objectives In the BLISS-LN study, belimumab improved kidney outcomes in adult patients with active lupus nephritis. This 28-week open-label extension of BLISS-LN assessed belimumab's... Show moreBackground and objectives In the BLISS-LN study, belimumab improved kidney outcomes in adult patients with active lupus nephritis. This 28-week open-label extension of BLISS-LN assessed belimumab's safety and efficacy. Design, setting, participants, & measurements Eligible patients completing BLISS-LN received monthly intravenous belimumab 10 mg/kg plus standard therapy. End points included safety, open-label week 28 primary efficacy renal response (urine protein-creatinine ratio [UPCR] <_0.7, eGFR no more than 20% below open-label baseline value or >_60 ml/min per 1.73 m2, no prohibited medications) and complete renal response (UPCR < 0.5, eGFR no more than 10% below open-label baseline value or >_90 ml/min per 1.73 m2, no prohibited medications), and UPCR and eGFR by visit. Responses were also analyzed post hoc using the double-blind phase criteria. Results Of 257 enrolled patients, 255 were treated (safety population: n=123 switched from placebo-tobelimumab; n=132 remained on belimumab); 245 (97%) patients completed the study. Adverse events and serious adverse events were experienced by 62% and 4% of placebo-to-belimumab patients, respectively, and by 70% and 8% of belimumab-to-belimumab patients, respectively. One death occurred in the placebo-to-belimumab group. From open-label baseline to week 28, increases occurred in the proportions of patients achieving primary efficacy renal response (placebo-to-belimumab: from 60% to 67%; belimumab-to-belimumab: from 70% to 75%) and complete renal response (placebo-to-belimumab: from 36% to 48%; belimumab-to-belimumab: from 48% to 62%). Based on double-blind phase criteria, changes also occurred in the proportions achieving primary efficacy renal response (placebo-to-belimumab: from 54% to 53%; belimumab-to-belimumab: from 66% to 52%) and complete renal response (placebo-to-belimumab: from 34% to 35%; belimumab-to-belimumab: from 46% to 41%). The seeming decrease in response rates in the belimumab-to-belimumab groups was attributed to discontinuations/administration of glucocorticoids for non-SLE reasons as opposed to nephritis. Median UPCR and eGFR values were similar at open-label baseline and week 28. Conclusions No new safety signals were identified, and efficacy was generally maintained throughout the open label phase. contributing the affiliations listed at the article. Correspondence: Dr. Richard Division of Rheumatology, Northwell Donald and Zucker School Medicine, Northwell Suite 302, NY 11021. RFurie@northwell.edu Show less
RA has a complex multifactorial aetiology, of which many elements remain unknown. Genetic and environmental risk factors play a major role in disease development. Over the past few years,... Show moreRA has a complex multifactorial aetiology, of which many elements remain unknown. Genetic and environmental risk factors play a major role in disease development. Over the past few years, understanding of the genetic basis of the susceptibility to RA has increased dramatically and the identified risk loci were confirmed to account for 51% of the total genetic effect of which 36% explained by HLA in addition to 15% non-HLA genetic factors. The challenge remains to identify the rest of those genetic effects and explore how these variants interact with each other as well as environmental factors to induce RA. Although autoantibody formation is characteristic for RA, the range of antibodies formed in RA is not entirely specific for RA. Additionally, the majority of studies exploring the test characteristics of RF, anti-CCP and anti-MCV compare RA patients to healthy controls while in clinical practice those tests are used to differentiate early RA from other forms of early inflammatory arthritis. Because the focus is now shifted towards early therapy a new tool to identify early RA replacing the classic 1987 ACR classification criteria was warranted. The ultimate goal of personalized treatment decision making incorporates genetic, serological as well as clinical factors. Show less
