10 Years of belimumab experience: What have we learnt?

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting both adults and children. Belimumab is the only biologic approved for SLE, and the first in a class of drugs known as B-lymphocyte stimulator-specific inhibitors. The introduction of intravenous belimumab in 2011 was a major advance, being the first new therapy approved for SLE in over 50 years. As of April 2021, more than 7200 people with SLE have received belimumab in clinical studies, and it is approved in over 75 countries for the treatment of adults with SLE. A subcutaneous, self-injectable belimumab formulation was licensed in 2017 by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Belimumab was then approved for use in children in Europe, the USA and Japan in 2019, and China and Brazil in 2020. Recently, belimumab became the first FDA-approved drug for the treatment of adults with active lupus nephritis (LN), the most-common severe manifestation of SLE. Over the past 10 years, belimumab has established its position as a disease modifier in the SLE treatment paradigms. Robust evidence from randomised clinical studies and observational, real-world studies has demonstrated the tolerability and efficacy of belimumab for reducing disease activity and the risk of new, severe SLE flares. This enables patients to taper their glucocorticoid use, which limits damage accumulation. Significantly more patients with active LN met the criteria for renal responses and were at less risk of a renal-related event or death after receiving belimumab plus standard therapy, compared with standard therapy on top of mandatory steroid reduction. Ongoing clinical studies are evaluating belimumab’s effectiveness in various indications beyond SLE. Post-marketing and registry studies are gathering additional data on key areas such as pregnancy outcomes after belimumab exposure and belimumab co-administration with other biologics.

In lupus nephritis, specificin situinflammatory states are associated with refractory disease and progression to renal failure

“…Canonically, lupus nephritis is thought of as arising from a systemic break in B cell tolerance leading to glomerular antibody deposition and inflammation. This model, supported by large bodies of evidence in both humans and mice 8,33 , has led to clinical trials targeting B cells and Tfh cells [34][35][36][37][38][39][40] .…”

Type I Interferons in Systemic Lupus Erythematosus: A Journey from Bench to Bedside

“…The prevalence of SLE has been increasing over time, from 40 per 100,000 in the 1970s to 100 per 100,000 since the 2000, while the incidence has been relatively constant, ranging from 4.8 to 7.2 per 100,000 [ 4 ]. This numerical discrepancy between prevalence (cross-sectional estimate of the number of cases per 100,000 of the population per year) and incidence (number of new cases per 100,000 of the population per year) likely reflects the improved diagnosis and survival rates over time, as well as the lifelong nature of this disease [ 5 , 6 ]. While the survival rates of SLE patients have increased over the past 5 decades, organ damage, particularly to the renal and neuropsychiatric systems, has hindered further improvement in survival [ 2 ].…”

“…Organ damage may also be attributed to the chronic use of glucocorticoids, leading to increased cardiovascular events, osteonecrosis and osteoporosis with fractures [ 5 ]. This is undesirable, as glucocorticoids remain the mainstay of SLE therapy since its approval by the US Food and Drug Administration (FDA) in 1955 [ 6 ].…”

Belimumab in the treatment of systemic lupus erythematosus: 20 years of basic research, 10 years of clinical practice

“…Важным шагом в направлении решения этой проблемы явилась разработка препарата белимумаб (БЛМ), представляющего собой человеческие мАТ (IgG1λ) к BAFF (B cell-activating factor belonging to the TNF family). БЛМ является первым «таргетным» генно-инженерным биологическим препаратом (ГИБП), специально разработанным для лечения СКВ [15][16][17] [18][19][20][21]. BAFF относится к классу мембрано-связанных белков типа II и, подвергаясь расщеплению фурином, высвобождается с клеточных мембран, образует растворимый биологически активный BAFF-гомодимер, который является основной формой BAFF в кровяном русле.…”

“…В этой связи привлекают внимание данные о том, что у мышей, дефицитных по BAFFрецепторам, и на фоне введения анти-BAFF Таблица 1. Основные этапы разработки и внедрения белимумаба в клиническую практику [15,17] [65].…”