Y K O Teng

Leiden University Medical Centre | LUMC · Department of Nephrology

Systemic lupus erythematosus (SLE) is marked by excessive complement activation, contributing to tissue damage. Complement activation can be detected in many organs including the skin, kidney, and brain. The involvement of the central nervous system is particularly relevant to understanding neuropsychiatric SLE (NPSLE), one of the poorest understoo...

Objectives Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX). Methods In this phase 3, double-blind BLISS-BELIEVE trial (GSK S...

Background Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare and severe autoimmune disease, characterized by a pauci-immune necrotizing vasculitis leading to inflammation and damage of major organs. In AAV, autoantibodies against neutrophil cytoplasmic antigens, including proteinase-3 (PR3) or myeloperoxidase (MPO),...

Background Glucocorticoids (GCs) are important for the management of systemic lupus erythematosus (SLE); however, chronic use is associated with significant adverse effects and organ damage. Despite the general recommendation to taper GCs in order to minimise organ damage accrual, detailed guidance on how to taper is lacking. Objectives We outline...

Objectives Autoreactive memory B cells contribute to chronic and progressive courses in autoimmune diseases like systemic lupus erythematosus (SLE). The efficacy of belimumab (BEL), the first approved biologic treatment for SLE and lupus nephritis (LN), is generally attributed to depletion of activated naïve B cells and inhibition of B cell activat...

Background Despite continuous advancement, treatment of lupus nephritis (LN) remains challenging. Recent guidelines now include a regimen incorporating tacrolimus as a first-line treatment option. Even though tacrolimus is effective in combination with mycophenolate and corticosteroids, concerns remain regarding long-term use, given its association...

Objective Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Tacrolimus is a calcineurin inhibitor that finds its origin in solid organ transplantation, but is also effectively used in lupus nephritis. In a transplant setting, tacrolimus is associated with an increased cardiovascular risk, including nephrot...

Objectives To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. Methods An international Task Force formed the questions for the systematic literature reviews (January 2018–December 2022), followed by formulation and finalisation of the statements after a series of meetings. A...

Objective AURORA 2 evaluated the long‐term safety, tolerability, and efficacy of voclosporin compared to placebo in patients with lupus nephritis (LN) receiving an additional two years of treatment following completion of the one‐year AURORA 1 study. Methods Enrolled patients continued their double‐blinded treatment of voclosporin or placebo rando...

Introduction Immunocompromised kidney patients are at increased risk of prolonged SARS-CoV-2 infection and related complications. Preclinical evidence demonstrates a more potent inhibitory effect of voclosporin on SARS-CoV-2 replication than tacrolimus in vitro. We investigated the potential antiviral effects of voclosporin on SARS-CoV-2 in immunoc...

The therapeutic armamentarium of the lupologist is expanding, notably when faced with one of the most frequent severe systemic lupus erythematosus (SLE) organ manifestation: Lupus nephritis (LN). Based on real-practice case studies, we will address the latest guideline recommendations for the management of LN. With novel agents at hand, we will mak...

Introduction: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cyto-plasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m 2 in the avacopan group and 4.1 ml/min per 1.73 m 2 in the pred...

Background Anti-neutrophil cytoplasmatic antibody (ANCA) associated vasculitis (AAV) is a rare, life-threatening, systemic auto-immune disease.[1] Due to the low prevalence, multiple treating disciplines and poor registration, including ICD-10 classification, identifying AAV patients for (pre-)clinical studies, research and health care evaluation i...

Background In 2022 the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) presented new classification criteria for the three subsets of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV): granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and Eosinophilic Gr...

Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 in...

Background Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Methods Using EULAR standardised operating pro...

Despite the continuing development of immunomodulatory agents and supportive care, the prognosis associated with lupus nephritis (LN) has not improved substantially in the past decade, with end-stage kidney disease still developing in 5-30% of patients within 10 years of LN diagnosis. Moreover, inter-ethnic variation in the tolerance of, clinical r...

Objective This integrated analysis evaluates the efficacy and safety of voclosporin, a novel calcineurin inhibitor, at 23.7 mg twice daily in combination with mycophenolate mofetil (MMF) and oral glucocorticoids in lupus nephritis (LN) using pooled data from two large phase II and phase III clinical trials. The purpose was to expand the pool of pat...

For patients with immune-mediated inflammatory diseases (IMIDs), concerns exist about increased disease activity after vaccination. We aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with IMIDs, and determine risk factors for increased disease activity. In this substudy of a prospective observational cohort stud...

Background: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases. Objective: To study if elevated Fab glycosylation is a common feature of autoimmunity, we investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell-me...

Jolijn R van Leeuwen,1,* Tamara Popov,2,* Achim Obergfell,2 Ton J Rabelink,1 YK Onno Teng1 1Center of Expertise for Lupus-, Vasculitis- and Complement-Mediated Systemic Diseases (LuVaCs), Department of Internal Medicine - Nephrology Section, Leiden University Medical Center, Leiden, the Netherlands; 2Vifor Pharma Ltd, Glattbrugg, Switzerland*These...

Background This study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia. Methods This was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (≤38) results, four groups were des...

Background: Studies have suggested incremental short-term adverse events (AE) after repeated vaccination. In this report, we assessed occurrence and risk factors for short-term AEs following repeated SARS-CoV-2 vaccination in patients with various immune-mediated inflammatory diseases (IMIDs). Methods: Self-reported daily questionnaires on AEs d...

Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion,...

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 safety and efficacy. Design, setting, participants, & measurements: Eligible patients completing BLISS-LN received monthly intravenous belimumab 10...

Purpose Belimumab (BEL), a recombinant human monoclonal antibody directed against B-cell activating factor (BAFF), is the first approved biological agent for patients with systemic lupus erythematosus (SLE) and a high level of disease activity or lupus nephritis (LN). BEL inhibits primary humoral immune responses by depleting naive B-cells that are...

Introduction Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown that the effect on achieving (clinical) remission, frequency and severity of relapses is eq...

Infective endocarditis (IE) may be misdiagnosed as ANCA-associated vasculitis (AAV), especially when antineutrophil cytoplasmic antibodies (ANCA) are detected. Distinguishing IE from AAV is crucial to guide therapy. However, little is known about ANCA positivity in IE patients. We present a case report and systematic review of the literature on pat...

Objectives Diagnosing patients with ANCA-associated vasculitis (AAV) can be challenging due to its rarity and complexity. Diagnostic delay may have severe consequences such as chronic organ damage or even death. Because few studies have addressed diagnostic pathways to identify opportunities to improve, we performed a clinical audit to evaluate the...

Introduction Le contrôle du LS reste un besoin médical non couvert. Le rationnel d’un traitement séquentiel BEL et RTX dans le LS a été précédemment publié. Cette étude a évalué l’efficacité et la tolérance de BEL associé à un cycle de RTX chez des patients (pts) LS, en utilisant de nouveaux critères de contrôle de la maladie et de rémission. Pati...

Kidney transplant recipients (KTRs) are at increased risk for a more severe course of COVID-19, due to their pre-existing comorbidity and immunosuppression. Consensus protocols recommend lowering immunosuppression in KTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the optimal combination remains unclear. Calcin...

Background Voclosporin (VCS), a novel calcineurin inhibitor, was approved in the US in January 2021 for the treatment of adult patients with active lupus nephritis (LN) in combination with background immunosuppressive therapy. The Phase 3 AURORA 1 study showed that the addition of VCS to mycophenolate mofetil (MMF) and low-dose steroids in patients...

Background BEL is approved for active SLE and lupus nephritis (adults only). Despite failed trials, ¹ RTX remains in the SLE treatment armamentarium. Sequential BEL and RTX therapy offers a promising strategy to target B cells by distinct but complementary mechanisms. Objectives To assess the pharmacodynamic effects of BEL and a single RTX cycle o...

Background Belimumab (BEL), a recombinant human monoclonal antibody directed against B-cell activating factor (BAFF), is the first approved biological agent for patients with active systemic lupus erythematosus (SLE) and lupus nephritis (LN). ¹ BEL inhibits primary humoral immune responses by depleting naïve B cells that are dependent on BAFF for t...

Background ANCA-associated vasculitides (AAV) are characterized by recurrent, chronic small vessel inflammation and deleterious organ damage. The main targets of ANCA are myeloperoxidase (MPO) and proteinase 3 (PR3). ANCA, B cells and the complement system are crucial to AAV pathogenesis, as evidenced by the clinical benefit of B cell depletion wit...

Kidney transplant recipients (KTRs) are at increased risk of severe COVID-19 disease compared to the general population. This is partly driven by their use of immunosuppressive therapy, which influences inflammatory responses and viral loads. Current guidelines suggest to withdraw mycophenolate while calcineurin inhibitors are often continued durin...

BACKGROUND AND AIMS Voclosporin, a novel calcineurin inhibitor, was approved in the USA in January 2021 for the treatment of adult patients with active lupus nephritis in combination with background immunosuppressive therapy. Voclosporin has a favorable metabolic profile and a consistent dose-concentration relationship, eliminating the need for the...

BACKGROUND AND AIMS Belimumab (BEL), a recombinant human monoclonal antibody directed against B-cell activating factor (BAFF), is the first approved biological agent for patients with systemic lupus erythematosus (SLE) and a high level of disease activity or lupus nephritis (LN). BEL inhibits primary humoral immune responses by depleting naive B-ce...

Introduction: Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depleti...

Background Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 b...

BACKGROUND During the COVID-19 pandemic, several home-monitoring programs have described the success of reducing hospital admissions, but only a few studies investigated the experiences of patients and healthcare professionals. OBJECTIVE The objective of our study was to determine the patients’ and healthcare professionals’ perception on the usefu...

Background: During the COVID-19 pandemic, several home-monitoring programs have described the success of reducing hospital admissions, but only a few studies investigated the experiences of patients and healthcare professionals. Objective: The objective of our study was to determine the patients' and healthcare professionals' experience on the s...

Background Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders treated with specific immunosuppressants. Disease-overarching studies, and data on recall responses and third vaccinations are scarce. Our primary objective was to investigate the effects...

Background BEL is approved for patients (pts) with systemic lupus erythematosus (SLE). We evaluated intravenous (IV) BEL in active LN. Methods This 104-week trial (GSK Study BEL114054; NCT01639339) randomized adults with active LN (class III, IV, and/or V) 1:1 to monthly BEL 10 mg/kg IV or PBO, plus standard therapy (ST) with high-dose corticoster...

Objective To achieve consensus on a definition of remission in SLE (DORIS). Background Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a defin...

We performed a post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). A...

Objective Managing complex and rare systemic autoimmune diseases such as anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) can be challenging and is often accompanied by undesirable variations in clinical practice. Adequate understanding of clinical practice can help identify essential issues to improve the care for AAV patien...

Background Belimumab (BLM), a recombinant human monoclonal antibody directed against B-cell activating factor (BAFF), is the first approved biological agent for patients with active severe systemic lupus erythematosus (SLE) and lupus nephritis (LN). There is clinical evidence that combining BLM with B cell depleting therapy can ameliorate disease a...

Background Patients with an immune mediated inflammatory disorder or post solid organ transplantation (IMIDT), are at risk for infectious complications especially if they are treated with immunosuppressive drugs (imeds). There is still great uncertainty whether these IMIDT patients are more susceptible to COVID-19 than controls, and/or should be ad...

Background and Aims Lupus nephritis (LN) is the most common severe manifestation of systemic lupus erythematosus (SLE), occurring in up to 40% of patients (pts) with SLE over their disease course, and resulting in 10–20% of pts progressing to end-stage kidney disease.1-3 The BLISS-LN (GSK Study BEL114054; NCT01639339) study demonstrated that the ad...

Background and Aims B-cell depletion with rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Nevertheless, relapses are frequent after RTX, often preceded by B-cell repopulation suggesting that residual autoreactive B-cells persist despite therapy. Therefore, this study...

Background and Aims Belimumab (BLM), a recombinant human IgG-1λ monoclonal antibody directed against B-cell activating factor (BAFF), is the first approved biological agent for patients with active severe systemic lupus erythematosus (SLE) and lupus nephritis (LN). There is clinical evidence that combining belimumab with B cell depleting therapy ca...

Objectives: SLE and/or antiphospholipid syndrome (SLE/APS) are complex and rare systemic autoimmune diseases that predominantly affect women of childbearing age. Women with SLE/APS are at high risk of developing complications during pregnancy. Therefore, clinical practice guidelines recommend that patients with SLE/APS should receive multidiscipli...

Background Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis. Methods This multicentre, double-blind...

The year 2020 has been an extraordinary year in many ways but especially for patients with lupus nephritis (LN), as 2020 saw two novel agents (belimumab and voclosporin) finding FDA-approval for the treatment of LN. These agents will both enrich the therapeutic armamentarium, allowing physicians to better treat their LN patients, as well as broaden...

Therapeutic plasma exchange (TPE) is indicated as a treatment for a wide array of diseases, extensively addressed in the Guidelines of the American Society for Apheresis. In pregnancy, TPE is an uncommon event and application is largely based on extrapolation of efficacy and safety in a non-pregnant population. This review intends to describe the c...

Background B-cell depletion with rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Nevertheless, relapses are frequent after RTX, often preceded by B-cell repopulation suggesting that residual autoreactive B-cells persist despite therapy. Therefore, this study aimed to...

Background: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. Methods: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conduct...