Lessons learned from the failure of several recent trials with biologic treatment in systemic lupus erythematosus

2018 ◽  
Vol 18 (9) ◽  
pp. 989-996 ◽  
Author(s):  
Zdenka Hruskova ◽  
Vladimir Tesar
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Lessons Learned ◽  
Systemic Lupus ◽  
Biologic Treatment

scholarly journals Fever of Multiple Possible Origins

2021 ◽  
Vol 16 (2) ◽  
pp. 43-48
Author(s):  
David Spillane ◽  
Jeffrey Wiseman
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Inflammatory Markers ◽  
Bone Marrow Aspirate ◽  
Final Diagnosis ◽  
Lessons Learned ◽  
Prise En Charge ◽  
Systemic Lupus ◽  
Lupus Érythémateux Systémique ◽  
La Modification

A 60-year-old man presented with 1 week of fever despite broad-spectrum antibiotics for presumed pyelonephritis based on extended spectrum bacteriuria, recent bladder catheterization, and a negative search for other infections. He developed a maculopapular truncal rash, and pancytopenia with persistent fevers and worsening inflammatory markers despite modifying then stopping antibiotics. The non-specific clinical features at presentation and absence of hemophagocytosis on the initial bone marrow aspirate confounded multiple subspecialists and delayed the final diagnosis of hemophagocytic lymphohistiocytosis (HLH). Once this syndrome was elucidated, he responded well to dexamethasone and etoposide. An underlying diagnosis of systemic lupus erythematosus with aortic vasculitis was made, which in combination with pyelonephritis likely precipitated HLH. We summarize current concepts, pitfalls, and lessons learned in the diagnosis and management of HLH. RésuméUn homme de 60 ans se présente à l’hôpital à la suite d’une semaine de fièvre malgré la prise d’antibiotiques à large spectre pour traiter une pyélonéphrite soupçonnée, fondée sur une bactériurie à spectre étendu, un cathétérisme vésical récent et une recherche infructueuse d’autres infections. Il a développé une éruption cutanée maculopapulaire sur le tronc et une pancytopénie accompagnée d’une fièvre persistante et d’une augmentation des marqueurs de l’inflammation malgré la modification, puis l’arrêt des antibiotiques. Les manifestations cliniques non spécifiques à la présentation et l’absence d’hémophagocytose lors de la ponction médullaire initiale ont confondu de multiples surspécialistes et retardé le diagnostic définitif de lymphohistiocytose hémophagocytaire (LHH). Une fois que ce syndrome a été élucidé, le patient a bien répondu au traitement par la dexaméthasone et l’étoposide. Un diagnostic sous-jacent de lupus érythémateux systémique accompagné d’une vascularite de l’aorte a été posé qui, combiné à la pyélonéphrite, a probablement précipité la LHH. Nous résumons les concepts actuels, les pièges et les leçons apprises dans le diagnostic et la prise en charge de la LHH.

scholarly journals Developing novel drugs for systemic lupus erythematosus. Lessons learned from the belimumab trials

2012 ◽  
Vol 3 (3) ◽  
pp. 209-222
Author(s):  
Cristina Pamfil ◽  
Antonis Fanouriakis ◽  
Dimitrios T Boumpas
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Standard Of Care ◽  
Lessons Learned ◽  
Phase Iii ◽  
Systemic Lupus ◽  
Novel Therapy ◽  
Key Factor ◽  
B Cell Homeostasis

Systemic lupus erythematosus is the prototypic autoimmune disease with a broad range of clinical manifestations and a complex pathogenesis. B-cells hold a central role in its pathogenesis, not only as autoantibody producing cells, but also by producing other inflammatory mediators and by presenting autoantigens to autoreactive T cells. BlyS, a soluble ligand of the TNF cytokine family, is a key factor affecting B-cell homeostasis and survival and its blockade ameliorated the disease in animal models and preclinical studies of SLE. Following an unsuccessful phase II trial of belimumab, a monoclonal antibody targeting BlyS, two large phase III studies in patients with mild-to-moderate disease, BLISS-52 and BLISS-76, met their primary endpoints showing better efficacy of the drug over standard of care alone. To this end, development of a novel more sensitive responder index and improvements in study designs were crucial. As a result, belimumab became the first drug to get approval for the treatment of SLE after more than 50 years. In this paper we discuss the rationale, development, indications, lessons learned, pitfalls and challenges for this novel therapy and point-out to additional issues that need to be addressed in the future.http://dx.doi.org/10.7175/rhc.v3i3.206

scholarly journals Cerebral Microstructure Analysis by Diffusion-Based MRI in Systemic Lupus Erythematosus: Lessons Learned and Research Directions

2021 ◽  
Vol 12 (1) ◽  
pp. 70
Author(s):  
Ettore Silvagni ◽  
Alessandra Bortoluzzi ◽  
Massimo Borrelli ◽  
Andrea Bianchi ◽  
Enrico Fainardi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Diffusion Tensor ◽  
Lessons Learned ◽  
Quantitative Mri ◽  
Microstructure Analysis ◽  
Future Research ◽  
Water Molecules ◽  
Systemic Lupus ◽  
Research Perspectives

Diffusion-based magnetic resonance imaging (MRI) studies, namely diffusion-weighted imaging (DWI) and diffusion-tensor imaging (DTI), have been performed in the context of systemic lupus erythematosus (SLE), either with or without neuropsychiatric (NP) involvement, to deepen cerebral microstructure alterations. These techniques permit the measurement of the variations in random movement of water molecules in tissues, enabling their microarchitecture analysis. While DWI is recommended as part of the initial MRI assessment of SLE patients suspected for NP involvement, DTI is not routinely part of the instrumental evaluation for clinical purposes, and it has been mainly used for research. DWI and DTI studies revealed less restricted movement of water molecules inside cerebral white matter (WM), expression of a global loss of WM density, occurring in the context of SLE, prevalently, but not exclusively, in case of NP involvement. More advanced studies have combined DTI with other quantitative MRI techniques, to further characterize disease pathogenesis, while brain connectomes analysis revealed structural WM network disruption. In this narrative review, the authors provide a summary of the evidence regarding cerebral microstructure analysis by DWI and DTI studies in SLE, focusing on lessons learned and future research perspectives.

Management of non-renal non-neurologic persistent lupus activity in real world patients from Argentina

Lupus ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1167-1173
Author(s):  
M Scolnik ◽  
V Scaglioni ◽  
G J Pons-Estel ◽  
E R Soriano
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Confidence Interval ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Interquartile Range ◽  
University Hospital ◽  
Systemic Lupus ◽  
Biologic Treatment ◽  
Disease Heterogeneity

Management of systemic lupus erythematosus patients is challenging because of disease heterogeneity. Although treatment of renal nephritis is more standardized, treating non-renal lupus activity remains controversial. Our objective was to identify non-renal, non-neurologic persistent active systemic lupus erythematosus patients in our cohort and described therapeutic behaviors in them. All systemic lupus erythematosus patients (American College of Rheumatology and/or Systemic Lupus Erythematosus International Collaborating Clinics criteria) seen at a university hospital between 2000 and 2017 were included and electronic medical records manually reviewed. Persistent lupus activity was defined as a patient with a Systemic Lupus Erythematosus Disease Activity Index score ≥ 6 (without renal and central nervous system manifestations) despite being on a stable treatment regimen for ≥ 30 days. Stable treatment could include prednisone alone (7.5–40 mg/d) or combined with antimalarial drugs and immunosuppressant therapies. A total of 257 lupus patients were included, 230 females (89.5%, 95% confidence interval 85.1–92.7), mean age at diagnosis 29.9 years (SD 16.4). After a median cohort follow-up of 5.7 years (interquartile range 2.4–10.2), 14 patients (5.4%, 95% confidence interval 3.2–9.0) showed persistent non-renal non neurologic lupus activity, with a median disease duration of 11.3 years (interquartile range 3.6–19.4). At that time, 12/14 (85.7 %, 95% confidence interval 52.6–97.0%) had low complement and 11/14 (78.6 %, 95% confidence interval 46.5–93.9%) had positive antiDNA antibodies. The main reasons for being refractory were mucocutaneous disease (50%, 95% confidence interval 23.5–76.5) and arthritis (42.9%, 95% confidence interval 18.5–71.2). Therapeutic choices after being refractory were: only increasing corticosteroid dose in one patient, starting rituximab in four, belimumab in eight, and in one mycophenolate and rituximab; with good response in all of them. In conclusion, 5.4% of systemic lupus erythematosus patients in our cohort were considered to have non-renal non neurologic persistent lupus activity, with mucocutaneous and arthritis the main manifestations. In total, 92.8% of these patients started a biologic treatment at this point (rituximab or belimumab).

scholarly journals Healthcare Utilization and Costs of Systemic Lupus Erythematosus by Disease Severity in the United States

2020 ◽  
pp. jrheum.191187 ◽  
Author(s):  
Irene B. Murimi-Worstell ◽  
Dora H. Lin ◽  
Hong Kan ◽  
Jonothan Tierce ◽  
Xia Wang ◽  
...  
Keyword(s):  
United States ◽  
Systemic Lupus Erythematosus ◽  
Disease Severity ◽  
Healthcare Utilization ◽  
Lupus Erythematosus ◽  
Severe Disease ◽  
The United States ◽  
Administrative Claims ◽  
Systemic Lupus ◽  
Biologic Treatment

Objective To quantify healthcare utilization and costs by disease severity for patients with systemic lupus erythematosus (SLE) in the United States. Methods We conducted descriptive analyses of Humedica electronic health record (EHR) data from 2011 to 2015 (utilization analysis) and integrated Optum administrative claims/Humedica EHR data from 2012 to 2015 (cost analysis) for patients with SLE. All-cause utilization outcomes examined were hospitalizations, outpatient visits, emergency department (ED) visits, and prescription drug use. Analyses of costs stratified by disease severity were limited to patients enrolled in an Optum-participating health insurance plan for ≥ 1 year after the earliest observed SLE diagnosis date. Costs were converted to 2016 US dollars (US$). Results Healthcare utilization was evaluated in 17,257 patients with SLE. Averaged over the 2011–2015 study period, 13.7% of patients had ≥ 1 hospitalization per year, 25.7% had ≥ 1 ED visit, and 94.4% had ≥ 1 outpatient visit. Utilization patterns were generally similar across each year studied. Annually, 88.0% of patients had ≥ 1 prescription, including 1.3% who used biologics. Biologic treatment doubled between 2011 (0.7%) and 2015 (1.4%). Cost analyses included 397 patients. From 2012 to 2015, patients with severe SLE had mean annual costs of $52,951, compared with $28,936 and $21,052 for patients with moderate and mild SLE, respectively. Patients with severe SLE had increased costs in all service categories: inpatient, ED, clinic/ office visits, and pharmacy. Conclusion Patients from the US with SLE, especially individuals with moderate or severe disease, utilize significant healthcare resources and incur high medical costs.

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