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The 2016 ACR congress

1 Dec, 16 | by flee

The ACR congress also featured, as it always does, a lot of exciting activities and new findings on SLE. Lupus gives up its secrets only very slowly, but there were many presentations from researchers working on elucidating the etiology and pathophysiology of this disease. I was most impressed by results from different groups that point at potentially important roles for extracellular vesicles in SLE. I was also pleased to see how many clinical researchers were analyzing the prevalence of remission in SLE using a newly developed framework. There were no major new therapeutic successes reported at this congress, but there is high anticipation for the continuation of the earlier promising results with therapeutics that target the interferon pathway. For me, another highlight was the Editorial Board meeting for the still young open-access journal Lupus Science and Medicine. Together with Dr. Jill Buyon from New York I have the honor of being editor for this publication, which is supported by a partnership between the Lupus Foundation of America and the BMJ publishing group. We are now entering our third year and the Editorial Board unanimously felt that the journal has had a most exciting and promising development, with more than 170 manuscripts submitted and many very interesting and often cited results having been published already in this short time.

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Lupus Awareness Month and Lupus Science & Medicine

1 May, 16 | by flee

Lupus, SLE, or “systemic lupus erythematosus” is a disease that affects millions of people worldwide, a disease that strikes mostly women in all age groups including adolescents and young adults, a disease that can cause chronic or recurring symptoms from many different parts of the body, a disease that can be treated to some extent, but it cannot be cured – and yet it is a disease that most people do not know much about. That’s why as Editors of the journal Lupus Science & Medicine we are delighted that the Lupus Awareness Month initiative has been taken in the hope of gaining a greater understanding of lupus among the larger public.

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Professor Jane Salmon about the PROMISSE study

15 Apr, 16 | by Ioannis Parodis

Dr. Jane Salmon is a Professor of Medicine and Professor of Obstetrics and Gynecology at Weill Cornell Medical College and the Collette Kean Research Professor at Hospital for Special Surgery in New York, USA. She is the principle investigator in the PROMISSE study, which has generated very important data and received great attention. 

– Professor Jane Salmon, what does the acronym PROMISSE stand for?

– PROMISSE stands for Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study. PROMISSE is the largest multicenter, multiethnic, and multiracial study to prospectively assess the frequency of adverse pregnancy outcomes and clinical and laboratory variables (including research biomarkers) that predict them, in women with or without high titer antiphospholipid antibodies (APL) and inactive SLE or mild or moderate SLE activity at conception. We enrolled over 700 patients from 2003 to 2014.

 

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Post ACR 2015: Professor Richard Furie about anifrolumab

30 Nov, 15 | by Ioannis Parodis

Professor Richard Furie is the chief of the Division of Rheumatology of the North Shore-Long Island Jewish Health System in New York. His research in the field of SLE is profound. At the 2015 ACR Annual Meeting in San Francisco, professor Furie presented results from a phase II trial of anifrolumab, a type I IFN receptor antagonist.

 

– Professor Furie, what is your general impression about this upcoming medication?

Never before have we seen such a successful phase II study in SLE. The magnitude, consistency, and breadth of responses were quite striking. Although the primary endpoint was a composite of the SRI at Day 169 and the requirement by Day 85 to reduce the prednisone dose to <10 mg/day (and not exceed the Day 1 dose) and sustain this dose until Day 169, other successful outcomes included the SRI without the steroid taper requirement, the BICLA, modified SRI’s, CLASI, and steroid tapering (300 mg group only).  The results were more dramatic in those subjects with high baseline IFN gene signatures.  If the same degree of efficacy occurs in phase III, the lupus community will have another drug.

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Professor Ronald van Vollenhoven about Lupus Science & Medicine

21 Sep, 15 | by Ioannis Parodis

Professor Ronald van Vollenhoven is the Head of the Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID) at Karolinska Institutet in Stockholm, Sweden, and one of the Editors-in-chief for Lupus Science & Medicine.

 

– Professor van Vollenhoven, we have heard you many times encouraging the rheumatologists to treat to target, both for rheumatoid arthritis and for systemic lupus erythematosus. Remission is the obvious target in RA. What is the target in SLE?

– In SLE it’s a bit more complicated because there really are several targets. Remission can be the primary target but we also have to achieve improvements in HQ-QOL, prevent flares, prevent lupus-related damage, and minimize glucocorticoid exposure.

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Challenges in understanding the role of pregnancy morbidity in cardiovascular risk in SLE

10 Nov, 14 | by ltempler

Dialogue by Julia F Simard and Jinoos Yazdany. Originally published here.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE).1 Despite extensive and ongoing research in this area, few risk factors, including traditional ones such as smoking and hypertension, explain a significant proportion of the risk. There is a robust scientific literature showing that the prevalence of cardiovascular risk factors such as endothelial dysfunction, hypertension and increased arterial stiffness increase after pre-eclampsia, as do future risks of metabolic syndrome and CVD.2 Given that a majority of patients with SLE are women of reproductive age and the reported early CVD morbidity in women with SLE, investigating the relationship between pre-eclampsia (and other pregnancy complications) and subsequent CVD risk is of great interest in SLE. To that end, investigators explored the link between pregnancy complications and subsequent CVD using cross-sectional data from 129 women with systemic lupus in this issue.3

Despite their clear question and the clinical significance, the study design and available data only hint at an answer. Although complications such as pre-eclampsia have been shown to be more common in SLE pregnancies compared with the general population, these are still relatively rare complications. Coupled together with a relatively uncommon disease (SLE), the study lacks the statistical power to make definitive conclusions and cannot fully account for potential confounders. However, the authors should be commended for accumulating the number of patients they did. This work should be viewed as exploratory, building a scientific foundation for more definitive studies that can unravel the relationship between SLE, pregnancy morbidity and subsequent CVD risk.

Whether pregnancy acts as a vascular stress test that unmasks endothelial vulnerability to injury that manifests as pre-eclampsia, or whether pre-eclampsia itself causes damage that is responsible for future CVD is unknown. Should pregnancy complications alert clinicians caring for women with SLE about subsequent CVD risks necessitating more aggressive risk factor modification? Should pre-eclampsia be viewed as a ‘failed cardiac stress test’? And lastly, does the presence of SLE and pre-eclampsia together substantially increase CVD risk, greater than would be expected with either risk factor alone? Lin and Ramsey-Goldman et al‘s discussion naturally begs each of these questions. To build upon the foundation of this work and assess these issues, some design, data collection and analytical considerations will need to be accounted for in future studies. It would be of interest to examine different pregnancy complications separately, since pre-eclampsia may confer a different risk than outcomes such as having an infant with low birth weight. Also, more fully exploring the timing of pre-eclampsia in relation to SLE diagnosis would be of interest, since presence of both conditions during pregnancy might confer a higher risk. It is important to note that the majority of patients (two-thirds) in Lin and Ramsey-Goldman’s study experienced pre-eclampsia before a diagnosis of SLE. It remains unclear how much time between pregnancy and CVD assessment and risk factor modification is needed, and whether the presence of other modifiable risk factors should change current screening and treatment practices. In addition, it would be interesting to understand how multiple pregnancies and multiple gestations influence these relationships.

As the body of evidence between CVD and pregnancy morbidity grows, this line of study may unlock key risk factors to aid in the identification and management of early CVD in women with SLE. To answer the clinical questions posed here and by the authors and to overcome the methodological challenges, there is a need for robust, longitudinal, clinically rich, population-based data.

 

 

Professor Bernard Lauwerys

5 Nov, 14 | by ltempler

This is the first in our series of author profiles. Please let me introduce you to Professor Bernard Lauwerys who published the paper “sIL7R concentrations in the serum reflect disease activity in the lupus kidney” which can be found here.

Hi Professor Lauwerys please can you tell us a bit about yourself and how you got started in scientific research?

I got involved in SLE research activities after I met Frédéric Houssiau in Brussels during my training in internal medicine and rheumatology. I did a Ph.D. thesis under his supervision about the role of cytokines in the pathogenesis of the disease. In the early 2000, I had the chance to spend 16 months in the laboratory of E.K. Wakeland at UT Southwestern Medical Center at Dallas, where powerful mouse models of the disease were being developed. Since I am back in Brussels, I share my time between clinical duties and translational research activities, taking advantage of our large recruitment of patients with systemic and inflammatory disorders.

What are the messages we should take from your paper?

Active renal disease in the course of lupus nephritis is suggested when rising serum anti-double stranded DNA titers are observed, together with decreased serum C3 levels and an active urinary sediment. Unfortunately, none of these tests are sensitive and specific enough to confirm that active renal inflammation is ongoing, hence the need for a kidney biopsy (and sometimes repeat kidney biopsies) in the initial workup and follow-up of these patients. In our previous work, we provided evidence that the soluble form of the IL-7Receptor (sIL7R) is produced in peripheral tissues upon inflammatory stimulants. In particular, we found that it is produced in the lupus kidney (and not by lupus PBMC), and that serum levels correlate with renal disease activity. In the present publication, we confirmed these observations in an independent cohort of patients, and found that rising sIL7R serum levels are a strong indication that active renal disease (renal BILAG A) is present or will be present in the next 3 months. The main advantage of the test is that it is an easily measurable serum indicator of inflammatory mechanisms happening in the target organ, in this case the kidney.

And what limitations should we be aware of?

As always, there are false negative and false positive cases. If the test had to be implemented in clinical practice, it would be important to use it in the context of other available tests, in the hands of experienced clinicians. As a matter of fact, we did demonstrate in the paper that combining sIL7R measurements with any of the other tests (anti double stranded DNA titers, serum C3, proteinuria) increase the performance of these tests to detect overtly active renal disease. I was also recently very thrilled to find out that one of the few false positive cases we had, did develop active renal disease shortly after publication of the manuscript.

If you wanted to repeat your study, what would you be looking out for that may have taken you by surprise the first time around?

We did not encounter such surprising result. Our study was already a confirmatory study.

What impact will your study have on the field?

There is a strong medical need for such markers of target organ involvement in SLE. In my view, measuring serum sIL7R concentrations in SLE nephritis patients is useful in order to detect relapsing renal disease early on. By opposition to anti-double stranded DNA antibodies or serum C3, sIL7R is not a marker of systemic disease activity, but is related to local inflammatory events. By opposition to proteinuria, it is not a marker of damage as well as of disease activity, but it only reflects disease activity. I am convinced that kidney biopsies are necessary when active renal disease is suspected in a SLE patient, but using sIL7R measurements might help better identify patients in whom the the procedure is warranted.

What still needs to be done in the field?

In real life situations, patients are not (always !) part of a well-identified cohort of individuals with a well-defined disease. sIL7R is produced in other organs where inflammation is present. We have published data about production of the molecule by rheumatoid arthritis synovial fibroblasts, upon stimulation with TNFalpha or IL1beta, and we are accumulating data about the link between serum sIL7R and disease activity in rheumatoid arthritis. Further development of the concept into a diagnostic tool will require additional tests in the context of a collaborative effort, but we are 100% ready to take this endeavour.

Had you heard of open access before submitting to Lupus Science and Medicine? What are your thoughts on open access?

Open Access is a strong improvement in terms of data visibility. I believe that all public funding agencies should include (and fund !) Open Access publishing in their contracts.

What advice would you offer to anyone starting out in the field?

A good clinimetry is the key to successful translational research activities. This is particularly true in the field of SLE, where clinical assessment of disease activity is a science as such. The samples used in the research need to be obtained from patients with a standardized and prospective clinical evaluation. In my view, this really makes the difference between signal and noise!

Lupus Science and Medicine blog

15 Sep, 14 | by BMJ

Welcome to the Lupus Science and Medicine blog. Over the coming weeks we will be introducing you to some of our key published authors. This is part of our new “author profiles” feature where you can find out more about their work, their interests and their advice for other people starting out in their field.

I will also be re-posting some of the journals key dialogue pieces which have been commissioned by one of our editors: Jill Buyon.

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