10 e-Letters

  • Letter to the Editor: belimumab versus anifrolumab in adults with systemic lupus erythematosus: an indirect comparison of clinical response at 52 weeks

    We read with interest the recent manuscript by Neupane et al. (2023) (1) in Lupus Science and Medicine, which compared the efficacy of anifrolumab and belimumab in adults with moderate-to-severe systemic lupus erythematosus (SLE). The study found that anifrolumab and belimumab are comparable in terms of SRI-4 response at 52 weeks using an indirect treatment comparison (ITC) analysis. The authors noted this was different from our ITC (Bruce et al. 2022) (2) findings where patients on anifrolumab were twice as likely to achieve an improvement in SRI-4 as belimumab.

    The difference in the results between Neupane et al. and our study might not be an actual difference but explained by differences in data utilised in the ITC analyses.

    First, different SRI-4 results were used. Neupane et al. utilised the SRI-4 results derived from pre-specified restricted medication rules for TULIP-1 whereas our study used results derived from amended medication rules (3). There was an error in the pre-specified restricted medication rules which were subsequently amended to ensure clinical appropriateness (3). As highlighted in our Letter in reply (6), the SRI-4 results derived from the amended rules were agreed to by the FDA and the EMA, and reported in the US Prescribing Information (5) and Summary of Product Characteristics (7). Regulators were aligned with the prespecified outcome definition used in TULIP-2 as well as the BLISS trials, thus they were the appropriate rules to use...

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  • Clustering and seroconversion in juvenile-onset SLE

    Ufuk Ilgen
    Rheumatology, Ankara University, Ankara, Turkey

    On behalf of all co-authors: Ufuk Ilgen, Mucteba Enes Yayla, Askin Ates, Ilyas Ercan Okatan, Emine Uslu Yurteri, Murat Torgutalp, Ayse Bahar Dincer Kelesoglu, Tahsin Murat Turgay, and Gulay Kinikli

    Dear Editor,

    We read the article by Bao S et al1 with interest. The authors cited our previous work2 by stating: “Prior research of aPL analysis in patients with JSLE did not include the other autoantibodies, and thus the results may not be convincing enough because the impact of the other autoantibodies was neglected in the disease course.” We have some concerns about the interpretation of our results:

    1. Our study did not include patients with juvenile-onset SLE. As clearly stated in Methods, all were adult patients. Disease duration did not either date back to childhood (Table 1).

    2. Potential impact of other autoantibodies on disease course was not neglected. As stated in Methods, all patients had a panel of 16 autoantibodies (against Sm, nucleosome, histone, PCNA, PO, SS-A 60 kDa, SS-A 52 kDa, SS-B, CENP-B, Scl-70, U1-RNP, Jo-1, PM/Scl, Mi-2, Ku, and dsDNA). However, none were found to be associated with antiphospholipid antibody status.

    3. The aim of our study was not to determine a relationship between a general autoantibody profile and SLE manifestations at all. Patients with serial antiphospholipid antibody measurements were included in the study.
    Some additi...

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  • Persistence of aPL, looking for the holy grail

    To the editor,

    We have read with interest the study from Khawaja et al. entitled ''Loss of antiphospholipid antibody (aPL) positivity post-thrombosis in systemic lupus erythematosus (SLE)''(1). The authors described 31 patients with antiphospholipid syndrome (APS) associated with systemic lupus erythematosus who presented loss of antiphospholipid antibodies (aPL) positivity after thrombotic events.

    They measured four types of aPL: IgM, IgG and IgA isotypes of anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). Complete disappearance after thrombosis was observed in 41% of APS patients for IgG aCL, 51% for those with IgM aCL, 50% for IgA aCL, and 20% for LAC. However, 60% of those who at the same time lost IgG aCL and 76% of those who became negative for LAC, reacquired the antibodies within five years. In contrast, only 37% and 17% of those who lost IgM or IgA aCL, reacquired the antibodies within five years, respectively. Finally, 14 (45%) patients never turned back positive during the follow-up period. They concluded that recurrence of aPL positivity is frequent in APS associated with SLE, after their disappearance in post-thrombotic states.

    Until now, long term oral anticoagulation (OAC) is the cornerstone of treatment for thrombotic primary and SLE-associated APS (2). The decision to withdraw OAC in APS patients when aPL become "persistently" negative remains a matter of debate. In the light of results fro...

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  • Overcoming the challenges in new lupus diagnostics

    Dr Olsen and Karp have summarised data from several important papers on the use of novel diagnostic tests for earlier diagnosis of SLE. I agree in the importance of this problem, for the early exclusion of SLE in people with benign ANA positivity, and early intervention in people destined to develop SLE or related disease.

    I also agree with the key challenges in such research. Previous studies have been limited by a retrospective design. Inclusion of patients with variable symptom duration or patient populations that were selected for certain clinical characteristics may bias findings by conditioning on the outcome. Also, putative biomarker results need to be appraised alongside routine diagnostic tests, not in isolation.

    These challenges were met in our previous study into these questions[1]. We invited all ANA-positive referrals to our centre with an onset of the symptoms that triggered referral within the past 12 months to participate, ensuring an unbiased sample appropriate to the clinical question. We collected detailed data on clinical presentation, routine immunology assessments, patient and physician reported severity, and family history, and integrated these data into our biomarker evaluation. Our patients were recruited and followed up prospectively in a standardised schedule of visits with strict assessment of criteria and a "flare hotline" in case new symptoms developed.

    By doing so, we were able to reliably demonstrate the value...

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  • SLE and Atherosclerosis: There Are Several Mechanisms To Highlight

    Dear editor;
    We have read with great interest the article published by Haque et al. which was about association between atherosclerotic process, cardiovascular outocomes and systemic lupus erythematosus (SLE). It is reported that only SDI score, triglyceride level and cyclophosphamide exposure was predictive for future cardiovascular events and factors related with plaque progression were defined(1).
    SLE is a multisystemic disorder and lupus nephritis is one of the main manifestions of the disease. It usually presents with proteinuria and deteriorated renal glomerular functions. Renin angiotensinogen antgiotensin system (RAAS) inhibitors are used in patients with lupus nephritis to reduce proteinuria and kidney function protection(3). Angiotensin II (AT II) has unfavorable effects on endothelial functions. AT II binds AT 1 receptors and promotes vasoconstriction and production of proinlammatory cytokines and proliferation factors. It is shown by several studies that RAAS inhibitors improves endothelial functions and induces the regression of atherosclerotic process(3).
    Microalbuminuria (MAU) and proteinuria are related with worse cardiovascular outcomes. Microalbuminuria causes endothelial dysfunction and associated with accelerated atherosclerosis(4). MESA study demonstrated that coronary calcification is significantly higher in patients with microalbuminuria than counterparts without MAU. Not only presence but also amount of MAU is associated with insu...

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  • Comment on: TNF-α and plasma albumin as biomarkers of disease activity in systemic lupus erythematosus

    Dear editor,
    We read with interest the article of Idborg et al.1 who recently analyzed the role of several inflammatory mediators, and their usefulness as biomarkers in the measurement of activity of disease and the identification of clinical subphenotypes in systemic lupus erythematosus (SLE). Although interesting, these results may benefit of further discussion in light of systems medicine.
    Authors concluded that the two main inflammatory mediators related with activity of SLE were TNF-α and p-albumin. However, previous studies have found that TNF-α and the TNF/IL-10 ratio were higher in patients with low activity of disease,2 and that TNF-α antagonists may induce SLE-like disease.3 These controversial data argues against a generalized model based on TNF-α as clinical activity biomarker, and advocate for the influence of other mediators in such a condition.
    As shown by Idborg et al., IL-6, IL-10, IL-15, MCP-1, IP-10, MIP-1α, ESR, anti-dsDNA and U-albumin/creatinine were also positively correlated with activity of disease,1 suggesting that the exclusive role of TNF-α and p-albumin on activity of disease is unlikely. In fact, the pathological functions of these biomarkers are not isolate since they emerge from the interactions among them and between cells and tissues (i.e., systems medicine).4
    In this sense, cytokine and autoantibody clusters (i.e., neutral, chemotactic/anti-phospholipid antibodies, and IFN-α/dsDNA) have been reported to be associat...

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  • Response to Editorial

    The Editor,
    Lupus Science and Medicine
    BMJ Journals

    Dear Madam/Sir,

    Our esteemed peer Dr. Boers has editorialised1 on our recently published study of associations of glucocorticoid use with damage accrual in SLE2, suggesting that studies of the type reported are ‘harmful’. As this is such a serious accusation, we feel compelled to respond, even though we suspect that in the end the views of the authors and of Dr Boers as serious physician-researchers are in fact highly aligned. Essentially, we do not resile from our view that long-term reliance on glucocorticoids for the control of inflammation in SLE carries harm, and that steroid-reducing regimens for SLE management are urgently needed. At no time in our report, and certainly not in our clinical practice, do we advise against the use of these drugs, though such an imprecation was implied (incorrectly) in Dr Boers’ editorial. Rather, it is our view that strategies to achieve control of disease activity with reduced reliance on glucocorticoids, such as improving the use of non-glucocorticoid agents or the introduction of novel therapies, are as urgently needed as ever – and that complacency about the chronic use of glucocorticoids in SLE is not an acceptable status quo.

    As we stated in the opening remarks, ‘The objective of the present study was to quantify damage accrual in a prospectively followed cohort of patients with SLE and determine the association of glucocorticoid use with damage...

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  • Prolonged QT interval and atherosclerosis in systemic lupus erythematosus

    Geraldino-Pardillaet al.1 recently published an interesting article analysing one of the most important aspects of systemic lupus erythematosus (SLE): the risk of cardiovascular disease, a leading cause of death in SLE patients. Although there were no healthy control group to compare, and the SLE patient sample size was limited, their conclusions are clinically valuable and should be taken into consideration.

    The usefulness of the corrected QT interval (QTc) as a marker of atherosclerosis risk is well-established in the general population and in some sub-groups with high cardiovascular risk. QTc prolongation is also linked to cardiovascular events and mortality during follow-up2-3. QTc interval prolongation in SLE patients has been described in previous studies4.However, no data on the clinical repercussions of this finding are available. Our research group recently published a paper on the positive correlation between QTc interval prolongation in SLE patients and higher arterial stiffness measured by pulse-wave velocity5. The association was independent of hypertension and age. Our data complement those published by Geraldino-Pardilla et al.1, suggesting an independent association between QTc interval prolongation and subclinical atherosclerosis. However, there is no evidence of the long-term clinical effects of this association. Prospective studies with large sample sizes and long follow-up periods are required to study the potential long-term effects. In any case...

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  • Calcidiol hypovitaminosis D and glucocorticoid therapy
    Norberto Ortego-Centeno

    Dear Editor,

    After reading the article by Carli et al.(1) we would like to share some thoughts that could be of practical use regarding vitamin D supplementation in patients on low-dose glucocorticoids therapy.

    In 2011, we published the results of a follow-up carried out in our unit (located in a hospital in Granada, a sunny city in the south of Spain) that included a cohort of 55 patients with systemi...

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  • Biological change or poor measurement instrument?
    Mauricio Restrepo-Escobar

    Dear Editors,

    We read with great interest the article of Greloni et al, "Value of repeat biopsy in lupus nephritis flares" and have some comments.

    There is a high probability that what they call "histologic transformation" is further evidence of the poor reproducibility of the interpretation of the renal biopsy in lupus nephritis and no evidence that there really been a change in the biological phenomenon o...

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