92 e-Letters

published between 2019 and 2022

  • Correspondence on “Comparative analysis of SGLT-2 expression in renal vasculitis and lupus nephritis” by Hakroush et al.

    We really appreciated the results of the exploratory study by Hakroush and colleagues, which provides further insights into the potential role of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with lupus nephritis and renal vasculitis.1 Unfortunately, at present, relevant clinical evidence is missing.
    It has been formerly known that focal segmental glomerulosclerosis (FSGS) is considered as a distinct phenotype of lupus podocytopathy, which is associated with a severe tubulo-interstitial injury and a much lower complete remission rate, compared to other phenotypes, such as mimimal change and mesangial proliferation.2,3
    According to a recently published, post-hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin compared to placebo resulted in a lower mean rate of estimated glomerular filtration rate decline among patients with baseline FSGS, although the result was not statistically significantly, possibly due to the small number of patients with FSGS (n = 104).4 Results of the EMPA-KIDNEY trial, which are anticipated within 2022, will provide more definitive answers on whether SGLT-2 inhibitors can play a crucial role in the therapeutic management of lupus nephritis the next years.5


    1. Hakroush S, Tampe D, Kluge IA, Baier E, Korsten P, Tampe B. Comparative analysis of SGLT-2 expression in renal vasculitis and lupus nephritis. Ann Rheum Dis. 2022...

    Show More
  • Correspondence on “Survival after COVID-19-associated organ failure among inpatients with systemic lupus erythematosus in France: a nationwide study” by Mageau et al.

    We read with great interest the article by Mageau et al.,1 who reported that COVID-19-associated organ failure (AOF) is associated with a poor late-onset outcome between days 30 (D30) and 90 (D90) among patients with systemic lupus erythematosus (SLE) in France. Conversely, they noted that an unchanged survival rate of patients with SLE with COVID-19-AOF will require hospitalization compared with patients without SLE COVID-19-AOF at D90. This study is a valuable addition to the literature. However, we share some concerns about this article to the authors.
    First, the selection bias may be suspect in this study. A selection bias occurs when those in charge of the recruitment or enrollment of patients (recruiters) selectively enroll patients into the study based on what the next observation allocation is likely to be.2 At D30, 43 (21.9%) in-hospital deaths were recorded among patients with SLE with COVID-19-AOF compared with 31,274 (27.6%) in the unmatched patients without SLE with COVID-19-AOF. At baseline (D30), they may enroll a sick patient in patients with SLE with COVID-19-AOF compared with patients without SLE with COVID-19-AOF. This strategy can lead to substantially biased estimates of the survival of patients with COVID-19-AOF between D30 and D90 and misleading conclusions.
    Second, prior studies have shown numerous AOFs, and disease severity of COVID-19 is independently associated with the increased risk of mortality.3,4 Furthermore, several para...

    Show More
  • Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination

    We read with great interest the article titled ‘Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination’ by Lu et al.1. The authors found that COVID-19 vaccination was associated with increased odds of gout flare and was negatively associated with colchicine prophylaxis. However, we would like to draw attention to some concerns.

    First, it is problematic to present multiple (over eight covariates) adjusted effect estimates from a single model in Table 3. The findings present in Table 3 may mix direct and total effect of each variable and make interpretation difficult2. Specifically, in current study, the authors aimed to assess the total effect of COVID-19 vaccination (the primary exposure) on the odds of gout flare while adjusting for other potential confounders3. Thus, the odds ratios for other covariates (e.g. colchicine prophylaxis treatment) are likely to reflect the direct effect of each covariate rather than total effect, and such a direct effect may be biased due to potential selection bias 4. For example, the odds ratio of sex increased dramatically from 0.82 in univariate analysis to 4.33 in model 2 analysis, which was biologically controversial.

    Second, the calculation of odds ratios for vaccination and its subgroups in Table 3 seems questionable. Using the same reference group (no vaccination), the odds ratio of gout flares for any COVID-19 vaccines was 4.57 (p< 0.001), for subgroup of Sinovac Life vaccine was 2....

    Show More
  • Air pollution and rheumatic musculoskeletal diseases, evidence for lifestyle modifications

    Dear Editor,
    We read with great interest the paper by Gwinnutt et al. on the recommendations regarding lifestyle behaviors and work participation to prevent progression of rheumatic and musculoskeletal diseases [1]. First, we applaud to the efforts of the EULAR task force to increase awareness around such important topic. Second, we congratulate with the authors for the attempt at harmonizing the recommendations on lifestyle and rheumatic musculoskeletal diseases (RMD) across European countries. We also acknowledge that trying to synthetize the available evidence regarding the impact of lifestyle on RMD is not an easy job. The task force focused on 6 main exposures (exercise, diet, weight, alcohol, smoking and work participation), which were probably chosen based on the relative World Health Organization (WHO) factsheets. However, we think that environmental air pollution, an important factor linked to RMD risk and aggravation [2–6], should have been at least mentioned in the manuscript. The WHO recently identified air pollution as: “one of the greatest environmental risk to health” [7]. According to the WHO report, 99% of the world population is living in places where the air quality guidelines are not met. Albeit 91% of premature deaths and disability related to air pollution affects the population living in low- and middle-income countries, European countries are impacted as well [8]. In addition, there is accumulating evidence that exposure to pollutants can be e...

    Show More
  • ‘Correspondence on “Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomized clinical trial” by “Araujo CSR et al”‘.

    We read with great interest the recent article written by Araujo CSR et al entitled “Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomized clinical trial” published in the Annals of Rheumatic Diseases on February 22, 2022 [1]. The major impact of this trial was the reinforcement of the immunogenic effect of a 2-week methotrexate discontinuation after each dose of the Sinovac-CoronaVac vaccine against SARS-CoV-2 compared to methotrexate continuation in patients with rheumatoid arthritis (seroconversion rates: 78.4% vs 54.5%, p-0.019 and geometric mean antibody titers: 34.2 (25.2–46.4) vs 16.8 (11.9–23.6), p=0.003, respectively).

    Previous experience with other non-COVID-19 vaccines, like the influenza or pneumococcal vaccines, has indicated that discontinuation of immunosuppresants improves the immunogenicity of a given vaccine [2,3]. Based on this knowledge, we had proposed that it would be beneficial for patients with autoimmune rheumatic diseases to get vaccinated against SARS-CoV-2 preferably when the underlying rheumatic disease is in remission and after temporal withdrawal of anti-metabolites within 10 days before and after each vaccine dose along with similar modifications in anti-cytokine drugs and corticosteroid dosages >10mg/ day (prednisone equivalent) [4]. In fact, applying that in a comparative study it was shown that the magnitude of antibody responses to mRNA-based S...

    Show More
  • Correspondence on "Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance"

    Ugarte-Gil, et al (1) recently published a study reporting several characteristics associated with severe COVID-19 outcomes in people with systemic lupus erythematosus(SLE). Demographic factors, comorbidities, active or untreated SLE, and patients treated with glucocorticoids were the most noticeable features. Even though several covariates had been taken into consideration to minimize the impacts of these confounders, we presume vaccination could play a crucial role in the COVID-19 outcomes.
    Previous studies had pointed out the protective effect that vaccination could provide against poor outcomes in the general population (2). In spite of a lack of evidence on the efficacy of COVID-19 vaccines in patients with SLE, achieving adequate sero-protection after receiving COVID-19 vaccine could be expected according to the expert opinion based on the knowledge on the use of other vaccines in this specific group of patients (3). A review article published by Wei Tang, et al (4) showed that commonly used immunosuppressants inclusive of glucocorticoids, methotrexate, mycophenolate mofetil/mycophenolic acid and rituximab might impede vaccine responses, causing less sufficient immune responses after getting COVID-19 vaccines in SLE patients. Hence, we suggest a subgroup analysis according to whether being vaccinated or not to have better data interpretation and to clarify the possible factors that may lead to critical consequences in SLE patients infected with COVID-19.

    Show More
  • Correspondence on “Multilevel factors predict medication adherence in rheumatoid arthritis: a 6-month cohort study” by Balsa et al.

    We read with great interest the recent publication by Balsa et al.,[1] which reported that patient–physician agreement on the treatment, the type of treatment prescribed (favoring second-line conventional disease-modifying rheumatic drugs and biological disease-modifying rheumatic drugs/targeted synthetic disease-modifying rheumatic drugs), and the patient feeling privileged by the medication received are effective predictors of medication adherence in patients with rheumatoid arthritis (RA). In contrast, sociodemographic or clinical factors were not associated with medication adherence. This study focuses on medication adherence as a significant clinical variable and is a valuable addition to the literature. However, some issues have not been addressed by the authors.
    First, epidemiologists agree that studies assessing a relation at one moment in time are called cross-sectional studies.[2] If the follow-up time is considered, the study is longitudinal, and it is either a cohort or a case-control study. A cohort or a case-control study must be applied to variables that can be reasonably assumed stable over time. However, this study was a six-month multicentre observational longitudinal prospective study, and medication adherence is related to psychological, communicational, and logistic factors measured at the same time. Therefore, this study is better labeled a cross-sectional study, since psychological, communicational, and logistic factors cannot be assumed to be...

    Show More
  • Standard cardiovascular risk scales for people with gout?

    Dear editor,
    I read with interest the recently published new EULAR recommendations for managing the cardiovascular risk in patients with inflammatory rheumatic diseases [1]. They were long-awaited, and opportunely the targeted diseases are now broader, as previous ones focused primarily on chronic inflammatory arthritis [2].

    With rising numbers worldwide, gout is a major cardiovascular risk factor directly linked to all forms of atherosclerotic diseases. By having gout, there is a 40% increased chance of dying from the coronary disease [3]. So, focused management to reduce these serious complications is necessary, and establishing an individual patient's risk is essential. Surprisingly, the experts rely on risk prediction using standard risk assessment tools, claiming the absence of validation studies. I should partially disagree at this point. Certainly, no longitudinal studies have evaluated the predicted rates of cardiovascular events in gout to date. However, our group studied the discriminative value of SCORE and Framingham tools in detecting patients with carotid plaques, a high-risk indicator [4]. A moderate discriminative capacity was unveiled, with areas under the curve of 0.711 for SCORE and 0.683 for Framingham [5]. Specificity was quite good, but the tools lacked enough sensitivity. Moreover, Gamala and colleagues incorporated gout into the modified Dutch SCORE as an inflammatory risk factor [6]. It led to a 28.3% upgrade to the high-risk stag...

    Show More
  • Calcinosis and obinutuzumab

    We thank the author for this comment and his interest in our report. We agree that obinutuzumab has shown efficacy in a phase 2 trial in rituximab-naïve SLE patients. In our report, three of four patients did not respond to rituximab prior to receiving obinutuzumab. In our CREST syndrome patient (case 4), the combined obinutuzumab/chemotherapy led to a remission of her chronic lymphatic leukemia; leukocyte counts dropped from >200/nl to normal values. During this therapy, cutaneous calcinosis located on the distal upper extremities gradually regressed until its disappearance in clinical examination. We thank the author for pointing out that due to multiple comedications the disappearance of calcinosis cannot be solely traced back to obinutuzumab. However, we are not aware of cases in which calcinosis resolved due to chemotherapy so that we think obinutuzumab might have been at least partially responsible for this improvement. Further studies are needed to corroborate the effect of obinutuzumab on cutaneous manifestations in systemic sclerosis.

  • Correspondence on “Blocking GM-CSF Receptor α with mavrilimumab reduces infiltrating cells, pro-inflammatory markers, and neoangiogenesis in ex-vivo cultured arteries from patients with giant cell arteritis”

    We read with great interest the article by Corbera-Bellalta et al. entitled “Blocking GM-CSF Receptor α with mavrilimumab reduces infiltrating cells, pro-inflammatory markers, and neoangiogenesis in ex-vivo cultured arteries from patients with giant cell arteritis” (1). We believe that the study is of great importance because it demonstrates that blocking the GM-CSF pathway alleviates crucial pathological hallmarks of giant cell arteritis (GCA). These hallmarks include leukocyte infiltration, production of pro-inflammatory cytokines, tissue destructive matrix metalloproteinases (MMP’s), and neoangiogenesis. Additionally, the recently reported preliminary data of the first phase II clinical trial of mavrilimumab in combination with a 26-week glucocorticoid (GC) taper in GCA patients is very promising (2). The primary end point, being the difference in the time to first relapse between mavrilimumab treatment and placebo was achieved (p=0.0263). Moreover, the sustained remission rate at 26 weeks was higher in the mavrilimumab vs placebo group (83.2% vs 49.9%, respectively, p =0.0038).

    Recently, we reported on a distinct CD206+ macrophage subset that produces YKL-40 and MMP-9 in GCA affected vessels (3, 4). We proposed a pathogenic model in which these CD206+ macrophages play major roles in fueling leukocyte infiltration, vascular destruction, and neoangiogenesis. Furthermore, we showed that these CD206+/MMP-9+/YKL-40+ tissue destructive and proinflammatory macrophage...

    Show More