102 e-Letters

published between 2020 and 2023

  • Cardiovascular risk factors are undertreated in ORAL Surveillance trial

    Dear Editor,
    We read with great interest the article by Christina Charles-Schoeman et al. recently published in Annals of the Rheumatic Diseases, reporting the results of a post-hoc analysis of the ORAL Surveillance trial . As it is widely known to the rheumatology community, ORAL surveillance failed to demonstrate noninferiority of tofacitinib versus TNF inhibitors (TNFi) with relation to the risk of major adverse cardiovascular events (MACE) and cancer in a population of rheumatoid arthritis (RA) patients enriched for baseline cardiovascular disease (CVD) risk factors.
    In their analysis, Charles-Schoeman et al.1 stratified ORAL Surveillance participants in two main cohorts, with and without a past history of atherosclerotic cardiovascular disease (ASCVD), respectively; the latter cohort was further categorized in incremental CVD risk classes according to the ASCVD pooled cohort equations (PCE). Compared to TNFi, the risk of MACE in tofacitinib recipients at the dose currently licensed for RA (5 mg two-times-per-day) was significantly higher only in patients with a history of ASCVD (HR (95% CI): 1.96 (0.87 to 4.40)), while no statistical difference in MACE occurrence was evident in patients with no history of ASCVD, regardless the estimated 10-year ASCVD risk.
    Besides providing a better description of the subpopulation of patients who may experience a clear increase in CVD risk, this stratification revealed some interesting clues that, in our opinion, d...

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  • Letter to the Editor: comment on the contradiction and standardization of the study.

    We have some comments on the retrospective study that looked at risk factors for severe COVID-19 in people with axial spondyloarthritis (axSpA), psoriasis (PsO), and psoriatic arthritis (PsA).1

    First, according to the findings of the study, the use of tumor necrosis factor (TNF) inhibitors was associated with decreased probabilities of severe COVID-19 outcomes. The author cites some previous studies using clinical database analysis to support the result. However, in recent research, Rebecca H Haberman et al obtained postvaccination blood samples from participants with immune-mediated inflammatory diseases and healthy controls and analyzed SARS-CoV-2-spike-specific antibody titers and neutralization capacity. Their results showed that TNF inhibitors might lead to a dampened humoral response to COVID-19 vaccinations, and the persistence of an adequate humoral response is significantly decreased by month 6. This finding supports the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases, specifically for those being treated with TNF inhibitors. Larger basic research is required to clarify these contradictions and evaluate the impact of other immunomodulatory strategies, which will assist in determining the appropriate timing and method for COVID-19 vaccinations. 2

    Second, based on the results of one sensitivity analysis, Janus kinase (JAK) inhibitor use was associated with a higher risk of death owing to COVID-19 (binary outco...

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  • Correspondence on "Risk factors for serious infections in ANCA-associated vasculitis" by Odler et al

    I am writing in regards to the article, "Risk factors for serious infections in ANCA-associated vasculitis" by Odler and colleagues, which published in the Annals of Rheumatic Diseases1. While the study provides valuable information on the risk factors for severe infections in patients with ANCA-associated vasculitis (AAV), there are certain limitations that must be taken into consideration when interpreting the results. One of the significant limitations of the study is the small sample size of only 197 patients. This limited sample size raises questions about the generalizability of the results and their statistical significance. The study results may only be applicable to the population represented in the sample and may not reflect the experiences of larger patient populations. Moreover, the small sample size may increase the likelihood of type I or type II errors and make it difficult to identify significant associations2. Another important limitation is that the study only includes participants from the RAVE trial, which is a specific population of AAV patients who meet certain inclusion criteria. Therefore, the results may not be generalizable to the broader population of AAV patients, who may have different risk factors, underlying comorbidities, and other factors that may impact the risk of severe infections3. Furthermore, the lack of a control group is another limitation of the study. The study only compared patients receiving rituximab or cyclophosphami...

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  • Correspondence on Influence of active versus placebo control on treatment responses in randomised controlled trials in rheumatoid arthritis" by Kerschbaumer et al

    I am writing a correspondence on the article "Influence of active versus placebo control on treatment responses in randomised controlled trials in rheumatoid arthritis" by Kerschbaumer et al 1. The authors' systematic approach to comparing the treatment effects of pharmaceutical compounds in rheumatoid arthritis clinical trials with placebo and active treatment controls is commendable. The results of the study, showing significantly higher responses in active comparator trials compared to placebo controlled trials, provide valuable insights into the influence of control groups in RCTs. However, I have a few critical points to raise regarding the study's methodology and conclusions. Firstly, the matching of active treatment arms to comparable regimens, populations, background therapy, and outcome reporting was based solely on the nature of the control group, which is not an ideal approach. This method of matching could have led to unequal comparison groups and biased results 2. In order to ensure that the comparison between active treatment and control groups is fair and accurate, a more comprehensive and systematic approach to matching should have been employed. Secondly, the conclusion that placebo controlled trials lead to smaller effect sizes of active compounds in RCTs compared with the same compound in head-to-head trials may be an overgeneralization. The authors did not consider other potential confounding factors that could explain the difference...

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    We read the article “2022 American College of Rheumatology/EULAR Classification Criteria for Giant Cell Arteritis" by Ponte et al. with great interest (1). There was a long-standing need for revision of classification criteria for giant cell arteritis (GCA) due to the insufficient sensitivity of the ACR 1990 criteria in recent studies (2). This could be explained by enrolment of patients with different clinical phenotypes to the cohorts depending on the improvement in the imaging methods in addition to clinician’s assessment over the years. Especially, implementation of cross-sectional imaging including FDG – PET improved the diagnosis of GCA and facilitated the recognition of disease patterns without cranial manifestations. Patients with isolated extra-cranial involvement were reported to have a diagnostic delay up to 5 months compared to classical GCA patients and late recognition of large vessel involvement could cause permanent organ damage (3). Thoracic aorta dilatation / aneurysm has been reported in 15% and large artery stenosis in 30% in patients with proven aortic inflammation (4). The ACR 1990 Criteria were not sufficient to identify this subgroup and patients who participate in clinical trials evaluating the efficacy of further treatment options. The new criteria were expected to fill this gap.

    We implemented new criteria to our single reference center cohort with long-term follow-up consisted of 89 patients with a median follow-up time of 4 years T...

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  • Correspondence on Individual patient data meta-analysis on continued use of glucocorticoids after their initiation as bridging therapy in patients with rheumatoid arthritis

    We are submitting a correspondence in regards to the paper "Individual patient data meta-analysis on continued use of glucocorticoids after their initiation as bridging therapy in patients with rheumatoid arthritis" by Lotte van Ouwerkerk et al.1 published in Ann Rheum Dis. 2022 Dec 16. The study is an important contribution to the field as it aimed to investigate the effectiveness of glucocorticoids (GC) as a bridging therapy for rheumatoid arthritis (RA) patients. The study combined data from 7 clinical trial arms that included GC bridging schedule in the initial treatment of RA, to investigate whether patients with RA can discontinue GC after GC 'bridging' and to identify factors that may affect this. The study has several strengths, such as the use of individual patient data meta-analysis which allows for a more comprehensive and detailed analysis. Additionally, the study's aim to investigate the effectiveness of GC as a bridging therapy is admirable, as it addresses an important question in the field of RA treatment2 3. However, the study also has some limitations that must be taken into account when interpreting the results. Firstly, the sample size of 1653 patients may not be representative of the general population of RA patients. This could limit the generalizability of the study's findings and may not fully capture the diversity of RA patients. Additionally, the study's short-term follow-up period of 18 months may not be enough...

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  • What can we learn from MS-IP regarding anti-OJ antibodies?

    Although, several novel autoantibodies in idiopathic inflammatory myopathies (IIM) have been described, a serological gap persists which poses a diagnostic challenge. In this context, we read with interest the article by Vulsteke et al. [1]. The untargeted protein immunoprecipitation combined with gel-free liquid chromatography-tandem mass spectrometry (IP-MS) identified a novel autoantibody to cytoplasmic cysteinyl-tRNA-synthetase (CARS1, anti-Ly). In addition, rare ASA, such as anti-OJ, anti-Zo and anti-KS, and common ASA could also be identified by IP-MS. Consequently, Vulsteke et al. [1] concluded that IP-MS is a promising method for discovery detection of autoantibodies, especially autoantibodies that target complex autoantigens.
    We agree that IP-MS represents a powerful discovery tool for novel autoantibodies. However, the gained knowledge is most valuable for more conventional in-vitro diagnostic platforms. Although the IP-MS method holds promise, due to the lack of standardization it is unlikely that it will be applicable for IVD solutions soon. Established alternative methods include ELISA [2], line immunoassay (LIA) and a recently developed particle-based multi-analyte technology (PMAT) that has been evaluated for the detection of MSA [3-5].
    Due to the antigen complexity, anti-OJ are among the most difficult MSA to detect [6, 7]. According to an international survey, despite concern about its accuracy, LIA is commonly used for the detection of MSA inc...

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  • Malignancy risk with tofacitinib versus TNF inhibitors in rheumatoid arthritis: results from the open-label, randomized controlled ORAL surveillance trial: Comment on the Article by Curtis et al.

    I read the paper by Curtis et al. with great interest [1]. A new analysis using this paper’s data has yielded important results that should be presented here.
    The authors state that (1) in patients with rheumatoid arthritis (RA) aged ≥50 years with ≥1 additional cardiovascular risk factor, the risk of adjudicated malignancies excluding non-melanoma skin cancer (NMSC), lung cancer and NMSC was higher with tofacitinib versus tumor necrosis factor inhibitor (TNFi); (2) lung cancer was the most frequently reported malignancy in tofacitinib-treated patients; and (3) history of atherosclerotic cardiovascular disease (ASCVD) or increasing risk scores were associated with higher malignancy incidence rates (IRs) across treatment.
    Atherosclerosis can be caused by various factors, such as smoking, high cholesterol, hypertension, hyperglycemia, diabetes, and genetic factors [2]. However, atherosclerosis can also develop due to infection [3]. These infections include Helicobacter pylori (H. pylori), pneumonia, periodontal disease, and viruses such as cytomegalovirus, human immunodeficiency virus (HIV), herpes simplex virus, Epstein-Barr virus (EBV), human papilloma viruses (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and recently, severe acute respiratory syndrome coronavirus-2 [3, 4].
    Some infections that cause atherosclerosis are thought to contribute to cancer in humans. The fractions of different types of cancer, and of all cancers worldwide and in dif...

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  • Correspondence on “ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update” by Ramiro et al.

    The recent Spondyloarthritis international Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations provided a comprehensive update on the management of axial spondyloarthritis (axSpA). (1) The 15 recommendations were agreed upon with two relevant updates and two newly formulated. Recommendation 9 was updated based on systematic literature review from 2016 up to January 1st, 2022, to include targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors (JAKi)) for patients with persistently high disease activity despite conventional treatments, where current practice is to start therapy with biological DMARDs (bDMARDs), tumour necrosis factor inhibitors (TNFi) or interleukin-17 inhibitors (IL-17i). (1, 2) The new therapeutic option is appreciated by physicians and patients as previously bDMARDs were the only option in patients with persistently high disease activity despite conventional treatments and the current practice was to start with TNFi therapy. (3) At the time of formulation of the recommendation data from only four phase 2/3 randomized controlled trials (RCT) in radiographic axSpA were available (N = 779). (2) Since the recommendation was published upadacitinib was approved by European Medicines Agency (EMA) for non-radiographic axSpA based on the data from a phase 3 SELECT-AXIS 2 trial. (1, 4) Additionally due to the safety signals seen with tofacitinib in rheumatoid arthritis (RA), until additional data becomes available a note...

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  • Is there adequate evidence for the adoption of multipliers for cardiovascular risk estimation in rheumatic autoimmune diseases?

    We read with interest the article by Conrad et al. [1] that advocated modification of cardiovascular risk (CVR) scores to incorporate risk multipliers for each rheumatic and musculoskeletal disease (RMD). The proposed multipliers were based on hazard ratios for incident cardiovascular diseases in a nationwide study of electronic medical records in the UK [2]. This proposal contradicts recent recommendations in the 2022 EULAR recommendations for CVR management in patients with RMDs [3]. Based on a review of the evidence, including data of elevated CVR in other nationwide studies, and appraisal by experts, these recommendations did not support use of CVR multipliers in RMDs [3]. It is therefore important to examine several issues raised by this proposal.
    First, the objective of study from which the multipliers were derived [1] was not to assess the added predictive validity of CVR score modifiers, but rather to examine the incidence of cardiovascular disease in patients with autoimmune diseases. Confidence in the validity of the multipliers is not high, considering that data on blood pressure were missing in one-third of patients, while data on cholesterol and smoking were missing in two-thirds and almost one-half, respectively [2]. Also, whether these risk estimates apply in countries with baseline CVRs different from the UK is unclear [3].
    Second, the suggested multipliers were based on risk estimates of a wide range of cardiac or vascular diseases, including p...

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