eLetters

92 e-Letters

published between 2019 and 2022

  • Correspondence on “Occupational inhalable agents constitute major risk factors for rheumatoid arthritis, particularly in the context of genetic predisposition and smoking” by Tang et al.

    We read with interest the publication by Tang and coauthors on occupational risks for rheumatoid arthritis (RA) (1), which builds on previous valuable observations from the Swedish EIRA cohort.

    Their findings can be further strengthened when contextualized with other studies of occupation and RA from the U.S. and the U.K., in which higher prevalences of inhalational risk exposure are found. Results from U.S. population-based surveys, with a combined sample of nearly 5000 ever-employed males, showed that work in silica-exposing jobs exclusive of mining was associated with greater than three-fold odds of RA in both of the two regions studied (Appalachia and the Southwest Mountain States).(2,3) Because such non-mining silica exposure was common (28% and 18%, respectively), the population attributable fraction (PAF) within these groups was considerable: 27% (95% CI 23%, 30%) and 17% (95% CI 13%, 20%), respectively.

    Results from a U.K. study show additional effects of inhalational exposures (with silica being the most common) on RA seropositivity, antibody titer, and age of onset. (4) A study of 726 men with RA from Cornwall demonstrated that inhalational exposures were strongly associated with having seropositive RA, with higher RF antibody titers and earlier age of onset compared to unexposed patients. In that study, 75% of subjects had inhalational exposures lasting more than one year, and the estimated PAF for being strongly RF positive RA was 24.2%.

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  • Comments on the article: “Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy"

    To the Editor
    I recently have read with great interest the article written by Dr. Feist et al. entitled “Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study” published in Annals of the Rheumatic Diseases (1). In this randomized double-blinded clinical study, the effect of a monoclonal antibody against a proinflammatory cytokine, interleukin-6, was compared to placebo. The study showed beneficial effects of Olokizumab in patients with rheumatoid arthritis on their clinical manifestations and their self-reported outcomes. This study provides strong evidence regarding the use of this monoclonal antibody for treatment of adult patients with moderate to severe active rheumatoid arthritis not responding to tumor necrosis factor inhibitors; however, there are several issues that worth mentioning.
    In this study, adult patients with active disease status who received methotrexate for at least 12 weeks prior to the initial screening of the study were enrolled. Based on the inclusion criteria of the study, the eligible participants were those individuals with moderate to severe rheumatoid arthritis who had not an adequate response to methotrexate alone and therefore, they were in need for disease-modifying antirheumatic drugs and they should had received and f...

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  • Correspondence on "Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis" by Solomon et al.

    We have read with interest the results of the study conducted by Solomon and colleagues, showing that addition of tumor necrosis factor inhibitor (TNFi) versus sulfasalazine and hydroxychloroquine on methotrexate regimen among individuals with rheumatoid arthritis (RA) did not result in a significantly greater reduction in arterial inflammation, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta.1 A closer look at participants' baseline characteristics revealed that a significant proportion of recruited patients (45.2%) had concomitant arterial hypertension.1 Renin-angiotensin system (RAS) blockers have been shown to exert at some extent anti-inflammatory effects,2 partially explaining the relatively low TBR among patients with established atherosclerotic cardiovascular disease, treated with angiotensin converting enzyme inhibitors.3 Similarly, in subjects with a recent acute coronary syndrome, treatment with an angiotensin-II receptor blocker resulted in a significant reduction in TBR over a 6 month period of treatment.4 Therefore, we strongly believe that a subgroup analysis of the primary endpoint according to baseline use of RAS blockers would provide useful additional insights into the interesting research hypothesis formulated by Solomon and colleagues.

    1. Solomon DH, Giles JT, Liao KP, et al. Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arth...

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  • Correspondence on “Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial”

    Correspondence

    Correspondence on “Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial”

    Satoshi Takanashi, M.D., Ph.D.

    Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Correspondence: Satoshi Takanashi, M.D., Ph.D.
    Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
    TEL: +81-3-5363-3786
    FAX: +81-3-5379-5037
    Email: satoshi-takanashi@hotmail.co.jp
    ORCID: 0000-0002-3607-2140


    I read the paper by Michael Bonelli et al in your journal with great interest [1]. They showed the effectiveness and safety of tocilizumab for polymyalgia rheumatica (PMR) by conducting the first double-blind, randomised, placebo-controlled study (PMR-SPARE trial). Because majority of patients with PMR are elderly, there is an urgent need to establish a treatment strategy to reduce the adverse events of glucocorticoids. While clinical trials on PMR are limited, this study was well-designed and provided valuable results. Here, I would like to comment to clarify the further usefulness of this study and development of PMR management in the future focusing on the necessity for novel a criteria of remission and relapse, biomarkers reflecting disease activity under the IL-6 b...

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  • Correspondence on ‘Early identification of axial psoriatic arthritis among patients with psoriasis: a prospective multicentre study’

    With great interest, we read the study by Proft et al. 1In this prospective multicenter study, the authors applied a dermatologist-centered screening tool followed by a structured rheumatologic examination, including MRI of the sacroiliac joints and spine, for the early identification of psoriatic arthritis with axial involvement (axPsA). We endorse the authors for completing an important clinical study, the results of which could have important implications for the early identification of axPsA in patients with psoriasis. However, there are some aspects that need to be focused on and discussed.
    First, there is some controversy regarding the definition of axPsA. Some studies have emphasized the importance of imaging, and the presence of sacroiliac arthritis with grade 3 unilaterally or grade 2 and above bilaterally, or spinal syndesmophyte(s) according to CASPAR criteria is defined as axPsA.2 It has also been suggested that axPsA requires meeting the modified New York criteria of AS criteria or applying the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA), which require the presence of inflammatory back pain (IBP) in the patient. However, back pain is not always present in patients with axPsA. The use of chronic back pain as the primary screening condition is debatable. One study showed that up to 44% to 55% of patients with axPsA had only imaging involvement (including sacroiliac joints or spine...

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  • Cardiovascular risk with tofacitinib in Rheumatoid Arthritis: the clinical relevance of atherosclerotic cardiovascular disease on treatment decisions.

    On October 28th, the European Medicine Agency extended to the entire class of Janus Kinase inhibitors (JAKi) the recommendation to use a JAKi only if no suitable therapeutic alternatives are available in patients older than 65 years, those at increased risk of MACE, and those who smoke or have smoked extensively in the past [1].
    The ORAL surveillance would have shown that patients with active rheumatoid arthritis (RA) aged ≥50 years and with at least one additional cardiovascular (CV) risk factor (current smoker, hypertension, low high-density lipoprotein cholesterol, diabetes mellitus, family history of premature coronary heart disease, extra-articular rheumatoid arthritis, or history of coronary artery disease) had an increased risk of major adverse cardiovascular events (MACE) with tofacitinib versus tumour necrosis factor inhibitors (TNFi) [2]. In the ORAL Surveillance not all risk factors were well balanced between the tofacitinib and TNFi arms, i.e, unstable angina was more prevalent in patients taking tofacitinib 5 mg than in those on TNFi (17/1438 vs 7/1444, respectively; Chi-square=4.174, p=0.04), as reported in the Table S2 of the main study [2]. This bias presumably influenced the higher rate of MACE observed in the tofacitinib group. Therefore, we were not surprised that the post-hoc analysis published by Charles-Schoemann et al showed that the difference between tofacitinib and TNFi in the risk of MACE was primarily seen in patients with a history of...

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  • Correspondence on “Recapture and retreatment rates with ixekizumab after withdrawal of therapy in patients with axial spondyloarthritis: results at week 104 from a randomised placebo-controlled withdrawal study”

    Title: Correspondence on “Recapture and retreatment rates with ixekizumab after withdrawal of therapy in patients with axial spondyloarthritis: results at week 104 from a randomised placebo-controlled withdrawal study”
    To the Editor
    I recently have read with great interest the research paper written by Dr. Landewé et al. entitled “Recapture and retreatment rates with ixekizumab after withdrawal of therapy in patients with axial spondyloarthritis: results at week 104 from a randomised placebo-controlled withdrawal study” published recently in Annals of the Rheumatic Diseases (1). In this study, patients with axial spondyloarthritis in remission who were on ixekizumab were randomised to either continue the treatment or withdraw to placebo. The study compared the rate of occurrence of flare between these two arms and assessed the efficacy of readministration of ixekizumab. This study provided strong evidence regarding treatment discontinuation with ixekizumab in patients with axial spondyloarthritis with a well-developed design and proper sample size; however, there are some points that should be more discussed in the article.
    In the limitation, the authors have reported that they did not use Ankylosing Spondylitis Disease Activity Score (ASDAS) to define whether a patient had a flare or not; however, in the methods section of this article and their previously published article (2) and also in the protocol of COAST-Y (NCT03129100), this composite index, ASDA...

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  • Correspondence on ‘Isolated axial disease in psoriatic arthritis and ankylosing spondylitis with psoriasis’

    With great interest, we have read the article by Timothy et al. exclusively examined the prevalence and differences associated with isolated axial PsA (axPsA) and isolated axial AS with psoriasis.1 To some extent, we agree with the authors that isolated axPsA and isolated axial AS with psoriasis may be two distinct clinical phenotypes. However, we would like to raise a few important issues that need to be addressed.
    First, the definition of patients with axPsA needs to be discussed. Patients with PsA may have only isolated syndesmophytes without sacroiliitis, one study showed that up to a third of all patients with axPsA have spondylitis without sacroiliitis. 2 In this study, patients with axPsA were identified only by the presence of sacroiliitis on radiographs, which was defined as the presence of sacroiliitis ( grade 2 bilateral or  grade 3 unilateral) on sacroiliac joint radiographs, according to the 1984 AS modified New York criteria. However, some patients with axPsA could present with spondylitis alone but without sacroiliitis, who were not included in the study. Therefore, the overall spectrum of axPsA in this study may be underestimated.
    Second, AS patients with psoriasis must be defined with caution. In terms of clinical features, axPsA differs from AS in several ways, most notably in the radiographic patterns of the disease. axPsA shows radiographic features such as asymmetric sacroiliitis, nonmarginal (which includes “chunky” and “comma”), asymmet...

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  • Correspondence on “Stage-specific roles of microbial dysbiosis and metabolic disorders in rheumatoid arthritis” by Cheng et al.

    Cheng et al. recently reported the changes in fecal microbiota and peripheral blood metabolites in patients with rheumatoid arthritis (RA) across four stages of the disease. In addition, they performed 16S rRNA sequencing and identified bacteria in synovial fluid of RA. and successfully isolated and identified many microbes in synovial fluid samples of RA patients at the stage 4 (RAS4). Moreover, substances shaped like bacteria in rod-like or spherical forms were also observed under scanning electron microscopy.1 This is the first time that bacteria were successfully isolated from the synovial fluid of RA and this finding deserves attention.
    First, it is always an interesting question whether bacteria are actually present in the synovial fluid of RA. Up to date, several studies have reported the presence of microbial DNA in joint effusion of RA by 16S rRNA gene sequencing technology (Table 1). However, there is no direct evidence on isolation of bacteria from RA synovial fluid. The synovial fluid is usually sterile, and RA is a kind of chronic non-infectious arthritis induced by autoimmune disorder.2 It was indeed reported that bacteria were found in the synovial fluid of RA, however, this was mainly because of multiple arthroscopic washouts and joint injections. Unfortunately, the history information of repeated arthroscopy or arthrocentesis was missing in RAS4 of which bacteria were isolated from synovial fluid in this article. Thus, it is uncertain if these isolat...

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  • Biologics targeted to skin in psoriasis patients can prevent psoriatic arthritis: killing two birds with one stone?

    The question of whether the use of biologic disease-modifying antirheumatic drugs (bDMARDs) can prevent psoriatic arthritis (PsA) in psoriasis (PsO) patients may be confusing. Some observational studies reported that biologic therapies were associated with a decreased risk of PsA1-2, but other studies did not3-5.
    We read with great interest the recent article published in Annals of the Rheumatic Diseases by Gisondiet and colleagues regarding the impact of biologic therapy on development of PsA1. This study is very interesting and important; however, we would like to share with the authors our perplexities about the conclusions drawn from this report.
    First and foremost, Gisondiet et al identified that treatment with bDMARDs was significantly associated with a lower risk of incident PsA in moderate-to-severe PsO (aHR 0.27, 95%CI 0.11 to 0.66) compared with nb-UVB phototherapy. However, we noted that this association was reversed if HRs were calculated using propensity score matching (PSM) data (aHR 2.07, 95%CI 0.87 to 4.93, Supplementary Table 2), and the explanation provided by the authors may be related to the limited sample size after PSM. In fact, these well-known risk factors, including age, scalp psoriasis, nail psoriasis, psoriasis duration, and family history of PsA, showed larger effect values after PSM even with smaller sample sizes. Thus, we reckon that, rather than a smaller sample size, this discrepancy is more likely the consequence of the pre-matc...

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