4 e-Letters

published between 2020 and 2023

  • 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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