481 e-Letters

  • Bimekizumab's Remarkable Potential in Transforming Axial Spondyloarthritis

    Dear Editor,
    I am writing to draw your attention to the profound implications of the article by Baraliakos et al. (1). This study is a beacon of hope for individuals living with axial spondyloarthritis (axSpA) and underscores the potential of Bimekizumab (BKZ) as a transformative treatment.
    The study's findings reveal that BKZ, a monoclonal antibody inhibiting interleukin (IL)-17A and IL-17F, has exhibited unparalleled efficacy in patients with both non-radiographic (nr-) and radiographic (r-) axSpA. These results are not just promising; they are monumental. The study demonstrates that improvements achieved with BKZ at Week 16 persist to Week 52. Key metrics, including Assessment of SpondyloArthritis International Society ≥40% response, Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels, and MRI inflammation of the sacroiliac joints/spine, continued to improve in patients who received BKZ.
    Of equal significance is the fact that patients who transitioned from a placebo to BKZ at Week 16 experienced comparable results to those who received BKZ from the outset. This underlines the sustained efficacy of BKZ and its potential to improve the quality of life for axSpA patients. Furthermore, BKZ demonstrated the ability to reduce objective measures of inflammation, such as MRI scores and hs-CRP levels, consistently across treatment groups. These reductions correlate with improvements in patient-reported outcomes, includ...

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  • Duration of Rituximab maintenance in ANCA-associated vasculitis

    We read with great interest the pooled analysis of the MAINRITSAN trials and believe that certain study conclusions and inferences warrant further discussion and clarification (1).

    Since the MAINRITSAN trials represent the largest body of Class I evidence regarding rituximab maintenance in AAV, any inference drawn from them needs to be carefully worded since it is likely to be translated into clinical practice as standard-of-care with immediate effect. In this light, we believe that the authors’ conclusion that “extending RTX to 36 months does not appear to reduce the long- term relapse rate compared with 18 months of fixed- dose RTX and should probably only be considered in patients at high risk of relapse” should be a bit guarded for the following reasons.

    As pointed out previously by us after the publication of MAINRITSAN-3, ANCA-associated vasculitides warrant long-term maintenance therapy with rituximab (at least for 4 years as opined by the MAINRITSAN-3 authors in response) (2,3). However, the conclusions of the current pooled analysis seem rather contradictory and in fact, counterintuitive. A closer look at the Kaplan-Meier survival curve for overall relapses (Figure 2B of the pooled analysis) shows that the plot of the 36-month fixed/fixed RTX seems to clearly diverge from the other groups including the 18-month fixed RTX after month 30 (when the effect of the last dose of RTX is expected to have worn off), a fact which is reinforced by the obtained...

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    Dear Editor,

    I am writing to express our particular interest in the article "Rheuma-VOR study: optimising healthcare of rheumatic diseases by multiprofessional coordinating centres" by Dreher et al (1), where a prospective multicenter study was conducted with the implementation of an early referral strategy that succeeded in reducing the rheumatological medical care waiting time to 6.6 months, compared to the usual reference time of 27.7 months.

    It is undeniable that the delay in referring patients with suspected rheumatoid arthritis remains a challenge. In a report conducted at a second-level hospital in Mexico, we evaluated 206 referrals to the rheumatology service from the primary level of care. We found an average of 28.2 (SD 46.9) months elapsed from the onset of symptoms to rheumatological evaluation (2).

    In contrast, the study by van Nies et al conducted in the Netherlands established an early referral clinic, which managed to reduce the referral time from the general practitioner to 2 weeks and the total time elapsed from the onset of symptoms to rheumatological care to 10.6 weeks. 59% (n=162) received attention within the first 12 weeks after the onset of symptoms (3).

    Within the referral system at the Mexican Social Security Institute in Monterrey, Mexico, we implemented an early referral program with the aim of reducing referral times. The program was applied to patients evaluated at the primary level who presented hand arth...

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  • Discrepancy in Patient and Control Numbers in the Article "Proteomic and Genomic Profiling of Plasma Exosomes from Patients with Ankylosing Spondylitis"

    Dear Editors of the Annals of the Rheumatic Diseases,

    I am writing to bring to your attention a discrepancy I have identified in Table 1 of the article titled "Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis" published in your esteemed journal. The error pertains to the numbers of patients and controls listed in the table, which do not align with the description provided in the "Patient and public involvement" section of the article's MATERIALS AND METHODS.

    This inconsistency has the potential to mislead readers and may impact their understanding and interpretation of the study's findings. After careful consideration and verification, it is evident that the data provided in Table 1 should accurately reflect the numbers described in the "Patient and public involvement" section. I respectfully recommend rectifying the table to ensure alignment with the stated patient and public involvement.

    I appreciate the opportunity provided by the Annals of the Rheumatic Diseases for open discourse, which serves to uphold the integrity and accuracy of scientific research. My intention is to contribute to the improvement of the published work, ensuring its accuracy and reliability. Addressing this discrepancy will further enhance the quality of the published work and provide readers with the precise and reliable information they seek.

    Thank you for your attention to this matter...

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  • Response to "Treat-to-target recommendations on giant cell arteritis and polymyalgia rheumatica" by Dejaco et al.

    We read the “Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica” with great interest [1], as it provides a much-needed and updated approach to the management of polymyalgia rheumatica (PMR), a relatively common condition with significant disease burden. As indicated by the Research Agenda listed in the paper, there remains much to be learned about the clinical management of PMR. Specifically, we would like to emphasize the gaps in research regarding the physiological and clinical nuances in optimizing corticosteroid (CS) tapering.

    By adapting a T2T approach, clinicians can strive towards the ideal goal of minimizing both symptom flare-ups and cumulative steroid exposure, with significant risk due to steroid usage. As this provides a qualitative guideline, the challenge is to determine an optimal tapering rate. Steroid tapering for PMR has often been recognized as an “art” that can be unpredictable and rarely has a smooth trajectory. A meta-analysis showed that the pooled relapse rate at 1 year from treatment initiation was 43% [2].

    Our interest in these unanswered questions came from the personal case study of W.D. (a retired physician) who documented his tapering process. He was treated for a total of almost three years with four flares of PMR, with multiple flares in the third and fourth episodes, and the addition of methotrexate, ultimately resulting in a cumulative total of 9,130 mg of prednisone. This prompted our explorat...

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  • Continued/late glucocorticoid use in rheumatoid arthritis with initial glucocorticoid bridging therapy

    Dear Editor,

    I read the individual patient data metaanalysis by van Ouwerkerk et al [1] on the comparison of long term glucocorticoid use in initial glucocorticoid bridgers and non-bridgers with interest. Other than inevitable limitations such as the absence of randomised trials with low-dose glucocorticoid bridging, per protocol duration and tapering of the bridging glucocorticoid doses, and heterogeneity of disease severity and disease-modifying anti-rheumatic drug (DMARD) use in the comparator arms, which were discussed by the authors, I believe this study had an important and unmentioned limitation on its main conclusion: the similarity of late glucocorticoid use after bridging was completed in bridgers and non-bridgers.

    The authors argued that after a planned ending of the bridging period, glucocorticoid use was higher in the initial bridgers compared to non-bridgers only 12 months after randomisation and no longer significantly higher at 18 and 24 months. The pooled frequency of glucocorticoid use in bridgers vs. non-bridgers were 21% vs. 6% corresponding to an OR of 3.27 (1.06-10.08) [1]. The frequencies were not reported but represented in a figure for the months 18 and 24. The reported ORs were 1.6 (0.46-5.6) and 1.7 (0.58-4.97) for the months 18 and 24. The risk ratios, which looked like at least 1.5 if not more particularly for the month 24 according to the figure, were not found to be significant. However, to be able to confidently (such as with 8...

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  • Correspondence on “EULAR recommendations for the management of systemic lupus erythematosus: 2023 update” by “Fanouriakis A, et al”

    Correspondence on “EULAR recommendations for the management of systemic lupus erythematosus: 2023 update” by “Fanouriakis A, et al”

    I read the recently updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) with great interest.[1] In recommendation 8, voclosporine was categorized alongside belimumab and tacrolimus. However, I am concerned about recommending voclosporine as an initial induction therapy for active lupus nephritis (LN).
    The effectiveness of voclosporine, when added to a rapid-reduction glucocorticoid regimen and mycophenolate (MMF, typically administered at 2 g/day), has been demonstrated to be superior to placebo.[2] However, it is important to note that this study significantly deviated from the trials involving belimumab or tacrolimus[3, 4] as it included a large number of patients who were refractory to MMF. This indicates that 55% of the participants while taking MMF, met one of the inclusion criteria: a current urine protein creatinine ratio (UPCR) of ≥1·5. These individuals were then randomised to either the placebo or voclosporine group. Patients with these specific characteristics, if placed in the placebo group, would have been reintroduced to MMF, despite its previous ineffectiveness in addressing their lupus nephritis. Therefore, the treatment effect in the placebo group was assumed to be considerably lower. As expected, the efficacy of incorporating voclosporine was observed solely in the patient group...

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  • Comment on the 2023 update of the EULAR recommendations for the management of systemic lupus erythematosus by Fanouriakis, et al

    Dear Editor,

    The 2023 update of the EULAR recommendations for the management of systemic lupus erythematosus (SLE) recommend hydroxychloroquine (HCQ) for all patients with SLE at a target dose of 5 mg/kg real body weight (RBW)/day but also suggest individualizing the regimen in accordance with the risk of flares or retinal toxicity. The updated recommendations also emphasize the importance of non-pharmacological interventions, including the cessation of smoking, which may interfere with the efficacy of antimalarial agents, as seen in patients with cutaneous lupus erythematosus (CLE). 1 However, the evidence on the efficacy of the target dose of 5 mg/kg(RBW)/day and the effect of smoking on SLE is scarce.

    In Japan, HCQ was approved in 2015 after a double-blind randomized clinical trial demonstrated a favorable effect on CLE. The approved dosage was based on 6.5 mg/kg of ideal body weight (IBW), namely, 200 mg/day for IBW ˂46 kg; 200 mg and 400 mg on alternating days for IBW ≥ 46 kg and ˂ 62 kg; and 400 mg/day for IBW ≥62 kg. The steady-state maximum whole blood HCQ level (ng/ml) at these dosages were simulated with 630.3±220.4, 942.7±191.2 and 850.3±174.5, respectively.23 Thereafter, a multicentric, prospective study evaluating the effect of HCQ on SLE and CLE in the real world setting was conducted for post-marketing surveillance in accordance with the Good Post-Marketing Study ordinance of the Ministry of Health, Labour and Welfare of Japan. 4

    The ob...

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  • Correspondence on "EULAR recommendations for the management of systemic lupus erythematosus: 2023 update" by "Antonis Fanouriakis, et al”"

    We are thrilled and grateful to see an update of the systemic lupus erythematosus (SLE) treatment recommendations after 4 years’ time since 2019. Because of the efforts of a Task Force of world-leading SLE experts, we are now able to follow these useful recommendations in daily clinical practice. In this version, several new ideas to treat SLE come into view. We are now entering the era of biologics, with more on the way, which might significantly change the way we treat SLE. Apart from rituximab, belimumab, and anifrolumab, there is another B cell related biologic, telitacicept, a BLyS/APRIL dual inhibitor, with a successful phase II trial1; larger confirmatory trials are currently underway. As recommended in the version, early diagnosis and treatment are emphasized. The biologics are used earlier than before, not requiring conventional immunosuppresants first; this change is a bit step forward, indicating that early intervention is important.

    The treatment of SLE is like walking on a blade. Balancing the benefits and harms is an art, for which the use of glucocorticoids (GC) is a typical example. I totally agree that the use of GC is only for ‘bridging therapy’ in SLE. But we can expect that, different from the treatment of rheumatoid arthritis (RA), the taper of GC in SLE is not as easy as in RA and the duration will be longer. In this recommendation, it is clearly stated that GC should be taped gradually. However, in terms of the cessation of GC, it is not clear...

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  • Correspondence on “Determination of the most appropriate ACR response definition for contemporary drug approval trials in rheumatoid arthritis”

    With great interest, we have read the recent article by Konzett et al1 on determination of the most powerful American College of Rheumatology (ACR) response definition (ACR20, 50 or 70) between active treatment and placebo in RA trials. In this well-designed study, the authors systematically analyzed the time courses of ACR20, 50 and 70 responses from randomized, double-blind, placebo-controlled, phase II and phase III RA drug approval trials. The conclusion was ACR20 remains the most sensitive discriminator at early time points in the novel therapeutics (bDMARDs and tsDMARDs) placebo-controlled RA trials.

    However, the placebo response seems ignored in the comparison of response trajectories of ACR20, 50 and 70. First, we noticed that the authors showed longitudinal dynamics of different ACR response rates and concluded ACR20 response provided highly sensitive to early treatment effect (Figure 2)1. The “treatment effect” in this case should be the relative effect of treatment compared with placebo ( treatment response - placebo response)2, however, it appears that the mean normalized ACR response rates in Figure 2 relies solely on data from the treatment group, without factoring in the placebo group. The placebo response rate in RA clinical trials has significantly increased in the era of bDMARDs/tsDMARDs3, which has also been confirmed in the supplementary material section 8.21. A substantial placebo response can hinder the ability to discern treatment effects4. Th...

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