Muhammed Abdulkerim Sahin, MD
Research Assistant
İstanbul University-Cerrahpaşa Faculty Of Medicine, İstanbul, TÜRKİYE
ORCID: 0000-0001-8077-8549
E-mail: md.abdulkerim@gmail.com
Yusuf Yazici, MD
Clinical Associate Professor of Medicine
NYU Grossman School of Medicine, New York, NY
ORCID: 0000-0002-7605-5759
E-mail: yusuf.yazici@nyulangone.org
We have read with interest the paper by De Miguel E et al., " Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica" (1). We had a few questions about the prospective nature of the cohort. The authors state that "Demographic, clinical and laboratory baseline data were collected prospectively.” and also that “Follow-up data regarding treatment and occurrence of relapses at months 3, 6, 12, 18 and 24 were retrieved retrospectively.” If this was a prospectively designed study cohort, patients would be continuously enrolled, and let's say 6 months into the start of the study, the initial patients who enrolled in the first weeks of the study would have their month 3 visits likely completed. Why wouldn't the follow up data for the initial patients coming for their month 3 visit, or any patient follow up data, be prospectively planned to be collected at that time, rather than retrospectively collected at a later date? Retrieving...
Muhammed Abdulkerim Sahin, MD
Research Assistant
İstanbul University-Cerrahpaşa Faculty Of Medicine, İstanbul, TÜRKİYE
ORCID: 0000-0001-8077-8549
E-mail: md.abdulkerim@gmail.com
Yusuf Yazici, MD
Clinical Associate Professor of Medicine
NYU Grossman School of Medicine, New York, NY
ORCID: 0000-0002-7605-5759
E-mail: yusuf.yazici@nyulangone.org
We have read with interest the paper by De Miguel E et al., " Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica" (1). We had a few questions about the prospective nature of the cohort. The authors state that "Demographic, clinical and laboratory baseline data were collected prospectively.” and also that “Follow-up data regarding treatment and occurrence of relapses at months 3, 6, 12, 18 and 24 were retrieved retrospectively.” If this was a prospectively designed study cohort, patients would be continuously enrolled, and let's say 6 months into the start of the study, the initial patients who enrolled in the first weeks of the study would have their month 3 visits likely completed. Why wouldn't the follow up data for the initial patients coming for their month 3 visit, or any patient follow up data, be prospectively planned to be collected at that time, rather than retrospectively collected at a later date? Retrieving important treatment and relapse data retrospectively would surely lead to missing and lower quality data.
There is also the issue of a major drop in patient numbers in the subclinical GCA cohort. Seventy-nine patients with subclinical GCA were identified from the mother study (2), but 39 needed to be excluded due to incomplete data, or not meeting the 1-year follow-up criterion. This is half of the patients. How many were due to missing data and what was the reason for the missing data if this study was set up as a prospective study with the goal of recruiting unselected patients? This large amount of dropout is not seen in the PMR cohort. What is the authors' explanation for these different dropout rates?
Finally, we have also noted discrepancies in some of the actual data as they are reported in the paper. In the results section of the abstract, it is stated that “Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722).” This is reported as (32.2±15.8 vs 35.5±12.1, p=0.406) in Table 2.
In Table 1, the mean GC dose at baseline for the 50 subclinical GCA/PMR patients is given as 36.6 ± 14.3. Again, in Table 2, when the same 50 patients are divided into those with no relapses compared to those who relapsed, the baseline GC doses are 35.5 ± 12.1 and 32.2 ±15.8 mg, respectively. Both of these means are lower than the combined group means, and it is hard to understand why this would be the case.
In the abstract, it is stated that "Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0 ± 5.2 versus 15.2 ± 7.9 mg daily (p<0.001)". However, these patients at month 3 have different GC doses reported in table 2 (13.4 ± 7.1 vs 18.8 ± 7.5 (p=0.016)). The values reported in the abstract are more consistent with the GC doses at Month 3 for isolated PMR vs subclinical GCA/PMR groups in Table 1, not the subgroups of relapsed vs non-relapsed patients under the subclinical GCA/PMR cohorts.
References
1. De Miguel E, Karalilova R, Macchioni P, Ponte C, Conticini E, Cowley S, Tomelleri A, Monti S, Monjo I, Batalov Z, Klinowski G, Falsetti P, Kane DJ, Campochiaro C, Hočevar A. Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica. Ann Rheum Dis. 2023 Nov 6:ard-2023-224768. doi: 10.1136/ard-2023-224768.
2. De Miguel E, Macchioni P, Conticini E, et al (2023) Prevalence and characteristics of subclinical giant cell arteritis in polymyalgia rheumatica. Rheumatology 63:158–164. https://doi.org/10.1093/rheumatology/kead189
With regard to the article on ‘2023 ACR/EULAR antiphospholipid syndrome classification criteria’ by ‘Medha et al’, we believe that it contains substantial inadequacies in the obstetric domain, which weakens the application of this guideline in the antiphospholipid syndrome classification.
Firstly, on the clinical criteria obstetric domain, the classification arbitrarily divides fetal death into two categories------pregnancy loss between 10 weeks 0 days and 15 weeks 6 days gestation (early fetal death), or between 16 weeks 0 days and 34 weeks 0 days gestation, which has no support from previous consensus to set 16 weeks as a cutoff point1,2. In addition, since the author bestow the same weigh on these two categories, makes the dividing line even more unnecessary. And on top of that, in terms of fetal death, the classification slights to take pregnancy loss beyond 34 weeks of gestation into account. In our dataset of the past 7 years, the incidence of pregnancy loss beyond 34 gestational weeks in all diagnosed obstetric antiphospholipid syndrome associated fetal loss cases is 4.3% (3/70). Also, it is in accordance with other datasets in which include fetal loss beyond 34 gestational weeks as bona fide OAPS patients3. Hence, this particular classification serves no purpose in increasing its specificity, while jeopardizing its sensitivity.
Secondly, the preeclampsia with severe features column fails to include placental abruption4, heart failure5 and He...
With regard to the article on ‘2023 ACR/EULAR antiphospholipid syndrome classification criteria’ by ‘Medha et al’, we believe that it contains substantial inadequacies in the obstetric domain, which weakens the application of this guideline in the antiphospholipid syndrome classification.
Firstly, on the clinical criteria obstetric domain, the classification arbitrarily divides fetal death into two categories------pregnancy loss between 10 weeks 0 days and 15 weeks 6 days gestation (early fetal death), or between 16 weeks 0 days and 34 weeks 0 days gestation, which has no support from previous consensus to set 16 weeks as a cutoff point1,2. In addition, since the author bestow the same weigh on these two categories, makes the dividing line even more unnecessary. And on top of that, in terms of fetal death, the classification slights to take pregnancy loss beyond 34 weeks of gestation into account. In our dataset of the past 7 years, the incidence of pregnancy loss beyond 34 gestational weeks in all diagnosed obstetric antiphospholipid syndrome associated fetal loss cases is 4.3% (3/70). Also, it is in accordance with other datasets in which include fetal loss beyond 34 gestational weeks as bona fide OAPS patients3. Hence, this particular classification serves no purpose in increasing its specificity, while jeopardizing its sensitivity.
Secondly, the preeclampsia with severe features column fails to include placental abruption4, heart failure5 and Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome6 as severe complications in line with other features like pulmonary oedema. Take placental abruption as an example, it has been reported to be a severe feature for OAPS7,8. Also, it is a consensus that eclampsia is a vital manifestation of placental insufficiency1,9, but this article leaves it out in the obstetric domain.
Lastly, the definition of fetal growth restriction (FGR) is mixed up with that of small for gestational age (SGA). FGR is a pathologic condition in which the fetus fails to reach its biologically based growth potential, while SGA a physiological condition in which infants with birthweights less than 10th percentile for gestational age10. This equivocation could undermine the fidelity and specificity of this classification.
Contributors Concept and writing: CZ, TC and XF. Revising: XF.
Competing interests: None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval This study was approved by the Ethics Committee of West China Second University Hospital.
REFERENCES:
1. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). Journal of Thrombosis and Haemostasis. 2006 Feb;4(2):295–306.
2. Silver RM. Fetal Death. Obstetrics & Gynecology. 2007 Jan;109(1):153–67.
3. Belhocine M, Coutte L, Martin Silva N, Morel N, Guettrot-Imbert G, Paule R, et al. Intrauterine fetal deaths related to antiphospholipid syndrome: a descriptive study of 65 women. Arthritis Research & Therapy. 2018 Nov 6;20(1).
4. Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G, Mercier E, Marchetti T, Balducchi JP ., et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood. 2013 Nov 7;123(3):404–13.
5. Atsushi S, Hiroshi S, Yasuyuki T, Chikara M Hidenori Y, Seibu M, et al. [Peripartum cardiomyopathy with antiphospholipid antibody: a case report]. J Cardiol. 2006 May; 47(5): 261-6.
6. Clark CA, Davidovits J, Spitzer KA, Laskin CA. The lupus anticoagulant: results from 2257 patients attending a high-risk pregnancy clinic. Blood [Internet]. 2013 Jul 18 [cited 2023 Apr 9];122(3):341–7; quiz 466.
7. Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, Sáez-Comet L, Lefkou E, Mekinian A, et al. Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry. Rheumatology. 2019 Oct 3;
8. Soh MC, Pasupathy D, Gray G, Nelson-Piercy C. Persistent antiphospholipid antibodies do not contribute to adverse pregnancy outcomes. Rheumatology. 2013 May 16;52(9):1642–7.
9. Wang Y, Niu J, Wang J, Ye R, Zhao Y. Patient with antiphospholipid syndrome accompanied by pre-eclampsia who developed hellp syndrome and eclampsia after abortion. Chinese Medical Journal [Internet]. 2012 Nov 1 [cited 2024 Feb 22];125(22):4142
10. ACOG Practice Bulletin No. 204. Obstetrics & Gynecology. 2019 Feb;133(2):e97–109.
I read the report by Zonozoi et al. with great interest (1). It is of particular importance to note that while the intent of this trial was to compare biomarker-driven strategies for maintenance of remission in ANCA-associated vasculitis, the design of the trial resulted in a much different outcome. Given the result that more than seven times as much rituximab was given to patients in the B-cell biomarker arm relative to the autoantibody biomarker arm, the practical and main result of this trial is a comparison of continuing or discontinuing rituximab after ~2 years of remission on rituximab. Since the MAINRITSAN3 trial has shown that discontinuing rituximab after ~2 years of remission has a large impact on relapse rates, a trial that effectively compares biomarkers would need to have similar amounts of rituximab in each arm in order to prevent the result from being dominated by excess or lack of rituximab (2). In concordance, the results of the current trial are nearly identical to those of MAINRITSAN3, with a 4% relapse rate in the heavily treated arms of both trials, and 21% and 26% relapse rate with little or no treatment, respectively. As it turns out, since doses of rituximab were 1000 mg in the current trial and 500 mg in MAINRITSAN3, the total dose of rituximab during the maintenance phase of the heavily treated arms were almost identical for both trials as well.
In this study, only a minority of clinical relapses (no more than 6 of 20 patients with potent...
I read the report by Zonozoi et al. with great interest (1). It is of particular importance to note that while the intent of this trial was to compare biomarker-driven strategies for maintenance of remission in ANCA-associated vasculitis, the design of the trial resulted in a much different outcome. Given the result that more than seven times as much rituximab was given to patients in the B-cell biomarker arm relative to the autoantibody biomarker arm, the practical and main result of this trial is a comparison of continuing or discontinuing rituximab after ~2 years of remission on rituximab. Since the MAINRITSAN3 trial has shown that discontinuing rituximab after ~2 years of remission has a large impact on relapse rates, a trial that effectively compares biomarkers would need to have similar amounts of rituximab in each arm in order to prevent the result from being dominated by excess or lack of rituximab (2). In concordance, the results of the current trial are nearly identical to those of MAINRITSAN3, with a 4% relapse rate in the heavily treated arms of both trials, and 21% and 26% relapse rate with little or no treatment, respectively. As it turns out, since doses of rituximab were 1000 mg in the current trial and 500 mg in MAINRITSAN3, the total dose of rituximab during the maintenance phase of the heavily treated arms were almost identical for both trials as well.
In this study, only a minority of clinical relapses (no more than 6 of 20 patients with potential relapse; assuming the six who did receive rituximab would have otherwise relapsed) were detected in advance by serological relapse, as indicated by a four- or five-fold increase in ANCA level. Boomsma et al. has shown that low antibody titers had much better sensitivity for predicting relapse without significant loss of specificity (3). A look back at data from the current study may provide insight into whether a lower threshold for an increase in ANCA level might be useful to predict relapses in time for effective intervention.
References:
1. Zonozi R, Cortazar FB, Jeyabalan A, et al. Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial. Ann Rheum Dis 2024;83:351-359. doi: 10.1136/ard-2023-224489
2. Charles P, Perrodeau É, Samson M, et al. Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial. Ann Intern Med 2020;173:179-187. doi: 10.7326/M19-3827
3. Boomsma MM, Stegeman CA, Van Der Leij MJ, et al. Prediction of relapses in Wegener’s granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study. Arthritis & Rheumatism 2000;43:2025–33. doi: 10.1002/1529-0131(200009)43:9<2025::AID-ANR13>3.0.CO;2-O.
We read the article “Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial” with interest as we believe that this may cause a paradigm shift in the way that these patients are managed. However, as Immunologists, we have some reservations with regards to the impact that these changes may have.
The authors report administering much higher doses of rituximab to patients enrolled in the B cell arm of the study, compared to the ANCA arm (mean 3.6g vs 0.5g per person), and the decision to re-introduce rituximab was based on a very low cutoff of ≥10 cells/mm3 (=0.01 x109/L; local reference range >0.1 x109/L). As such, we would expect a much more pronounced immunosuppressive effect in those patients and, not surprisingly, a higher rate of serious infectious adverse events were reported in the B cell arm. More importantly, 2 patient deaths due to COVID-19 were noted in this group, while none in the ANCA arm.
Several similar cases of persistent or fatal COVID-19 infection in patients treated with rituximab have been reported in the literature[1,2]. Severe infectious sequalae due to multiple other viruses have also been reported, including hepatitis B, VZV, CMV, enterovirus, adenovirus, JC virus, BK virus, HPV, HSV and others[3]. A similar pattern emerges in patients with absent B cells due to any other cause, which suggests a key role for peripheral B cells in their development[4].
We read the article “Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial” with interest as we believe that this may cause a paradigm shift in the way that these patients are managed. However, as Immunologists, we have some reservations with regards to the impact that these changes may have.
The authors report administering much higher doses of rituximab to patients enrolled in the B cell arm of the study, compared to the ANCA arm (mean 3.6g vs 0.5g per person), and the decision to re-introduce rituximab was based on a very low cutoff of ≥10 cells/mm3 (=0.01 x109/L; local reference range >0.1 x109/L). As such, we would expect a much more pronounced immunosuppressive effect in those patients and, not surprisingly, a higher rate of serious infectious adverse events were reported in the B cell arm. More importantly, 2 patient deaths due to COVID-19 were noted in this group, while none in the ANCA arm.
Several similar cases of persistent or fatal COVID-19 infection in patients treated with rituximab have been reported in the literature[1,2]. Severe infectious sequalae due to multiple other viruses have also been reported, including hepatitis B, VZV, CMV, enterovirus, adenovirus, JC virus, BK virus, HPV, HSV and others[3]. A similar pattern emerges in patients with absent B cells due to any other cause, which suggests a key role for peripheral B cells in their development[4].
In this study data on the time to B cell repopulation (≥10 cells/mm3) after rituximab are only given for all patients (9.44 months). However, our and others’ experience is that this can take much longer and that patients can end up requiring lifelong immunoglobulin replacement[5,6].
Patients were reported to have stable serum IgG in the B cell arm of this study, but this was improved
in the ANCA arm. However previous studies have identified that up to 38.54% of patients can have hypogammaglobulinaemia post rituximab use[7], and that this is persistent in a significant proportion[8,9]. Even in patients that retain normal IgG levels, poor responses to vaccination may remain due to low peripheral B cell numbers.
We would recommend, as a minimum, to carefully monitor the infection history and the immunoglobulin levels of patients that receive this treatment, in order to prevent these problems.
References
1 Choi B, Choudhary MC, Regan J, et al. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. New England Journal of Medicine. 2020;383:2291–3.
2 Furlan A, Forner G, Cipriani L, et al. COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge. Front Immunol. 2021;12:763412.
3 Grammatikos A, Donati M, Johnston SL, et al. Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies . Frontiers in Immunology . 2021;12:3454. https://www.frontiersin.org/article/10.3389/fimmu.2021.731643
4 Grammatikos A, Moghaddas F, Reeve H, et al. Low circulating B cells in immunocompromised individuals are linked to poorer antibody responses to vaccines and a predisposition to viral infections. Journal of Allergy and Clinical Immunology: Global. Published Online First: 22 September 2022. doi: 10.1016/J.JACIG.2022.07.008
5 Patel PD, Rubinstein A. B Cell Reconstitution Following Rituximab in Autoimmune Disorders. Journal of Allergy and Clinical Immunology. 2012;129:AB215.
6 Sarantopoulos S, Stevenson KE, Kim HT, et al. Recovery of B-cell homeostasis after rituximab in chronic graft-versus-host disease. Blood. 2011;117:2275.
7 Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk. 2013;13:106–11.
8 Makatsori M, Kiani-Alikhan S, Manson AL, et al. Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. QJM. 2014;107:821–8.
9 Labrosse R, Barmettler S, Derfalvi B, et al. Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients. J Allergy Clin Immunol. 2021;148:523-532.e8.
I am writing to submit a formal review and feedback on the article titled "Comparison of the Effect of Golimumab Monotherapy vs. Golimumab in Combination with NSAIDs on Radiographic Progression in Axial Spondyloarthritis: The CONSUL Trial"(1) authored by Proft et al. This communication aims to provide constructive insights into the methodology of the study.
The utilization of a randomized controlled trial (RCT) design is a commendable strength of the research, facilitating a robust comparison between treatment groups. The inclusion of patients at high risk for progression is also noteworthy, enhancing the study's relevance to a population where intervention effects are of particular importance.
However, a critical examination of the study's methodology reveals certain considerations that warrant attention. The absence of blinding for both patients and investigators introduces the potential for bias in reporting subjective outcomes. This lack of blinding(2), coupled with the uneven distribution of prior biologic Disease-Modifying Anti-Rheumatic Drug (bDMARD) use between groups at baseline, necessitates cautious interpretation of treatment effects.(3)
Furthermore, the relatively modest sample size (n=109) poses limitations on the statistical power of the study, potentially affecting the generalizability of its findings. Acknowledging that results from this specific population may not universally extend to broader axial Spondyloarthrit...
I am writing to submit a formal review and feedback on the article titled "Comparison of the Effect of Golimumab Monotherapy vs. Golimumab in Combination with NSAIDs on Radiographic Progression in Axial Spondyloarthritis: The CONSUL Trial"(1) authored by Proft et al. This communication aims to provide constructive insights into the methodology of the study.
The utilization of a randomized controlled trial (RCT) design is a commendable strength of the research, facilitating a robust comparison between treatment groups. The inclusion of patients at high risk for progression is also noteworthy, enhancing the study's relevance to a population where intervention effects are of particular importance.
However, a critical examination of the study's methodology reveals certain considerations that warrant attention. The absence of blinding for both patients and investigators introduces the potential for bias in reporting subjective outcomes. This lack of blinding(2), coupled with the uneven distribution of prior biologic Disease-Modifying Anti-Rheumatic Drug (bDMARD) use between groups at baseline, necessitates cautious interpretation of treatment effects.(3)
Furthermore, the relatively modest sample size (n=109) poses limitations on the statistical power of the study, potentially affecting the generalizability of its findings. Acknowledging that results from this specific population may not universally extend to broader axial Spondyloarthritis (axSpA) populations or non-responders to golimumab is crucial.(4)
The absence of blinding(5) for adverse events and the allowance of NSAID use in the monotherapy group introduce complexities(6) that may impact the accurate interpretation of adverse events and the isolated assessment of the golimumab effect on radiographic progression.
In conclusion, while the CONSUL Trial contributes valuable insights into the comparison of Golimumab monotherapy and its combination with NSAIDs, it is imperative to address these noted limitations for a more comprehensive understanding of the study's implications for clinical practice.
Thank you for considering this formal review. I believe a meticulous examination of these points will enhance the scientific discourse surrounding this significant research.
Sincerely,
I-Han, Cheng, MD
Chung Shan Medical University
Taichung, Taiwan
James Cheng-Chung Wei, MD, PhD
Department of Allergy, Immunology & Rheumatology
Chung Shan Medical University Hospital
Taichung, Taiwan
1. Proft F, Torgutalp M, Muche B, Rios Rodriguez V, Listing J, Protopopov M, et al. Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial. Ann Rheum Dis. 2024.
2. Forbes D. Blinding: an essential component in decreasing risk of bias in experimental designs. Evid Based Nurs. 2013;16(3):70-1.
3. Fleischmann R. Biologic disease-modifying anti-rheumatic drugs and kinase inhibitors: differences in efficacy and safety in rheumatoid arthritis. Clin Rheumatol. 2021;40(11):4369-72.
4. Gentles SJ, Charles C, Nicholas DB, Ploeg J, McKibbon KA. Reviewing the research methods literature: principles and strategies illustrated by a systematic overview of sampling in qualitative research. Syst Rev. 2016;5(1):172.
5. Moustgaard H, Clayton GL, Jones HE, Boutron I, Jorgensen L, Laursen DRT, et al. Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study. BMJ. 2020;368:l6802.
6. Toussirot E, Vauchy C, Binda D, Michel F. Golimumab in radiographic and nonradiographic axial spondyloarthritis: a review of clinical trials. Drug Des Devel Ther. 2016;10:2087-94.
We read with great interest the article by Peng et al [1]. Here, the authors demonstrate that immunosuppressive agents with or without low-dose steroids used during the maintenance phase decrease the rate of relapse. Consistent with the literature, serum IgG4 [2–5], total IgE levels [2] and eosinophil ratio [2,4,6] were found to be associated with relapse. We are interested to know if other factors reported in the literature, such as the number of organs involved [3,4,7] and the clinical phenotype according to latent class analysis (as described in Lanzillotta et al. [8]) are associated with an increased risk of relapse in this study.
One point not highlighted in the study is that while approximately half of the patients in Group 1 (withdrawal of both steroid and immunosuppressives) experienced a relapse after 18 months, the other half did not. This finding raises important questions about determining the optimal length of treatment and timing of treatment withdrawal. Low-dose steroids or immunosuppressive agents are recommended for maintaining remission in IgG4-RD [9]. However, the duration of remission maintenance is unknown. We are interested to know which factors are associated with continued remission in steroid and immunosuppressive withdrawal group, which may guide future studies.
References
1. Peng L, Nie Y, Zhou J, et al. Withdrawal of immunosuppressants and low-dose steroids in patients with stable IgG4-RD (WInS IgG4-RD): an investigator-initi...
We read with great interest the article by Peng et al [1]. Here, the authors demonstrate that immunosuppressive agents with or without low-dose steroids used during the maintenance phase decrease the rate of relapse. Consistent with the literature, serum IgG4 [2–5], total IgE levels [2] and eosinophil ratio [2,4,6] were found to be associated with relapse. We are interested to know if other factors reported in the literature, such as the number of organs involved [3,4,7] and the clinical phenotype according to latent class analysis (as described in Lanzillotta et al. [8]) are associated with an increased risk of relapse in this study.
One point not highlighted in the study is that while approximately half of the patients in Group 1 (withdrawal of both steroid and immunosuppressives) experienced a relapse after 18 months, the other half did not. This finding raises important questions about determining the optimal length of treatment and timing of treatment withdrawal. Low-dose steroids or immunosuppressive agents are recommended for maintaining remission in IgG4-RD [9]. However, the duration of remission maintenance is unknown. We are interested to know which factors are associated with continued remission in steroid and immunosuppressive withdrawal group, which may guide future studies.
References
1. Peng L, Nie Y, Zhou J, et al. Withdrawal of immunosuppressants and low-dose steroids in patients with stable IgG4-RD (WInS IgG4-RD): an investigator-initiated, multicentre, open-label, randomised controlled trial. Ann Rheum Dis. 2024;ard-2023-224487.
2. Wallace ZS, Mattoo H, Mahajan VS, et al. Predictors of disease relapse in IgG4-related disease following rituximab. Rheumatol Oxf Engl. 2016;55:1000–8.
3. Sasaki T, Akiyama M, Kaneko Y, et al. Risk factors of relapse following glucocorticoid tapering in IgG4-related disease. Clin Exp Rheumatol. 2018;36 Suppl 112:186–9.
4. Peng Y, Li JQ, Zhang PP, et al. Clinical outcomes and predictive relapse factors of IgG4-related disease following treatment: a long-term cohort study. J Intern Med. 2019;286:542–52.
5. hoi SJ, Ahn SM, Oh JS, et al. Serum IgG4 level during initial treatment as a predictor of relapse in IgG4-related disease. PloS One. 2023;18:e0282852.
6. Lu H, Teng F, Zhang P, et al. Differences in clinical characteristics of IgG4-related disease across age groups: a prospective study of 737 patients. Rheumatol Oxf Engl. 2021;60:2635–46.
7. Sekiguchi H, Horie R, Kanai M, et al. IgG4-Related Disease: Retrospective Analysis of One Hundred Sixty-Six Patients. Arthritis Rheumatol Hoboken NJ. 2016;68:2290–9.
8. Lanzillotta M, Campochiaro C, Mancuso G, et al. Clinical phenotypes of IgG4-related disease reflect different prognostic outcomes. Rheumatol Oxf Engl. 2020;59:2435–42.
9. Maritati F, Peyronel F, Vaglio A. IgG4-related disease: a clinical perspective. Rheumatol Oxf Engl. 2020;59:iii123–31.
The authors report that AS is associated with an increased mortality, more so among the females (1). Their observations further strengthen the recent understanding that women are not so lucky (2) after all, when they acquire AS. However, we would like to point out to a neglected point in the current report, an issue related to the proposed sex differences in the risk of death.
The mean age of entry of AS patients into this work was 44 years. On the other hand, we know that AS usually starts well before age 30 and according to one study, at a median age of 25 for males and 28 for females (3). Thus, most of the patients in the current report had AS years before entering this study. Therefore, the current report really concerns the fate of AS patients after quite a number of years of disease duration. A previous study about mortality in AS had shown that males and females had a similar survival after disease onset for about a decade after which the decrease in male survival became apparent. On the other hand, it took 35 years from disease onset when the female survival began to decrease (4). It follows that the design of the current work does not allow us to assess the survival of AS from the time of disease onset.
Finally, we surely agree with the authors that more work is needed to assess the proposed increased mortality among women with AS.
We read with great interest the study by Zonozi and colleagues, which presented the outcomes of a randomized trial comparing rituximab dosing strategies for maintaining remission in ANCA vasculitis [1]. The study proposed that rituximab dosed for B-cell repopulation results in fewer clinical relapses than when dosed for a rise in ANCA level. While acknowledging the valuable contribution of this study, we would like to express a few concerns related to methodology.
First, the authors chose to evaluate B-cell repopulation by assessing CD20-positive B-cell levels in peripheral blood. This deviation from the conventional approach of assessing CD19-positive B-cell levels, as seen in prior studies [2,3], prompts inquiries about the reasoning behind selecting CD20 as a marker for repopulation. This is particularly important considering its role in the rituximab dosing strategy within the B-cell arm.
Second, the study design suggests a dosage of 1gm in the B-cell arm for B-cell repopulation and 2gm, typically a remission induction dose in the ANCA arm, for serological flare. This differs from the usual practise of 500mg observed in MAINRITSAN2 and MAINRITSAN3 trials for maintenance of remission, and it would be beneficial to understand the reasoning behind this choice within the context of this study [2,3].
Third, a study by Thiel and colleagues demonstrated a significantly prolonged duration of B-cell depletion following rituximab treatmen...
We read with great interest the study by Zonozi and colleagues, which presented the outcomes of a randomized trial comparing rituximab dosing strategies for maintaining remission in ANCA vasculitis [1]. The study proposed that rituximab dosed for B-cell repopulation results in fewer clinical relapses than when dosed for a rise in ANCA level. While acknowledging the valuable contribution of this study, we would like to express a few concerns related to methodology.
First, the authors chose to evaluate B-cell repopulation by assessing CD20-positive B-cell levels in peripheral blood. This deviation from the conventional approach of assessing CD19-positive B-cell levels, as seen in prior studies [2,3], prompts inquiries about the reasoning behind selecting CD20 as a marker for repopulation. This is particularly important considering its role in the rituximab dosing strategy within the B-cell arm.
Second, the study design suggests a dosage of 1gm in the B-cell arm for B-cell repopulation and 2gm, typically a remission induction dose in the ANCA arm, for serological flare. This differs from the usual practise of 500mg observed in MAINRITSAN2 and MAINRITSAN3 trials for maintenance of remission, and it would be beneficial to understand the reasoning behind this choice within the context of this study [2,3].
Third, a study by Thiel and colleagues demonstrated a significantly prolonged duration of B-cell depletion following rituximab treatment in ANCA vasculitis, specifically around 21 months in GPA/MPA compared to rheumatoid arthritis and connective tissue diseases, as measured by CD19 positive B-cells [4]. This contrasts with the current study's findings, where the median time to B-cell repopulation was reported as 9.44 months using CD20-positive B-cells measured every 3 months. This approach resulted in a higher mean cumulative dose of 3.6gm per person in the B-cell arm compared to a mean of 0.5gm per person in the ANCA arm. Considering these differences, whether the lower relapse rate observed in the B-cell arm could be attributed to the higher cumulative dose?
Moreover, study conducted by Delestre et al. indicated that the extension of rituximab maintenance to 36 months did not demonstrate a reduction in the relapse rate when compared to an 18-month fixed rituximab regimen [5]. This observation was derived from a pooled analysis of the MAINRITSAN2 and MAINRITSAN3 trials [2,3].
Given these findings, it prompts consideration of whether this study design could be deemed applicable for patients who have undergone 18 months of fixed rituximab maintenance and we agree with the authors, that further exploration is required for an effective and safe remission maintenance strategy.
Conflict of Interest: None
References:
1. Zonozi R, Cortazar FB, Jeyabalan A, Sauvage G, Nithagon P, Huizenga NR, Rosenthal JM, Sipilief A, Cosgrove K, Laliberte KA, Rhee EP, Pendergraft WF 3rd, Niles JL. Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial. Ann Rheum Dis. 2023, PMID: 38123922
2. Charles P, Terrier B, Perrodeau É, Cohen P, Faguer S, Huart A, et al. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis. 2018 ;77(8):1143–9
3. Charles P, Perrodeau É, Samson M, Bonnotte B, Néel A, Agard C, et al. Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial. Ann Intern Med. 2020 ;173(3):179–87
4. Thiel J, Rizzi M, Engesser M, Dufner AK, Troilo A, Lorenzetti R, et al. B-cell repopulation kinetics after rituximab treatment in ANCA-associated vasculitides compared to rheumatoid arthritis, and connective tissue diseases: a longitudinal observational study on 120 patients. Arthritis Res Ther. 2017 ;19(1):101
5. Delestre F, Charles P, Karras A, Pagnoux C, Néel A, Cohen P, et al. Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials. Ann Rheum Dis. 2024 ;83(2):233–41
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.
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.
Dear Editors:
We read with interest the article by Moulin et al. entitled ‘Counteracting tryptophan metabolism alterations as a new therapeutic strategy for rheumatoid arthritis’.1 Alterations in tryptophan (Trp) metabolism have been documented in the context of rheumatoid arthritis (RA). The aim of this study was to ascertain whether these alterations contribute to the development of RA and can be regarded as potential therapeutic targets. Based on the authors' findings, both preclinical and clinical data suggest that modifications in Trp metabolism actively contribute to the pathogenesis of RA and may represent a novel therapeutic approach.
Following a comprehensive analysis of the article, we have identified an error that requires further investigation and rectification. According to the data presented in Table 1, it is apparent that within the ESPOIR cohort, 45 individuals (77.5%) out of the 574 patients are identified as female. However, it is imperative to acknowledge that the accurate representation should indicate that a total of 445 individuals (77.5%) out of the 574 patients are indeed female.
Nevertheless, we would like to express our gratitude to the authors for shedding light on the involvement of Trp metabolism alterations in the pathogenesis of RA and proposing it as a potential novel therapeutic avenue.
Reference
1. Moulin D, Millard M, Taïeb M, et al. Counteracting tryptophan metabolism alterations as a new therapeutic s...
Dear Editors:
We read with interest the article by Moulin et al. entitled ‘Counteracting tryptophan metabolism alterations as a new therapeutic strategy for rheumatoid arthritis’.1 Alterations in tryptophan (Trp) metabolism have been documented in the context of rheumatoid arthritis (RA). The aim of this study was to ascertain whether these alterations contribute to the development of RA and can be regarded as potential therapeutic targets. Based on the authors' findings, both preclinical and clinical data suggest that modifications in Trp metabolism actively contribute to the pathogenesis of RA and may represent a novel therapeutic approach.
Following a comprehensive analysis of the article, we have identified an error that requires further investigation and rectification. According to the data presented in Table 1, it is apparent that within the ESPOIR cohort, 45 individuals (77.5%) out of the 574 patients are identified as female. However, it is imperative to acknowledge that the accurate representation should indicate that a total of 445 individuals (77.5%) out of the 574 patients are indeed female.
Nevertheless, we would like to express our gratitude to the authors for shedding light on the involvement of Trp metabolism alterations in the pathogenesis of RA and proposing it as a potential novel therapeutic avenue.
Reference
1. Moulin D, Millard M, Taïeb M, et al. Counteracting tryptophan metabolism alterations as a new therapeutic strategy for rheumatoid arthritis. Ann Rheum Dis 2023;Epub ahead of print.
Muhammed Abdulkerim Sahin, MD
Research Assistant
İstanbul University-Cerrahpaşa Faculty Of Medicine, İstanbul, TÜRKİYE
ORCID: 0000-0001-8077-8549
E-mail: md.abdulkerim@gmail.com
Yusuf Yazici, MD
Clinical Associate Professor of Medicine
NYU Grossman School of Medicine, New York, NY
ORCID: 0000-0002-7605-5759
E-mail: yusuf.yazici@nyulangone.org
We have read with interest the paper by De Miguel E et al., " Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica" (1). We had a few questions about the prospective nature of the cohort. The authors state that "Demographic, clinical and laboratory baseline data were collected prospectively.” and also that “Follow-up data regarding treatment and occurrence of relapses at months 3, 6, 12, 18 and 24 were retrieved retrospectively.” If this was a prospectively designed study cohort, patients would be continuously enrolled, and let's say 6 months into the start of the study, the initial patients who enrolled in the first weeks of the study would have their month 3 visits likely completed. Why wouldn't the follow up data for the initial patients coming for their month 3 visit, or any patient follow up data, be prospectively planned to be collected at that time, rather than retrospectively collected at a later date? Retrieving...
Show MoreWith regard to the article on ‘2023 ACR/EULAR antiphospholipid syndrome classification criteria’ by ‘Medha et al’, we believe that it contains substantial inadequacies in the obstetric domain, which weakens the application of this guideline in the antiphospholipid syndrome classification.
Show MoreFirstly, on the clinical criteria obstetric domain, the classification arbitrarily divides fetal death into two categories------pregnancy loss between 10 weeks 0 days and 15 weeks 6 days gestation (early fetal death), or between 16 weeks 0 days and 34 weeks 0 days gestation, which has no support from previous consensus to set 16 weeks as a cutoff point1,2. In addition, since the author bestow the same weigh on these two categories, makes the dividing line even more unnecessary. And on top of that, in terms of fetal death, the classification slights to take pregnancy loss beyond 34 weeks of gestation into account. In our dataset of the past 7 years, the incidence of pregnancy loss beyond 34 gestational weeks in all diagnosed obstetric antiphospholipid syndrome associated fetal loss cases is 4.3% (3/70). Also, it is in accordance with other datasets in which include fetal loss beyond 34 gestational weeks as bona fide OAPS patients3. Hence, this particular classification serves no purpose in increasing its specificity, while jeopardizing its sensitivity.
Secondly, the preeclampsia with severe features column fails to include placental abruption4, heart failure5 and He...
I read the report by Zonozoi et al. with great interest (1). It is of particular importance to note that while the intent of this trial was to compare biomarker-driven strategies for maintenance of remission in ANCA-associated vasculitis, the design of the trial resulted in a much different outcome. Given the result that more than seven times as much rituximab was given to patients in the B-cell biomarker arm relative to the autoantibody biomarker arm, the practical and main result of this trial is a comparison of continuing or discontinuing rituximab after ~2 years of remission on rituximab. Since the MAINRITSAN3 trial has shown that discontinuing rituximab after ~2 years of remission has a large impact on relapse rates, a trial that effectively compares biomarkers would need to have similar amounts of rituximab in each arm in order to prevent the result from being dominated by excess or lack of rituximab (2). In concordance, the results of the current trial are nearly identical to those of MAINRITSAN3, with a 4% relapse rate in the heavily treated arms of both trials, and 21% and 26% relapse rate with little or no treatment, respectively. As it turns out, since doses of rituximab were 1000 mg in the current trial and 500 mg in MAINRITSAN3, the total dose of rituximab during the maintenance phase of the heavily treated arms were almost identical for both trials as well.
In this study, only a minority of clinical relapses (no more than 6 of 20 patients with potent...
Show MoreWe read the article “Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial” with interest as we believe that this may cause a paradigm shift in the way that these patients are managed. However, as Immunologists, we have some reservations with regards to the impact that these changes may have.
The authors report administering much higher doses of rituximab to patients enrolled in the B cell arm of the study, compared to the ANCA arm (mean 3.6g vs 0.5g per person), and the decision to re-introduce rituximab was based on a very low cutoff of ≥10 cells/mm3 (=0.01 x109/L; local reference range >0.1 x109/L). As such, we would expect a much more pronounced immunosuppressive effect in those patients and, not surprisingly, a higher rate of serious infectious adverse events were reported in the B cell arm. More importantly, 2 patient deaths due to COVID-19 were noted in this group, while none in the ANCA arm.
Several similar cases of persistent or fatal COVID-19 infection in patients treated with rituximab have been reported in the literature[1,2]. Severe infectious sequalae due to multiple other viruses have also been reported, including hepatitis B, VZV, CMV, enterovirus, adenovirus, JC virus, BK virus, HPV, HSV and others[3]. A similar pattern emerges in patients with absent B cells due to any other cause, which suggests a key role for peripheral B cells in their development[4].
...Show MoreI am writing to submit a formal review and feedback on the article titled "Comparison of the Effect of Golimumab Monotherapy vs. Golimumab in Combination with NSAIDs on Radiographic Progression in Axial Spondyloarthritis: The CONSUL Trial"(1) authored by Proft et al. This communication aims to provide constructive insights into the methodology of the study.
The utilization of a randomized controlled trial (RCT) design is a commendable strength of the research, facilitating a robust comparison between treatment groups. The inclusion of patients at high risk for progression is also noteworthy, enhancing the study's relevance to a population where intervention effects are of particular importance.
However, a critical examination of the study's methodology reveals certain considerations that warrant attention. The absence of blinding for both patients and investigators introduces the potential for bias in reporting subjective outcomes. This lack of blinding(2), coupled with the uneven distribution of prior biologic Disease-Modifying Anti-Rheumatic Drug (bDMARD) use between groups at baseline, necessitates cautious interpretation of treatment effects.(3)
Furthermore, the relatively modest sample size (n=109) poses limitations on the statistical power of the study, potentially affecting the generalizability of its findings. Acknowledging that results from this specific population may not universally extend to broader axial Spondyloarthrit...
Show MoreWe read with great interest the article by Peng et al [1]. Here, the authors demonstrate that immunosuppressive agents with or without low-dose steroids used during the maintenance phase decrease the rate of relapse. Consistent with the literature, serum IgG4 [2–5], total IgE levels [2] and eosinophil ratio [2,4,6] were found to be associated with relapse. We are interested to know if other factors reported in the literature, such as the number of organs involved [3,4,7] and the clinical phenotype according to latent class analysis (as described in Lanzillotta et al. [8]) are associated with an increased risk of relapse in this study.
One point not highlighted in the study is that while approximately half of the patients in Group 1 (withdrawal of both steroid and immunosuppressives) experienced a relapse after 18 months, the other half did not. This finding raises important questions about determining the optimal length of treatment and timing of treatment withdrawal. Low-dose steroids or immunosuppressive agents are recommended for maintaining remission in IgG4-RD [9]. However, the duration of remission maintenance is unknown. We are interested to know which factors are associated with continued remission in steroid and immunosuppressive withdrawal group, which may guide future studies.
References
Show More1. Peng L, Nie Y, Zhou J, et al. Withdrawal of immunosuppressants and low-dose steroids in patients with stable IgG4-RD (WInS IgG4-RD): an investigator-initi...
The authors report that AS is associated with an increased mortality, more so among the females (1). Their observations further strengthen the recent understanding that women are not so lucky (2) after all, when they acquire AS. However, we would like to point out to a neglected point in the current report, an issue related to the proposed sex differences in the risk of death.
The mean age of entry of AS patients into this work was 44 years. On the other hand, we know that AS usually starts well before age 30 and according to one study, at a median age of 25 for males and 28 for females (3). Thus, most of the patients in the current report had AS years before entering this study. Therefore, the current report really concerns the fate of AS patients after quite a number of years of disease duration. A previous study about mortality in AS had shown that males and females had a similar survival after disease onset for about a decade after which the decrease in male survival became apparent. On the other hand, it took 35 years from disease onset when the female survival began to decrease (4). It follows that the design of the current work does not allow us to assess the survival of AS from the time of disease onset.
Finally, we surely agree with the authors that more work is needed to assess the proposed increased mortality among women with AS.
Dear Editor,
We read with great interest the study by Zonozi and colleagues, which presented the outcomes of a randomized trial comparing rituximab dosing strategies for maintaining remission in ANCA vasculitis [1]. The study proposed that rituximab dosed for B-cell repopulation results in fewer clinical relapses than when dosed for a rise in ANCA level. While acknowledging the valuable contribution of this study, we would like to express a few concerns related to methodology.
First, the authors chose to evaluate B-cell repopulation by assessing CD20-positive B-cell levels in peripheral blood. This deviation from the conventional approach of assessing CD19-positive B-cell levels, as seen in prior studies [2,3], prompts inquiries about the reasoning behind selecting CD20 as a marker for repopulation. This is particularly important considering its role in the rituximab dosing strategy within the B-cell arm.
Second, the study design suggests a dosage of 1gm in the B-cell arm for B-cell repopulation and 2gm, typically a remission induction dose in the ANCA arm, for serological flare. This differs from the usual practise of 500mg observed in MAINRITSAN2 and MAINRITSAN3 trials for maintenance of remission, and it would be beneficial to understand the reasoning behind this choice within the context of this study [2,3].
Third, a study by Thiel and colleagues demonstrated a significantly prolonged duration of B-cell depletion following rituximab treatmen...
Show MoreDear 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...
Show MoreDear Editors:
We read with interest the article by Moulin et al. entitled ‘Counteracting tryptophan metabolism alterations as a new therapeutic strategy for rheumatoid arthritis’.1 Alterations in tryptophan (Trp) metabolism have been documented in the context of rheumatoid arthritis (RA). The aim of this study was to ascertain whether these alterations contribute to the development of RA and can be regarded as potential therapeutic targets. Based on the authors' findings, both preclinical and clinical data suggest that modifications in Trp metabolism actively contribute to the pathogenesis of RA and may represent a novel therapeutic approach.
Following a comprehensive analysis of the article, we have identified an error that requires further investigation and rectification. According to the data presented in Table 1, it is apparent that within the ESPOIR cohort, 45 individuals (77.5%) out of the 574 patients are identified as female. However, it is imperative to acknowledge that the accurate representation should indicate that a total of 445 individuals (77.5%) out of the 574 patients are indeed female.
Nevertheless, we would like to express our gratitude to the authors for shedding light on the involvement of Trp metabolism alterations in the pathogenesis of RA and proposing it as a potential novel therapeutic avenue.
Reference
Show More1. Moulin D, Millard M, Taïeb M, et al. Counteracting tryptophan metabolism alterations as a new therapeutic s...
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