Response on “Performance analysis of a deep-learning algorithm to detect the presence of inflammation in MRI of sacroiliac joints in patients with axial spondyloarthritis” by Nicolaes et al.
Dear Editor,
We appreciate the study by Nicolaes et al. for providing valuable insights into the role of deep-learning algorithms in detecting sacroiliac joint (SIJ) inflammation in axial spondyloarthritis (axSpA). Their work demonstrates the potential of AI-assisted imaging in musculoskeletal diagnosis, and they have acknowledged several study limitations, which we will not replicate. Instead, we highlight key areas for further improvement.
First, MRI Positivity Criteria and Diagnostic Accuracy. This study applies the 2009 ASAS MRI criteria, which primarily focus on bone marrow edema (BME). However, the 2016 ASAS update incorporates structural lesions (erosion, sclerosis, fat metaplasia) to improve specificity (1). Integrating these updated criteria in future model training may enhance clinical applicability.
Second, MRI Field Strength and Data Representation. This study predominantly uses 1.5T MRI, with underrepresentation of 3T MRI, which offers better resolution for detecting subtle inflammatory changes (2). Additionally, the inclusion of 1.0T MRI, despite its lower resolution and declining clinical use, may affect model performance. Ensuring a balanced MRI dataset with optimized field strength representation could improve the reliability of AI predictions....
Response on “Performance analysis of a deep-learning algorithm to detect the presence of inflammation in MRI of sacroiliac joints in patients with axial spondyloarthritis” by Nicolaes et al.
Dear Editor,
We appreciate the study by Nicolaes et al. for providing valuable insights into the role of deep-learning algorithms in detecting sacroiliac joint (SIJ) inflammation in axial spondyloarthritis (axSpA). Their work demonstrates the potential of AI-assisted imaging in musculoskeletal diagnosis, and they have acknowledged several study limitations, which we will not replicate. Instead, we highlight key areas for further improvement.
First, MRI Positivity Criteria and Diagnostic Accuracy. This study applies the 2009 ASAS MRI criteria, which primarily focus on bone marrow edema (BME). However, the 2016 ASAS update incorporates structural lesions (erosion, sclerosis, fat metaplasia) to improve specificity (1). Integrating these updated criteria in future model training may enhance clinical applicability.
Second, MRI Field Strength and Data Representation. This study predominantly uses 1.5T MRI, with underrepresentation of 3T MRI, which offers better resolution for detecting subtle inflammatory changes (2). Additionally, the inclusion of 1.0T MRI, despite its lower resolution and declining clinical use, may affect model performance. Ensuring a balanced MRI dataset with optimized field strength representation could improve the reliability of AI predictions.
Finally, Bridging Imaging and Clinical Decision-Making. This study highlights interpretation differences between radiologists and rheumatologists, with radiologists demonstrating higher accuracy in SIJ inflammation detection. Since rheumatologists integrate clinical and laboratory data (e.g., CRP, HLA-B27) in their assessment (3), AI models may benefit from multi-modal integration, enhancing their diagnostic application in clinical practice (4).
In conclusion, Nicolaes et al. present an important contribution to AI-assisted axSpA diagnosis. By incorporating updated MRI criteria, optimizing MRI dataset representation, and integrating clinical considerations, future studies can further strengthen the clinical efficiency of AI in musculoskeletal imaging.
________________________________________
References
1. Lambert RGW, Bakker PAC, van der Heijde D, et al. Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group. Ann Rheum Dis. 2016;75(11):1958–63.
2. Bressem KK, Adams LC, Proft F, et al. Deep learning detects changes indicative of axial spondyloarthritis at MRI of sacroiliac joints. Radiology. 2022;305(3):655–65.
3. Maksymowych WP, Lambert RG, Baraliakos X, et al. Data-driven definitions for active and structural MRI lesions in the sacroiliac joint in spondyloarthritis and their predictive utility. Rheumatology (Oxford). 2021;60(10):4778–89.
4. de Hooge M, van den Berg R, Navarro-Compán V, et al. Magnetic resonance imaging of the sacroiliac joints in the early detection of spondyloarthritis: no added value of gadolinium compared with short tau inversion recovery sequence. Rheumatology (Oxford). 2013;52(7):1220–4.
Sincerely,
Chun-Chieh Wang, MD
National Yang Ming Chiao Tung University
James WEI, MD.,PhD.
Professor, Chung Shan Medical University
We read with great interest the article by Brown et al.,1 who reported that the lower incidence rates of acute anterior uveitis in patients with axial spondyloarthritis receiving bimekizumab (a dual-IL-17A/F inhibitor) than in those not receiving bimekizumab. This study is a valuable addition to the literature. However, we have some concerns that we would like to share with the authors.
First, this study may be suspected of selection bias. Selection bias occurs when the recruiters, that is, those responsible for recruiting or enrolling patients selectively include individuals based on the expected outcome of the next observation allocation.2 In the pooled phase 3 BE MOBILE 1 and 2 double-blind trial, patients treated with placebo had a higher rate of history of uveitis (19.0%) than those treated with bimekizumab (14.9%) at baseline. This could suggest that higher-risk patients may have been enrolled in the group receiving placebo, which could lead to biased estimates of the incidence of uveitis and potentially misleading conclusions.
Second, previous studies have reported a higher risk for incidental uveitis in patients with axial spondyloarthritis who are female, have a family history of uveitis, have a history of uveitis themselves, are HLA-B27 positive, have longer disease duration, have prior TNFi exposure, are older, have a history of smoking, have a history of inflammatory bowel disease, and have higher baseline high-sensitivity C-reactive protein levels....
We read with great interest the article by Brown et al.,1 who reported that the lower incidence rates of acute anterior uveitis in patients with axial spondyloarthritis receiving bimekizumab (a dual-IL-17A/F inhibitor) than in those not receiving bimekizumab. This study is a valuable addition to the literature. However, we have some concerns that we would like to share with the authors.
First, this study may be suspected of selection bias. Selection bias occurs when the recruiters, that is, those responsible for recruiting or enrolling patients selectively include individuals based on the expected outcome of the next observation allocation.2 In the pooled phase 3 BE MOBILE 1 and 2 double-blind trial, patients treated with placebo had a higher rate of history of uveitis (19.0%) than those treated with bimekizumab (14.9%) at baseline. This could suggest that higher-risk patients may have been enrolled in the group receiving placebo, which could lead to biased estimates of the incidence of uveitis and potentially misleading conclusions.
Second, previous studies have reported a higher risk for incidental uveitis in patients with axial spondyloarthritis who are female, have a family history of uveitis, have a history of uveitis themselves, are HLA-B27 positive, have longer disease duration, have prior TNFi exposure, are older, have a history of smoking, have a history of inflammatory bowel disease, and have higher baseline high-sensitivity C-reactive protein levels.3-5 However, the baseline characteristics between the two groups in this study were not fully defined. As the number of patients with a family history of uveitis or a history of inflammatory bowel disease was not available, omitted variable bias may occur due to unmeasured factors.
Despite our concerns regarding the study by Brown et al.,1 we applaud the authors for their commendable work and hope that this study will benefit readers. We look forward to further research on the important topic of low uveitis rates in patients with axial spondyloarthritis treated with medications and hope that early preventive approaches will benefit these patients.
Contributors All authors reviewed the draft and approved the submission of the manuscript.
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.
References:
1. Brown MA, Rudwaleit M, van Gaalen FA, et al. Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials. Ann Rheum Dis 2024;83:1722-30.
2. Neyens T. Did an effect of kidney transplantation on COVID-19 mortality go unnoticed due to selection bias? Transpl Int 2021;34:773-5.
3. Yasmin MR, Islam MN, Pannu ZR, et al. Prevalence and risk factors for uveitis in spondyloarthritis. Int J Rheum Dis 2022;25:517-22..
4. Yaşar Bilge NŞ, Kalyoncu U, Atagündüz P, et al. Uveitis-related Factors in Patients With Spondyloarthritis: TReasure Real-Life Results. Am J Ophthalmol 2021;228:58-64.
5. Cinakli H, Ediboglu ED, Solmaz D, et al. Factors associated with acute anterior uveitis history in patients with axial spondyloarthritis: Results of a longitudinal study. Int J Rheum Dis 2024;27:e15076.
We read with interest the recommendations for diagnosis and management of Still's disease by Fautrel et al[1]. The first overarching principle is that systemic juvenile idiopathic arthritis and adult-onset Still's disease are the same disease[1,2]. The Task Force also emphasized the need for a better understanding of the pathophysiology of Still's disease and its severe or life-threatening manifestations, the first of which is Still's lung disease. However, the recommendations omitted important data from under-represented populations that could have confirmed or disrupted the current understanding of Still's disease. Here, we would like to recall important findings in African Caribbean (AC) patients.
In a population of approximately 750,000, there is a similar incidence of 0.4/100,000 of Still’s disease in AC juveniles and adults, similar to predominantly Caucasian European or North American populations[3–5]. A comparison of the clinical and biological characteristics has shown that the cardinal symptoms of Still's disease, such as joint involvement and inflammatory biology, are similar between children and adults[5]. Diagnostic criteria for children (ILAR) and adults (Yamaguchi and/or Fautrel criteria) were consistent and overlapped in the majority of cases (80%), regardless of age. The therapeutic arsenal used was the same in children and adults, as reported[1,2,5], with minor variations[5]. The results obtained in...
We read with interest the recommendations for diagnosis and management of Still's disease by Fautrel et al[1]. The first overarching principle is that systemic juvenile idiopathic arthritis and adult-onset Still's disease are the same disease[1,2]. The Task Force also emphasized the need for a better understanding of the pathophysiology of Still's disease and its severe or life-threatening manifestations, the first of which is Still's lung disease. However, the recommendations omitted important data from under-represented populations that could have confirmed or disrupted the current understanding of Still's disease. Here, we would like to recall important findings in African Caribbean (AC) patients.
In a population of approximately 750,000, there is a similar incidence of 0.4/100,000 of Still’s disease in AC juveniles and adults, similar to predominantly Caucasian European or North American populations[3–5]. A comparison of the clinical and biological characteristics has shown that the cardinal symptoms of Still's disease, such as joint involvement and inflammatory biology, are similar between children and adults[5]. Diagnostic criteria for children (ILAR) and adults (Yamaguchi and/or Fautrel criteria) were consistent and overlapped in the majority of cases (80%), regardless of age. The therapeutic arsenal used was the same in children and adults, as reported[1,2,5], with minor variations[5]. The results obtained in this cohort confirm in AC patients the principle that Still's disease is the same in juvenile and adult patients.
However, there are important differences compared with data from other ethnic groups.
Firstly, whereas an atypical rash (persistent, urticarial or pruritic) was not found in children, it was 2.5 times more common than the typical rash in adult patients with Still's disease (70% for the atypical rash versus 30% for the typical rash)[3,5,6]. The appearance of an atypical rash is therefore much more common in AC patients than in other ethnic groups and may reflect a greater intrinsic severity of Still’s disease in these patients compared with others[7].
Secondly, lung disease (LD), a major concern in Still's disease, occurs in AC patients in a completely different way than described in the literature and recommendations. It is rare in children (4%) but common in adults, and 30% of AC adult patients with Still's disease have parenchymal lung disease[3,5]. The CT-scan findings are similar to those described, i.e. condensations or ground-glass opacities, but the presentation of LD in this population is original and different from that described. Indeed, the literature and recommendations suggest a possible hypersensitivity to anti-IL1 or anti-IL6, or the hypothesis of cytokine plasticity following blockade of the IL1 or IL6 pathways[1,8–10]. However, all the patients developed LD prior to treatment and, conversely, no LD has been diagnosed after the introduction of these therapies or during follow-up in either the pediatric or adult cohorts. Symptomatic patients improved with the introduction of treatment. Only one patient had macrophagic activation syndrome (MAS) concurrently with LD[3]. Although genetic and molecular analyses were unavailable, the occurrence of LD in AC patients does not corroborate the supposed pathophysiological pathways, which thus remain to be elucidated.
To conclude, Still's disease also appears to be the same disease in juvenile and adult AC patients. However, those patients have peculiarities that challenge the pathophysiological pathways of the cardinal and non-cardinal manifestations of the disease. We believe that the research agenda of the Task Force should be enhanced by the inclusion of an evaluation of differences according to ethnic origin, specifically the inclusion of patients of African descent. There is no doubt that this will lead to a better comprehension of the disease, just as it did for other rheumatic diseases.
References:
1 Fautrel B, Mitrovic S, De Matteis A, et al. EULAR/PReS recommendations for the diagnosis and management of Still’s disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still’s disease. Ann Rheum Dis. 2024;83:1614–27. doi: 10.1136/ard-2024-225851
2 De Matteis A, Bindoli S, De Benedetti F, et al. Systemic juvenile idiopathic arthritis and adult-onset Still’s disease are the same disease: evidence from systematic reviews and meta-analyses informing the 2023 EULAR/PReS recommendations for the diagnosis and management of Still’s disease. Ann Rheum Dis. 2024;83:1748–61. doi: 10.1136/ard-2024-225853
3 De Fritsch E, Louis-Sidney F, Felix A, et al. Epidemiology, characteristics, treatments, and outcomes of adult-onset Still’s disease in Afro-Caribbeans: Results from a population-based study in Martinique, French West Indies. J Autoimmun. 2023;139:103086. doi: 10.1016/j.jaut.2023.103086
4 Felix A, Delion F, Suzon B, et al. Systemic juvenile idiopathic arthritis in French Afro-Caribbean children, a retrospective cohort study. Pediatr Rheumatol. 2022;20:98. doi: 10.1186/s12969-022-00766-8
5 Felix A, De Fritsch E, Delion F, et al. Lifetime clinical presentation of Still’s disease in the Afro-descendant population of the French West Indies. Joint Bone Spine. 2024;105821. doi: 10.1016/j.jbspin.2024.105821
6 Suzon B, Thomas P, De Fritsch E, et al. POS1182 Characteristics of adult-onset still’s disease skin eruption in individuals of african ancestry. Ann Rheum Dis. 2024;83:546. doi: http://dx.doi.org/10.1136/annrheumdis-2024-eular.714
7 Zuelgaray E, Battistella M, Sallé De Chou C, et al. Increased severity and epidermal alterations in persistent versus evanescent skin lesions in adult-onset Still disease. J Am Acad Dermatol. 2018;79:969–71. doi: 10.1016/j.jaad.2018.05.020
9 Binstadt BA, Nigrovic PA. The Conundrum of Lung Disease and Drug Hypersensitivity‐like Reactions in Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2022;74:1122–31. doi: 10.1002/art.42137
10 Saper VE, Ombrello MJ, Tremoulet AH, et al. Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles. Ann Rheum Dis. 2022;81:406–15. doi: 10.1136/annrheumdis-2021-220578
Osteoarthritis (OA) is the most common joint disorder, with an estimated 250 million individuals are currently affected worldwide.1 Unfortunately, current treatments for OA are limited to pain relief and symptom management.2-5 A few studies have evaluated the efficacy of blood flow restriction (BFR) in OA treatment;3 however, the exact effectiveness of BFR in OA remains largely unknown. We read with deep interest a recent article published in this journal by Jacobs et al, who found that incorporating BFR into a traditional exercise program resulted in sustained improvements in pain, symptoms, and functional measures for patients with knee OA (KOA).4 We appreciate the great work performed by the authors; nevertheless, some valuable questions need to be explored further.
First, this study only included a specific subgroup of KOA patients without obesity (body mass index (BMI) ≥ 30 kg/m2) or comorbidities (eg, cardiovascular, neurological, or metabolic conditions). However, OA is closely linked with obesity and comorbidities such as hypertension and diabetes.3, 6 It was reported that subjects with obesity were 6.8 times more likely to develop KOA than normal-weight controls,7 and the level of obesity is directly associated with the clinical consequences of KOA.8 Furthermore, it was found that 67% of OA patients had at least one comorbidity.9 Thus, this study limits the generalizability of the findings to other KOA patients. Since it remains unclear whether obesity and...
Osteoarthritis (OA) is the most common joint disorder, with an estimated 250 million individuals are currently affected worldwide.1 Unfortunately, current treatments for OA are limited to pain relief and symptom management.2-5 A few studies have evaluated the efficacy of blood flow restriction (BFR) in OA treatment;3 however, the exact effectiveness of BFR in OA remains largely unknown. We read with deep interest a recent article published in this journal by Jacobs et al, who found that incorporating BFR into a traditional exercise program resulted in sustained improvements in pain, symptoms, and functional measures for patients with knee OA (KOA).4 We appreciate the great work performed by the authors; nevertheless, some valuable questions need to be explored further.
First, this study only included a specific subgroup of KOA patients without obesity (body mass index (BMI) ≥ 30 kg/m2) or comorbidities (eg, cardiovascular, neurological, or metabolic conditions). However, OA is closely linked with obesity and comorbidities such as hypertension and diabetes.3, 6 It was reported that subjects with obesity were 6.8 times more likely to develop KOA than normal-weight controls,7 and the level of obesity is directly associated with the clinical consequences of KOA.8 Furthermore, it was found that 67% of OA patients had at least one comorbidity.9 Thus, this study limits the generalizability of the findings to other KOA patients. Since it remains unclear whether obesity and comorbidities have an impact on the efficacy of BRF for KOA, we are unsure whether it would be appropriate to conduct a clinical trial of this subgroup of patients to examine the effect of BRF on KOA.
Second, more details on the criteria for patient selection should be provided. Studies found that previous knee injuries including fracture, anterior cruciate ligament injuries, meniscal tear, and/or knee operations were vital risk factors for KOA progression.10 Thus, it is interesting to learn whether there were important differences in these risk factors between the two groups at the baseline. Furthermore, some other confounders, such as the patients’ physical activity level, pain duration, occupation, drinking status, smoking status, etc. may need to be addressed. Is it possible that patients in the control group had lower social status and consequently higher physical workload and higher severity of KOA at the follow-up than the BFR group? In addition, factors that may influence activities of daily living and thus functional performance, such as tendon stiffness and condition of other ligaments, were not addressed.
Third, the dropout rates of the two groups were relatively high (control group: 28.3% (17/60); BFR group: 26.7% (16/60)) and the reasons for dropouts were not addressed in detail. Dropout is a critical source of bias in clinical trials and generally, an acceptable overall dropout rate is considered ≤ 20%.11, 12 Moreover, more patients were lost to follow-up in the control group (n = 8; 13.3%) than the BFR group (n = 3; 5%).13 Patients who were lost to follow-up often had a different prognosis than those who completed the study. For example, some patients in the control group may not return for follow-up because they had less pain and better functions and thus felt no need to return to see the doctors. Thus, these issues may have compromised the study's validity.
Finally, the authors did not describe whether there were differences in any other OA treatments between the groups during the follow-up period, such as non-steroidal anti-inflammatory drugs (NSAIDs), glucosamine, and intra-articular hyaluronic acid or steroid injection.4, 5 These treatments may have influenced the results.
We respect the authors' great contributions and would be very interested in their response to the above issues.
Reference
1. Hunter, D.J. and S. Bierma-Zeinstra, Osteoarthritis. Lancet, 2019. 393(10182): 1745-1759.
2. Kloppenburg, M., F.P. Kroon, F.J. Blanco, M. Doherty, K.S. Dziedzic, E. Greibrokk, I.K. Haugen, G. Herrero-Beaumont, H. Jonsson, I. Kjeken, E. Maheu, R. Ramonda, M.J. Ritt, W. Smeets, et al., 2018 update of the EULAR recommendations for the management of hand osteoarthritis. Annals of the Rheumatic Diseases, 2019. 78(1): 16-24.
3. Wei, G., K. Lu, M. Umar, Z. Zhu, W.W. Lu, J.R. Speakman, Y. Chen, L. Tong, and D. Chen, Risk of metabolic abnormalities in osteoarthritis: a new perspective to understand its pathological mechanisms. Bone Res, 2023. 11(1): 63.
4. Moseng, T., T.P.M. Vliet Vlieland, S. Battista, D. Beckwée, V. Boyadzhieva, P.G. Conaghan, D. Costa, M. Doherty, A.G. Finney, T. Georgiev, M. Gobbo, N. Kennedy, I. Kjeken, F.P.B. Kroon, et al., EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update. Ann Rheum Dis, 2024. 83(6): 730-740.
5. Kolasinski, S.L., T. Neogi, M.C. Hochberg, C. Oatis, G. Guyatt, J. Block, L. Callahan, C. Copenhaver, C. Dodge, D. Felson, K. Gellar, W.F. Harvey, G. Hawker, E. Herzig, et al., 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis & Rheumatology, 2020. 72(2): 220-233.
6. Chen, Y., Y.C. Huang, C.H. Yan, K.Y. Chiu, Q. Wei, J. Zhao, X.E. Guo, F. Leung, and W.W. Lu, Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients. Bone Res, 2017. 5: 17034.
7. Coggon, D., I. Reading, P. Croft, M. McLaren, D. Barrett, and C. Cooper, Knee osteoarthritis and obesity. Int J Obes Relat Metab Disord, 2001. 25(5): 622-7.
8. Raud, B., C. Gay, C. Guiguet-Auclair, A. Bonnin, L. Gerbaud, B. Pereira, M. Duclos, Y. Boirie, and E. Coudeyre, Level of obesity is directly associated with the clinical and functional consequences of knee osteoarthritis. Scientific Reports, 2020. 10(1): 3601.
9. Swain, S., A. Sarmanova, C. Coupland, M. Doherty, and W. Zhang, Comorbidities in Osteoarthritis: A Systematic Review and Meta-Analysis of Observational Studies. Arthritis Care & Research, 2020. 72(7): 991-1000.
10. Snoeker, B., A. Turkiewicz, K. Magnusson, R. Frobell, D. Yu, G. Peat, and M. Englund, Risk of knee osteoarthritis after different types of knee injuries in young adults: a population-based cohort study. British Journal of Sports Medicine, 2020. 54(12): 725-730.
11. Amico, K.R., Percent total attrition: a poor metric for study rigor in hosted intervention designs. Am J Public Health, 2009. 99(9): 1567-75.
12. Bell, M.L., M.G. Kenward, D.L. Fairclough, and N.J. Horton, Differential dropout and bias in randomised controlled trials: when it matters and when it may not. Bmj, 2013. 346: e8668.
13. Jacobs, E., L. Stroobant, J. Victor, D. Elewaut, T. Tampere, S. Wallaert, E. Witvrouw, J. Schuermans, and E. Wezenbeek, Vascular occlusion for optimising the functional improvement in patients with knee osteoarthritis: a randomised controlled trial. Ann Rheum Dis, 2024.
Dear Editor,
I read with keen interest the article titled "Evaluation and Prediction of Relapse Risk in Stable Systemic Lupus Erythematosus Patients After Glucocorticoid Withdrawal (PRESS): An Open-Label, Multicentre, Non-Inferiority, Randomised Controlled Study in China." This study adds valuable data to the growing body of literature regarding glucocorticoid (GC) withdrawal and the role of hydroxychloroquine (HCQ) maintenance in sustaining clinical remission in systemic lupus erythematosus (SLE) patients. The non-inferiority design allows a meaningful comparison across three therapeutic arms, helping to delineate the clinical risks associated with GC discontinuation, with or without HCQ.
A particular strength of this study is its three-arm, multicenter design, which enabled a robust comparison and increased the external validity of findings within the Han Chinese population. However, we believe that additional insights into subgroup analyses could further enhance understanding of the clinical predictors of relapse, especially regarding factors such as baseline SLE Disease Activity Index (SLEDAI), organ involvement, serological markers, and previous treatment history. The reported lower relapse in patients with only mucocutaneous involvement and those maintained on HCQ monotherapy is notable, yet these preliminary findings warrant further stratification to assess potential risk differentials across other organ systems.
One critical limitation a...
Dear Editor,
I read with keen interest the article titled "Evaluation and Prediction of Relapse Risk in Stable Systemic Lupus Erythematosus Patients After Glucocorticoid Withdrawal (PRESS): An Open-Label, Multicentre, Non-Inferiority, Randomised Controlled Study in China." This study adds valuable data to the growing body of literature regarding glucocorticoid (GC) withdrawal and the role of hydroxychloroquine (HCQ) maintenance in sustaining clinical remission in systemic lupus erythematosus (SLE) patients. The non-inferiority design allows a meaningful comparison across three therapeutic arms, helping to delineate the clinical risks associated with GC discontinuation, with or without HCQ.
A particular strength of this study is its three-arm, multicenter design, which enabled a robust comparison and increased the external validity of findings within the Han Chinese population. However, we believe that additional insights into subgroup analyses could further enhance understanding of the clinical predictors of relapse, especially regarding factors such as baseline SLE Disease Activity Index (SLEDAI), organ involvement, serological markers, and previous treatment history. The reported lower relapse in patients with only mucocutaneous involvement and those maintained on HCQ monotherapy is notable, yet these preliminary findings warrant further stratification to assess potential risk differentials across other organ systems.
One critical limitation acknowledged by the authors is the short follow-up period (33 weeks), which may not fully capture the long-term relapse risk or potential late-onset adverse effects associated with GC discontinuation. SLE is a relapsing-remitting disease, and the risk of relapse after drug tapering could extend beyond the 33-week time frame. Longer follow-up, ideally spanning 1–2 years, would provide more robust data on the durability of remission, as well as additional insights into delayed relapses and cumulative adverse events.
Moreover, while the authors used a “best observation carried forward” (BOCF) approach to handle missing data, they acknowledge that this method may not completely mitigate potential biases in estimating relapse rates. Sensitivity analysis using a "worst observation carried forward" (WOCF) approach strengthened the robustness of the findings, yet BOCF remains vulnerable to selection biases, particularly given the increased dropout rate in the dual maintenance group, which was assumed to have no relapse. Alternative methods, such as multiple imputation, could provide a more nuanced understanding of missing data impacts in future studies.
Lastly, the ethnic homogeneity of the cohort, with predominance of Chinese Han patients, presents another limitation. SLE manifestations and treatment responses vary across ethnic groups due to genetic, immunologic, and environmental factors. Future studies involving multiethnic cohorts could help validate the applicability of these findings more broadly and address whether HCQ monotherapy after GC withdrawal could be an optimal strategy across diverse SLE populations.
In conclusion, the PRESS trial offers promising evidence supporting HCQ monotherapy as a relapse-preventive measure after GC withdrawal in clinically inactive SLE patients. The findings bring us closer to an evidence-based approach for tapering GCs in SLE, where HCQ maintenance may enable clinicians to reduce cumulative steroid exposure and its associated side effects without compromising disease control. We commend the authors on this significant contribution to SLE management and encourage further trials that expand on these results to provide a more precise framework for GC tapering and discontinuation.
Reference
1. Fei Y, Zhao L, Wu L, et al. Evaluation and prediction of relapse risk in stable systemic lupus erythematosus patients after glucocorticoid withdrawal (PRESS): an open-label, multicentre, non-inferiority, randomised controlled study in China. Annals of the Rheumatic Diseases Published Online First: 13 November 2024. doi: 10.1136/ard-2024-225826.
I am writing to express my observations and constructive feedback on the recent study titled "Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials" published in your esteemed journal[1]. I commend the authors for their significant contribution to the field of rheumatology and the comprehensive analysis they have provided. However, I would like to highlight two aspects of the study design that, in my opinion, warrant further consideration.
1. Choice of Placebo Over Tumor Necrosis Factor Inhibitors
While the use of a placebo-controlled design is a standard and valuable approach in clinical trials, I believe that the current study would have greatly benefited from the inclusion of a comparator group treated with tumor necrosis factor inhibitors (TNFi). TNFi are currently recommended for patients with axial spondyloarthritis (axSpA) who have a history of recurrent acute anterior uveitis (AAU)[2]. The decision to use a placebo control, without comparing the efficacy and safety of bimekizumab directly against TNFi, limits the study’s ability to contextualize its findings within the existing therapeutic landscape. A direct comparison with TNFi would provide more robust evidence regarding the relative efficacy of bimekizumab, thereby offering clearer guidance for clinical practice.
2. Lack of Statistical Analysis in Table 1 and Table 2
The baseline characte...
I am writing to express my observations and constructive feedback on the recent study titled "Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials" published in your esteemed journal[1]. I commend the authors for their significant contribution to the field of rheumatology and the comprehensive analysis they have provided. However, I would like to highlight two aspects of the study design that, in my opinion, warrant further consideration.
1. Choice of Placebo Over Tumor Necrosis Factor Inhibitors
While the use of a placebo-controlled design is a standard and valuable approach in clinical trials, I believe that the current study would have greatly benefited from the inclusion of a comparator group treated with tumor necrosis factor inhibitors (TNFi). TNFi are currently recommended for patients with axial spondyloarthritis (axSpA) who have a history of recurrent acute anterior uveitis (AAU)[2]. The decision to use a placebo control, without comparing the efficacy and safety of bimekizumab directly against TNFi, limits the study’s ability to contextualize its findings within the existing therapeutic landscape. A direct comparison with TNFi would provide more robust evidence regarding the relative efficacy of bimekizumab, thereby offering clearer guidance for clinical practice.
2. Lack of Statistical Analysis in Table 1 and Table 2
The baseline characteristics and demographic data presented in Table 1 and Table 2 of the study are crucial for understanding the study population and ensuring the comparability of treatment groups. However, the absence of statistical analyses to compare these baseline characteristics between the groups is a notable omission. Conducting and reporting statistical tests, such as t-tests for continuous variables and chi-square tests for categorical variables, would allow for the assessment of any significant differences between the groups. This, in turn, would help in ensuring that the groups are well-matched and that any observed treatment effects are not confounded by baseline imbalances. The inclusion of these statistical analyses is essential for validating the internal validity of the study findings.
Conclusion
In conclusion, while the study provides valuable insights into the efficacy of bimekizumab in reducing uveitis rates among axSpA patients, addressing the aforementioned points would enhance the robustness and clinical applicability of the findings. I hope these suggestions are received in the constructive spirit intended and contribute to ongoing and future research efforts in this important area.
Thank you for considering my comments. I look forward to future publications that continue to advance our understanding and treatment of axSpA.
Yours sincerely,
Caifeng Li
Reference
1. Brown MA, Rudwaleit M, Van Gaalen FA, et al. Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials. Ann. Rheum. Dis. , ard-2024-225933 (2024).
2. Ramiro S, Nikiphorou E, Sepriano A, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann. Rheum. Dis. 82(1), 19–34 (2023).
Dear Editor,
I thoroughly enjoyed reading the EULAR and PReS recommendations on the diagnosis and management of Still’s disease, authored by Fautrel et al., as a result of the joint efforts of these two communities (1). I congratulate the task force on their work on behalf of all physicians.
However, I would like to highlight some points that need further clarification and share my concerns.
1- As is well known, Still’s disease has various clinical courses: monocyclic, polycyclic, and chronic articular (2). The disease progression, outcomes, and treatment needs of these patients can differ. In addition to this classification, there are forms where systemic inflammation predominates, usually accompanied by macrophage activation syndrome, and forms characterized by chronic arthritis. Including these differences in the recommendations and shaping treatment suggestions accordingly would be more clinically beneficial.
2- In the proposed treatment algorithm and its explanation, it is recommended to initiate treatments targeting interleukin-1 or interleukin-6 regardless of the disease activity. The rationale given is that although there are small randomized controlled trials on therapies targeting interleukin-1 or interleukin-6, accumulated real-world data support the effectiveness of these agents. On the other hand, there is limited data regarding conventional DMARDs, and a randomized controlled trial in systemic JIA patients suggested that methotrexate w...
Dear Editor,
I thoroughly enjoyed reading the EULAR and PReS recommendations on the diagnosis and management of Still’s disease, authored by Fautrel et al., as a result of the joint efforts of these two communities (1). I congratulate the task force on their work on behalf of all physicians.
However, I would like to highlight some points that need further clarification and share my concerns.
1- As is well known, Still’s disease has various clinical courses: monocyclic, polycyclic, and chronic articular (2). The disease progression, outcomes, and treatment needs of these patients can differ. In addition to this classification, there are forms where systemic inflammation predominates, usually accompanied by macrophage activation syndrome, and forms characterized by chronic arthritis. Including these differences in the recommendations and shaping treatment suggestions accordingly would be more clinically beneficial.
2- In the proposed treatment algorithm and its explanation, it is recommended to initiate treatments targeting interleukin-1 or interleukin-6 regardless of the disease activity. The rationale given is that although there are small randomized controlled trials on therapies targeting interleukin-1 or interleukin-6, accumulated real-world data support the effectiveness of these agents. On the other hand, there is limited data regarding conventional DMARDs, and a randomized controlled trial in systemic JIA patients suggested that methotrexate was not superior to placebo. In this ranking, the long-standing use of conventional DMARDs, especially methotrexate, and the fact that clinicians who manage this patient group effectively and safely use these agents in clinical practice, have been overlooked, which may lead to various problems. One of the largest series on the use of conventional DMARDs in the treatment of Still’s disease was published by Kalyoncu et al., where 254 out of 306 patients (83%) achieved remission with corticosteroids and methotrexate ± other conventional DMARDs (3). Among 97 patients who received only corticosteroids and methotrexate, 85 (87.6%) achieved remission (3). In another recent study by Ruscitti et al., involving 171 Still’s disease patients registered in the AIDA Network Still Disease Registry, clinical remission was achieved in 38.6% of patients, regardless of whether they received a combination of any conventional or biological DMARDs (4). All these data show that conventional DMARDs, particularly methotrexate, cannot be easily excluded from the treatment process.
3- The authors mention that conventional DMARDs can be used in countries where treatments targeting interleukin-1 or interleukin-6 are not accessible. In countries where both options are available, this treatment hierarchy may lead to medicolegal problems. For instance, a patient diagnosed with Still’s disease who achieves remission with methotrexate might file a complaint with health authorities because interleukin-based therapies were not initiated.
REFERENCES
1. Fautrel B, Mitrovic S, De Matteis A, Bindoli S, Antón J, Belot A, et al. EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease. Ann Rheum Dis. 2024.
2. Manger B, Rech J, Schett G. Use of methotrexate in adult-onset Still's disease. Clin Exp Rheumatol. 2010;28(5 Suppl 61):S168-71.
3. Kalyoncu U, Solmaz D, Emmungil H, Yazici A, Kasifoglu T, Kimyon G, et al. Response rate of initial conventional treatments, disease course, and related factors of patients with adult-onset Still's disease: Data from a large multicenter cohort. J Autoimmun. 2016;69:59-63.
4. Ruscitti P, Sota J, Vitale A, Lopalco G, Iannone F, Morrone M, et al. The administration of methotrexate in patients with Still's disease, "real-life" findings from AIDA Network Still Disease Registry. Semin Arthritis Rheum. 2023;62:152244.
The level of evidence for efficacy of conventional DMARDs is really low. The only high level evidence (i.e. a clinical trial does not show any benefit compared to placebo at a very low level of response (i.e ACR 30). Drugs such as methotrexate have been used for decades before bDMARDs effective in Still´s disease become available. The task force did not exclude that MTX may be of help for some patients or be a resource in some settings where IL-1 or IL-6 inhibitors cannot be used. The task force wanted to highlight that the ultimate goal is clinical inactive disease off medication and that this ambitious goal requires to use IL-1 or IL-6 inhibitors without loosing time with methotrexate or other potentially ineffective treatment, with the risk of missing the window of opportunity and, therefore endangering the long-term outcome of the patients.
Dear Authors and Publishers
alle the graphs are not readable - how can we benefit from your findings if the table and graphs are so low in resolution that one can not even guess what the graph is showing
kind regards christian marx
Dear Editor,
I am writing in response to the recent publication titled "Allogenic bone marrow–derived mesenchymal stromal cell–based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)” [1]. This article provides a thorough investigation into the use of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) for treating chronic low back pain (LBP) due to intervertebral disc degeneration (IDD). Given the significant burden that chronic LBP places on individuals and healthcare systems worldwide, the RESPINE study represents an essential contribution to the evolving field of regenerative medicine and cell-based therapies.
The methodology employed in this trial, including its prospective, multicentre, double-blind, and placebo-controlled design, sets a high standard for research in this area. By randomizing 114 patients to receive either a single intradiscal injection of allogeneic BM-MSCs or a sham placebo, the study aimed to address the challenge of determining the therapeutic efficacy of MSC-based interventions for chronic LBP. The blinding of subjects, radiographic reviewers, and clinical assessors ensured that bias was minimized throughout the trial, enhancing the validity of the reported outcomes.
An interesting point raised in the article concerns the comparison between different cell types, such as nucleus pulposus cells (NPCs) and extracellular vesicles (EVs), as po...
Dear Editor,
I am writing in response to the recent publication titled "Allogenic bone marrow–derived mesenchymal stromal cell–based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)” [1]. This article provides a thorough investigation into the use of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) for treating chronic low back pain (LBP) due to intervertebral disc degeneration (IDD). Given the significant burden that chronic LBP places on individuals and healthcare systems worldwide, the RESPINE study represents an essential contribution to the evolving field of regenerative medicine and cell-based therapies.
The methodology employed in this trial, including its prospective, multicentre, double-blind, and placebo-controlled design, sets a high standard for research in this area. By randomizing 114 patients to receive either a single intradiscal injection of allogeneic BM-MSCs or a sham placebo, the study aimed to address the challenge of determining the therapeutic efficacy of MSC-based interventions for chronic LBP. The blinding of subjects, radiographic reviewers, and clinical assessors ensured that bias was minimized throughout the trial, enhancing the validity of the reported outcomes.
An interesting point raised in the article concerns the comparison between different cell types, such as nucleus pulposus cells (NPCs) and extracellular vesicles (EVs), as potential alternatives to MSCs for treating IDD. The referenced studies by Han et al. and Ambrosio et al. indicate that NPC-derived EVs might have superior regenerative effects in maintaining disc integrity compared to MSC-derived EVs. These findings suggest that the choice of cell type plays a critical role in influencing the regenerative outcomes and that future trials should focus on optimizing the selection of cellular therapies to target the specific pathology of IDD.
It is also commendable that the study reports a favorable safety profile for the allogeneic BM-MSC injections, with no serious adverse events directly related to the treatment over the 24-month follow-up period. This supports the notion that allogeneic MSCs can be safely administered in a clinical setting, with minimal risk of immune rejection or other complications, an essential consideration for broader clinical application. However, the immunomodulatory properties of MSCs and their ability to evade host immune responses continue to require detailed investigation to fully understand their long-term implications in allogeneic contexts.
The limitations noted in the study, including the relatively small sample size for MRI-based structural assessments and the absence of discography for precise patient selection, are important considerations that may have affected the power and specificity of the results. Expanding future studies to include larger cohorts with extended follow-up durations and refined diagnostic criteria could provide a clearer picture of the potential benefits of MSC-based therapies for IDD.
In conclusion, while the RESPINE trial did not conclusively establish the efficacy of allogeneic BM-MSCs for chronic LBP due to IDD, it adds a valuable piece to the puzzle in understanding the role of cell-based therapies in regenerative medicine. It highlights the importance of patient selection, the potential for combinatory treatment approaches, and the need to continue exploring different cell types or adjunctive therapies that could enhance the regenerative response. The study's rigorous design and comprehensive analysis set a benchmark for future trials that aim to bring innovative, biologically-based solutions to the challenging field of chronic LBP management.
Reference
1. Pers Y, Soler-Rich R, Vadalà G, et alAllogenic bone marrow–derived mesenchymal stromal cell–based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)Annals of the Rheumatic Diseases Published Online First: 11 October 2024. doi: 10.1136/ard-2024-225771
Response on “Performance analysis of a deep-learning algorithm to detect the presence of inflammation in MRI of sacroiliac joints in patients with axial spondyloarthritis” by Nicolaes et al.
Show MoreDear Editor,
We appreciate the study by Nicolaes et al. for providing valuable insights into the role of deep-learning algorithms in detecting sacroiliac joint (SIJ) inflammation in axial spondyloarthritis (axSpA). Their work demonstrates the potential of AI-assisted imaging in musculoskeletal diagnosis, and they have acknowledged several study limitations, which we will not replicate. Instead, we highlight key areas for further improvement.
First, MRI Positivity Criteria and Diagnostic Accuracy. This study applies the 2009 ASAS MRI criteria, which primarily focus on bone marrow edema (BME). However, the 2016 ASAS update incorporates structural lesions (erosion, sclerosis, fat metaplasia) to improve specificity (1). Integrating these updated criteria in future model training may enhance clinical applicability.
Second, MRI Field Strength and Data Representation. This study predominantly uses 1.5T MRI, with underrepresentation of 3T MRI, which offers better resolution for detecting subtle inflammatory changes (2). Additionally, the inclusion of 1.0T MRI, despite its lower resolution and declining clinical use, may affect model performance. Ensuring a balanced MRI dataset with optimized field strength representation could improve the reliability of AI predictions....
We read with great interest the article by Brown et al.,1 who reported that the lower incidence rates of acute anterior uveitis in patients with axial spondyloarthritis receiving bimekizumab (a dual-IL-17A/F inhibitor) than in those not receiving bimekizumab. This study is a valuable addition to the literature. However, we have some concerns that we would like to share with the authors.
Show MoreFirst, this study may be suspected of selection bias. Selection bias occurs when the recruiters, that is, those responsible for recruiting or enrolling patients selectively include individuals based on the expected outcome of the next observation allocation.2 In the pooled phase 3 BE MOBILE 1 and 2 double-blind trial, patients treated with placebo had a higher rate of history of uveitis (19.0%) than those treated with bimekizumab (14.9%) at baseline. This could suggest that higher-risk patients may have been enrolled in the group receiving placebo, which could lead to biased estimates of the incidence of uveitis and potentially misleading conclusions.
Second, previous studies have reported a higher risk for incidental uveitis in patients with axial spondyloarthritis who are female, have a family history of uveitis, have a history of uveitis themselves, are HLA-B27 positive, have longer disease duration, have prior TNFi exposure, are older, have a history of smoking, have a history of inflammatory bowel disease, and have higher baseline high-sensitivity C-reactive protein levels....
Dear Editor,
We read with interest the recommendations for diagnosis and management of Still's disease by Fautrel et al[1]. The first overarching principle is that systemic juvenile idiopathic arthritis and adult-onset Still's disease are the same disease[1,2]. The Task Force also emphasized the need for a better understanding of the pathophysiology of Still's disease and its severe or life-threatening manifestations, the first of which is Still's lung disease. However, the recommendations omitted important data from under-represented populations that could have confirmed or disrupted the current understanding of Still's disease. Here, we would like to recall important findings in African Caribbean (AC) patients.
In a population of approximately 750,000, there is a similar incidence of 0.4/100,000 of Still’s disease in AC juveniles and adults, similar to predominantly Caucasian European or North American populations[3–5]. A comparison of the clinical and biological characteristics has shown that the cardinal symptoms of Still's disease, such as joint involvement and inflammatory biology, are similar between children and adults[5]. Diagnostic criteria for children (ILAR) and adults (Yamaguchi and/or Fautrel criteria) were consistent and overlapped in the majority of cases (80%), regardless of age. The therapeutic arsenal used was the same in children and adults, as reported[1,2,5], with minor variations[5]. The results obtained in...
Show MoreOsteoarthritis (OA) is the most common joint disorder, with an estimated 250 million individuals are currently affected worldwide.1 Unfortunately, current treatments for OA are limited to pain relief and symptom management.2-5 A few studies have evaluated the efficacy of blood flow restriction (BFR) in OA treatment;3 however, the exact effectiveness of BFR in OA remains largely unknown. We read with deep interest a recent article published in this journal by Jacobs et al, who found that incorporating BFR into a traditional exercise program resulted in sustained improvements in pain, symptoms, and functional measures for patients with knee OA (KOA).4 We appreciate the great work performed by the authors; nevertheless, some valuable questions need to be explored further.
First, this study only included a specific subgroup of KOA patients without obesity (body mass index (BMI) ≥ 30 kg/m2) or comorbidities (eg, cardiovascular, neurological, or metabolic conditions). However, OA is closely linked with obesity and comorbidities such as hypertension and diabetes.3, 6 It was reported that subjects with obesity were 6.8 times more likely to develop KOA than normal-weight controls,7 and the level of obesity is directly associated with the clinical consequences of KOA.8 Furthermore, it was found that 67% of OA patients had at least one comorbidity.9 Thus, this study limits the generalizability of the findings to other KOA patients. Since it remains unclear whether obesity and...
Show MoreDear Editor,
Show MoreI read with keen interest the article titled "Evaluation and Prediction of Relapse Risk in Stable Systemic Lupus Erythematosus Patients After Glucocorticoid Withdrawal (PRESS): An Open-Label, Multicentre, Non-Inferiority, Randomised Controlled Study in China." This study adds valuable data to the growing body of literature regarding glucocorticoid (GC) withdrawal and the role of hydroxychloroquine (HCQ) maintenance in sustaining clinical remission in systemic lupus erythematosus (SLE) patients. The non-inferiority design allows a meaningful comparison across three therapeutic arms, helping to delineate the clinical risks associated with GC discontinuation, with or without HCQ.
A particular strength of this study is its three-arm, multicenter design, which enabled a robust comparison and increased the external validity of findings within the Han Chinese population. However, we believe that additional insights into subgroup analyses could further enhance understanding of the clinical predictors of relapse, especially regarding factors such as baseline SLE Disease Activity Index (SLEDAI), organ involvement, serological markers, and previous treatment history. The reported lower relapse in patients with only mucocutaneous involvement and those maintained on HCQ monotherapy is notable, yet these preliminary findings warrant further stratification to assess potential risk differentials across other organ systems.
One critical limitation a...
Dear Editor,
I am writing to express my observations and constructive feedback on the recent study titled "Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials" published in your esteemed journal[1]. I commend the authors for their significant contribution to the field of rheumatology and the comprehensive analysis they have provided. However, I would like to highlight two aspects of the study design that, in my opinion, warrant further consideration.
1. Choice of Placebo Over Tumor Necrosis Factor Inhibitors
While the use of a placebo-controlled design is a standard and valuable approach in clinical trials, I believe that the current study would have greatly benefited from the inclusion of a comparator group treated with tumor necrosis factor inhibitors (TNFi). TNFi are currently recommended for patients with axial spondyloarthritis (axSpA) who have a history of recurrent acute anterior uveitis (AAU)[2]. The decision to use a placebo control, without comparing the efficacy and safety of bimekizumab directly against TNFi, limits the study’s ability to contextualize its findings within the existing therapeutic landscape. A direct comparison with TNFi would provide more robust evidence regarding the relative efficacy of bimekizumab, thereby offering clearer guidance for clinical practice.
2. Lack of Statistical Analysis in Table 1 and Table 2
Show MoreThe baseline characte...
Dear Editor,
Show MoreI thoroughly enjoyed reading the EULAR and PReS recommendations on the diagnosis and management of Still’s disease, authored by Fautrel et al., as a result of the joint efforts of these two communities (1). I congratulate the task force on their work on behalf of all physicians.
However, I would like to highlight some points that need further clarification and share my concerns.
1- As is well known, Still’s disease has various clinical courses: monocyclic, polycyclic, and chronic articular (2). The disease progression, outcomes, and treatment needs of these patients can differ. In addition to this classification, there are forms where systemic inflammation predominates, usually accompanied by macrophage activation syndrome, and forms characterized by chronic arthritis. Including these differences in the recommendations and shaping treatment suggestions accordingly would be more clinically beneficial.
2- In the proposed treatment algorithm and its explanation, it is recommended to initiate treatments targeting interleukin-1 or interleukin-6 regardless of the disease activity. The rationale given is that although there are small randomized controlled trials on therapies targeting interleukin-1 or interleukin-6, accumulated real-world data support the effectiveness of these agents. On the other hand, there is limited data regarding conventional DMARDs, and a randomized controlled trial in systemic JIA patients suggested that methotrexate w...
Dear Authors and Publishers
alle the graphs are not readable - how can we benefit from your findings if the table and graphs are so low in resolution that one can not even guess what the graph is showing
kind regards christian marx
Dear Editor,
Show MoreI am writing in response to the recent publication titled "Allogenic bone marrow–derived mesenchymal stromal cell–based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)” [1]. This article provides a thorough investigation into the use of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) for treating chronic low back pain (LBP) due to intervertebral disc degeneration (IDD). Given the significant burden that chronic LBP places on individuals and healthcare systems worldwide, the RESPINE study represents an essential contribution to the evolving field of regenerative medicine and cell-based therapies.
The methodology employed in this trial, including its prospective, multicentre, double-blind, and placebo-controlled design, sets a high standard for research in this area. By randomizing 114 patients to receive either a single intradiscal injection of allogeneic BM-MSCs or a sham placebo, the study aimed to address the challenge of determining the therapeutic efficacy of MSC-based interventions for chronic LBP. The blinding of subjects, radiographic reviewers, and clinical assessors ensured that bias was minimized throughout the trial, enhancing the validity of the reported outcomes.
An interesting point raised in the article concerns the comparison between different cell types, such as nucleus pulposus cells (NPCs) and extracellular vesicles (EVs), as po...
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