Dear Editor,
We read with great interest the recent paper published in ARD by Fu et al.
Based on their prospective open-label randomised control trial in 270 patients with active Class III/IV/V lupus nephritis, the authors conclude that the efficacy and safety profile of leflunomide is non-inferior to azathioprine for maintenance therapy of LN.
Importantly, this study was designed as a non-inferiority trial with the non-inferiority margin set at 12% for the primary outcome (flare at 36 months of maintenance-phase follow-up), meaning that the lower bound of the two-sided 95% CI for the difference in flare rates between LEF and AZA (as reference) should exceed −12%. Unexpectedly for a non-inferiority trial, the difference between groups for all data was considered significant at p<0.05.
Time to kidney flare was reported as not statistically different between the LEF group (17/108 patients, 15.7%; median time: 16 months) compared with that in the AZA group (19/107 patients, 17.8%; median time 14 months) during the 36 months of follow-up, yielding a Hazard Ratio (HR) of 0.89 (95%CI: 0.57-1.21), with the lower bound of the 95%CI below the non-inferiority margin (-12%) which should be interpreted as an inclusive non-inferiority trial.
We therefore believe that the main conclusion of the authors is not supported by the data presented, and as leflunomide is currently not shown as non-inferior to azathioprine for the maintenance of LN.
To,
The Editor, A R D
Sir,
This has reference to the EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome [1]. These recommendations will help most of the practicing rheumatologists in getting actively involved the prevention of atherosclerotic cardiovascular disease in RMDs. However, I seek one clarification the answer of which, I did not find in this document. What exact measure/instrument should I be using to guide me for pharmacological intervention for appropriate lipid-control? Should I be only using any one of the ‘CVD 10-y risk prediction instruments’ (modified Framingham Risk score, ‘SCORE’, ‘QRISK3’) and using a cut-off of 10-year-risk of > 5% as a guide to initiate pharmacological intervention for lipid-control (besides life-style change recommendations)? Or should I use the widely endorsed recommendations/guidelines from different cardiology/cholesterol societies around the world? For example, presently most such recommendations suggest the formulae ‘total cholesterol minus_HDL-cholesterol’ or ‘total cholesterol/HDL-cholesterol ratio’ providing cutoff values (>120 or 130mg/dL/>3.5 to 5, respectively) above which pharmacological intervention for lipid-control must be initiated. Opinion of the experts will be highly appreciated.
Yours Truly
Anand N. Malaviya, Department of Rheumatology.
ISIC Superspeciali...
To,
The Editor, A R D
Sir,
This has reference to the EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome [1]. These recommendations will help most of the practicing rheumatologists in getting actively involved the prevention of atherosclerotic cardiovascular disease in RMDs. However, I seek one clarification the answer of which, I did not find in this document. What exact measure/instrument should I be using to guide me for pharmacological intervention for appropriate lipid-control? Should I be only using any one of the ‘CVD 10-y risk prediction instruments’ (modified Framingham Risk score, ‘SCORE’, ‘QRISK3’) and using a cut-off of 10-year-risk of > 5% as a guide to initiate pharmacological intervention for lipid-control (besides life-style change recommendations)? Or should I use the widely endorsed recommendations/guidelines from different cardiology/cholesterol societies around the world? For example, presently most such recommendations suggest the formulae ‘total cholesterol minus_HDL-cholesterol’ or ‘total cholesterol/HDL-cholesterol ratio’ providing cutoff values (>120 or 130mg/dL/>3.5 to 5, respectively) above which pharmacological intervention for lipid-control must be initiated. Opinion of the experts will be highly appreciated.
Yours Truly
Anand N. Malaviya, Department of Rheumatology.
ISIC Superspeciality Hospital, Vasant Kunj, New Delhi – 110070
Email: anand_malaviya@yahoo.com
Reference:
1.Drosos GC, Vedder D, Houben E, et al. Ann Rheum Dis Epub ahead of print: [2nd February 2022]. doi:10.1136/
annrheumdis-2021-221733
We appreciate Drs. Kardas’ and Küçük’s interest in the new 2022 ACR/EULAR Classification Criteria for ANCA-associated vasculitis (1-3) and will take this opportunity to respond to the points they raised. The key concept to reiterate and clarify is that the classification criteria are only intended for use as inclusion criteria for clinical research. Therefore, it is not appropriate to use the criteria as diagnostic tools in a clinical setting. These criteria were designed to be used when considering who to include within a clinical trial of a particular subtype of AAV only after a complex clinical assessment has taken place. Thus, application of these criteria assumes drug exposure, malignancy, infection, and many other conditions that could mimic vasculitis have been excluded.
It is important to re-emphasize that inclusion and applications of weights for specific items in the criteria were based on rigorous data-driven methods and items were, in part, included to differentiate among the three forms of ANCA-associated vasculitis. Decisions about item selection and weighting were made keeping in mind the value of the items relative to other items through the regression methods used in the analyses. With these concepts in mind, it is easier to understand how items present in more than one type of vasculitis but in differing frequencies may be included in one but not another set of criteria. For example, pulmonary involvement incorporates multiple findings suc...
We appreciate Drs. Kardas’ and Küçük’s interest in the new 2022 ACR/EULAR Classification Criteria for ANCA-associated vasculitis (1-3) and will take this opportunity to respond to the points they raised. The key concept to reiterate and clarify is that the classification criteria are only intended for use as inclusion criteria for clinical research. Therefore, it is not appropriate to use the criteria as diagnostic tools in a clinical setting. These criteria were designed to be used when considering who to include within a clinical trial of a particular subtype of AAV only after a complex clinical assessment has taken place. Thus, application of these criteria assumes drug exposure, malignancy, infection, and many other conditions that could mimic vasculitis have been excluded.
It is important to re-emphasize that inclusion and applications of weights for specific items in the criteria were based on rigorous data-driven methods and items were, in part, included to differentiate among the three forms of ANCA-associated vasculitis. Decisions about item selection and weighting were made keeping in mind the value of the items relative to other items through the regression methods used in the analyses. With these concepts in mind, it is easier to understand how items present in more than one type of vasculitis but in differing frequencies may be included in one but not another set of criteria. For example, pulmonary involvement incorporates multiple findings such as infiltrates, nodules, mass, fibrosis/interstitial lung disease, and others. Hence, inflammation on imaging is not the same as interstitial lung disease but is a broader finding. Inclusion of different forms of lung involvement in the criteria for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) showed statistically significant differences between patients with these forms of vasculitis and patients from the comparator group (Supplementary Material 6).
A data-driven approach underpins the methodology of the DCVAS study, from definition of appropriate cases (e.g. GPA or EGPA) via use of an external panel of blinded experts, through to statistical analysis using large-scale international development and validation cohorts. It would not be appropriate to change the weightings of key items defined during this process in an ad hoc manner at the end of analysis. This process may have identified interesting features not previously noted in other, smaller datasets, such as the relatively high rate of eosinophilia in cases of GPA, that could warrant future investigation.
References
1 Grayson PC, Ponte C, Suppiah R, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis 2022;81:309–14. doi:10.1136/annrheumdis-2021-221794
2 Robson JC, Grayson PC, Ponte C, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis 2022;81:315–20. doi:10.1136/annrheumdis-2021-221795
3 Suppiah R, Robson JC, Grayson PC, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Ann Rheum Dis 2022;81:321–6. doi:10.1136/annrheumdis-2021-221796
We read with great interest the recently published classification criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides [1–3]. As stated elsewhere, it is hoped these criteria will further allow more homogenous patients groups to be included in clinical studies [4]. Here we would like to make several points of interest.
First, we believe the weight of laboratory criteria for granulomatosis with polyangiitis and microscopic angiitis is too high. Although it is stated in both the methodology and discussion sections that these criteria should only be applied after a diagnosis of small or medium vessel vasculitis has been made and vasculitis mimics have been excluded, this may not always be possible in a real-life setting. For instance, drug-induced [5] or paraneoplastic [6] vasculitis cases without overt clinical findings typically associated with microscopic polyangiitis (MPA) may inadvertently classified as primary MPA by the virtue of having perinuclear ANCA or anti-myeloperoxidase antibody positivity. We believe this may be prevented by lowering the point value of laboratory criteria or requiring the concomitant presence of both clinical and laboratory, imaging or biopsy criteria for classification, similar to other classification criteria used for other conditions such as systemic lupus erythematosus [7].
Second, nearly one third of patients classified as granulomatosis with polyangiitis (GPA) were reported to have maximum eosinophil...
We read with great interest the recently published classification criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides [1–3]. As stated elsewhere, it is hoped these criteria will further allow more homogenous patients groups to be included in clinical studies [4]. Here we would like to make several points of interest.
First, we believe the weight of laboratory criteria for granulomatosis with polyangiitis and microscopic angiitis is too high. Although it is stated in both the methodology and discussion sections that these criteria should only be applied after a diagnosis of small or medium vessel vasculitis has been made and vasculitis mimics have been excluded, this may not always be possible in a real-life setting. For instance, drug-induced [5] or paraneoplastic [6] vasculitis cases without overt clinical findings typically associated with microscopic polyangiitis (MPA) may inadvertently classified as primary MPA by the virtue of having perinuclear ANCA or anti-myeloperoxidase antibody positivity. We believe this may be prevented by lowering the point value of laboratory criteria or requiring the concomitant presence of both clinical and laboratory, imaging or biopsy criteria for classification, similar to other classification criteria used for other conditions such as systemic lupus erythematosus [7].
Second, nearly one third of patients classified as granulomatosis with polyangiitis (GPA) were reported to have maximum eosinophil count of ≥1×10⁹/L. Although atypical GPA cases with eosinophilia have been rarely reported in the literature [8] and this rate is lower than the comparator group (45%), we feel both rates are uncharacteristically high and requires further discussion.
Finally, presence of interstitial lung disease as a classification criterion has been included in MPA but not for GPA. The Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) cohort data for pulmonary involvement shows 13.7% of GPA cases had inflammation on imaging, compared to 23.4% of MPA cases [9]. While the rate is lower, about one in every ten cases classified as GPA had pulmonary inflammation. In addition, ANCA can be positive in primary interstitial lung diseases, with varying rates reported in the literature [10]. We feel these also require further discussion.
1 Grayson PC, Ponte C, Suppiah R, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis 2022;81:309–14. doi:10.1136/annrheumdis-2021-221794
2 Robson JC, Grayson PC, Ponte C, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis 2022;81:315–20. doi:10.1136/annrheumdis-2021-221795
3 Suppiah R, Robson JC, Grayson PC, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Ann Rheum Dis 2022;81:321–6. doi:10.1136/annrheumdis-2021-221796
4 Koster MJ, Warrington KJ. ACR and EULAR bring AAV classification into the twenty-first century. Nat Rev Rheumatol Published Online First: 7 April 2022. doi:10.1038/s41584-022-00777-5
5 Pendergraft WF, Niles JL. Trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (ANCA) vasculitis. Curr Opin Rheumatol 2014;26:42–9. doi:10.1097/BOR.0000000000000014
6 Folci M, Ramponi G, Shiffer D, et al. ANCA-Associated Vasculitides and Hematologic Malignancies: Lessons from the Past and Future Perspectives. J Immunol Res 2019;2019:1732175. doi:10.1155/2019/1732175
7 Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019;78:1151–9. doi:10.1136/annrheumdis-2018-214819
8 Shoda H, Kanda H, Tanaka R, et al. Wegener’s Granulomatosis with Eosinophilia. Intern Med 2005;44:750–3. doi:10.2169/internalmedicine.44.750
9 Makhzoum J-P, Grayson PC, Ponte C, et al. Pulmonary involvement in primary systemic vasculitides. Rheumatology 2021;61:319–30. doi:10.1093/rheumatology/keab325
10 Kadura S, Raghu G. Antineutrophil cytoplasmic antibody-associated interstitial lung disease: a review. Eur Respir Rev 2021;30. doi:10.1183/16000617.0123-2021
Correspondence on ‘Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial’ by Bandak et al.
Author Affiliations:
1. Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 510280
2. Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 510280
Corresponding Author: Zhaohua Zhu, PhD. Clinical Research Centre, Zhujiang Hospital, Southern Medical University. No.253 Industrial Avenue, Haizhu District, Guangzhou, Guangdong Province, China, 510280 (Email: zhaohua.zhu@utas.edu.au).
Word count: 415
We read with great interest the article by Bandak et al 1. The authors conducted an open-label, single centre randomised controlled trial involving 206 knee osteoarthritis (OA) patients in an attempt to discriminate the effect of exercise and education from a placebo control on joint symptoms. They reported that an 8-week exercise and education programme provided equivalent efficacies for improving OA symptoms and function to 4 intra-articular saline injections over 8 weeks. The findings question the recommendation of exercise and education as OA symptoms management strategies. However, we believe the effect of exercise and education cannot be negated, as some p...
Correspondence on ‘Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial’ by Bandak et al.
Author Affiliations:
1. Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 510280
2. Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 510280
Corresponding Author: Zhaohua Zhu, PhD. Clinical Research Centre, Zhujiang Hospital, Southern Medical University. No.253 Industrial Avenue, Haizhu District, Guangzhou, Guangdong Province, China, 510280 (Email: zhaohua.zhu@utas.edu.au).
Word count: 415
We read with great interest the article by Bandak et al 1. The authors conducted an open-label, single centre randomised controlled trial involving 206 knee osteoarthritis (OA) patients in an attempt to discriminate the effect of exercise and education from a placebo control on joint symptoms. They reported that an 8-week exercise and education programme provided equivalent efficacies for improving OA symptoms and function to 4 intra-articular saline injections over 8 weeks. The findings question the recommendation of exercise and education as OA symptoms management strategies. However, we believe the effect of exercise and education cannot be negated, as some points of this article require further discussion.
First, for delivering placebo treatment, the use of intra-articular injection, a procedure that can increase pain-relieving effect of inert substance 2, may have leaded to significant unbalanced potential placebo responses in two groups. Even if an open-label design could diminish the contextual effects, as described by the authors, it is still difficult to conclude the isolated effect of exercise and education with new biases arising from the discrepancies between the two arms (e.g., varying contact time with clinicians). A significant favour to the exercise and education group in participants’ global assessment outcome in Table 2 is a hint of poor comparability. Therefore, using a low intensity exercise or an attention control, which shares similar procedure with exercise and education, may be a better placebo control design 3,4.
Second, an 8-week exercise and education programme may be too short to observe the significant effects as most previous trials examining the effect of excise and education intervention for OA have reported long-lasting and significantly superior effect over non-surgical interventions for at least 16 weeks 5.
Third, the efficacy of exercise for OA can be affected by various factors, especially comorbid diseases 6. We notice that 24.5% participants in the intervention group and 29.8% in the control group were obese (BMI ≥ 30), who were likely to suffer from cardiovascular and metabolic disorders at the same time. It is reasonable to assume that different subgroups of participants would react differently to exercise and education intervention. Thus, more details of demographic characteristics and subgroup analysis should be provided.
Finally, it is worth presenting the results of both within and between groups differences for the primary and secondary outcomes, as they would give additional information for a more comprehensive conclusion.
To sum up, we believe that the effect of exercise and education in OA management would be confirmed by better-designed randomised controlled trials.
Ethics statements: Not required.
Patient consent of publication: Not required.
Conflict of Interest Disclosure: None reported.
Contributors: YL, YM and ZZ draft this correspondence. CD and ZZ were involved in revising and editing the correspondence.
Funding: The present study was supported by the National Natural Science Foundation of China (32000925).
Patient and public involvement: Patients and/or public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review: Not commissioned; internally peer reviewed.
References
1. Bandak E, Christensen R, Overgaard A, et al. Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial. Annals of the Rheumatic Diseases 2022;81:537-543.
2. Zhang W, Robertson J, Jones AC, et al. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67(12):1716-1723.
3. Messier SP, Mihalko SL, Beavers DP, et al. Effect of high-intensity strength training on knee pain and knee joint compressive forces amoung adults with knee osteoarthritis: the START randomized clinical trial. JAMA. 2021;325(7):646-657.
4. Henriksen M, Klokker L, Graven-Nielsen T, et al. Association of exercise therapy and reduction of pain sensitivity in patients with knee osteoarthritis: a randomized controlled trial. Arthritis Care Res (Hoboken). 2014;66(12):1836-1843.
5. Kechichian A, Lafrance S, Matifat E, et al. Multimodal interventions including rehabilitation exercise for older adults with chronic musculoskeletal pain: a systematic review and meta-analyses of randomized controlled trials. J Geriatr Phys Ther. 2022;45(1):34-49.
6. de Rooij M, Steultjens MPM, Avezaat E, et al. Restrictions and contraindications for exercise therapy in patients with hip and knee osteoarthritis and comorbidity. Phys Ther Rev 2013;18:101-11.
We read with great interest the article reported by De Mits and colleagues [1] suggesting that lockdown during the COVID-19 pandemic decreased chest expansion but did not have any impact on spinal mobility or disease activity in patients with spondyloarthritis (SpA).
We conducted a similar study in France during the first lockdown (17th March-10th May 2020), which included all patients with SpA from our centre, who received bDMARDs administered intravenously in the immunotherapy unit of our outpatient clinic. In this unit, a standardized procedure is applied to collect clinical, biological and if necessary, imaging data at each clinical visit. During this period of lockdown, patients had at least one clinical examination. The Visual Analog Scale (VAS) values for pain, asthenia and activity, as well as the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) were collected and averaged from two clinical visits, one before (pre-lockdown) and one after (post-lockdown) and then compared with the data collected during lockdown. Fifty-nine patients ((mean ± SD) 52±12 years at the time of the study, 33 men, 26 women) were included during the study period. All patients had stable disease and none developed COVID-19 symptoms during this period. We also included a cohort of 50 patients (mean age of 62 years at the time of the study, 10 men, 40 women) with rheumatoid arthritis. The VAS values for pain, asthenia and...
We read with great interest the article reported by De Mits and colleagues [1] suggesting that lockdown during the COVID-19 pandemic decreased chest expansion but did not have any impact on spinal mobility or disease activity in patients with spondyloarthritis (SpA).
We conducted a similar study in France during the first lockdown (17th March-10th May 2020), which included all patients with SpA from our centre, who received bDMARDs administered intravenously in the immunotherapy unit of our outpatient clinic. In this unit, a standardized procedure is applied to collect clinical, biological and if necessary, imaging data at each clinical visit. During this period of lockdown, patients had at least one clinical examination. The Visual Analog Scale (VAS) values for pain, asthenia and activity, as well as the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) were collected and averaged from two clinical visits, one before (pre-lockdown) and one after (post-lockdown) and then compared with the data collected during lockdown. Fifty-nine patients ((mean ± SD) 52±12 years at the time of the study, 33 men, 26 women) were included during the study period. All patients had stable disease and none developed COVID-19 symptoms during this period. We also included a cohort of 50 patients (mean age of 62 years at the time of the study, 10 men, 40 women) with rheumatoid arthritis. The VAS values for pain, asthenia and activity and DAS 28 Disease activity score were collected in this rheumatoid arthritis cohort.
Patients from our lockdown cohort were not assessed by measuring Bath Ankylosing Spondylitis Metrology Index (BASMI) or chest expansion as in the study of De Mits et al. These authors claimed that lockdown had no effect on spinal mobility. The reason given in their article was the fact that patients performed sport at home. However, a French study published in 2022 highlighted that 65% of the general population reduced their sport activities during the lockdown and even beyond [2]. In our opinion, the duration of the lockdown period was too short to have a sizable impact on spinal metrology.
Furthermore, they reported that the lockdown had no effect on their patients’ general health perception using the SF-36 questionnaire and disease activity for two-thirds of them. In our SpA cohort, the self-reported VAS for disease activity was significantly higher during lockdown ((mean ± SD) 4.7/10 ± 2.5 versus 4.0±2.1 pre-lockdown and 4.1±1.8 post-lockdown; p = 0.017), although the BASDAI and BASFI did not change during the same period. Such a profile was not found in our rheumatoid arthritis cohort, since the self-reported VAS for disease activity significantly decreased from the pre- to the post-lockdown period (p=0.0032), even if DAS 28 scores remained stable during the follow-up period. Taken together, these findings are in accordance with those reported from other populations. Indeed, a negative impact of lockdown on rheumatism activity was also found in other chronic inflammatory diseases like juvenile idiopathic arthritis with a significant rate of reactivation during lockdown [3], but also osteoarthritis with an impact on pain, joint function, physical function and physical activity, while the mental component remained unchanged during lockdown [4].
Thus, it appears that lockdown and its resulting sedentary lifestyle may have had a higher negative impact on disease activity in spondyloarthritis than in rheumatoid arthritis patients.
Bibliography
1 De Mits S, De Craemer A-S, Deroo L, et al. Unexpected impact of COVID-19 lockdown on spinal mobility and health perception in spondyloarthritis. Ann Rheum Dis 2021;80:1638–40. doi:10.1136/annrheumdis-2021-220584
2 Bérard E, Huo Yung Kai S, Coley N, et al. One-Year Impact of COVID-19 Lockdown-Related Factors on Cardiovascular Risk and Mental Health: A Population-Based Cohort Study. Int J Environ Res Public Health 2022;19:1684. doi:10.3390/ijerph19031684
3 Conti G, Galletta F, Carucci NS, et al. Negative effect of lockdown on juvenile idiopathic arthritis patients. Clin Rheumatol 2021;40:3723–7. doi:10.1007/s10067-021-05694-8
4 Endstrasser F, Braito M, Linser M, et al. The negative impact of the COVID-19 lockdown on pain and physical function in patients with end-stage hip or knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2020;28:2435–43. doi:10.1007/s00167-020-06104-3
We thank Patoulias and colleagues for pointing out the relevance of clinical studies for the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in renal vasculitis and lupus nephritis.1 As discussed recently, relevant clinical evidence is missing because patients with autoimmune diseases were excluded from most renal outcome trials for SGLT-2 inhibitors.2-4 An exception for the use of SGLT-2 inhibitors in renal autoimmune diseases is the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial (DAPA-CKD, ClinicalTrials.gov Identifier: NCT03036150).5 In DAPA-CKD, the researchers evaluated the effects of SGLT-2 inhibitor dapagliflozin, along with angiotensin-blocking agents, on the progression of CKD, including those with immunoglobulin A nephropathy (IgAN).5 Overall, a 39% reduction in the primary outcome (≥50% decline in eGFR, end-stage kidney disease, or death from cardiovascular or renal causes) was observed.5 Interestingly, patients with IgAN showed an unprecedented 71% reduction in the primary outcome, suggesting that CKD treatment may be equally beneficial in renal autoimmune diseases once the initial phase of remission induction is achieved and kidney function stabilized.6 Patients with renal vasculitis and lupus nephritis have a significantly increased risk for cardiovascular morbidity and mortality, with both inflammation and long-term use of immunosuppressants contributing to this risk.2 Therefore, SGLT-2 inhibitors could ultimately...
We thank Patoulias and colleagues for pointing out the relevance of clinical studies for the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in renal vasculitis and lupus nephritis.1 As discussed recently, relevant clinical evidence is missing because patients with autoimmune diseases were excluded from most renal outcome trials for SGLT-2 inhibitors.2-4 An exception for the use of SGLT-2 inhibitors in renal autoimmune diseases is the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial (DAPA-CKD, ClinicalTrials.gov Identifier: NCT03036150).5 In DAPA-CKD, the researchers evaluated the effects of SGLT-2 inhibitor dapagliflozin, along with angiotensin-blocking agents, on the progression of CKD, including those with immunoglobulin A nephropathy (IgAN).5 Overall, a 39% reduction in the primary outcome (≥50% decline in eGFR, end-stage kidney disease, or death from cardiovascular or renal causes) was observed.5 Interestingly, patients with IgAN showed an unprecedented 71% reduction in the primary outcome, suggesting that CKD treatment may be equally beneficial in renal autoimmune diseases once the initial phase of remission induction is achieved and kidney function stabilized.6 Patients with renal vasculitis and lupus nephritis have a significantly increased risk for cardiovascular morbidity and mortality, with both inflammation and long-term use of immunosuppressants contributing to this risk.2 Therefore, SGLT-2 inhibitors could ultimately contribute to organ protection in renal autoimmune diseases by reducing CKD progression and cardiovascular risk.2 Results of the Study of Heart and Kidney Protection With Empagliflozin trial (EMPA-KIDNEY, ClinicalTrials.gov Identifier: NCT03594110) are anticipated within 2022, and will provide one step towards a more definitive answers on whether SGLT-2 inhibitors are relevant in the therapeutic management of renal autoimmune diseases, including lupus nephritis.7
References
1. Hakroush S, Tampe D, Kluge IA, et al. Comparative analysis of SGLT-2 expression in renal vasculitis and lupus nephritis. Ann Rheum Dis 2022 doi: 10.1136/annrheumdis-2022-222167 [published Online First: 2022/02/27]
2. Saemann M, Kronbichler A. Call for action in ANCA-associated vasculitis and lupus nephritis: promises and challenges of SGLT-2 inhibitors. Ann Rheum Dis 2021 doi: 10.1136/annrheumdis-2021-221474 [published Online First: 2021/12/01]
3. Patoulias D. Correspondence on 'Call for action in ANCA-associated vasculitis and lupus nephritis: promises and challenges of SGLT-2 inhibitors' by Saemann and Kronbichler. Ann Rheum Dis 2022 doi: 10.1136/annrheumdis-2021-221953 [published Online First: 2022/01/15]
4. Saemann M, Kronbichler A. Response to: Correspondence on 'Call for action in ANCA-associated vasculitis and lupus nephritis: promises and challenges of SGLT-2 inhibitors' by Saemann and Kronbichler. Ann Rheum Dis 2022 doi: 10.1136/annrheumdis-2021-221982 [published Online First: 2022/01/15]
5. Heerspink HJL, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2020;383(15):1436-46. doi: 10.1056/NEJMoa2024816 [published Online First: 2020/09/25]
6. Wheeler DC, Toto RD, Stefansson BV, et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int 2021;100(1):215-24. doi: 10.1016/j.kint.2021.03.033 [published Online First: 2021/04/21]
7. Group E-KC. Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. Nephrol Dial Transplant 2022 doi: 10.1093/ndt/gfac040 [published Online First: 2022/03/04]
We thank Tsung-Yuan Yang and colleagues for their interest in our findings on survival after COVID-19 associated organ-failure among SLE population. They raised two interesting questions on the method that we used.
First, they suspect a selection bias because we selected, for the unmatched analysis, patients still alive at D30 to measure the survival in the D30-D90 period while SLE patients had a lower mortality during the D0-D30 period. They stated that selecting patients based on what the next observation allocation is likely to be can lead to biased estimates. We agree with them, and, as we already wrote in the discussion section, “Such observation may be biased because patients with SLE are younger and more frequently female” which could explain the better prognosis during the D0-D30 period. Besides, we used D30 as a landmark not by choice, but because, in the matched analysis, (Figure 2) the Kaplan-Meier curves crossed at D30, and the proportional hazard assumption was therefore not respected. We did not drive conclusions from this unmatched analysis which was here mainly to show the importance of our matching procedure.
Second, they raised the concern that “the baseline characteristics between the two groups were not defined in this study”. We partly disagree on this comment. As a matter of fact, we presented in Table 1 (unmatched analysis) and in Table 2 (matched analysis) the baseline characteristic of our studied populations. We presented all the data...
We thank Tsung-Yuan Yang and colleagues for their interest in our findings on survival after COVID-19 associated organ-failure among SLE population. They raised two interesting questions on the method that we used.
First, they suspect a selection bias because we selected, for the unmatched analysis, patients still alive at D30 to measure the survival in the D30-D90 period while SLE patients had a lower mortality during the D0-D30 period. They stated that selecting patients based on what the next observation allocation is likely to be can lead to biased estimates. We agree with them, and, as we already wrote in the discussion section, “Such observation may be biased because patients with SLE are younger and more frequently female” which could explain the better prognosis during the D0-D30 period. Besides, we used D30 as a landmark not by choice, but because, in the matched analysis, (Figure 2) the Kaplan-Meier curves crossed at D30, and the proportional hazard assumption was therefore not respected. We did not drive conclusions from this unmatched analysis which was here mainly to show the importance of our matching procedure.
Second, they raised the concern that “the baseline characteristics between the two groups were not defined in this study”. We partly disagree on this comment. As a matter of fact, we presented in Table 1 (unmatched analysis) and in Table 2 (matched analysis) the baseline characteristic of our studied populations. We presented all the data that we had regarding the simplified acute physiology score 2 (SAPS 2) which is also a classification tool for individual’s risk mortality in hospital (1) and an analogue of APACHE 2 used in France. However, we acknowledge that this score is only collected in intensive care units (ICUs), so it was available only for patients admitted in these units. As presented in table 2, and even though SAPS 2 was not part of the matching variables, this score was distributed similarly between SLE and non-SLE matched populations.
Overall, we provide evidence that, after considering age, sex, and several comorbidities, SLE patients have a late-onset poor prognosis after COVID-19 AOF.
References:
1-Le Gall J, Lemeshow S, Saulnier F. A New Simplified Acute Physiology Score (SAPS II) Based on a European/North American Multicenter Study. JAMA. 1993;270(24):2957–2963.
We read with interest the article by Sjef M van der Linden et al, in which factors predicting axial spondylarthritis (axSpA) was identified. We appreciate their delicate works and point out some issues which may improve the outcome of the study.
First, a total of 1178 subjects were enrolled for completion of questionnaire and related physical examination and blood tests. Altogether 162 participants (123 probands and 360 first-degree relatives) have died during follow-up with unknown cause of death. However, only 485 participants were entered for statistically analysis. Although it is a long-period cohort study spanning 35 years, a high missing rate of data was still doubted. We suggested a second look on data retrieval and management.
Second, the author took participants’ reply of having used topical corticosteroid as the proof the acute anterior uveitis (AAU), which is quite unreliable. Instead, medical record should be retrieved for all participants. The mainstay of treatment in uveitis is corticosteroid eyedrops, dexamethasone 0.1% and prednisolone 1% are the first choice among them. Depending on the course and progress of uveitis, subconjunctival, posterior sub-tenon, or intravitreal injection of steroids preparation was indicated, even with combination use of systemic corticosteroid, and corticosteroid-sparing agents comprising non-steroidal anti-inflammatory drugs (NSAIDs), anti-metabolites (methotrexate), cycloplegic drug (atropine...
We read with interest the article by Sjef M van der Linden et al, in which factors predicting axial spondylarthritis (axSpA) was identified. We appreciate their delicate works and point out some issues which may improve the outcome of the study.
First, a total of 1178 subjects were enrolled for completion of questionnaire and related physical examination and blood tests. Altogether 162 participants (123 probands and 360 first-degree relatives) have died during follow-up with unknown cause of death. However, only 485 participants were entered for statistically analysis. Although it is a long-period cohort study spanning 35 years, a high missing rate of data was still doubted. We suggested a second look on data retrieval and management.
Second, the author took participants’ reply of having used topical corticosteroid as the proof the acute anterior uveitis (AAU), which is quite unreliable. Instead, medical record should be retrieved for all participants. The mainstay of treatment in uveitis is corticosteroid eyedrops, dexamethasone 0.1% and prednisolone 1% are the first choice among them. Depending on the course and progress of uveitis, subconjunctival, posterior sub-tenon, or intravitreal injection of steroids preparation was indicated, even with combination use of systemic corticosteroid, and corticosteroid-sparing agents comprising non-steroidal anti-inflammatory drugs (NSAIDs), anti-metabolites (methotrexate), cycloplegic drug (atropine 1%) and anti-TNF-alpha monoclonal antibodies (Infliximab and adalimumab).[1, 2]
Third, confounding factors as infection, trauma, and cigarettes smoking were not recognized, because AAU can be a feature of trauma (including ocular surgery), systemic or localized inflammation, or herps simplex infection, and significantly associated with cigarette smoking.[3] So far, ankylosing spondylitis (AS) has been proved to be significantly associated with infection (Klebsiella pneumoniae, Salmonella, Yersinia; osteomyelitis), mechanical stress, male gender, vitamin D deficiency, and smoking (including e-cigarettes) apart from carrier of human leukocyte antigen B27 (HLA B27) allele.[4, 5] Therefore, we strongly suggest account for these confounding variables before any analysis.
Fourth, the author addressed a 157-item postal questionnaire, based on manifestation of AS, dealing with symptoms of the region of back pain and AAU. The accuracy of the questionnaire was doubted due to deficiency of using evidence. Scales measuring AS, such as Bath Ankylosing Spondylitis Disease Activity Index (BADSI) and Bath Ankylosing Spondylitis Functional Index (BASFI), have high sensitivity, good validity and reliability.[6] They were also efficient tools for evaluation of severity of AS during out-patient department status, and might be better choice in this study.
Jing-Xing Li, MD, MSa,b,c, James Cheng-Chung Wei, MD, PhDd,e,f
aDepartment of General Medicine, China Medical University Hospital, Taichung, Taiwan.
bCollege of Medicine, China Medical University, Taichung, Taiwan
cGraduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan
dDepartment of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
eInstitute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan
fGraduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
Potential conflict or interest: None.
Reprints not available from the authors.
Correspondence to: James Cheng-Chung Wei, MD, PhD, Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
E-mail: jccwei@gmail.com
References
1. Wakefield, D., D. Clarke, and P. McCluskey, Recent Developments in HLA B27 Anterior Uveitis. Front Immunol, 2020. 11: p. 608134.
2. Ahn, S.M., et al., Risk of Acute Anterior Uveitis in Ankylosing Spondylitis According to the Type of Tumor Necrosis Factor-Alpha Inhibitor and History of Uveitis: A Nationwide Population-Based Study. J Clin Med, 2022. 11(3).
3. Yuen, B.G., et al., Association between Smoking and Uveitis: Results from the Pacific Ocular Inflammation Study. Ophthalmology, 2015. 122(6): p. 1257-61.
4. Zhang, X., et al., Association Between Infections and Risk of Ankylosing Spondylitis: A Systematic Review and Meta-Analysis. Front Immunol, 2021. 12: p. 768741.
5. Hwang, M.C., L. Ridley, and J.D. Reveille, Ankylosing spondylitis risk factors: a systematic literature review. Clin Rheumatol, 2021. 40(8): p. 3079-3093.
6. Zochling, J., Measures of symptoms and disease status in ankylosing spondylitis: Ankylosing Spondylitis Disease Activity Score (ASDAS), Ankylosing Spondylitis Quality of Life Scale (ASQoL), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Global Score (BAS-G), Bath Ankylosing Spondylitis Metrology Index (BASMI), Dougados Functional Index (DFI), and Health Assessment Questionnaire for the Spondylarthropathies (HAQ-S). Arthritis Care Res (Hoboken), 2011. 63 Suppl 11: p. S47-58.
We really appreciated the results of the exploratory study by Hakroush and colleagues, which provides further insights into the potential role of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with lupus nephritis and renal vasculitis.1 Unfortunately, at present, relevant clinical evidence is missing.
It has been formerly known that focal segmental glomerulosclerosis (FSGS) is considered as a distinct phenotype of lupus podocytopathy, which is associated with a severe tubulo-interstitial injury and a much lower complete remission rate, compared to other phenotypes, such as mimimal change and mesangial proliferation.2,3
According to a recently published, post-hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin compared to placebo resulted in a lower mean rate of estimated glomerular filtration rate decline among patients with baseline FSGS, although the result was not statistically significantly, possibly due to the small number of patients with FSGS (n = 104).4 Results of the EMPA-KIDNEY trial, which are anticipated within 2022, will provide more definitive answers on whether SGLT-2 inhibitors can play a crucial role in the therapeutic management of lupus nephritis the next years.5
References
1. Hakroush S, Tampe D, Kluge IA, Baier E, Korsten P, Tampe B. Comparative analysis of SGLT-2 expression in renal vasculitis and lupus nephritis. Ann Rheum Dis. 2022...
We really appreciated the results of the exploratory study by Hakroush and colleagues, which provides further insights into the potential role of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with lupus nephritis and renal vasculitis.1 Unfortunately, at present, relevant clinical evidence is missing.
It has been formerly known that focal segmental glomerulosclerosis (FSGS) is considered as a distinct phenotype of lupus podocytopathy, which is associated with a severe tubulo-interstitial injury and a much lower complete remission rate, compared to other phenotypes, such as mimimal change and mesangial proliferation.2,3
According to a recently published, post-hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin compared to placebo resulted in a lower mean rate of estimated glomerular filtration rate decline among patients with baseline FSGS, although the result was not statistically significantly, possibly due to the small number of patients with FSGS (n = 104).4 Results of the EMPA-KIDNEY trial, which are anticipated within 2022, will provide more definitive answers on whether SGLT-2 inhibitors can play a crucial role in the therapeutic management of lupus nephritis the next years.5
References
1. Hakroush S, Tampe D, Kluge IA, Baier E, Korsten P, Tampe B. Comparative analysis of SGLT-2 expression in renal vasculitis and lupus nephritis. Ann Rheum Dis. 2022 Feb 25:annrheumdis-2022-222167. doi: 10.1136/annrheumdis-2022-222167. Epub ahead of print.
2. Hu W, Chen Y, Wang S, et al. Clinical-Morphological Features and Outcomes of Lupus Podocytopathy. Clin J Am Soc Nephrol 2016;11:585-92. doi:10.2215/CJN.06720615
3. Chen D, Hu W. Lupus podocytopathy: a distinct entity of lupus nephritis. J Nephrol 2018;31:629-34. doi:10.1007/s40620-017-0463-1
4. Wheeler DC, Jongs N, Stefansson BV, et al. Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: A prespecified analysis of the DAPA-CKD trial [published online ahead of print, 2021 Nov 25]. Nephrol Dial Transplant 2021;gfab335. doi:10.1093/ndt/gfab335
5. EMPA-KIDNEY Collaborative Group . Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial [published online ahead of print, 2022 Mar 3]. Nephrol Dial Transplant 2022;gfac040. doi:10.1093/ndt/gfac040
Dear Editor,
We read with great interest the recent paper published in ARD by Fu et al.
Based on their prospective open-label randomised control trial in 270 patients with active Class III/IV/V lupus nephritis, the authors conclude that the efficacy and safety profile of leflunomide is non-inferior to azathioprine for maintenance therapy of LN.
Importantly, this study was designed as a non-inferiority trial with the non-inferiority margin set at 12% for the primary outcome (flare at 36 months of maintenance-phase follow-up), meaning that the lower bound of the two-sided 95% CI for the difference in flare rates between LEF and AZA (as reference) should exceed −12%. Unexpectedly for a non-inferiority trial, the difference between groups for all data was considered significant at p<0.05.
Time to kidney flare was reported as not statistically different between the LEF group (17/108 patients, 15.7%; median time: 16 months) compared with that in the AZA group (19/107 patients, 17.8%; median time 14 months) during the 36 months of follow-up, yielding a Hazard Ratio (HR) of 0.89 (95%CI: 0.57-1.21), with the lower bound of the 95%CI below the non-inferiority margin (-12%) which should be interpreted as an inclusive non-inferiority trial.
We therefore believe that the main conclusion of the authors is not supported by the data presented, and as leflunomide is currently not shown as non-inferior to azathioprine for the maintenance of LN.
To,
Show MoreThe Editor, A R D
Sir,
This has reference to the EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome [1]. These recommendations will help most of the practicing rheumatologists in getting actively involved the prevention of atherosclerotic cardiovascular disease in RMDs. However, I seek one clarification the answer of which, I did not find in this document. What exact measure/instrument should I be using to guide me for pharmacological intervention for appropriate lipid-control? Should I be only using any one of the ‘CVD 10-y risk prediction instruments’ (modified Framingham Risk score, ‘SCORE’, ‘QRISK3’) and using a cut-off of 10-year-risk of > 5% as a guide to initiate pharmacological intervention for lipid-control (besides life-style change recommendations)? Or should I use the widely endorsed recommendations/guidelines from different cardiology/cholesterol societies around the world? For example, presently most such recommendations suggest the formulae ‘total cholesterol minus_HDL-cholesterol’ or ‘total cholesterol/HDL-cholesterol ratio’ providing cutoff values (>120 or 130mg/dL/>3.5 to 5, respectively) above which pharmacological intervention for lipid-control must be initiated. Opinion of the experts will be highly appreciated.
Yours Truly
Anand N. Malaviya, Department of Rheumatology.
ISIC Superspeciali...
We appreciate Drs. Kardas’ and Küçük’s interest in the new 2022 ACR/EULAR Classification Criteria for ANCA-associated vasculitis (1-3) and will take this opportunity to respond to the points they raised. The key concept to reiterate and clarify is that the classification criteria are only intended for use as inclusion criteria for clinical research. Therefore, it is not appropriate to use the criteria as diagnostic tools in a clinical setting. These criteria were designed to be used when considering who to include within a clinical trial of a particular subtype of AAV only after a complex clinical assessment has taken place. Thus, application of these criteria assumes drug exposure, malignancy, infection, and many other conditions that could mimic vasculitis have been excluded.
It is important to re-emphasize that inclusion and applications of weights for specific items in the criteria were based on rigorous data-driven methods and items were, in part, included to differentiate among the three forms of ANCA-associated vasculitis. Decisions about item selection and weighting were made keeping in mind the value of the items relative to other items through the regression methods used in the analyses. With these concepts in mind, it is easier to understand how items present in more than one type of vasculitis but in differing frequencies may be included in one but not another set of criteria. For example, pulmonary involvement incorporates multiple findings suc...
Show MoreWe read with great interest the recently published classification criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides [1–3]. As stated elsewhere, it is hoped these criteria will further allow more homogenous patients groups to be included in clinical studies [4]. Here we would like to make several points of interest.
Show MoreFirst, we believe the weight of laboratory criteria for granulomatosis with polyangiitis and microscopic angiitis is too high. Although it is stated in both the methodology and discussion sections that these criteria should only be applied after a diagnosis of small or medium vessel vasculitis has been made and vasculitis mimics have been excluded, this may not always be possible in a real-life setting. For instance, drug-induced [5] or paraneoplastic [6] vasculitis cases without overt clinical findings typically associated with microscopic polyangiitis (MPA) may inadvertently classified as primary MPA by the virtue of having perinuclear ANCA or anti-myeloperoxidase antibody positivity. We believe this may be prevented by lowering the point value of laboratory criteria or requiring the concomitant presence of both clinical and laboratory, imaging or biopsy criteria for classification, similar to other classification criteria used for other conditions such as systemic lupus erythematosus [7].
Second, nearly one third of patients classified as granulomatosis with polyangiitis (GPA) were reported to have maximum eosinophil...
Correspondence on ‘Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial’ by Bandak et al.
Yang Li1, MD; Yiying Mai1, MD; Changhai Ding1, Prof; Zhaohua Zhu1,2, PhD
Author Affiliations:
1. Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 510280
2. Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 510280
Corresponding Author: Zhaohua Zhu, PhD. Clinical Research Centre, Zhujiang Hospital, Southern Medical University. No.253 Industrial Avenue, Haizhu District, Guangzhou, Guangdong Province, China, 510280 (Email: zhaohua.zhu@utas.edu.au).
Word count: 415
We read with great interest the article by Bandak et al 1. The authors conducted an open-label, single centre randomised controlled trial involving 206 knee osteoarthritis (OA) patients in an attempt to discriminate the effect of exercise and education from a placebo control on joint symptoms. They reported that an 8-week exercise and education programme provided equivalent efficacies for improving OA symptoms and function to 4 intra-articular saline injections over 8 weeks. The findings question the recommendation of exercise and education as OA symptoms management strategies. However, we believe the effect of exercise and education cannot be negated, as some p...
Show MoreWe read with great interest the article reported by De Mits and colleagues [1] suggesting that lockdown during the COVID-19 pandemic decreased chest expansion but did not have any impact on spinal mobility or disease activity in patients with spondyloarthritis (SpA).
Show MoreWe conducted a similar study in France during the first lockdown (17th March-10th May 2020), which included all patients with SpA from our centre, who received bDMARDs administered intravenously in the immunotherapy unit of our outpatient clinic. In this unit, a standardized procedure is applied to collect clinical, biological and if necessary, imaging data at each clinical visit. During this period of lockdown, patients had at least one clinical examination. The Visual Analog Scale (VAS) values for pain, asthenia and activity, as well as the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) were collected and averaged from two clinical visits, one before (pre-lockdown) and one after (post-lockdown) and then compared with the data collected during lockdown. Fifty-nine patients ((mean ± SD) 52±12 years at the time of the study, 33 men, 26 women) were included during the study period. All patients had stable disease and none developed COVID-19 symptoms during this period. We also included a cohort of 50 patients (mean age of 62 years at the time of the study, 10 men, 40 women) with rheumatoid arthritis. The VAS values for pain, asthenia and...
We thank Patoulias and colleagues for pointing out the relevance of clinical studies for the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in renal vasculitis and lupus nephritis.1 As discussed recently, relevant clinical evidence is missing because patients with autoimmune diseases were excluded from most renal outcome trials for SGLT-2 inhibitors.2-4 An exception for the use of SGLT-2 inhibitors in renal autoimmune diseases is the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial (DAPA-CKD, ClinicalTrials.gov Identifier: NCT03036150).5 In DAPA-CKD, the researchers evaluated the effects of SGLT-2 inhibitor dapagliflozin, along with angiotensin-blocking agents, on the progression of CKD, including those with immunoglobulin A nephropathy (IgAN).5 Overall, a 39% reduction in the primary outcome (≥50% decline in eGFR, end-stage kidney disease, or death from cardiovascular or renal causes) was observed.5 Interestingly, patients with IgAN showed an unprecedented 71% reduction in the primary outcome, suggesting that CKD treatment may be equally beneficial in renal autoimmune diseases once the initial phase of remission induction is achieved and kidney function stabilized.6 Patients with renal vasculitis and lupus nephritis have a significantly increased risk for cardiovascular morbidity and mortality, with both inflammation and long-term use of immunosuppressants contributing to this risk.2 Therefore, SGLT-2 inhibitors could ultimately...
Show MoreWe thank Tsung-Yuan Yang and colleagues for their interest in our findings on survival after COVID-19 associated organ-failure among SLE population. They raised two interesting questions on the method that we used.
Show MoreFirst, they suspect a selection bias because we selected, for the unmatched analysis, patients still alive at D30 to measure the survival in the D30-D90 period while SLE patients had a lower mortality during the D0-D30 period. They stated that selecting patients based on what the next observation allocation is likely to be can lead to biased estimates. We agree with them, and, as we already wrote in the discussion section, “Such observation may be biased because patients with SLE are younger and more frequently female” which could explain the better prognosis during the D0-D30 period. Besides, we used D30 as a landmark not by choice, but because, in the matched analysis, (Figure 2) the Kaplan-Meier curves crossed at D30, and the proportional hazard assumption was therefore not respected. We did not drive conclusions from this unmatched analysis which was here mainly to show the importance of our matching procedure.
Second, they raised the concern that “the baseline characteristics between the two groups were not defined in this study”. We partly disagree on this comment. As a matter of fact, we presented in Table 1 (unmatched analysis) and in Table 2 (matched analysis) the baseline characteristic of our studied populations. We presented all the data...
Dear Editor,
We read with interest the article by Sjef M van der Linden et al, in which factors predicting axial spondylarthritis (axSpA) was identified. We appreciate their delicate works and point out some issues which may improve the outcome of the study.
First, a total of 1178 subjects were enrolled for completion of questionnaire and related physical examination and blood tests. Altogether 162 participants (123 probands and 360 first-degree relatives) have died during follow-up with unknown cause of death. However, only 485 participants were entered for statistically analysis. Although it is a long-period cohort study spanning 35 years, a high missing rate of data was still doubted. We suggested a second look on data retrieval and management.
Second, the author took participants’ reply of having used topical corticosteroid as the proof the acute anterior uveitis (AAU), which is quite unreliable. Instead, medical record should be retrieved for all participants. The mainstay of treatment in uveitis is corticosteroid eyedrops, dexamethasone 0.1% and prednisolone 1% are the first choice among them. Depending on the course and progress of uveitis, subconjunctival, posterior sub-tenon, or intravitreal injection of steroids preparation was indicated, even with combination use of systemic corticosteroid, and corticosteroid-sparing agents comprising non-steroidal anti-inflammatory drugs (NSAIDs), anti-metabolites (methotrexate), cycloplegic drug (atropine...
Show MoreWe really appreciated the results of the exploratory study by Hakroush and colleagues, which provides further insights into the potential role of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with lupus nephritis and renal vasculitis.1 Unfortunately, at present, relevant clinical evidence is missing.
It has been formerly known that focal segmental glomerulosclerosis (FSGS) is considered as a distinct phenotype of lupus podocytopathy, which is associated with a severe tubulo-interstitial injury and a much lower complete remission rate, compared to other phenotypes, such as mimimal change and mesangial proliferation.2,3
According to a recently published, post-hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin compared to placebo resulted in a lower mean rate of estimated glomerular filtration rate decline among patients with baseline FSGS, although the result was not statistically significantly, possibly due to the small number of patients with FSGS (n = 104).4 Results of the EMPA-KIDNEY trial, which are anticipated within 2022, will provide more definitive answers on whether SGLT-2 inhibitors can play a crucial role in the therapeutic management of lupus nephritis the next years.5
References
1. Hakroush S, Tampe D, Kluge IA, Baier E, Korsten P, Tampe B. Comparative analysis of SGLT-2 expression in renal vasculitis and lupus nephritis. Ann Rheum Dis. 2022...
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