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
Dear editor,
I read with interest the recently published new EULAR recommendations for managing the cardiovascular risk in patients with inflammatory rheumatic diseases [1]. They were long-awaited, and opportunely the targeted diseases are now broader, as previous ones focused primarily on chronic inflammatory arthritis [2].
With rising numbers worldwide, gout is a major cardiovascular risk factor directly linked to all forms of atherosclerotic diseases. By having gout, there is a 40% increased chance of dying from the coronary disease [3]. So, focused management to reduce these serious complications is necessary, and establishing an individual patient's risk is essential. Surprisingly, the experts rely on risk prediction using standard risk assessment tools, claiming the absence of validation studies. I should partially disagree at this point. Certainly, no longitudinal studies have evaluated the predicted rates of cardiovascular events in gout to date. However, our group studied the discriminative value of SCORE and Framingham tools in detecting patients with carotid plaques, a high-risk indicator [4]. A moderate discriminative capacity was unveiled, with areas under the curve of 0.711 for SCORE and 0.683 for Framingham [5]. Specificity was quite good, but the tools lacked enough sensitivity. Moreover, Gamala and colleagues incorporated gout into the modified Dutch SCORE as an inflammatory risk factor [6]. It led to a 28.3% upgrade to the high-risk stag...
Dear editor,
I read with interest the recently published new EULAR recommendations for managing the cardiovascular risk in patients with inflammatory rheumatic diseases [1]. They were long-awaited, and opportunely the targeted diseases are now broader, as previous ones focused primarily on chronic inflammatory arthritis [2].
With rising numbers worldwide, gout is a major cardiovascular risk factor directly linked to all forms of atherosclerotic diseases. By having gout, there is a 40% increased chance of dying from the coronary disease [3]. So, focused management to reduce these serious complications is necessary, and establishing an individual patient's risk is essential. Surprisingly, the experts rely on risk prediction using standard risk assessment tools, claiming the absence of validation studies. I should partially disagree at this point. Certainly, no longitudinal studies have evaluated the predicted rates of cardiovascular events in gout to date. However, our group studied the discriminative value of SCORE and Framingham tools in detecting patients with carotid plaques, a high-risk indicator [4]. A moderate discriminative capacity was unveiled, with areas under the curve of 0.711 for SCORE and 0.683 for Framingham [5]. Specificity was quite good, but the tools lacked enough sensitivity. Moreover, Gamala and colleagues incorporated gout into the modified Dutch SCORE as an inflammatory risk factor [6]. It led to a 28.3% upgrade to the high-risk stage. Until the existence of validation cohorts, these results should be considered. Using risk scales developed for the general population without including inflammatory items carries a significant probability of false-negative categorization, especially at the intermediate-risk level [5,6]. Conversely, a high-risk categorization is quite confident.
Furthermore, the 2022 Recommendations might have encouraged the routine use of carotid ultrasound to detect subclinical atherosclerosis - several papers sustain this approach in our diseases [7,8]. The process is quick and reliable, and the widespread presence of ultrasound in our clinics, not requiring specific probes or software, facilitates its implementation.
Cardiovascular comorbidity is an outstanding problem and remains the first cause of death in our rheumatic patients [9]. Therefore, a major step forward is needed to ameliorate it.
References.
1 Drosos GC, Vedder D, Houben E, et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Annals of the Rheumatic Diseases Published Online First: 1 February 2022. doi:10.1136/annrheumdis-2021-221733
2 Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis 2017;76:17–28. doi:10.1136/annrheumdis-2016-209775
3 Clarson LE, Chandratre P, Hider SL, et al. Increased cardiovascular mortality associated with gout: a systematic review and meta-analysis. Eur J Prev Cardiol 2015;22:335–43. doi:10.1177/2047487313514895
4 Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021;42:3227–337. doi:10.1093/eurheartj/ehab484
5 Andrés M, Bernal JA, Sivera F, et al. Cardiovascular risk of patients with gout seen at rheumatology clinics following a structured assessment. Ann Rheum Dis 2017;76:1263–8. doi:10.1136/annrheumdis-2016-210357
6 Gamala M, Jacobs JWG, Linn-Rasker SP, et al. Cardiovascular risk in patients with new gout: should we reclassify the risk? Clin Exp Rheumatol 2020;38:533–5.
7 Roman MJ, Shanker B-A, Davis A, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003;349:2399–406. doi:10.1056/NEJMoa035471
8 Corrales A, González-Juanatey C, Peiró ME, et al. Carotid ultrasound is useful for the cardiovascular risk stratification of patients with rheumatoid arthritis: results of a population-based study. Ann Rheum Dis 2014;73:722–7. doi:10.1136/annrheumdis-2012-203101
9 England BR, Sayles H, Michaud K, et al. Cause-Specific Mortality in Male US Veterans With Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 2016;68:36–45. doi:10.1002/acr.22642
We read with great interest the recent article written by Araujo CSR et al entitled “Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomized clinical trial” published in the Annals of Rheumatic Diseases on February 22, 2022 [1]. The major impact of this trial was the reinforcement of the immunogenic effect of a 2-week methotrexate discontinuation after each dose of the Sinovac-CoronaVac vaccine against SARS-CoV-2 compared to methotrexate continuation in patients with rheumatoid arthritis (seroconversion rates: 78.4% vs 54.5%, p-0.019 and geometric mean antibody titers: 34.2 (25.2–46.4) vs 16.8 (11.9–23.6), p=0.003, respectively).
Previous experience with other non-COVID-19 vaccines, like the influenza or pneumococcal vaccines, has indicated that discontinuation of immunosuppresants improves the immunogenicity of a given vaccine [2,3]. Based on this knowledge, we had proposed that it would be beneficial for patients with autoimmune rheumatic diseases to get vaccinated against SARS-CoV-2 preferably when the underlying rheumatic disease is in remission and after temporal withdrawal of anti-metabolites within 10 days before and after each vaccine dose along with similar modifications in anti-cytokine drugs and corticosteroid dosages >10mg/ day (prednisone equivalent) [4]. In fact, applying that in a comparative study it was shown that the magnitude of antibody responses to mRNA-based S...
We read with great interest the recent article written by Araujo CSR et al entitled “Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomized clinical trial” published in the Annals of Rheumatic Diseases on February 22, 2022 [1]. The major impact of this trial was the reinforcement of the immunogenic effect of a 2-week methotrexate discontinuation after each dose of the Sinovac-CoronaVac vaccine against SARS-CoV-2 compared to methotrexate continuation in patients with rheumatoid arthritis (seroconversion rates: 78.4% vs 54.5%, p-0.019 and geometric mean antibody titers: 34.2 (25.2–46.4) vs 16.8 (11.9–23.6), p=0.003, respectively).
Previous experience with other non-COVID-19 vaccines, like the influenza or pneumococcal vaccines, has indicated that discontinuation of immunosuppresants improves the immunogenicity of a given vaccine [2,3]. Based on this knowledge, we had proposed that it would be beneficial for patients with autoimmune rheumatic diseases to get vaccinated against SARS-CoV-2 preferably when the underlying rheumatic disease is in remission and after temporal withdrawal of anti-metabolites within 10 days before and after each vaccine dose along with similar modifications in anti-cytokine drugs and corticosteroid dosages >10mg/ day (prednisone equivalent) [4]. In fact, applying that in a comparative study it was shown that the magnitude of antibody responses to mRNA-based SARS-CoV-2 vaccines improved when methotrexate was withheld for a 10-day period before and after each dose compared to when all treatment regimens were maintained [median antibody titers: 7.88 (6.51-8.47) vs 5.20 (2.85-7.30), p<0.001, respectively] [5]. We are glad to see that Araujo CSR and colleagues came to the same conclusion by discontinuing methotrexate for 2 weeks after each vaccine dose. All these highly indicate that methotrexate withdrawal following vaccination improves immunogenicity of COVID-19 vaccines. However, in contrast to our observations that treatment modifications were not accompanied by more disease flares [10/73 (13.7%) vs 7/48 (14.6%), p=0.8910], in the trial by Araujo CSR et al the occurrence of disease flares was higher among those who temporarily interrupted methotrexate compared to those who continued their treatment [23/60 (38.3%) vs 14/69 (20.3%), p=0.024].
In conclusion, this randomized study by Araujo CSR et al confirms our early observations and reinforces current recommendations of methotrexate withdrawal during COVID-19 vaccination along with active disease activity surveillance according to patient’s characteristics and withdrawal periods.
REFERENCES
1. Araujo CSR, Medeiros-Ribeiro AC, Saad CGS, et al Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial Ann Rheum Dis Published Online First: 22 February 2022. doi: 10.1136/annrheumdis-2021-221916.
2. Park JK, Lee YJ, Shin K, et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis 2018;77:annrheumdis-2018-213222–904.
3. Winthrop KL, Silverfield J, Racewicz A, et al. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis 2016;75:687–95.
4. Moutsopoulos HM. A recommended paradigm for vaccination of rheumatic disease patients with the SARS-CoV-2 vaccine. J Autoimmun. 2021 Jul;121:102649. doi: 10.1016/j.jaut.2021.102649. Epub 2021 May 1. PMID: 33984571; PMCID: PMC8088234.
5. Tzioufas AG et al. A prospective multicenter study assessing humoral immunogenicity and safety of the mRNA SARS-CoV-2 vaccines in Greek patients with systemic autoimmune and autoinflammatory rheumatic diseases. J Autoimmun. 2021 Dec;125:102743. doi: 10.1016/j.jaut.2021.102743. Epub 2021 Oct 28. PMID: 34757289; PMCID: PMC8552665.
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.
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 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
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
Dear Editor,
I want to congratulate Kvacskay et al. on an ingenious case series. While we have had evidence of the efficacy of obninutuzumab in lupus nephritis (2) in phase 2 trials and the RIM trial did show the efficacy of rituximab in anti-Jo1 positive myositis hence the expected responses with obinutuzumab, owing to its greater and more effective B cell depletion. The most interesting of the cases was case 4, where, according to the authors, obinutuzumab led to clearance of calcinosis in the patient. In a case series by Narváez et al.(4) only 50% of the patients with calcinosis in systemic sclerosis responded to rituximab (none of them had a complete response) in the systematic review, only one patient had a complete response to the treatment; overall among 19 patients, only 1 had complete response, so complete response with obinutuzumab is quite exciting as nothing sort of works for calcinosis.
When the authors mean complete response, do they mean complete radiological response and clinical response?
Also, the patient was given chlorambucil and bendamustine for her CLL, so the authors' attributing the response was solely due to obinutuzumab is doubtful.
1. Kvacskay P, Merkt W, Günther J, et al. Obinutuzumab in connective tissue diseases after former rituximab-non-response: a case series. Annals of the Rheumatic Diseases. Published Online First: 13 January 2022. doi: 10.1136/annrheumdis-2021-221756
2.Furie RA, Aroca G, Cascino MD, e...
Dear Editor,
I want to congratulate Kvacskay et al. on an ingenious case series. While we have had evidence of the efficacy of obninutuzumab in lupus nephritis (2) in phase 2 trials and the RIM trial did show the efficacy of rituximab in anti-Jo1 positive myositis hence the expected responses with obinutuzumab, owing to its greater and more effective B cell depletion. The most interesting of the cases was case 4, where, according to the authors, obinutuzumab led to clearance of calcinosis in the patient. In a case series by Narváez et al.(4) only 50% of the patients with calcinosis in systemic sclerosis responded to rituximab (none of them had a complete response) in the systematic review, only one patient had a complete response to the treatment; overall among 19 patients, only 1 had complete response, so complete response with obinutuzumab is quite exciting as nothing sort of works for calcinosis.
When the authors mean complete response, do they mean complete radiological response and clinical response?
Also, the patient was given chlorambucil and bendamustine for her CLL, so the authors' attributing the response was solely due to obinutuzumab is doubtful.
1. Kvacskay P, Merkt W, Günther J, et al. Obinutuzumab in connective tissue diseases after former rituximab-non-response: a case series. Annals of the Rheumatic Diseases. Published Online First: 13 January 2022. doi: 10.1136/annrheumdis-2021-221756
2.Furie RA, Aroca G, Cascino MD, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Annals of the Rheumatic Diseases 2022;81:100-107.
3. Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013;65(2):314-324. doi:10.1002/art.37754
4. Narváez, Javier et al. “Effectiveness and safety of rituximab for the treatment of refractory systemic sclerosis associated calcinosis: A case series and systematic review of the literature.” Autoimmunity reviews vol. 18,3 (2019): 262-269. doi:10.1016/j.autrev.2018.10.006
Dear Editor, we read the article entitle “Attenuated response to fourth dose SARS-CoV-2 vaccination in patients with autoimmune disease: a case series [1]” with a great interest. The efficacy of COVID-19 vaccine among specific groups of vaccine recipients with underlying disease is a current important clinical issue. For many groups of patients, including to those with autoimmune diseases, the low immune response to standard vaccination is observed. Extra-dose vaccination is proposed. For the fourth dose of COVID-19 vaccine, it is currently a new idea. Few reports are published. The clinical evidence is required for supporting whether the fourth dose of vaccine will be useful or not and whether there will be any risk of too much vaccination [2]. This report is one of an early publication on this issue. A previous publication is on kidney transplant case. As expected, the high immune response after the fourth dose of vaccine is observed [3]. However, as also seen in the present report, there are various types of first, second and third dose vaccines that each subject in the series received and it might affect the final immune response after the fourth dose vaccine administration. Also, there is usually no confirmation to rule out a possible incidence of asymptomatic COVID-19 infection which might occur in the period between doses of COVID-19 vaccines. These important concerns should be addressed and control of those confounding factors is important if further clinical res...
Dear Editor, we read the article entitle “Attenuated response to fourth dose SARS-CoV-2 vaccination in patients with autoimmune disease: a case series [1]” with a great interest. The efficacy of COVID-19 vaccine among specific groups of vaccine recipients with underlying disease is a current important clinical issue. For many groups of patients, including to those with autoimmune diseases, the low immune response to standard vaccination is observed. Extra-dose vaccination is proposed. For the fourth dose of COVID-19 vaccine, it is currently a new idea. Few reports are published. The clinical evidence is required for supporting whether the fourth dose of vaccine will be useful or not and whether there will be any risk of too much vaccination [2]. This report is one of an early publication on this issue. A previous publication is on kidney transplant case. As expected, the high immune response after the fourth dose of vaccine is observed [3]. However, as also seen in the present report, there are various types of first, second and third dose vaccines that each subject in the series received and it might affect the final immune response after the fourth dose vaccine administration. Also, there is usually no confirmation to rule out a possible incidence of asymptomatic COVID-19 infection which might occur in the period between doses of COVID-19 vaccines. These important concerns should be addressed and control of those confounding factors is important if further clinical researches on the fourth dose of COVID-19 vaccine is planned.
Conflict of interest
Authors ask for waiving for any charge for this correspondence.
References
1. Teles M, Connolly CM, Frey S, Chiang TP, Alejo JJ, Boyarsky BJ, Shah AA, Albayda J, Christopher-Stine L, Werbel WA, Segev DL, Paik JJ. Attenuated response to fourth dose SARS-CoV-2 vaccination in patients with autoimmune disease: a case series. Ann Rheum Dis. 2022 Jan 17:annrheumdis-2021-221641. doi: 10.1136/annrheumdis-2021-221641. Online ahead of print.
2. Burki TK. Fourth dose of COVID-19 vaccines in Israel. Lancet Respir Med. 2022 Jan 11:S2213-2600(22)00010-8.
3. . Caillard S, Thaunat O, Benotmane I, Masset C, Blancho G. Antibody Response to a Fourth Messenger RNA COVID-19 Vaccine Dose in Kidney Transplant Recipients: A Case SeriesAnn Intern Med. 2022 Jan 11:L21-0598. doi: 10.7326/L21-0598. Online ahead of print.Kamar N, Abravanel F, Marion O, Romieu-Mourez R, Couat C, Del Bello A, Izopet J. Assessment of 4 Doses of SARS-CoV-2 Messenger RNA-Based Vaccine in Recipients of a Solid Organ Transplant. JAMA Netw Open. 2021 Nov 1;4(11):e2136030.
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 MoreDear editor,
I read with interest the recently published new EULAR recommendations for managing the cardiovascular risk in patients with inflammatory rheumatic diseases [1]. They were long-awaited, and opportunely the targeted diseases are now broader, as previous ones focused primarily on chronic inflammatory arthritis [2].
With rising numbers worldwide, gout is a major cardiovascular risk factor directly linked to all forms of atherosclerotic diseases. By having gout, there is a 40% increased chance of dying from the coronary disease [3]. So, focused management to reduce these serious complications is necessary, and establishing an individual patient's risk is essential. Surprisingly, the experts rely on risk prediction using standard risk assessment tools, claiming the absence of validation studies. I should partially disagree at this point. Certainly, no longitudinal studies have evaluated the predicted rates of cardiovascular events in gout to date. However, our group studied the discriminative value of SCORE and Framingham tools in detecting patients with carotid plaques, a high-risk indicator [4]. A moderate discriminative capacity was unveiled, with areas under the curve of 0.711 for SCORE and 0.683 for Framingham [5]. Specificity was quite good, but the tools lacked enough sensitivity. Moreover, Gamala and colleagues incorporated gout into the modified Dutch SCORE as an inflammatory risk factor [6]. It led to a 28.3% upgrade to the high-risk stag...
Show MoreWe read with great interest the recent article written by Araujo CSR et al entitled “Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomized clinical trial” published in the Annals of Rheumatic Diseases on February 22, 2022 [1]. The major impact of this trial was the reinforcement of the immunogenic effect of a 2-week methotrexate discontinuation after each dose of the Sinovac-CoronaVac vaccine against SARS-CoV-2 compared to methotrexate continuation in patients with rheumatoid arthritis (seroconversion rates: 78.4% vs 54.5%, p-0.019 and geometric mean antibody titers: 34.2 (25.2–46.4) vs 16.8 (11.9–23.6), p=0.003, respectively).
Previous experience with other non-COVID-19 vaccines, like the influenza or pneumococcal vaccines, has indicated that discontinuation of immunosuppresants improves the immunogenicity of a given vaccine [2,3]. Based on this knowledge, we had proposed that it would be beneficial for patients with autoimmune rheumatic diseases to get vaccinated against SARS-CoV-2 preferably when the underlying rheumatic disease is in remission and after temporal withdrawal of anti-metabolites within 10 days before and after each vaccine dose along with similar modifications in anti-cytokine drugs and corticosteroid dosages >10mg/ day (prednisone equivalent) [4]. In fact, applying that in a comparative study it was shown that the magnitude of antibody responses to mRNA-based S...
Show MoreDear 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 MoreCorrespondence 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 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...
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).
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...
Dear Editor,
I want to congratulate Kvacskay et al. on an ingenious case series. While we have had evidence of the efficacy of obninutuzumab in lupus nephritis (2) in phase 2 trials and the RIM trial did show the efficacy of rituximab in anti-Jo1 positive myositis hence the expected responses with obinutuzumab, owing to its greater and more effective B cell depletion. The most interesting of the cases was case 4, where, according to the authors, obinutuzumab led to clearance of calcinosis in the patient. In a case series by Narváez et al.(4) only 50% of the patients with calcinosis in systemic sclerosis responded to rituximab (none of them had a complete response) in the systematic review, only one patient had a complete response to the treatment; overall among 19 patients, only 1 had complete response, so complete response with obinutuzumab is quite exciting as nothing sort of works for calcinosis.
When the authors mean complete response, do they mean complete radiological response and clinical response?
Also, the patient was given chlorambucil and bendamustine for her CLL, so the authors' attributing the response was solely due to obinutuzumab is doubtful.
1. Kvacskay P, Merkt W, Günther J, et al. Obinutuzumab in connective tissue diseases after former rituximab-non-response: a case series. Annals of the Rheumatic Diseases. Published Online First: 13 January 2022. doi: 10.1136/annrheumdis-2021-221756
Show More2.Furie RA, Aroca G, Cascino MD, e...
Dear Editor, we read the article entitle “Attenuated response to fourth dose SARS-CoV-2 vaccination in patients with autoimmune disease: a case series [1]” with a great interest. The efficacy of COVID-19 vaccine among specific groups of vaccine recipients with underlying disease is a current important clinical issue. For many groups of patients, including to those with autoimmune diseases, the low immune response to standard vaccination is observed. Extra-dose vaccination is proposed. For the fourth dose of COVID-19 vaccine, it is currently a new idea. Few reports are published. The clinical evidence is required for supporting whether the fourth dose of vaccine will be useful or not and whether there will be any risk of too much vaccination [2]. This report is one of an early publication on this issue. A previous publication is on kidney transplant case. As expected, the high immune response after the fourth dose of vaccine is observed [3]. However, as also seen in the present report, there are various types of first, second and third dose vaccines that each subject in the series received and it might affect the final immune response after the fourth dose vaccine administration. Also, there is usually no confirmation to rule out a possible incidence of asymptomatic COVID-19 infection which might occur in the period between doses of COVID-19 vaccines. These important concerns should be addressed and control of those confounding factors is important if further clinical res...
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