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
We read with great interest the article by Mageau et al.,1 who reported that COVID-19-associated organ failure (AOF) is associated with a poor late-onset outcome between days 30 (D30) and 90 (D90) among patients with systemic lupus erythematosus (SLE) in France. Conversely, they noted that an unchanged survival rate of patients with SLE with COVID-19-AOF will require hospitalization compared with patients without SLE COVID-19-AOF at D90. This study is a valuable addition to the literature. However, we share some concerns about this article to the authors.
First, the selection bias may be suspect in this study. A selection bias occurs when those in charge of the recruitment or enrollment of patients (recruiters) selectively enroll patients into the study based on what the next observation allocation is likely to be.2 At D30, 43 (21.9%) in-hospital deaths were recorded among patients with SLE with COVID-19-AOF compared with 31,274 (27.6%) in the unmatched patients without SLE with COVID-19-AOF. At baseline (D30), they may enroll a sick patient in patients with SLE with COVID-19-AOF compared with patients without SLE with COVID-19-AOF. This strategy can lead to substantially biased estimates of the survival of patients with COVID-19-AOF between D30 and D90 and misleading conclusions.
Second, prior studies have shown numerous AOFs, and disease severity of COVID-19 is independently associated with the increased risk of mortality.3,4 Furthermore, several para...
We read with great interest the article by Mageau et al.,1 who reported that COVID-19-associated organ failure (AOF) is associated with a poor late-onset outcome between days 30 (D30) and 90 (D90) among patients with systemic lupus erythematosus (SLE) in France. Conversely, they noted that an unchanged survival rate of patients with SLE with COVID-19-AOF will require hospitalization compared with patients without SLE COVID-19-AOF at D90. This study is a valuable addition to the literature. However, we share some concerns about this article to the authors.
First, the selection bias may be suspect in this study. A selection bias occurs when those in charge of the recruitment or enrollment of patients (recruiters) selectively enroll patients into the study based on what the next observation allocation is likely to be.2 At D30, 43 (21.9%) in-hospital deaths were recorded among patients with SLE with COVID-19-AOF compared with 31,274 (27.6%) in the unmatched patients without SLE with COVID-19-AOF. At baseline (D30), they may enroll a sick patient in patients with SLE with COVID-19-AOF compared with patients without SLE with COVID-19-AOF. This strategy can lead to substantially biased estimates of the survival of patients with COVID-19-AOF between D30 and D90 and misleading conclusions.
Second, prior studies have shown numerous AOFs, and disease severity of COVID-19 is independently associated with the increased risk of mortality.3,4 Furthermore, several parameters may predict disease severity and overall survival for COVID-19. For example, Acute Physiology and Chronic Health Evaluation II score is a classification tool used to measure disease severity and predict an individual’s risk of mortality in a hospital.5 Hence, the number of AOF and disease severity are clinically important risk factors. However, the baseline characteristics between the two groups were not defined in this study. As the number of AOF and disease severity of COVID-19 between the two groups was not available in this study, residual confounding bias may occur because of unmeasured factors.
Although we have some concerns regarding the study by Mageau et al.,1 we applaud the authors for their commendable work and hope that this study will benefit readers. We look forward to further work on the important topic of the predictive factors of survival after COVID-19-AOF among inpatients with SLE and hope that early preventive application for mortality will benefit patients with SLE with COVID-19-AOF.
References:
1. Mageau A, Papo T, Ruckly S, et al. Survival after COVID-19-associated organ failure among inpatients with systemic lupus erythematosus in France: a nationwide study. Ann Rheum Dis 2022;81:569-74.
2. Neyens T. Did an effect of kidney transplantation on COVID-19 mortality go unnoticed due to selection bias? Transpl Int 2021;34:773-5.
3. Meijs DAM, van Bussel BCT, Stessel B, et al. Better COVID-19 intensive care unit survival in females, independent of age, disease severity, comorbidities, and treatment. Sci Rep 2022:12:734.
4. Del Valle MD, Kim-Schulze S, Huang HH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 2020;26:1636–43.
5. Zou X, Li S, Fang M, et al. Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019. Crit Care Med 2020;48:e657–65.
We read with great interest the article titled ‘Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination’ by Lu et al.1. The authors found that COVID-19 vaccination was associated with increased odds of gout flare and was negatively associated with colchicine prophylaxis. However, we would like to draw attention to some concerns.
First, it is problematic to present multiple (over eight covariates) adjusted effect estimates from a single model in Table 3. The findings present in Table 3 may mix direct and total effect of each variable and make interpretation difficult2. Specifically, in current study, the authors aimed to assess the total effect of COVID-19 vaccination (the primary exposure) on the odds of gout flare while adjusting for other potential confounders3. Thus, the odds ratios for other covariates (e.g. colchicine prophylaxis treatment) are likely to reflect the direct effect of each covariate rather than total effect, and such a direct effect may be biased due to potential selection bias 4. For example, the odds ratio of sex increased dramatically from 0.82 in univariate analysis to 4.33 in model 2 analysis, which was biologically controversial.
Second, the calculation of odds ratios for vaccination and its subgroups in Table 3 seems questionable. Using the same reference group (no vaccination), the odds ratio of gout flares for any COVID-19 vaccines was 4.57 (p< 0.001), for subgroup of Sinovac Life vaccine was 2....
We read with great interest the article titled ‘Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination’ by Lu et al.1. The authors found that COVID-19 vaccination was associated with increased odds of gout flare and was negatively associated with colchicine prophylaxis. However, we would like to draw attention to some concerns.
First, it is problematic to present multiple (over eight covariates) adjusted effect estimates from a single model in Table 3. The findings present in Table 3 may mix direct and total effect of each variable and make interpretation difficult2. Specifically, in current study, the authors aimed to assess the total effect of COVID-19 vaccination (the primary exposure) on the odds of gout flare while adjusting for other potential confounders3. Thus, the odds ratios for other covariates (e.g. colchicine prophylaxis treatment) are likely to reflect the direct effect of each covariate rather than total effect, and such a direct effect may be biased due to potential selection bias 4. For example, the odds ratio of sex increased dramatically from 0.82 in univariate analysis to 4.33 in model 2 analysis, which was biologically controversial.
Second, the calculation of odds ratios for vaccination and its subgroups in Table 3 seems questionable. Using the same reference group (no vaccination), the odds ratio of gout flares for any COVID-19 vaccines was 4.57 (p< 0.001), for subgroup of Sinovac Life vaccine was 2.90 (p= 0.011), and for Sinopharm BIBP vaccine and other vaccines were 0.55 (p= 0.09) and 0.70 (p= 0.32), respectively. Of note, Sinopharm BIBP and other vaccines cases accounted for 45.9% of all COVID-19 vaccines assessed in this study as shown in Table 1. One would expect that the odds ratio of gout flare for any COVID-19 vaccines should be less than 2.90 (i..e, the odds ratio of gout flares for Sinovac Life vaccine). Using results provided in Table 1 and Table 2, we recalculated the crude odds ratio of gout flares for any COVID-19 vaccines (i.e., Sinovac Life vaccine, Sinopharm BIBP vaccine, and other vaccines combined), the odds ratio of gout flares was 1.65, not 4.57, suggesting either effect estimate for any COVID-19 vaccines or effect estimates for subgroups of vaccines may be incorrect.
To sum up, the concerns regarding “Table 2 Fallacy” and miscalculations of effect sizes in Table 3 should be taken into consideration to make this study more convincing and validating. We appreciate the work done by the authors and are looking forward to their responses.
Ethics statements: Not required.
Patient consent for publication: Not required.
Conflict of Interest Disclosures: None reported.
Contributors: TF, PC and ZZ drafted this correspondence. YL, MZ and SC were involved in revising and editing the correspondence.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review: Not commissioned; internally peer reviewed
References
1. Lu J, He Y, Terkeltaub R, et al. Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination. Ann Rheum Dis 2022 doi: 10.1136/annrheumdis-2022-222199 [published Online First: 2022/03/13]
2. Westreich D, Greenland S. The table 2 fallacy: presenting and interpreting confounder and modifier coefficients. Am J Epidemiol 2013;177(4):292-8. doi: 10.1093/aje/kws412 [published Online First: 2013/02/02]
3. Robins JM, Greenland S. Identifiability and exchangeability for direct and indirect effects. Epidemiology 1992;3(2):143-55. doi: 10.1097/00001648-199203000-00013 [published Online First: 1992/03/01]
4. Hernan MA, Hernandez-Diaz S, Werler MM, et al. Causal knowledge as a prerequisite for confounding evaluation: an application to birth defects epidemiology. Am J Epidemiol 2002;155(2):176-84. doi: 10.1093/aje/155.2.176 [published Online First: 2002/01/16]
5. Susser ES, S.; Morabia, A,; Bromet, E, J. . Psychiatric epidemiology 2006
6. Szklo M. Population-based cohort studies. Epidemiol Rev 1998;20(1):81-90. doi: 10.1093/oxfordjournals.epirev.a017974 [published Online First: 1998/10/08]
7. Schwartz S, Campbell UB, Gatto NM, et al. Toward a Clarification of the Taxonomy of "Bias" in Epidemiology Textbooks. Epidemiology 2015;26(2):216-22. doi: 10.1097/Ede.0000000000000224
Dear Editor,
We read with great interest the paper by Gwinnutt et al. on the recommendations regarding lifestyle behaviors and work participation to prevent progression of rheumatic and musculoskeletal diseases [1]. First, we applaud to the efforts of the EULAR task force to increase awareness around such important topic. Second, we congratulate with the authors for the attempt at harmonizing the recommendations on lifestyle and rheumatic musculoskeletal diseases (RMD) across European countries. We also acknowledge that trying to synthetize the available evidence regarding the impact of lifestyle on RMD is not an easy job. The task force focused on 6 main exposures (exercise, diet, weight, alcohol, smoking and work participation), which were probably chosen based on the relative World Health Organization (WHO) factsheets. However, we think that environmental air pollution, an important factor linked to RMD risk and aggravation [2–6], should have been at least mentioned in the manuscript. The WHO recently identified air pollution as: “one of the greatest environmental risk to health” [7]. According to the WHO report, 99% of the world population is living in places where the air quality guidelines are not met. Albeit 91% of premature deaths and disability related to air pollution affects the population living in low- and middle-income countries, European countries are impacted as well [8]. In addition, there is accumulating evidence that exposure to pollutants can be e...
Dear Editor,
We read with great interest the paper by Gwinnutt et al. on the recommendations regarding lifestyle behaviors and work participation to prevent progression of rheumatic and musculoskeletal diseases [1]. First, we applaud to the efforts of the EULAR task force to increase awareness around such important topic. Second, we congratulate with the authors for the attempt at harmonizing the recommendations on lifestyle and rheumatic musculoskeletal diseases (RMD) across European countries. We also acknowledge that trying to synthetize the available evidence regarding the impact of lifestyle on RMD is not an easy job. The task force focused on 6 main exposures (exercise, diet, weight, alcohol, smoking and work participation), which were probably chosen based on the relative World Health Organization (WHO) factsheets. However, we think that environmental air pollution, an important factor linked to RMD risk and aggravation [2–6], should have been at least mentioned in the manuscript. The WHO recently identified air pollution as: “one of the greatest environmental risk to health” [7]. According to the WHO report, 99% of the world population is living in places where the air quality guidelines are not met. Albeit 91% of premature deaths and disability related to air pollution affects the population living in low- and middle-income countries, European countries are impacted as well [8]. In addition, there is accumulating evidence that exposure to pollutants can be effectively reduced by simple environment and lifestyle related strategies [9]. Nevertheless, the evidence is still scarce as regards intervention in RMD. For these reasons, we think that future recommendations for the lifestyle modifications in RMD should at least acknowledge the air pollution problem in the research agenda.
References
1 Gwinnutt JM, Wieczorek M, Balanescu A, et al. 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Annals of the Rheumatic Diseases Published Online First: 7 March 2022. doi:10.1136/annrheumdis-2021-222020
2 Adami G, Viapiana O, Rossini M, et al. Association between environmental air pollution and rheumatoid arthritis flares. Rheumatology (Oxford) Published Online First: 20 January 2021. doi:10.1093/rheumatology/keab049
3 Adami G, Rossini M, Viapiana O, et al. Environmental Air Pollution Is a Predictor of Poor Response to Biological Drugs in Chronic Inflammatory Arthritides. ACR Open Rheumatol 2021;3:451–6. doi:10.1002/acr2.11270
4 Bellinato F, Adami G, Vaienti S, et al. Association Between Short-term Exposure to Environmental Air Pollution and Psoriasis Flare. JAMA Dermatol Published Online First: 16 February 2022. doi:10.1001/jamadermatol.2021.6019
5 Adami G, Pontalti M, Cattani G, et al. Association between long-term exposure to air pollution and immune-mediated diseases: a population-based cohort study. RMD Open;In Press-Accepted. doi:10.1136/rmdopen-2021-002055
6 Adami G, Cattani G, Rossini M, et al. Association between exposure to fine particulate matter and osteoporosis: a population-based cohort study. Osteoporos Int Published Online First: 15 July 2021. doi:10.1007/s00198-021-06060-9
7 Ambient (outdoor) air pollution. https://www.who.int/news-room/fact-sheets/detail/ambient-(outdoor)-air-quality-and-health (accessed 11 Mar 2022).
8 Khomenko S, Cirach M, Pereira-Barboza E, et al. Premature mortality due to air pollution in European cities: a health impact assessment. The Lancet Planetary Health 2021;5:e121–34. doi:10.1016/S2542-5196(20)30272-2
9 Bennett DH, Moran RE, Krakowiak P, et al. Reductions in particulate matter concentrations resulting from air filtration: A randomized sham-controlled crossover study. Indoor Air 2022;32:e12982. doi:10.1111/ina.12982
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.
Ugarte-Gil, et al (1) recently published a study reporting several characteristics associated with severe COVID-19 outcomes in people with systemic lupus erythematosus(SLE). Demographic factors, comorbidities, active or untreated SLE, and patients treated with glucocorticoids were the most noticeable features. Even though several covariates had been taken into consideration to minimize the impacts of these confounders, we presume vaccination could play a crucial role in the COVID-19 outcomes.
Previous studies had pointed out the protective effect that vaccination could provide against poor outcomes in the general population (2). In spite of a lack of evidence on the efficacy of COVID-19 vaccines in patients with SLE, achieving adequate sero-protection after receiving COVID-19 vaccine could be expected according to the expert opinion based on the knowledge on the use of other vaccines in this specific group of patients (3). A review article published by Wei Tang, et al (4) showed that commonly used immunosuppressants inclusive of glucocorticoids, methotrexate, mycophenolate mofetil/mycophenolic acid and rituximab might impede vaccine responses, causing less sufficient immune responses after getting COVID-19 vaccines in SLE patients. Hence, we suggest a subgroup analysis according to whether being vaccinated or not to have better data interpretation and to clarify the possible factors that may lead to critical consequences in SLE patients infected with COVID-19. ...
Ugarte-Gil, et al (1) recently published a study reporting several characteristics associated with severe COVID-19 outcomes in people with systemic lupus erythematosus(SLE). Demographic factors, comorbidities, active or untreated SLE, and patients treated with glucocorticoids were the most noticeable features. Even though several covariates had been taken into consideration to minimize the impacts of these confounders, we presume vaccination could play a crucial role in the COVID-19 outcomes.
Previous studies had pointed out the protective effect that vaccination could provide against poor outcomes in the general population (2). In spite of a lack of evidence on the efficacy of COVID-19 vaccines in patients with SLE, achieving adequate sero-protection after receiving COVID-19 vaccine could be expected according to the expert opinion based on the knowledge on the use of other vaccines in this specific group of patients (3). A review article published by Wei Tang, et al (4) showed that commonly used immunosuppressants inclusive of glucocorticoids, methotrexate, mycophenolate mofetil/mycophenolic acid and rituximab might impede vaccine responses, causing less sufficient immune responses after getting COVID-19 vaccines in SLE patients. Hence, we suggest a subgroup analysis according to whether being vaccinated or not to have better data interpretation and to clarify the possible factors that may lead to critical consequences in SLE patients infected with COVID-19.
Interestingly, the ordinal regression models examining the association between medication usage and disease severity of COVID-19 in this study revealed more favorable outcomes when SLE was treated with belimumab (1). A meta-analysis conducted by Singh et al (5) concluded six randomized controlled trials that belimumab showed clinically significant efficacy in comparison with placebo in participants with SLE at 52 weeks. Taken together with the better COVID-19 outcomes in patients using belimumab in the present study and evidence regarding the promising results of belimumab provided by former studies, we regard belimumab may be a potential direction for future research in SLE patients infected with COVID-19.
(1) Ugarte-Gil, M.F., Alarcón, G.S., Izadi, Z., et al. 2022. Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance. Annals of the Rheumatic Diseases annrheumdis–202. doi:10.1136/annrheumdis-2021-221636
(2) Tartof, S.Y., Slezak, J.M., Fischer, et al. 2021. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. The Lancet 398, 1407–1416. doi:10.1016/s0140-6736(21)02183-8
(3) Mason, A., Anver, H., Lwin, et al. 2021. Lupus, vaccinations and COVID-19: What we know now. Lupus 30, 1541–1552.doi:10.1177/09612033211024355
(4) Tang, W., Gartshteyn, Y., Ricker, E., et al. 2021. The Use of COVID-19 Vaccines in Patients with SLE. Current Rheumatology Reports 23. doi:10.1007/s11926-021-01046-2
(5) Singh JA, Shah NP, Mudano AS.2021. Belimumab for systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Feb 25;2(2):CD010668. doi: 10.1002/14651858.CD010668
We read with great interest the recent publication by Balsa et al.,[1] which reported that patient–physician agreement on the treatment, the type of treatment prescribed (favoring second-line conventional disease-modifying rheumatic drugs and biological disease-modifying rheumatic drugs/targeted synthetic disease-modifying rheumatic drugs), and the patient feeling privileged by the medication received are effective predictors of medication adherence in patients with rheumatoid arthritis (RA). In contrast, sociodemographic or clinical factors were not associated with medication adherence. This study focuses on medication adherence as a significant clinical variable and is a valuable addition to the literature. However, some issues have not been addressed by the authors.
First, epidemiologists agree that studies assessing a relation at one moment in time are called cross-sectional studies.[2] If the follow-up time is considered, the study is longitudinal, and it is either a cohort or a case-control study. A cohort or a case-control study must be applied to variables that can be reasonably assumed stable over time. However, this study was a six-month multicentre observational longitudinal prospective study, and medication adherence is related to psychological, communicational, and logistic factors measured at the same time. Therefore, this study is better labeled a cross-sectional study, since psychological, communicational, and logistic factors cannot be assumed to be...
We read with great interest the recent publication by Balsa et al.,[1] which reported that patient–physician agreement on the treatment, the type of treatment prescribed (favoring second-line conventional disease-modifying rheumatic drugs and biological disease-modifying rheumatic drugs/targeted synthetic disease-modifying rheumatic drugs), and the patient feeling privileged by the medication received are effective predictors of medication adherence in patients with rheumatoid arthritis (RA). In contrast, sociodemographic or clinical factors were not associated with medication adherence. This study focuses on medication adherence as a significant clinical variable and is a valuable addition to the literature. However, some issues have not been addressed by the authors.
First, epidemiologists agree that studies assessing a relation at one moment in time are called cross-sectional studies.[2] If the follow-up time is considered, the study is longitudinal, and it is either a cohort or a case-control study. A cohort or a case-control study must be applied to variables that can be reasonably assumed stable over time. However, this study was a six-month multicentre observational longitudinal prospective study, and medication adherence is related to psychological, communicational, and logistic factors measured at the same time. Therefore, this study is better labeled a cross-sectional study, since psychological, communicational, and logistic factors cannot be assumed to be stable over time.
Second, the sociodemographic factors are not predictive factors for medication adherence among patients with RA in this study. However, other socioeconomic variables such as race, employment status, and cultural differences[3] were not fully captured in this dataset, which may have impacted medication adherence in patients with RA. The differences in characteristics between all three groups further emphasize the need to better incorporate these types of socioeconomic variables into the methods for identifying predictive factors and managing high-risk patients in both routine clinical care and clinical research studies, particularly in relation to medication adherence.
Third, it is interesting that at six months, 86.0% and 80.6% of the patients adhered to the medications based on a Compliance Questionnaire Rheumatology (CQR) score and Reported Adherence to Medication (RAM) score (self-report adherence), respectively. Previous studies have clearly demonstrated that self-reports tend to overestimate adherence behavior compared with other assessment methods.[4, 5] However, the percentage of adherence in self-report RAM scores is less than in CQR scores in this study. Hence, there might be a self-serving bias in self-report RAM that authors should consider. Although the authors did an exceptional job of outlining the importance of acknowledging and counteracting the types of biases, other circumstances should be considered in self-report assessments.
In conclusion, although we have some concerns about the study by Balsa et al.,1 we applaud the authors for their commendable work and hope that this study will benefit readers. We look forward to further work on the important topic of medication adherence management and hope that integrating multifaceted interventions for the improvement of medication adherence will benefit patients with RA.
Contributors All authors reviewed the draft and approved the submission of the manuscript.
Competing interests None declared.
References:
1. Balsa A, García de Yébenes MJ, Carmona L, et al. Multilevel factors predict medication adherence in rheumatoid arthritis: a 6-month cohort study. Ann Rheum Dis 2022;81:327-34.
2. Dekkers OM, Groenwold RHH. Study design: what's in a name? Eur J Endocrinol 2020;183:E11-3.
3. Salt E, Frazier SK. Predictors of medication adherence in patients with rheumatoid arthritis. Drug Dev Res 2011;72:756-63.
4. Bright EE, Stanton AL. Correspondence between objective and self-reported endocrine therapy adherence among women with breast cancer. Ann Behav Med 2019;53:849-57.
5. van Breukelen-van der Stoep DF, Zijlmans J, van Zeben D, et al. Adherence to cardiovascular prevention strategies in patients with rheumatoid arthritis. Scand J Rheumatol 2015;44:443-8.
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 thank the author for this comment and his interest in our report. We agree that obinutuzumab has shown efficacy in a phase 2 trial in rituximab-naïve SLE patients. In our report, three of four patients did not respond to rituximab prior to receiving obinutuzumab. In our CREST syndrome patient (case 4), the combined obinutuzumab/chemotherapy led to a remission of her chronic lymphatic leukemia; leukocyte counts dropped from >200/nl to normal values. During this therapy, cutaneous calcinosis located on the distal upper extremities gradually regressed until its disappearance in clinical examination. We thank the author for pointing out that due to multiple comedications the disappearance of calcinosis cannot be solely traced back to obinutuzumab. However, we are not aware of cases in which calcinosis resolved due to chemotherapy so that we think obinutuzumab might have been at least partially responsible for this improvement. Further studies are needed to corroborate the effect of obinutuzumab on cutaneous manifestations in systemic sclerosis.
We read with great interest the article by Corbera-Bellalta et al. entitled “Blocking GM-CSF Receptor α with mavrilimumab reduces infiltrating cells, pro-inflammatory markers, and neoangiogenesis in ex-vivo cultured arteries from patients with giant cell arteritis” (1). We believe that the study is of great importance because it demonstrates that blocking the GM-CSF pathway alleviates crucial pathological hallmarks of giant cell arteritis (GCA). These hallmarks include leukocyte infiltration, production of pro-inflammatory cytokines, tissue destructive matrix metalloproteinases (MMP’s), and neoangiogenesis. Additionally, the recently reported preliminary data of the first phase II clinical trial of mavrilimumab in combination with a 26-week glucocorticoid (GC) taper in GCA patients is very promising (2). The primary end point, being the difference in the time to first relapse between mavrilimumab treatment and placebo was achieved (p=0.0263). Moreover, the sustained remission rate at 26 weeks was higher in the mavrilimumab vs placebo group (83.2% vs 49.9%, respectively, p =0.0038).
Recently, we reported on a distinct CD206+ macrophage subset that produces YKL-40 and MMP-9 in GCA affected vessels (3, 4). We proposed a pathogenic model in which these CD206+ macrophages play major roles in fueling leukocyte infiltration, vascular destruction, and neoangiogenesis. Furthermore, we showed that these CD206+/MMP-9+/YKL-40+ tissue destructive and proinflammatory macrophage...
We read with great interest the article by Corbera-Bellalta et al. entitled “Blocking GM-CSF Receptor α with mavrilimumab reduces infiltrating cells, pro-inflammatory markers, and neoangiogenesis in ex-vivo cultured arteries from patients with giant cell arteritis” (1). We believe that the study is of great importance because it demonstrates that blocking the GM-CSF pathway alleviates crucial pathological hallmarks of giant cell arteritis (GCA). These hallmarks include leukocyte infiltration, production of pro-inflammatory cytokines, tissue destructive matrix metalloproteinases (MMP’s), and neoangiogenesis. Additionally, the recently reported preliminary data of the first phase II clinical trial of mavrilimumab in combination with a 26-week glucocorticoid (GC) taper in GCA patients is very promising (2). The primary end point, being the difference in the time to first relapse between mavrilimumab treatment and placebo was achieved (p=0.0263). Moreover, the sustained remission rate at 26 weeks was higher in the mavrilimumab vs placebo group (83.2% vs 49.9%, respectively, p =0.0038).
Recently, we reported on a distinct CD206+ macrophage subset that produces YKL-40 and MMP-9 in GCA affected vessels (3, 4). We proposed a pathogenic model in which these CD206+ macrophages play major roles in fueling leukocyte infiltration, vascular destruction, and neoangiogenesis. Furthermore, we showed that these CD206+/MMP-9+/YKL-40+ tissue destructive and proinflammatory macrophages are induced upon GM-CSF signaling. In agreement with our findings, Corbera-Bellata et al. show that blockade of the GM-CSF Receptor α with mavrilimumab resulted in marked reduction in expression of CD206 (transcript) and MMP-9 (transcript & protein levels), leukocyte infiltration and neoangiogenesis.
We would like to put forward that YKL-40, also known as human cartilage-glycoprotein 39 or Chitinase 3-like 1/CHI3L1), could be a relevant biomarker to aid GCA patient stratification for treatment with mavrilimumab. YKL-40 is highly expressed by macrophages in inflammatory conditions and its overexpression is highly driven by GM-CSF (4, 5). Additionally, YKL-40 has been reported to be one of the upstream signals for MMP-9 expression by macrophages involved in tissue destruction and in the promotion of neovessel formation, two crucial processes in the pathogenesis of GCA (6, 7). Our group has previously reported that serum levels of YKL-40 are elevated at diagnosis and remain elevated during GC treatment in GCA patients (4, 8). Furthermore, higher levels of YKL-40 at diagnosis predicted a longer duration of GC treatment (8). In line with elevated YKL-40 levels, myeloid cells are also elevated in the circulation of GCA patients at diagnosis and during GC treatment (9). In tissue, macrophages remain present in the vessel wall after GC treatment (10). Thus, it appears that macrophages producing YKL-40, likely skewed by GM-CSF, are insufficiently targeted by GC treatment. As mavrilimumab treatment blocks the GM-CSF pathway and thereby affects the myeloid compartment, patients with high YKL-40 levels at baseline may especially benefit from mavrilimumab treatment. Future studies should evaluate whether serum levels of YKL-40 predict the response to mavrilimumab. Furthermore, it would be interesting to determine to what extent mavrilimumab is able to suppress the persistent YKL-40 response in patients with GCA. Taken together, we propose that serum YKL-40 measurements could be of interest for precision medicine and monitoring treatment efficacy of patients with GCA in the context of mavrilimumab treatment.
References:
1. M. Corbera-Bellalta, et al., Blocking GM-CSF receptor α with mavrilimumab reduces infiltrating cells, pro-inflammatory markers and neoangiogenesis in ex vivo cultured arteries from patients with giant cell arteritis. Ann. Rheum. Dis., annrheumdis-2021-220873 (2022).
2. M. C. Cid, et al., Mavrilimumab (anti GM-CSF Receptor α Monoclonal Antibody) Reduces Time to Flare and Increases Sustained Remission in a Phase 2 Trial of Patients with Giant Cell Arteritis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10).
3. W. F. Jiemy, et al., Distinct macrophage phenotypes skewed by local granulocyte macrophage colony‐stimulating factor (GM‐CSF) and macrophage colony‐stimulating factor (M‐CSF) are associated with tissue destruction and intimal hyperplasia in giant cell arteritis. Clin. Transl. Immunol. 9 (2020).
4. Y. van Sleen, et al., A Distinct Macrophage Subset Mediating Tissue Destruction and Neovascularization in Giant Cell Arteritis: Implication of the YKL-40 - IL-13 Receptor α2 Axis. Arthritis Rheumatol. (2021) https:/doi.org/10.1002/ART.41887 (July 28, 2021).
5. J. S. Johansen, K. S. Krabbe, K. Moller, B. K. Pedersen, Circulating YKL-40 levels during human endotoxaemia. Clin. Exp. Immunol. 140, 343–348 (2005).
6. S. Libreros, R. Garcia-Areas, P. Keating, R. Carrio, V. L. Iragavarapu-Charyulu, Exploring the role of CHI3L1 in “pre-metastatic” lungs of mammary tumor-bearing mice. Front. Physiol. 4, 392 (2013).
7. R. Watanabe, et al., MMP (matrix metalloprotease)-9-producing monocytes enable T cells to invade the vessel wall and cause vasculitis. Circ. Res. 123, 700–715 (2018).
8. Y. van Sleen, et al., Markers of angiogenesis and macrophage products for predicting disease course and monitoring vascular inflammation in giant cell arteritis. Rheumatology (Oxford). 58, 1383–1392 (2019).
9. Y. van Sleen, et al., Leukocyte Dynamics Reveal a Persistent Myeloid Dominance in Giant Cell Arteritis and Polymyalgia Rheumatica. Front. Immunol. 10 (2019).
10. J. J. Maleszewski, et al., Clinical and pathological evolution of giant cell arteritis: A prospective study of follow-up temporal artery biopsies in 40 treated patients. Mod. Pathol. 30, 788–796 (2017).
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...
Show MoreWe read with great interest the article by Mageau et al.,1 who reported that COVID-19-associated organ failure (AOF) is associated with a poor late-onset outcome between days 30 (D30) and 90 (D90) among patients with systemic lupus erythematosus (SLE) in France. Conversely, they noted that an unchanged survival rate of patients with SLE with COVID-19-AOF will require hospitalization compared with patients without SLE COVID-19-AOF at D90. This study is a valuable addition to the literature. However, we share some concerns about this article to the authors.
Show MoreFirst, the selection bias may be suspect in this study. A selection bias occurs when those in charge of the recruitment or enrollment of patients (recruiters) selectively enroll patients into the study based on what the next observation allocation is likely to be.2 At D30, 43 (21.9%) in-hospital deaths were recorded among patients with SLE with COVID-19-AOF compared with 31,274 (27.6%) in the unmatched patients without SLE with COVID-19-AOF. At baseline (D30), they may enroll a sick patient in patients with SLE with COVID-19-AOF compared with patients without SLE with COVID-19-AOF. This strategy can lead to substantially biased estimates of the survival of patients with COVID-19-AOF between D30 and D90 and misleading conclusions.
Second, prior studies have shown numerous AOFs, and disease severity of COVID-19 is independently associated with the increased risk of mortality.3,4 Furthermore, several para...
We read with great interest the article titled ‘Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination’ by Lu et al.1. The authors found that COVID-19 vaccination was associated with increased odds of gout flare and was negatively associated with colchicine prophylaxis. However, we would like to draw attention to some concerns.
First, it is problematic to present multiple (over eight covariates) adjusted effect estimates from a single model in Table 3. The findings present in Table 3 may mix direct and total effect of each variable and make interpretation difficult2. Specifically, in current study, the authors aimed to assess the total effect of COVID-19 vaccination (the primary exposure) on the odds of gout flare while adjusting for other potential confounders3. Thus, the odds ratios for other covariates (e.g. colchicine prophylaxis treatment) are likely to reflect the direct effect of each covariate rather than total effect, and such a direct effect may be biased due to potential selection bias 4. For example, the odds ratio of sex increased dramatically from 0.82 in univariate analysis to 4.33 in model 2 analysis, which was biologically controversial.
Second, the calculation of odds ratios for vaccination and its subgroups in Table 3 seems questionable. Using the same reference group (no vaccination), the odds ratio of gout flares for any COVID-19 vaccines was 4.57 (p< 0.001), for subgroup of Sinovac Life vaccine was 2....
Show MoreDear Editor,
Show MoreWe read with great interest the paper by Gwinnutt et al. on the recommendations regarding lifestyle behaviors and work participation to prevent progression of rheumatic and musculoskeletal diseases [1]. First, we applaud to the efforts of the EULAR task force to increase awareness around such important topic. Second, we congratulate with the authors for the attempt at harmonizing the recommendations on lifestyle and rheumatic musculoskeletal diseases (RMD) across European countries. We also acknowledge that trying to synthetize the available evidence regarding the impact of lifestyle on RMD is not an easy job. The task force focused on 6 main exposures (exercise, diet, weight, alcohol, smoking and work participation), which were probably chosen based on the relative World Health Organization (WHO) factsheets. However, we think that environmental air pollution, an important factor linked to RMD risk and aggravation [2–6], should have been at least mentioned in the manuscript. The WHO recently identified air pollution as: “one of the greatest environmental risk to health” [7]. According to the WHO report, 99% of the world population is living in places where the air quality guidelines are not met. Albeit 91% of premature deaths and disability related to air pollution affects the population living in low- and middle-income countries, European countries are impacted as well [8]. In addition, there is accumulating evidence that exposure to pollutants can be e...
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...
Show MoreUgarte-Gil, et al (1) recently published a study reporting several characteristics associated with severe COVID-19 outcomes in people with systemic lupus erythematosus(SLE). Demographic factors, comorbidities, active or untreated SLE, and patients treated with glucocorticoids were the most noticeable features. Even though several covariates had been taken into consideration to minimize the impacts of these confounders, we presume vaccination could play a crucial role in the COVID-19 outcomes.
Show MorePrevious studies had pointed out the protective effect that vaccination could provide against poor outcomes in the general population (2). In spite of a lack of evidence on the efficacy of COVID-19 vaccines in patients with SLE, achieving adequate sero-protection after receiving COVID-19 vaccine could be expected according to the expert opinion based on the knowledge on the use of other vaccines in this specific group of patients (3). A review article published by Wei Tang, et al (4) showed that commonly used immunosuppressants inclusive of glucocorticoids, methotrexate, mycophenolate mofetil/mycophenolic acid and rituximab might impede vaccine responses, causing less sufficient immune responses after getting COVID-19 vaccines in SLE patients. Hence, we suggest a subgroup analysis according to whether being vaccinated or not to have better data interpretation and to clarify the possible factors that may lead to critical consequences in SLE patients infected with COVID-19.
...
We read with great interest the recent publication by Balsa et al.,[1] which reported that patient–physician agreement on the treatment, the type of treatment prescribed (favoring second-line conventional disease-modifying rheumatic drugs and biological disease-modifying rheumatic drugs/targeted synthetic disease-modifying rheumatic drugs), and the patient feeling privileged by the medication received are effective predictors of medication adherence in patients with rheumatoid arthritis (RA). In contrast, sociodemographic or clinical factors were not associated with medication adherence. This study focuses on medication adherence as a significant clinical variable and is a valuable addition to the literature. However, some issues have not been addressed by the authors.
Show MoreFirst, epidemiologists agree that studies assessing a relation at one moment in time are called cross-sectional studies.[2] If the follow-up time is considered, the study is longitudinal, and it is either a cohort or a case-control study. A cohort or a case-control study must be applied to variables that can be reasonably assumed stable over time. However, this study was a six-month multicentre observational longitudinal prospective study, and medication adherence is related to psychological, communicational, and logistic factors measured at the same time. Therefore, this study is better labeled a cross-sectional study, since psychological, communicational, and logistic factors cannot be assumed to be...
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...
Show MoreWe thank the author for this comment and his interest in our report. We agree that obinutuzumab has shown efficacy in a phase 2 trial in rituximab-naïve SLE patients. In our report, three of four patients did not respond to rituximab prior to receiving obinutuzumab. In our CREST syndrome patient (case 4), the combined obinutuzumab/chemotherapy led to a remission of her chronic lymphatic leukemia; leukocyte counts dropped from >200/nl to normal values. During this therapy, cutaneous calcinosis located on the distal upper extremities gradually regressed until its disappearance in clinical examination. We thank the author for pointing out that due to multiple comedications the disappearance of calcinosis cannot be solely traced back to obinutuzumab. However, we are not aware of cases in which calcinosis resolved due to chemotherapy so that we think obinutuzumab might have been at least partially responsible for this improvement. Further studies are needed to corroborate the effect of obinutuzumab on cutaneous manifestations in systemic sclerosis.
We read with great interest the article by Corbera-Bellalta et al. entitled “Blocking GM-CSF Receptor α with mavrilimumab reduces infiltrating cells, pro-inflammatory markers, and neoangiogenesis in ex-vivo cultured arteries from patients with giant cell arteritis” (1). We believe that the study is of great importance because it demonstrates that blocking the GM-CSF pathway alleviates crucial pathological hallmarks of giant cell arteritis (GCA). These hallmarks include leukocyte infiltration, production of pro-inflammatory cytokines, tissue destructive matrix metalloproteinases (MMP’s), and neoangiogenesis. Additionally, the recently reported preliminary data of the first phase II clinical trial of mavrilimumab in combination with a 26-week glucocorticoid (GC) taper in GCA patients is very promising (2). The primary end point, being the difference in the time to first relapse between mavrilimumab treatment and placebo was achieved (p=0.0263). Moreover, the sustained remission rate at 26 weeks was higher in the mavrilimumab vs placebo group (83.2% vs 49.9%, respectively, p =0.0038).
Recently, we reported on a distinct CD206+ macrophage subset that produces YKL-40 and MMP-9 in GCA affected vessels (3, 4). We proposed a pathogenic model in which these CD206+ macrophages play major roles in fueling leukocyte infiltration, vascular destruction, and neoangiogenesis. Furthermore, we showed that these CD206+/MMP-9+/YKL-40+ tissue destructive and proinflammatory macrophage...
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