Correspondence on “Rheumatoid arthritis prevention: any takers?”
We read with great and special interest the editorial recently published in Rheumatic and Musculoskeletal Diseases by Falahee and Raza. 1 The authors clearly and elegantly state the clinical context in relation to current and potential interventions aimed to delay the onset, reduce the likelihood, or mitigate the severity of rheumatoid arthritis (RA). In addition, the authors present some data based on the perspectives and preferences of individuals who had participated in clinical trials aimed to achieve RA prevention and, on the challenges, related to recruitment for the research community as well. 2
Preventive strategies targeting RA—especially in the preclinical phases—have recently been developed. Currently, this is an exciting field of research on chronic diseases and more specifically in the field of rheumatology to delineate interventions to modify or at least to delay the onset of RA. There is information provided in the literature related to assessing therapeutic approaches based on pharmacological interventions, such as glucocorticoids, 3 methotrexate, 4 hydroxychloroquine, 5 statins, 6 B cell directed therapy 7 and T-cell co-stimulation modulation. 8
In contrast, studies on non-pharmacological preventive strategies in high-risk populations for RA are scarce. Thus, some cohort studies are exploring the efficacy of the modification of risk factors previously established as potentia...
Correspondence on “Rheumatoid arthritis prevention: any takers?”
We read with great and special interest the editorial recently published in Rheumatic and Musculoskeletal Diseases by Falahee and Raza. 1 The authors clearly and elegantly state the clinical context in relation to current and potential interventions aimed to delay the onset, reduce the likelihood, or mitigate the severity of rheumatoid arthritis (RA). In addition, the authors present some data based on the perspectives and preferences of individuals who had participated in clinical trials aimed to achieve RA prevention and, on the challenges, related to recruitment for the research community as well. 2
Preventive strategies targeting RA—especially in the preclinical phases—have recently been developed. Currently, this is an exciting field of research on chronic diseases and more specifically in the field of rheumatology to delineate interventions to modify or at least to delay the onset of RA. There is information provided in the literature related to assessing therapeutic approaches based on pharmacological interventions, such as glucocorticoids, 3 methotrexate, 4 hydroxychloroquine, 5 statins, 6 B cell directed therapy 7 and T-cell co-stimulation modulation. 8
In contrast, studies on non-pharmacological preventive strategies in high-risk populations for RA are scarce. Thus, some cohort studies are exploring the efficacy of the modification of risk factors previously established as potential contributors to disease initiation and progression. In this context, potential preventive strategies, such as control of body weight,9 nutritional habits,10 education11, and smoking cessation,12 have been proposed as potential targets. Clinical trials demonstrating a significant preventive effect for lifestyle or risk factor modification are difficult to perform. Therefore, more investigations in this area are needed to properly define preventive treatment options in high-risk populations to translate them into specific interventions.13
In addition, to the potential strategies defined by Falahhe et al., there is a missing ‘taker’ in the room that may be a cost-effective and non-pharmacological intervention to be considered in this approach to potentially prevent the development of RA. Periodontitis is a chronic inflammatory condition characterised by the progressive destruction of the periodontal ligament and alveolar bone.14 Periodontal disease is a common worldwide and inflammatory condition that has been considered to be associated with other systemic diseases, such as diabetes mellitus and cardiovascular disease.15 In the repertoire of conditions potentially associated with periodontal diseases, there is ample data supporting the strong association between periodontitis as a factor associated with developing RA. Many studies have reported that the presence of RA has been associated not only with an increased prevalence of periodontitis but also with a significant inflammatory periodontal involvement even in the early phase of the disease.16 Similarly, periodontitis has been considered to be a condition influencing the risk of developing RA in first-degree relatives17 and to be related to the progression of inflammatory involvement in RA as well.18
In an era of precision and personalised medicine, one could expect that targeting individuals in the preclinical phases of RA—either pharmacologically and/or through risk factor modifications—may optimise prevention. Hence, first-degree relatives of RA patients may constitute an interesting population to be targeted to evaluate the impact and/or favourable effect of preventive measures, including oral health interventions and periodontal treatment. Information is lacking in the literature in assessing the effectiveness of oral interventions and their impacts on the preclinical phases of RA. Therefore, it will be highly valuable for the academic community to consider the modulation of a periodontal inflammatory condition as a plausible and cost-effective measure to modulate the beginning and the development of RA.
References
1. Falahee M, Raza K. Rheumatoid arthritis prevention: any takers? RMD Open 2021;7:e001633. doi:10.1136/rmdopen-2021-001633
2. van Boheemen L, van Schaardenburg D. Predicting rheumatoid arthritis in at risk individuals. Clin Ther 2019; 41:1286–98
3. Bos WH, Dijkmans BA, Boers M, van de Stadt RJ, van Schaardenburg D. Effect of dexamethasone on autoantibody levels and arthritis development in patients with arthralgia: a randomised trial. Ann Rheum Dis 2010; 69:571–574
4. van Dongen H, van Aken J, Lard LR, Visser K, Ronday HK, Hulsmans HM, et al. Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2007; 56:1424–1432
5. Strategy to prevent the onset of Clinically- Apparent rheumatoid arthritis (StopRA). Available: http://clinicaltrials.gov/ct2/show/
NCT02603146
6. Van Boheemen L, Turk SA, Van Beers - Tas MH, et al. AB0230 Statins to Prevent Rheumatoid Arthritis: Inconclusive Results of the STAPRA Trial. Ann Rheum Dis 2020; 79:1415-1416
7. Gerlag DM, Safy M, Maijer KI, et al. Effects of B- cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis 2019; 78:179–85.
8. Al- Laith M, Jasenecova M, Abraham S, et al. Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi centre, randomised, double-blind, parallel group, placebo-controlled clinical trial protocol. Trials 2019; 20:429.
9. Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. Genetic and environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol 2017; 31:3-18
10. Zaccardelli A, Friedlander HM, Ford JA, Sparks JA. Potential of lifestyle changes for reducing the risk of developing rheumatoid arthritis: is an ounce of prevention worth a pound of cure? Clin Ther 2019; 41:1323–1345
11. Sparks JA, Iversen MD, Miller Kroouze R, Mahmoud TG, Triedman NA, Kalia SS, et al. Personalized risk estimator for rheumatoid arthritis (PRE-RA) family study: rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives. Contemp Clin Trials 2014; 39:145–157.
12. Liu X, Tedeschi SK, Barbhaiya M, Leatherwood CL, Speyer CB, Lu B, et al. Impact and timing of smoking cessation on reducing risk of rheumatoid arthritis among women in the nurses’ health studies. Arthritis Care Res 2019; 71:914–924
13. Alpizar-Rodriguez D, Finckh A. Is the prevention of rheumatoid arthritis possible? Clin Rheumatol. 2020; 39:1383-1389
14. Page RC, Kornman KS. The pathogenesis of human periodontitis: an introduction. Periodontol 2000 1997;14:9–11
15. Qin X, Zhao Y, Guo Y. Periodontal disease and myocardial infarction risk: A meta-analysis of cohort studies. Am J Emerg Med. 2021; 8; 48:103-109
16. Rovas A, Puriene A, Punceviciene E, Butrimiene I, Stuopelyte K, Jarmalaite S. Associations of periodontal status in periodontitis and rheumatoid arthritis patients. J Periodontal Implant Sci. 2021; 51:124-134
17. Unriza-Puin S, Bautista-Molano W, Lafaurie GI, et al. Are obesity, ACPAs and periodontitis conditions that influence the risk of developing rheumatoid arthritis in first-degree relatives? Clin Rheumatol 2017;36:799–806
18. Lundberg K, Wegner N, Yucel-Lindberg T, Venables PJ. Periodontitis in RA the citrullinated enolase connection. Nat Rev Rheumatol 2010; 6:727–730
The small randomized clinical trial by Lopes MI et al. has shown a meaningful benefit of colchicine in COVID- 19 patients. However, there are ambiguities in the written study design including the techniques opted for allocation concealment, blinding, and sample size calculations with six primary endpoints. Investigators were not able to analyze four major endpoints including mortality rate, causes of mortality, admission to ICU, and length of stay in ICU [1]. These results became hard to compare with other major studies such as preliminary findings of the RECOVERY trial where investigators have closed the recruitment of colchicine arm. There was no convincing evidence of mortality benefit in the colchicine group. Final results will show more data on secondary outcomes such as length of hospital stay and need for invasive mechanical ventilation [2].
This may not be the end of the road for colchicine as 26 study groups have been registered with clinicaltrial.gov to prove the beneficial effects of colchicine in COVID patients. At least four of these studies have already been completed. Preprint data from the COLCORONA trial shows a controversial conclusion of reduction in composite rate of death or hospitalization with colchicine in PCR confirmed non hospitalized patients [3]. Another small size COLORIT trial by Mareev V.Yu. et al. showed the median SHOCS score decreased from 8 to 2, i.e., from a moderate to a mild degree in the colchicine group. The...
The small randomized clinical trial by Lopes MI et al. has shown a meaningful benefit of colchicine in COVID- 19 patients. However, there are ambiguities in the written study design including the techniques opted for allocation concealment, blinding, and sample size calculations with six primary endpoints. Investigators were not able to analyze four major endpoints including mortality rate, causes of mortality, admission to ICU, and length of stay in ICU [1]. These results became hard to compare with other major studies such as preliminary findings of the RECOVERY trial where investigators have closed the recruitment of colchicine arm. There was no convincing evidence of mortality benefit in the colchicine group. Final results will show more data on secondary outcomes such as length of hospital stay and need for invasive mechanical ventilation [2].
This may not be the end of the road for colchicine as 26 study groups have been registered with clinicaltrial.gov to prove the beneficial effects of colchicine in COVID patients. At least four of these studies have already been completed. Preprint data from the COLCORONA trial shows a controversial conclusion of reduction in composite rate of death or hospitalization with colchicine in PCR confirmed non hospitalized patients [3]. Another small size COLORIT trial by Mareev V.Yu. et al. showed the median SHOCS score decreased from 8 to 2, i.e., from a moderate to a mild degree in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. SHOCS-COVID score includes the assessment of the patient’s clinical condition, CT score of pulmonary lesions, CRP, and D-dimer values [4]. Preprint results from one observational cross-sectional study from Columbia with analysis of 301 patients also found treatment with corticosteroids and colchicine for managing patients with severe COVID-19 pneumonia was associated with low mortality [5]. Although this study had a moderate risk of bias due to study design. Many more studies are on their way to completion and publication. A comprehensive meta-analysis will provide conclusive evidence if colchicine can be included in the standard of care for COVID-19 patients.
1- Lopes MI, Bonjorno LP, Giannini MC, et al Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial. RMD Open 2021;7:e001455. https://doi.org/10.1136/rmdopen-2020-001455
2- RECOVERY trial closes recruitment to colchicine treatment for patients hospitalised with COVID-19 — RECOVERY Trial. (n.d.). Retrieved March 21, 2021, from https://www.recoverytrial.net/news/recovery-trial-closes-recruitment-to-...
3- Tardif, J.-C., Bouabdallaoui, N., L’allier, P. L., et al Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19. MedRxiv, 2021.01.26.21250494. https://doi.org/10.1101/2021.01.26.21250494
4- Mareev V.Yu., Orlova Y.A., Plisyk A.G. et al Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study. Kardiologiia. 2021;61(2):15-27. https://doi.org/10.18087/cardio.2021.2.n1560
5- Miguel Alejandro Pinzón, Doris Cardona Arango, Juan Felipe Betancur et al. Clinical Outcome of Patients with COVID-19 Pneumonia Treated with Corticosteroids and Colchicine in Colombia, 23 October 2020, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-94922/v1]
Correspondence on “Rheumatoid arthritis prevention: any takers?”
Show MoreWe read with great and special interest the editorial recently published in Rheumatic and Musculoskeletal Diseases by Falahee and Raza. 1 The authors clearly and elegantly state the clinical context in relation to current and potential interventions aimed to delay the onset, reduce the likelihood, or mitigate the severity of rheumatoid arthritis (RA). In addition, the authors present some data based on the perspectives and preferences of individuals who had participated in clinical trials aimed to achieve RA prevention and, on the challenges, related to recruitment for the research community as well. 2
Preventive strategies targeting RA—especially in the preclinical phases—have recently been developed. Currently, this is an exciting field of research on chronic diseases and more specifically in the field of rheumatology to delineate interventions to modify or at least to delay the onset of RA. There is information provided in the literature related to assessing therapeutic approaches based on pharmacological interventions, such as glucocorticoids, 3 methotrexate, 4 hydroxychloroquine, 5 statins, 6 B cell directed therapy 7 and T-cell co-stimulation modulation. 8
In contrast, studies on non-pharmacological preventive strategies in high-risk populations for RA are scarce. Thus, some cohort studies are exploring the efficacy of the modification of risk factors previously established as potentia...
Dear Editor
The small randomized clinical trial by Lopes MI et al. has shown a meaningful benefit of colchicine in COVID- 19 patients. However, there are ambiguities in the written study design including the techniques opted for allocation concealment, blinding, and sample size calculations with six primary endpoints. Investigators were not able to analyze four major endpoints including mortality rate, causes of mortality, admission to ICU, and length of stay in ICU [1]. These results became hard to compare with other major studies such as preliminary findings of the RECOVERY trial where investigators have closed the recruitment of colchicine arm. There was no convincing evidence of mortality benefit in the colchicine group. Final results will show more data on secondary outcomes such as length of hospital stay and need for invasive mechanical ventilation [2].
Show MoreThis may not be the end of the road for colchicine as 26 study groups have been registered with clinicaltrial.gov to prove the beneficial effects of colchicine in COVID patients. At least four of these studies have already been completed. Preprint data from the COLCORONA trial shows a controversial conclusion of reduction in composite rate of death or hospitalization with colchicine in PCR confirmed non hospitalized patients [3]. Another small size COLORIT trial by Mareev V.Yu. et al. showed the median SHOCS score decreased from 8 to 2, i.e., from a moderate to a mild degree in the colchicine group. The...
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