Journal of Clinical Medicine

Research

23 pages, 4672 KiB

Open AccessArticle

Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis

by Thomas Häupl, Till Sörensen, Biljana Smiljanovic, Marine Darcy, Justus Scheder-Bieschin, Nico Steckhan, Anika M. Hartmann, Daniela A. Koppold, Bruno Stuhlmüller, Karl Skriner, Barbara M. Walewska, Berthold Hoppe, Marc Bonin, Gerd R. Burmester, Pascal Schendel, Eugen Feist, Karsten Liere, Martin Meixner, Christian Kessler, Andreas Grützkau and Andreas Michalsen Show full author list Hide full author list

J. Clin. Med. 2023, 12(13), 4359; https://doi.org/10.3390/jcm12134359 - 28 Jun 2023

Cited by 6 | Viewed by 2108

Abstract

Rheumatoid arthritis (RA) synovitis is dominated by monocytes/macrophages with inflammatory patterns resembling microbial stimulation. In search of triggers, we reduced the intestinal microbiome in 20 RA patients (open label study DRKS00014097) by bowel cleansing and 7-day fasting (≤250 kcal/day) and performed immune monitoring [...] Read more.

Rheumatoid arthritis (RA) synovitis is dominated by monocytes/macrophages with inflammatory patterns resembling microbial stimulation. In search of triggers, we reduced the intestinal microbiome in 20 RA patients (open label study DRKS00014097) by bowel cleansing and 7-day fasting (≤250 kcal/day) and performed immune monitoring and microbiome sequencing. Patients with metabolic syndrome (n = 10) served as a non-inflammatory control group. Scores of disease activity (DAS28/SDAI) declined within a few days and were improved in 19 of 20 RA patients after breaking the fast (median ∆DAS28 = −1.23; ∆SDAI = −43%) or even achieved remission (DAS28 < 2.6/n = 6; SDAI < 3.3/n = 3). Cytometric profiling with 46 different surface markers revealed the most pronounced phenomenon in RA to be an initially increased monocyte turnover, which improved within a few days after microbiota reduction and fasting. Serum levels of IL-6 and zonulin, an indicator of mucosal barrier disruption, decreased significantly. Endogenous cortisol levels increased during fasting but were insufficient to explain the marked improvement. Sequencing of the intestinal microbiota indicated that fasting reduced potentially arthritogenic bacteria and changed the microbial composition to species with broader metabolic capabilities. More eukaryotic, predominantly fungal colonizers were observed in RA, suggesting possible involvement. This study demonstrates a direct link between the intestinal microbiota and RA-specific inflammation that could be etiologically relevant and would support targeted nutritional interventions against gut dysbiosis as a causal therapeutic approach. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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10 pages, 407 KiB

Open AccessArticle

Clinical Features of Diabetes Mellitus on Rheumatoid Arthritis: Data from the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group

by Fabio Cacciapaglia, Francesca Romana Spinelli, Elena Bartoloni, Serena Bugatti, Gian Luca Erre, Marco Fornaro, Andreina Manfredi, Matteo Piga, Garifallia Sakellariou, Ombretta Viapiana, Fabiola Atzeni and Elisa Gremese

J. Clin. Med. 2023, 12(6), 2148; https://doi.org/10.3390/jcm12062148 - 9 Mar 2023

Cited by 4 | Viewed by 2739

Abstract

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are linked by underlying inflammation influencing their development and progression. Nevertheless, the profile of diabetic RA patients and the impact of DM on RA need to be elucidated. This cross-sectional study includes 1523 patients with RA [...] Read more.

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are linked by underlying inflammation influencing their development and progression. Nevertheless, the profile of diabetic RA patients and the impact of DM on RA need to be elucidated. This cross-sectional study includes 1523 patients with RA and no episodes of cardiovascular events, followed up in 10 Italian University Rheumatologic Centers between 1 January and 31 December 2019 belonging to the “Cardiovascular Obesity and Rheumatic DISease (CORDIS)” Study Group of the Italian Society of Rheumatology. The demographic and clinical features of DM RA patients were compared to non-diabetic ones evaluating factors associated with increased risk of DM. Overall, 9.3% of the RA patients had DM, and DM type 2 was more common (90.2%). DM patients were significantly older (p < 0.001), more frequently male (p = 0.017), with a significantly higher BMI and mean weight (p < 0.001) compared to non-diabetic patients. DM patients were less likely to be on glucocorticoids (p < 0.001), with a trend towards a more frequent use of b/ts DMARDs (p = 0.08), and demonstrated higher HAQ (p = 0.001). In around 42% of patients (n = 114), DM diagnosis preceded that of RA. Treatment lines were identical in diabetic and non-diabetic RA patients. DM is a comorbidity that may influence RA management and outcome. The association between DM and RA supports the theory of systemic inflammation as a condition underlying the development of both diseases. DM may not have a substantial impact on bDMARDs resistance, although further investigation is required to clarify the implications of biological therapy resistance in RA patients. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

12 pages, 972 KiB

Open AccessArticle

The Impact of b/tsDMARD Dose Reduction on Chronic Hepatitis B in Rheumatoid Arthritis Patients: A Two-Center Long-Term Safety Analysis

by Der-Yuan Chen, Hsin-Hua Chen, Shih-Hsin Chang, Yi-Ming Chen, Po-Hao Huang, Chia-Wei Hsieh, Joung-Liang Lan and Kuo-Tung Tang

J. Clin. Med. 2023, 12(1), 86; https://doi.org/10.3390/jcm12010086 - 22 Dec 2022

Cited by 1 | Viewed by 1823

Abstract

Background: We aimed to investigate the change of hepatitis B virus (HBV) viral loads and HBV reactivation (HBVr) in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Methods: This two-center analysis retrospectively investigated the virological and [...] Read more.

Background: We aimed to investigate the change of hepatitis B virus (HBV) viral loads and HBV reactivation (HBVr) in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Methods: This two-center analysis retrospectively investigated the virological and biochemical evidence of HBVr in RA patients who underwent b/tsDMARD dose reduction. Serum levels of viral loads were determined using real-time PCR. Serum levels of alanine transaminase (ALT) were determined using spectrophotometry. Results: Among a total of 40 HBsAg+ RA patients who tapered b/tsDMARDs, 14 (35%) used tocilizumab; 12 (30%) used tumor necrosis factor (TNF)-α inhibitors; and the rest used either abatacept or tofacitinib. We found that patients who had detectable HBV DNA before tapering achieved a one-log reduction in HBV DNA levels, in contrast to the findings in the other 12 patients who did not taper b/tsDMARDs (no change in HBV DNA levels with time). The incidence of HBVr (increased viral loads with hepatitis) was 4.62 (95%CI: 2.08, 10.28) and 2.26 (95%CI: 0.56, 9.02) events per 100 person-years before and after b/tsDMARD tapering, respectively. Conclusions: The HBV viral load decreased after the tapering of b/tsDMARDs in RA patients with detectable HBV DNA. Dose reduction in b/tsDMARDs might be beneficial. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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13 pages, 1390 KiB

Open AccessArticle

Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)

by Michaela Koehm, Ann C. Foldenauer, Tanja Rossmanith, Rieke Alten, Martin Aringer, Marina Backhaus, Gerd R. Burmester, Eugen Feist, Herbert Kellner, Klaus Krueger, Ulf Müller-Ladner, Andrea Rubbert-Roth, Hans-Peter Tony, Siegfried Wassenberg, Harald Burkhardt and Frank Behrens

J. Clin. Med. 2022, 11(24), 7316; https://doi.org/10.3390/jcm11247316 - 9 Dec 2022

Viewed by 1839

Abstract

Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known. Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized [...] Read more.

Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known. Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide. In the study reported here (Part 2), Part 1 responders received rituximab 500 or 1000 mg at W24/26 plus ongoing leflunomide. Patients were randomized at baseline to their eventual W24 treatment group. The Part 2 primary outcome was the mean Disease Activity Score-28 joints (DAS28) at W52, based on the last observation carried forward (LOCF) analyses and a two-sided analysis of variance. Patient-reported outcomes (PROs) and adverse events were evaluated. Results: Eighty-three patients received rituximab at W24/26 (31 rituximab→rituximab 1000 mg; 29 rituximab→rituximab 500 mg; 10 placebo→rituximab 1000 mg; 13 placebo→rituximab 500 mg). At W52, there were no significant differences in DAS28 between rituximab doses in patients originally treated with rituximab or those originally treated with placebo. In the Part 1 placebo group, the higher rituximab dose was associated with greater improvements in ACR response rates and some PROs. Adverse events were similar regardless of rituximab dose. Conclusions: Retreatment with rituximab 500 mg and 1000 mg showed comparable efficacy, whereas an initial dose of rituximab 500 mg was associated with lower response rates versus 1000 mg. Reduced treatment response with the lower dose in patients initially treated with placebo may have been influenced by small numbers and baseline disease activity. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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12 pages, 629 KiB

Open AccessArticle

Low Serum BAFF Concentration Is Associated with Response to TNF Inhibitors in Seropositive Patients with Rheumatoid Arthritis

by Borja Hernández-Breijo, Ioannis Parodis, Marta Novella-Navarro, Ana Martínez-Feito, Victoria Navarro-Compán, Mariana Díaz-Almirón, Dora Pascual-Salcedo, Alejandro Balsa and Chamaida Plasencia-Rodríguez

J. Clin. Med. 2022, 11(17), 5207; https://doi.org/10.3390/jcm11175207 - 2 Sep 2022

Cited by 1 | Viewed by 1680

Abstract

We investigated B-cell-activating factor (BAFF) in relation to response to treatment with TNF inhibitors (TNFis) in rheumatoid arthritis (RA). This was a longitudinal study including 158 patients with RA treated with TNFis and followed up for 6 months. Clinical response at 6 months [...] Read more.

We investigated B-cell-activating factor (BAFF) in relation to response to treatment with TNF inhibitors (TNFis) in rheumatoid arthritis (RA). This was a longitudinal study including 158 patients with RA treated with TNFis and followed up for 6 months. Clinical response at 6 months of treatment was defined according to the EULAR criteria for good responders (GRs). BAFF concentration was measured in serum samples, collected at baseline and at 6 months. Associations with EULAR response were evaluated using univariable and multivariable logistic regression models. ROC analysis was performed to determine the optimal threshold of serum BAFF concentration associated with good EULAR response to treatment. After 6 months of TNFi treatment, 24% of patients were GRs. They had a lower BMI, lower baseline DAS28 and lower baseline serum BAFF concentration than non-responders. After 6 months of TNFi treatment, autoantibody-positive patients who attained GR had significantly lower serum BAFF concentrations compared with patients who did not. Serum BAFF < 968 pg/mL at 6 months represented the concentration likely to best discriminate between GR and non-GR at 6 months of TNFi treatment. Autoantibody-seropositive patients who had serum BAFF < 968 pg/mL at 6 months demonstrated a more than four-fold increased probability to be GRs compared with patients with higher BAFF concentrations. In conclusion, serum BAFF concentrations were associated with response to TNFis in seropositive RA patients, corroborating the importance of the B-cell compartment in RA. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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9 pages, 530 KiB

Open AccessArticle

FCER1G Gene Hypomethylation in Patients with Rheumatoid Arthritis

by Dominika Podgórska, Marek Cieśla and Bogdan Kolarz

J. Clin. Med. 2022, 11(16), 4664; https://doi.org/10.3390/jcm11164664 - 9 Aug 2022

Cited by 4 | Viewed by 2107

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that, when improperly treated, leads to disability in patients. Various factors that may cause the development and activity of RA are being considered. Epigenetic factors are also receiving increasing attention. In our study, we analyzed [...] Read more.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that, when improperly treated, leads to disability in patients. Various factors that may cause the development and activity of RA are being considered. Epigenetic factors are also receiving increasing attention. In our study, we analyzed the association between FCER1G gene methylation and RA activity. We conducted our study in 50 RA patients and 24 controls. The patients were divided into two groups in terms of high disease activity and remission. Quantitative real-time methylation-specific PCR was used to analyze the methylation status of the investigated genes. We observed that RA patients have lower levels of methylation of the FCER1G gene compared to controls, but we did not find any difference in the methylation status of this gene between patients with high disease activity and remission. The results of this study suggest that FCER1G gene methylation may be a new potential epigenetic marker of RA that is independent of disease activity. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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22 pages, 1783 KiB

Open AccessArticle

TNF-α Inhibitors in Combination with MTX Reduce Circulating Levels of Heparan Sulfate/Heparin and Endothelial Dysfunction Biomarkers (sVCAM-1, MCP-1, MMP-9 and ADMA) in Women with Rheumatoid Arthritis

by Anna Szeremeta, Agnieszka Jura-Półtorak, Aleksandra Zoń-Giebel, Krystyna Olczyk and Katarzyna Komosińska-Vassev

J. Clin. Med. 2022, 11(14), 4213; https://doi.org/10.3390/jcm11144213 - 20 Jul 2022

Cited by 5 | Viewed by 2344

Abstract

Sulfated glycosaminoglycans (sGAGs) are likely to play an important role in the development and progression of rheumatoid arthritis (RA)-associated atherosclerosis. The present study investigated the effect of anti-tumor necrosis factor-α (anti-TNF-α) therapy in combination with methotrexate on plasma sGAG levels and serum markers [...] Read more.

Sulfated glycosaminoglycans (sGAGs) are likely to play an important role in the development and progression of rheumatoid arthritis (RA)-associated atherosclerosis. The present study investigated the effect of anti-tumor necrosis factor-α (anti-TNF-α) therapy in combination with methotrexate on plasma sGAG levels and serum markers of endothelial dysfunction. Among sGAG types, plasma chondroitin/dermatan sulfate (CS/DS) and heparan sulfate/heparin (HS/H) were characterized using electrophoretic fractionation. Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and asymmetric dimethylarginine (ADMA) were measured by immunoassays. The measurements were carried out four times: at baseline and after 3, 9 and 15 months of anti-TNF-α therapy. All analyzed parameters, excluding ADMA, were significantly elevated in patients with RA before the implementation of biological therapy compared to healthy subjects. Performed anti-TNF-α treatment led to a successive decrease in HS/H levels toward normal values, without any effect on CS/DS levels in female RA patients. The treatment was also effective at lowering the serum levels of sVCAM-1, MCP-1, MMP-9 and ADMA. Moreover, a significant positive correlation was found between the circulating HS/H and the 28 joint disease activity score based on the erythrocyte sedimentation rate (DAS28-ESR, r = 0.408; p <0.05), MCP-1 (r = 0.398; p <0.05) and ADMA (r = 0.396; p <0.05) in patients before the first dose of TNF-α inhibitor. In conclusion, a beneficial effect of anti-TNF-α therapy on cell-surface heparan sulfate proteoglycans (HSPGs)/HS turnover and endothelial dysfunction was observed in this study. This was manifested by a decrease in blood HS/H levels and markers of endothelial activation, respectively. Moreover, the decrease in the concentration of HS/H in the blood of patients during treatment, progressing with the decline in disease activity, indicates that the plasma HS/H profile may be useful for monitoring the efficacy of anti-TNF-α treatment in patients with RA. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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Review

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17 pages, 2178 KiB

Open AccessReview

Reversing the Inflammatory Process—25 Years of Tumor Necrosis Factor-α Inhibitors

by Katharina N. Muth, Juergen Rech, Florian O. Losch and André Hoerning

J. Clin. Med. 2023, 12(15), 5039; https://doi.org/10.3390/jcm12155039 - 31 Jul 2023

Cited by 10 | Viewed by 2165

Abstract

Immune-mediated inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, peripheral and/or axial spondyloarthritis, Crohn’s disease, and ulcerative colitis, are characterized by molecular and cellular changes in the immune system. Due to the systemic nature of these diseases, organs such as the liver or [...] Read more.

Immune-mediated inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, peripheral and/or axial spondyloarthritis, Crohn’s disease, and ulcerative colitis, are characterized by molecular and cellular changes in the immune system. Due to the systemic nature of these diseases, organs such as the liver or cardiovascular system are often affected by the inflammatory process. Tumor necrosis factor-α inhibitor therapy reduces the activation of pro-inflammatory signaling cascades, mitigates the chronic inflammatory process by restoring cellular balance, and alleviates clinical consequences, such as pain and tissue damage. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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29 pages, 2292 KiB

Open AccessReview

A JAK Inhibitor for Treatment of Rheumatoid Arthritis: The Baricitinib Experience

by Peter C. Taylor, Cedric Laedermann, Rieke Alten, Eugen Feist, Ernest Choy, Ewa Haladyj, Inmaculada De La Torre, Pascal Richette, Axel Finckh and Yoshiya Tanaka

J. Clin. Med. 2023, 12(13), 4527; https://doi.org/10.3390/jcm12134527 - 6 Jul 2023

Cited by 12 | Viewed by 7585

Abstract

Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved as monotherapy or in combination with methotrexate for treating adults with moderate-to-severe active rheumatoid arthritis (RA) and provides improvements in clinical signs, symptoms and patient-reported outcomes. Currently, baricitinib is approved for treating RA [...] Read more.

Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved as monotherapy or in combination with methotrexate for treating adults with moderate-to-severe active rheumatoid arthritis (RA) and provides improvements in clinical signs, symptoms and patient-reported outcomes. Currently, baricitinib is approved for treating RA in more than 75 countries. In several pivotal Phase II and III RA trials (RA-BALANCE, RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BEYOND), up to seven years of baricitinib treatment was well tolerated and provided rapid and sustained efficacy, which was confirmed in real-world settings. Safety signals for another JAK inhibitor, tofacitinib, have emerged, as observed in the post-marketing Phase IIIb/IV trial Oral Rheumatoid Arthritis Trial (ORAL) Surveillance; safety signals were subsequently highlighted in a retrospective study of baricitinib and consequently new recommendations and warnings and precautions for all JAK inhibitors have been issued. Ongoing studies to further characterise and clarify the benefit:risk of JAK inhibitors include registries and controlled trials. This capstone review summarises clinical and real-world data outlining the benefit:risk profile of baricitinib, confirming that the improved disease activity and physical function of patients with RA treated with this JAK inhibitor observed in clinical trials is translated into effectiveness in clinical practice, with a low rate of discontinuations. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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18 pages, 642 KiB

Open AccessReview

Anti-Drug Antibodies in the Biological Therapy of Autoimmune Rheumatic Diseases

by Oscar Pizano-Martinez, Edgar Mendieta-Condado, Mónica Vázquez-Del Mercado, Erika Aurora Martínez-García, Efrain Chavarria-Avila, Daniel Ortuño-Sahagún and Ana Laura Márquez-Aguirre

J. Clin. Med. 2023, 12(9), 3271; https://doi.org/10.3390/jcm12093271 - 4 May 2023

Cited by 10 | Viewed by 5267

Abstract

Autoimmune rheumatic diseases are a cluster of heterogeneous disorders that share some clinical symptoms such as pain, tissue damage, immune deregulation, and the presence of inflammatory mediators. Biologic disease-modifying antirheumatic drugs are some of the most effective treatments for rheumatic diseases. However, their [...] Read more.

Autoimmune rheumatic diseases are a cluster of heterogeneous disorders that share some clinical symptoms such as pain, tissue damage, immune deregulation, and the presence of inflammatory mediators. Biologic disease-modifying antirheumatic drugs are some of the most effective treatments for rheumatic diseases. However, their molecular and pharmacological complexity makes them potentially immunogenic and capable of inducing the development of anti-drug antibodies. TNF inhibitors appear to be the main contributors to immunogenicity because they are widely used, especially in rheumatoid arthritis. Immunogenicity response on these treatments is crucial since the appearance of ADAs has consequences in terms of safety and efficacy. Therefore, this review proposes an overview of the immunogenicity of biological agents used in autoimmune rheumatic diseases highlighting the prevalence of anti-drug antibodies. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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16 pages, 317 KiB

Open AccessReview

Lifestyle Factors and Their Influence on Rheumatoid Arthritis: A Narrative Review

by Christoph Schäfer and Gernot Keyßer

J. Clin. Med. 2022, 11(23), 7179; https://doi.org/10.3390/jcm11237179 - 2 Dec 2022

Cited by 19 | Viewed by 4190

Abstract

In recent years, a possible association of lifestyle factors with rheumatoid arthritis (RA) has attracted increasing public interest. The aim of this review is to provide an overview of the extent and the limitations of current evidence regarding lifestyle factors and RA. The [...] Read more.

In recent years, a possible association of lifestyle factors with rheumatoid arthritis (RA) has attracted increasing public interest. The aim of this review is to provide an overview of the extent and the limitations of current evidence regarding lifestyle factors and RA. The PubMed medical database was screened for epidemiological and prospective studies investigating the contribution of lifestyle factors to the development and the course of the disease. Large epidemiological studies have identified smoking, unhealthy diet and adiposity, as well as a low educational level and low socioeconomic status, as factors that increase the incidence of RA. In addition, several lifestyle habits influence the response of RA to antirheumatic drugs. Among others, smoking, obesity and poor physical activity are associated with a worse treatment outcome. Methodological problems often impair firm conclusions with respect to the causal role of these factors in the risk and the course of RA. However, current evidence is sufficient to recommend a healthy diet, the prevention of obesity, the cessation of smoking and the maintenance of a high level of physical activity to support the effectivity of modern antirheumatic medication. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

11 pages, 495 KiB

Open AccessReview

Curcumin: Useful add-on for Rheumatic Diseases?

by Stylianos Tomaras, Gernot Keyßer and Eugen Feist

J. Clin. Med. 2022, 11(10), 2908; https://doi.org/10.3390/jcm11102908 - 20 May 2022

Cited by 10 | Viewed by 3710

Abstract

Plant-derived nutraceuticals are proposed as new key instruments to represent a profound “back to basics” shift in medical treatment. Data accumulated over the past ten years suggest that curcumin, the major active compound of the turmeric plant, has anti-inflammatory properties. It has yet [...] Read more.

Plant-derived nutraceuticals are proposed as new key instruments to represent a profound “back to basics” shift in medical treatment. Data accumulated over the past ten years suggest that curcumin, the major active compound of the turmeric plant, has anti-inflammatory properties. It has yet to be determined whether the anti-inflammatory profile of curcumin is potent enough to justify the application of this substance as a nutritional supplement for patients with rheumatic diseases. To address this question, the most relevant in vitro studies that investigate the mechanism of action of curcumin were reviewed in this article. In addition, a total of 18 animal and human trials were evaluated. The pleiotropic, anti-inflammatory and immunomodulatory effects of curcumin were observed in animal studies. In addition, human trials demonstrated promising findings. In these studies, curcumin was able to reduce the expression of proinflammatory cytokines, lower the level of the C-reactive protein and improve clinical parameters. A limiting factor of the application of curcumin is the inconsistent bioavailability of the substance. Therefore, new formulations have been developed to improve the pharmacodynamic profile of curcumin. The future acceptance of the substance is dependent on new controlled clinical trials with a standardised formulation of curcumin administered as well as standard of care. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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8 pages, 1115 KiB

Open AccessBrief Report

‘Status Quo’ on Different Aspects of Gender Distribution in Rheumatology in Germany—Results from a Nationwide Online Survey among Physicians

by Sarah Ohrndorf, Martin Krusche, Xenofon Baraliakos, Eugen Feist, Barbara Gundelach, Isabell Haase, Bimba Franziska Hoyer, Uta Kiltz, Michaela Koehm, Anna Julia Voormann, Philipp Sewerin and Johanna Mucke

J. Clin. Med. 2023, 12(13), 4328; https://doi.org/10.3390/jcm12134328 - 27 Jun 2023

Cited by 2 | Viewed by 1137

Abstract

Objectives: Despite the increasing number of female medical students and fellows in Europe, women are still under-represented in higher academic careers and positions in medicine. The aim of this survey was to assess the ‘status quo’ on gender distribution among rheumatologists in Germany. [...] Read more.

Objectives: Despite the increasing number of female medical students and fellows in Europe, women are still under-represented in higher academic careers and positions in medicine. The aim of this survey was to assess the ‘status quo’ on gender distribution among rheumatologists in Germany. Methods: A web-based anonymous survey (21 questions with multiple answers and free text) using QuestionPro^® was distributed among rheumatologists in Germany via newsletters, social media and personal contact, including questions regarding hierarchical positions and work characteristics. Results: Among the total of 170 respondents (72% women, 28% men, 1% diverse), 48% were rheumatologists in training, 35% were trained rheumatologists and 7% were heads of rheumatology departments. Regarding the gender ratio at different hierarchical levels, 74% of respondents reported more men than women in leadership positions. Part-time work was possible in the departments of 86% of respondents, with more women working part-time (56%) compared to men (29%). Most respondents stated their impression that employees working part-time did not have the same career chances as full-time workers in their departments. In total, 66% agreed that activities to improve gender equity are necessary. The highest need was seen in reconciling work and family through, e.g., part-time models, flexible childcare options at work and a higher acceptance of part-time work in leadership positions. Conclusions: According to our results, a gender imbalance is prevalent among rheumatologists in Germany, with lower numbers of women evident at higher hierarchical levels. Traditional role assignments are still represented by a higher proportion of part-time work in women. The establishment of structural changes to achieve better gender equity is needed. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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8 pages, 551 KiB

Open AccessBrief Report

Physical Function of RA patients Tapering Treatment—A Post Hoc Analysis of the Randomized Controlled RETRO Trial

by Marlene Stephan, Koray Tascilar, Melek Yalcin-Mutlu, Melanie Hagen, Judith Haschka, Michaela Reiser, Fabian Hartmann, Arnd Kleyer, Axel J. Hueber, Bernhard Manger, Camille Figueiredo, Jayme Fogagnolo Cobra, Hans-Peter Tony, Stephanie Finzel, Stefan Kleinert, Jörg Wendler, Florian Schuch, Monika Ronneberger, Martin Feuchtenberger, Martin Fleck, Karin Manger, Wolfgang Ochs, Matthias Schmitt-Haendle, Hannes Martin Lorenz, Hubert Nüsslein, Rieke Alten, Joerg Henes, Klaus Krüger, Georg Schett and Jürgen Rech Show full author list Hide full author list

J. Clin. Med. 2023, 12(11), 3723; https://doi.org/10.3390/jcm12113723 - 28 May 2023

Cited by 1 | Viewed by 1680

Abstract

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, [...] Read more.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Treatment and Future Options)

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