Chronic inflammation plays a central role in the pathophysiology of various non-communicable diseases. Dietary interventions can reduce inflammation, in part due to their effect on the gut ...microbiome. This systematic review aims to determine the effect of dietary interventions, specifically fiber intake, on chronic inflammatory diseases and the microbiome. It aims to form hypotheses on the potential mediating effects of the microbiome on disease outcomes after dietary changes. Included were clinical trials which performed a dietary intervention with a whole diet change or fiber supplement (>5 g/day) and investigated the gut microbiome in patients diagnosed with chronic inflammatory diseases such as cardiovascular disease (CVD), type 2 diabetes (T2DM), and autoimmune diseases (e.g., rheumatoid arthritis (RA), inflammatory bowel disease (IBD)). The 30 articles which met the inclusion criteria had an overall moderate to high risk of bias and were too heterogeneous to perform a meta-analysis. Dietary interventions were stratified based on fiber intake: low fiber, high fiber, and supplemental fiber. Overall, but most pronounced in patients with T2DM, high-fiber plant-based dietary interventions were consistently more effective at reducing disease-specific outcomes and pathogenic bacteria, as well as increasing microbiome alpha diversity and short-chain fatty acid (SCFA)-producing bacteria, compared to other diets and fiber supplements.
To validate the presence and demonstrate the clinical value of the type I interferon (IFN)-signature during arthritis development.
In 115 seropositive arthralgia patients who were followed for the ...development of arthritis (Amsterdam Reade cohort), and 25 presymptomatic individuals who developed rheumatoid arthritis (RA) later, and 45 population-based controls (Northern Sweden cohort), the expression levels of 7 type I IFN response genes were determined with multiplex qPCR and an IFN-score was calculated. The diagnostic performance of the IFN-score was evaluated using Cox regression and Receiver Operating Characteristics (ROC)-curve analysis.
In 44 of the 115 at-risk individuals (38%) from the Amsterdam Reade cohort, arthritis developed after a median period of 8 months (IQR 5-13). Stratification of these individuals based on the IFN-score revealed that 15 out of 25 IFN(high) individuals converted to arthritis, compared with 29 out of 90 IFN(low) individuals (p=0.011). In the Northern Sweden cohort, the level of the IFN-score was also significantly increased in presymptomatic individuals who developed RA compared with population-based controls (p=0.002). Cox regression analysis of the Amsterdam Reade cohort showed that the hazard ratio (HR) for development of arthritis was 2.38 (p=0.008) for IFN(high) at-risk individuals after correction for anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). The ROC-curve area under the curve (AUC) for the IFN-score combined with ACPA and RF in the prediction of arthritis was 78.5% (p=0.0001, 95% CI 0.70 to 0.87).
The results demonstrated clinical utility for the IFN-signature as a biomarker in the prediction of arthritis development.
Guidelines suggest treatment in rheumatoid arthritis (RA) to target remission, in close consultation with the patient. Our recent qualitative study of the patients' perspective on remission in RA ...identified 26 domains. The current study aimed to identify a short list of the most important aspects to inform future research.
Patients with RA from the Netherlands, the UK, Austria, Denmark, France and the USA completed a survey that contained all domains identified in our qualitative study. They rated domains for importance ('not important', 'important' or 'essential' to characterise a period of remission) and if important or essential, whether this domain needs to be 'less', 'almost gone' or 'gone' to reflect remission. Respondents were also asked to determine their personal top 3 most important/essential domains. Frequency of specific domains in the top 3 was calculated, and domains were sorted on the percentage of patients that evaluated a particular domain as 'essential'.
Of 274 respondents, 75% were female, mean (SD) age 57(13) years, disease duration 12(9) years. The top 3 were as follows: pain (67%), fatigue (33%) and independence (19%); domains most frequently rated as 'essential' were as follows: pain (60%), being mobile (52%), physical function (51%), being independent (47%) and fatigue (41%). Pain needed to be less (13%), almost gone (42%) or gone (45%) to reflect remission. Similar patterns were seen for fatigue, independence, mobility and physical functioning.
Patients identified pain, fatigue and independence as the most important domains of RA disease activity that need to be improved to reflect remission.
Early, intensive treatment of rheumatoid arthritis (RA) with the combination of (initially high dose) prednisolone, methotrexate and sulfasalazine (COBRA therapy) considerably lowers disease activity ...and suppresses radiological progression, but is infrequently prescribed in daily practice. Attenuating the COBRA regimen might lessen concerns about side effects, but the efficacy of such strategies is unknown.
To compare the 'COBRA-light' strategy with only two drugs, comprising a lower dose of prednisolone (starting at 30 mg/day, tapered to 7.5 mg/day in 9 weeks) and methotrexate (escalated to 25 mg/week in 9 weeks) to COBRA therapy (prednisolone 60 mg/day, tapered to 7.5 mg/day in 6 weeks, methotrexate 7.5 mg/week and sulfasalazine 2 g/day).
An open, randomised controlled, non-inferiority trial in 164 patients with early active RA, all treated according to a treat to target strategy.
At baseline patients had moderately active disease: mean (SD) 44-joint disease activity score (DAS44) 4.13 (0.81) for COBRA and 3.95 (0.9) for COBRA-light. After 6 months, DAS44 significantly decreased in both groups (-2.50 (1.21) for COBRA and -2.18 (1.10) for COBRA-light). The adjusted difference in DAS44 improvement between the groups, 0.21 (95% CI -0.11 to 0.53), was smaller than the predefined clinically relevant difference of 0.5. Minimal disease activity (DAS44 <1.6) was reached in almost half of patients in both groups (49% and 41% in COBRA and COBRA-light, respectively).
At 6 months COBRA-light therapy is most likely non-inferior to COBRA therapy.
55552928.
Abstract
Low-grade inflammation and metabolic syndrome are seen in many chronic diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Lifestyle interventions which combine different ...non-pharmacological therapies have shown synergizing effects in improving outcomes in patients with other chronic diseases or increased risk thereof, especially cardiovascular disease. For RA and metabolic syndrome-associated OA (MSOA), whole food plant-based diets (WFPDs) have shown promising results. A WFPD, however, had not yet been combined with other lifestyle interventions for RA and OA patients. In this protocol paper, we therefore present Plants for Joints, a multidisciplinary lifestyle program, based on a WFPD, exercise, and stress management. The objective is to study the effect of this program on disease activity in patients with RA (randomized controlled trial RCT 1), on a risk score for developing RA in patients with anti-citrullinated protein antibody (ACPA) positive arthralgia (RCT 2) and on pain, stiffness, and function in patients with MSOA (RCT 3), all in comparison with usual care.
We designed three 16-week observer-blind RCTs with a waiting-list control group for patients with RA with low to moderate disease activity (2.6 ≤ Disease Activity Score DAS28 ≤ 5.1, RCT 1,
n
= 80), for patients at risk for RA, defined by ACPA-positive arthralgia (RCT 2,
n
= 16) and for patients with metabolic syndrome and OA in the knee and/or hip (RCT 3,
n
= 80). After personal counseling on diet and exercise, participants join 10 group meetings with 6–12 other patients to receive theoretical and practical training on a WFPD, exercise, and stress management, while medication remains unchanged. The waiting-list control group receives usual care, while entering the program after the RCT. Primary outcomes are: difference in mean change between intervention and control groups within 16 weeks for the DAS28 in RA patients (RCT 1), the RA-risk score for ACPA positive arthralgia patients (RCT 2), and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score for MSOA patients (RCT 3). Continued adherence to the lifestyle program is measured in a two-year observational extension study.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of rheumatoid arthritis (RA) treatment is remission. As treatment should be targeted at outcomes relevant to patients, it is important to understand how patients perceive remission, and to ...assess whether the current definition of remission adequately reflects these perceptions. The objective of this study is to explore the patient perspective on remission in RA.
Nine focus-group discussions in Austria, The Netherlands and UK were conducted, including patients in American College of Rheumatology (ACR)/ European League of Rheumatology (EULAR) remission, self-declared remission and in moderate/high disease activity. Moderators employed a prespecified interview guide helped to engage patients in a discussion on their experience with remission. Inductive thematic analysis was performed within each country, and identified themes were discussed across countries.
47 RA patients (66% women, disease duration 9 years) participated. Three major themes of patient-perceived remission emerged: (1) symptoms would either be absent or strongly reduced, (2) impact of the disease on daily life would diminish by increased independence, ability to do valued activities, improved mood and ability to cope; (3) leading to a return to normality, including work, family role and perception of others. Patients felt the concept of remission was influenced by ageing, side effects of medication, comorbidities, accrued damage to joints and disease duration. Opinions on duration of state, the role of medication and measurement instruments varied widely.
Patients characterise remission by the absence or reduction of symptoms, but more directly by decreased daily impact of their condition and the feeling of a return to normality. The next step is to study whether an additional patient-perceived measure of remission may add value to the ACR/EULAR definition of remission.
Anti-hinge Abs (AHAs) target neoepitopes exposed after proteolytic cleavage of IgG. In this study, we explored the diversity of protease- and IgG subclass-restricted AHAs and their potential as ...immunological markers in healthy donors (HDs) and patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). AHA reactivity against IgG-degrading enzyme of Streptococcus pyogenes (IdeS)- or pepsin-generated F(ab')
fragments of all four human IgG subclasses was determined. AHA reactivity against one or more out of eight F(ab')
targets was found in 68% (68 of 100) of HDs, 69% (68 of 99) of SLE patients, and 81% (79 of 97) of RA patients. Specific recognition of hinge epitopes was dependent on IgG subclass and protease used to create the F(ab')
targets, as confirmed by inhibition experiments with F(ab')
fragments and hinge peptides. Reactivity against IdeS-generated F(ab')
targets was found most frequently, whereas reactivity against pepsin-generated F(ab')
targets better discriminated between RA and HDs or SLE, with significantly higher AHA levels against IgG1/3/4. In contrast, AHA levels against pepsin-cleaved IgG2 were comparable. No reactivity against IdeS-generated IgG2-F(ab')
s was detected. The most discriminatory AHA reactivity in RA was against pepsin-cleaved IgG4, with a 35% prevalence, ≥5.8-fold higher than in HDs/SLE, and significantly higher levels (p < 0.0001). Cross-reactivity for F(ab')
s generated from different IgG subclasses was only observed for subclasses having homologous F(ab')
C termini (IgG1/3/4). For IgG2, two pepsin cleavage sites were identified; anti-hinge reactivity was restricted to only one of these. In conclusion, AHAs specifically recognize IgG subclass- and protease-restricted hinge neoepitopes. Their protease-restricted specificity suggests that different AHA responses developed under distinct inflammatory or infectious conditions and may be markers of, and participants in, such processes.
Gout is one of the most prevalent inflammatory rheumatic disease. It is preceded by hyperuricemia and associated with an increased risk for cardiovascular disease, both related to unhealthy diets. ...The objective of this systematic review is to better define the most appropriate diet addressing both disease activity and traditional cardiovascular risk factors in hyperuricemic patients. We included clinical trials with patients diagnosed with hyperuricemia or gout, investigating the effect of dietary interventions on serum uric acid (SUA) levels, gout flares and-if available-cardiovascular risk factors. Eighteen articles were included, which were too heterogeneous to perform a meta-analysis. Overall, the risk of bias of the studies was moderate to high. We distinguished four groups of dietary interventions: Calorie restriction and fasting, purine-low diets, Mediterranean-style diets, and supplements. Overall, fasting resulted in an increase of SUA, whilst small (SUA change +0.3 to -2.9 mg/dL) but significant effects were found after low-calorie, purine-low, and Mediterranean-style diets. Studies investigating the effect on cardiovascular risk factors were limited and inconclusive. Since Mediterranean-style diets/DASH (Dietary Approach to Stop Hypertension) have shown to be effective for the reduction of cardiovascular risk factors in other at-risk populations, we recommend further investigation of such diets for the treatment of gout.
To compare the effectiveness of longstanding (>52 weeks), supervised exercise therapy with usual care in adults with rheumatoid arthritis (RA) and severe functional limitations.
Participants were ...randomised 1:1 to the intervention (individualised goal-setting, active exercises, education and self-management regarding physical activity) or usual care. Primary endpoint was the change in the Patient-Specific Complaints activity ranked 1 (PSC1, 0-10) at 52 weeks. Secondary endpoints included the PSC activities ranked 2 and 3 (PSC2, PSC3), Health Assessment Questionnaire-Disability Index (HAQ-DI), Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL), 6-minute walk test (6MWT), Patient Reported Outcome Measurement Information System Physical Function-10 (PROMIS PF-10) and the Short Form-36 Physical and Mental Component Summary Scales (SF-36 PCS and MCS). (Serious) Adverse events (AEs) were recorded. Measurements were done by blinded assessors. Analyses at 52 weeks were based on the intention-to-treat principle.
In total, 217 people (90% female, age 58.8 (SD 12.9) years) were randomised (n=104 intervention, n=98 usual care available for analyses). At 52 weeks, the improvement of the PSC1 was significantly larger in the intervention group (mean difference (95% CI) -1.7 (-2.4, -1.0)). Except for the SF-36 MCS, all secondary outcomes showed significantly greater improvements favouring the intervention (PSC2 -1.8 (-2.4, -1.1), PSC3 -1.7 (-2.4, -1.0), PROMIS PF-10 +3.09 (1.80, 4.38), HAQ-DI -0.17 (-0.29, -0.06), RAQoL -2.03 (-3.39, -0.69), SF-36 PCS +3.83 (1.49, 6.17) and 6MWT +56 (38, 75) m). One mild, transient AE occurred in the intervention group.
Longstanding, supervised exercise therapy was more effective than usual care in people with RA and severe functional limitations.
Netherlands Trial Register (NL8235), included in the International Clinical Trial Registry Platform (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8235).
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