Nutrition and Diet in Rheumatoid Arthritis

Rheumatic and musculoskeletal diseases (RMDs) are chronic systemic immune/inflammatory conditions characterized by the interaction between gene predisposition, autoimmunity and environmental factors. A growing scientific interest has focused on the role of nutrition in RMDs, suggesting its significant contribution to the pathogenesis and prognosis of these diseases

Inequity and spondyloarthritis: focus on the role of socioeconomic factors in disease

This thesis focuses on health inequity in Spondyloarthritis (SpA) and potential drivers for this. The general lack of evidence on the role of socioeconomic factors, mainly at the level of the individual, but also at the wider societal level, on disease outcomes in SpA, stimulated the undertaking of the individual studies described in the thesis. The possibility to study socioeconomic factors give a unique dimension to the analyses presented and provide more insights that complement the existing body of evidence. The studies presented also highlight much unmet need in our understanding of disease and in particular the intricate relationships between biological and non-biological factors that drive adverse outcomes in SpA. Many of these relationships are naturally complex and the observed effects on outcomes, multifactorial in origin. The thesis has three overarching aims, all pertaining to better understanding the role of socioeconomic factors in SpA, from different angles, both at the individual as well as the country-level and the impact on outcomes, namely imaging and work outcomes.LUMC / Geneeskund

Remission vs low disease activity: function, quality of life and structural outcomes in the Early Rheumatoid Arthritis Study and Network

Objectives To examine associations between function, quality of life and structural outcomes in patients achieving remission vs low disease activity in early RA. Methods Demographic, clinical and radiographic variables were collected at baseline and then annually from the Early Rheumatoid Arthritis Study (ERAS) and Early Rheumatoid Arthritis Network (ERAN) inception cohorts in routine care from 1986 to 2012. Disease activity was categorized: mean DAS28 score between years 1 and 5: remission [mean remission DAS (mRDAS) <2.6] or low [mean low DAS (mLDAS) 2.6–3.2]; sustained low/remission DAS28 (sLDAS/sRDAS) at years 1 and 2; and sustained Boolean remission (sBR) at years 1 and 2. Changes in HAQ and Short Form 36 Health Survey Questionnaire [SF-36; physical (PCS) and mental (MCS) component score]) and total Sharp van der Heijde (SvdH) scores for each disease activity category were modelled using multi-level models. Covariates included year of onset, age, gender and DMARD use at first visit. Results Of 2701 patients, 562 (21%) were categorized mRDAS, 330 (12%) mLDAS, 279 (10%) sRDAS, 203 (7.5%) sLDAS and 93 (3%) sBR. Patients categorized as mRDAS had increasingly divergent improved HAQ, SF-36 PCS, MCS and total SvdH scores compared with mLDAS (P-values 0.001 to <0.0001, all time points). Patients categorized as sRDAS had better HAQ, SF-36 PCS and MCS scores (P-values 0.05 to <0.0001, all time points) and SvdH scores (P = 0.05, years 3–5) over sLDAS. sBR was associated with better HAQ, and SF-36 PCS and MCS scores over sLDAS (P-values 0.002 to <0.0001, all time points). Conclusion These findings from routine care support ACR/EULAR guidelines that remission is a preferable goal over low disease activity in early RA.Peer reviewedFinal Published versio

Achieving consensus on minimum data items (including core outcome domains) for a longitudinal observational cohort study in rheumatoid arthritis

Objectives: To obtain consensus on minimum data items for an observational cohort study in rheumatoid arthritis (RA) in the UK and to make available the process for similar studies and other rheumatic conditions. Methods: Individuals with a diverse range of expertise and backgrounds were invited to participate in a process to propose a minimal core dataset (MCD) for research studies, commissioned by Arthritis Research UK as part of the larger INBANK project. The group included patients and representatives from clinical and academic rheumatology, outcomes science, stratified medicine, health economics, national professional and academic bodies/ committees. A process was devised based on Outcome Measures in Rheumatology Clinical Trials (OMERACT) principles to review aims/objectives, definition of scope, identification of important research questions, and selection of key domains. Results: Following the initial multi-stakeholder meeting, subsequent teleconferences and email communications, consensus was obtained on: 1. Most important and relevant research questions; 2. Agreement on how the OMERACT Core Areas (life impact, pathophysiological manifestations, resource use and death) could form the basis of a MCD; 3. Consensus on 22 items for inclusion into a MCD. Workshops were undertaken for two essential items which required further exploration: work/social participation and co-morbidity. Conclusions: Consensus for proposed minimal data items for long-term observational cohort studies of RA in the UK posed novel challenges and opportunities, and was largely successful. Further work is needed to select instruments for two important items and to achieve compatibility with other UK national initiatives, and more widely across Europe

HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6:a systematic review and meta-analysis

OBJECTIVE: The objective of this study was to assess the possibility of HBV reactivation (HBVr) in patients with RA under anti-IL-6 treatment.METHODS: Using PubMed, Scopus and EMBASE, we performed a systematic literature search for articles related to HBVr in RA patients under anti-IL-6 treatment. The search was performed with no date limits and was last updated 28 January 2023. The results from all the databases were combined and duplicates were excluded, as were non-English articles, case reports, position articles, comments, and paediatric studies.RESULTS: Our initial search led to 427 articles; 28 were duplicates, 46 non-English, 169 reviews, 31 books/letters, 25 case reports, and 88 irrelevant to the meta-analysis aim; 21 were excluded due to inadequate information, leaving 19 articles, with a sum of 372 RA patients with chronic HBV (CHB) or resolved HBV infection, for further analysis. The overall risk for HBVr in RA patients with CHB was 6.7%, increasing to 37% when only RA patients with CHB and no antiviral prophylaxis were included. On the contrary, HBVr was close to 0% in RA patients with resolved HBV infection, irrespective of antiviral prophylaxis. All RA patients experiencing HBVr in these studies were successfully managed with antiviral treatment and/or drug withdrawal.CONCLUSION: Overall, anti-IL-6 treatment comes with a significant risk of HBVr in RA patients with CHB; risk is diminished when antiviral prophylaxis is used. In contrast, in RA patients with resolved HBV infection, the risk of HBVr seems to be extremely low. Large, well-designed studies (either controlled trials or multicentre/international observational studies) are warranted to further validate these results.</p

Large joints are progressively involved in rheumatoid arthritis irrespective of rheumatoid factor status-results from the early rheumatoid arthritis study.

This study aimed to examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of rheumatoid factor (RF). We used a historical longitudinal cohort of early RA patients. Patients were deemed RF negative if all repeated assessments were negative. The rate of progression from normal to any loss of range of movement (ROM) from years 3 to 14 were modelled using generalized estimating equations, for elbows, wrists, hips, knees and ankle, adjusting for confounders. Time to joint surgery was analysed using multivariable Cox models. A total of 1458 patients were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. Odds of loss of ROM increased over time in all joint regions assessed, at around 7-13% per year from year 3 to 14. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15-0.90), hip (HR 0.69, 0.48-0.99) and after 10 years at the knee (HR 0.41, 0.25-0.68). Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in composite disease activity indices. RF-negative and positive cases progressed similarly. Treat-to-target approaches should be followed irrespective of RF status

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio

Disease impact of rheumatoid arthritis in patients not treated with advanced therapies; survey findings from the National Rheumatoid Arthritis Society

Objective The aim was to reveal the everyday impact of living with RA in people not treated with advanced therapies (i.e. biologic or targeted synthetic DMARDs). Methods People with RA, with disease duration >2 years, not currently treated with advanced therapies, completed an online survey promoted by the National Rheumatoid Arthritis Society. Items covered demographics, current treatment, RA flare frequency, the Rheumatoid Arthritis Impact of Disease (RAID) tool and questions reflecting work status and ability. Descriptive and multivariable regression analyses were performed. Results There were 612 responses from patients having a mean age of 59 years, 88% female, 37.7% with disease duration 2–5 years and 27.9% with disease duration 5–10 years. In the last year, 90% reported an RA flare, with more than six flares in 23%. A RAID patient acceptable state was recorded in 12.4%. Each of the seven domains was scored in the high range by >50% respondents; 74.3% scored sleep problems and 72% fatigue in the high range. A need to change working hours was reported by 70%. Multivariable analyses revealed that increasing difficulties with daily physical activities, reduced emotional and physical well-being in the past week were all significantly associated with pain, number of flares and ability to cope (P < 0.005). The RAID score was significantly predictive of the number of flares. Conclusion Patients not currently treated with advanced therapies experience profound difficulties in everyday living with RA, across a broad range of measures. We advocate that patient-reported measures be used to facilitate holistic care, addressing inflammation and other consequences of RA on everyday life

Impact of patient global assessment on achieving remission in patients with rheumatoid arthritis: A multinational study using the METEOR database

OBJECTIVE: There is an ongoing debate about excluding patient's global assessment (PtGA) from composite and Boolean-based definitions of rheumatoid arthritis (RA) remission. This study aimed at determining the influence of PtGA on RA disease states, exploring differences across countries, and understanding the association between PtGA, measures of disease impact (symptoms), and markers of disease activity (inflammation). METHODS: Cross-sectional data from the Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology international database were used. We calculated the proportion of patients failing American College of Rheumatology/European League Against Rheumatism Boolean-based remission (4-variable remission) solely due to PtGA (PtGA-near-remission) in the overall sample and in the most representative countries (i.e., those with >3,000 patients in the database). Multivariable linear regression models were used to identify the main determinants of PtGA, grouped in predominantly inflammatory impact factors (28 tender joint counts, 28 swollen joint counts, and C-reactive protein level) and disease impact factors (pain and function). RESULTS: This study included 27,768 patients. Excluding PtGA from the Boolean-based definition (3-variable remission) increased the remission rate from 5.8% to 15.8%. The rate of PtGA-near-remission varied considerably between countries, from 1.7% in India to 17.9% in Portugal. One-third of the patients in PtGA-near-remission group scored PtGA >4 of 10. Pain and function were the main correlates of PtGA, with inflammation-related variables contributing less to the model (R2 = 0.57). CONCLUSION: PtGA is moderately related to joint inflammation overall, but only weakly so in low levels of disease activity. A considerable proportion of patients otherwise in biologic remission still perceive high PtGA, putting them at risk of excessive immunosuppressive treatment

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

Background: DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods: Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants [1] commencing anti-TNF therapy (n = 10813), or [2] changing between non-biologic DMARDs (n=2992), [3] Early Rheumatoid Arthritis Network participants (n=813), and [4] participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n=45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results: DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions: DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA