Higher Risk Of Rheumatoid Arthritis Research Articles

Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial

Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept. The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands. Participants (aged ≥18 years) at risk of rheumatoid arthritis positive for ACPA and rheumatoid factor with inflammatory joint pain were recruited. Exclusion criteria included previous episodes of clinical synovitis and previous use of corticosteroids or disease-modifying antirheumatic drugs. Participants were randomly assigned (1:1) using a computer-generated permuted block randomisation (block sizes of 2 and 4) stratified by sex, smoking, and country, to 125 mg abatacept subcutaneous injections weekly or placebo for 12 months, and then followed up for 12 months. Masking was achieved by providing four kits (identical in appearance and packaging) with pre-filled syringes with coded labels of abatacept or placebo every 3 months. The primary endpoint was the time to development of clinical synovitis in three or more joints or rheumatoid arthritis according to American College of Rheumatology and European Alliance of Associations for Rheumatology 2010 criteria, whichever was met first. Synovitis was confirmed by ultrasonography. Follow-up was completed on Jan 13, 2021. All participants meeting the intention-to-treat principle were included in the analysis. This trial was registered with EudraCT (2013-003413-18). Between Dec 22, 2014, and Jan 14, 2019, 280 individuals were evaluated for eligibility and, of 213 participants, 110 were randomly assigned to abatacept and 103 to placebo. During the treatment period, seven (6%) of 110 participants in the abatacept group and 30 (29%) of 103 participants in the placebo group met the primary endpoint. At 24 months, 27 (25%) of 110 participants in the abatacept group had progressed to rheumatoid arthritis, compared with 38 (37%) of 103 in the placebo group. The estimated proportion of participants remaining arthritis-free at 12 months was 92·8% (SE 2·6) in the abatacept group and 69·2% (4·7) in the placebo group. Kaplan-Meier arthritis-free survival plots over 24 months favoured abatacept (log-rank test p=0·044). The difference in restricted mean survival time between groups was 53 days (95% CI 28-78; p<0·0001) at 12 months and 99 days (95% CI 38-161; p=0·0016) at 24 months in favour of abatacept. During treatment, abatacept was associated with improvements in pain scores, functional wellbeing, and quality-of-life measurements, as well as low scores of subclinical synovitis by ultrasonography, compared with placebo. However, the effects were not sustained at 24 months. Seven serious adverse events occurred in the abatacept group and 11 in the placebo group, including one death in each group deemed unrelated to treatment. Therapeutic intervention during the at-risk phase of rheumatoid arthritis is feasible, with acceptable safety profiles. T-cell co-stimulation modulation with abatacept for 12 months reduces progression to rheumatoid arthritis, with evidence of sustained efficacy beyond the treatment period, and with no new safety signals. Bristol Myers Squibb.

Higher Risk of Rheumatoid Arthritis in Patients With Chronic Rhinosinusitis: Prospective Association in the U.K. Biobank and Genetic Evidence by Mendelian Randomization Analysis.

Previous studies have shown that respiratory diseases are associated with an increased risk of rheumatoid arthritis (RA). However, whether there is a correlation between chronic rhinosinusitis (CRS) and RA is not known. Due to the high incidence of CRS, it remains to be clarified whether we should pay additional attention to RA risk in the huge population of CRS. We used a 2-sample Mendelian randomization (MR) analysis to explore the causal effects of CRS on the incidence of RA. The inverse variance weighted (IVW) approach was used as the main analysis in the MR randomization study. Then, we used the data from the U.K. Biobank to examine the association between RA and CRS at the individual level in a prospective cohort. We identified patients with CRS at the time of recruitment and further followed the incidence of RA until 2021. The risk of developing RA in patients with CRS was determined by a multivariate Cox regression model. We used 3 multivariate Cox models to adjust for individual characteristics, lifestyle factors and concomitant diseases, respectively. The MR analysis by the IVW model suggested that the odds ratio of RA associated with genetically predicted CRS was 2.39 (95% CI [1.08-5.30]; p = .032). In the first multivariate model adjusting for individual characteristics, CRS was associated with a 47% increase of risk of developing RA (hazard ratio [HR] = 1.47; 95% CI [1.12-1.90]). In the second multivariate model adjusting for lifestyle factors, the HR of RA associated with CRS was 1.48 (95% CI [1.15-1.90]). In the third multivariate model, chronic sinusitis was associated with a 32% increase in RA risk (HR = 1.32; 95% CI [1.03-1.70]). CRS has a genetically causal effect on the incidence of RA, and the risk of RA is greatly higher in CRS at the individual level. This is the first study to reveal an association between CRS and RA. Due to the high incidence of CRS, it is recommended that additional attention should be paid to the increased RA risk in patients with CRS compared to that in common people.

Association of atypical anti-neutrophil cytoplasmic antibody with comorbidities and outcome in a hospital-based population

IntroductionAtypical anti-neutrophil cytoplasmic antibody (a-ANCA) is characterized by a positive fluorescence staining other than typical cytoplasmic or perinuclear ANCA. ANCA is associated with increased risk of dialysis and mortality in patients with ANCA vasculitis. However, comorbidities related to a-ANCA and whether a-ANCA exhibits an increased risk for renal failure and mortality remain unclear. This study aimed to explore the comorbidities and outcome associated with a-ANCA. Materials and methodsThis retrospective study enrolled 164 and 170 patients with typical ANCA and a-ANCA positivity, respectively, who visited Taichung Veterans General Hospital, Taiwan from January 2016 to March 2021. Logistic regression analysis was used to determine risk factors and the rheumatological diagnosis associated with a-ANCA. Cox proportional hazard regression and Kaplan–Meier curves were employed to identify variables associated with 5-year renal survival and mortality. ResultsPatients with a-ANCA had lower chance of ANCA-associated vasculitis (OR: 0.02, 95 % CI: 0.01–0.07 p < 0.001), and systemic lupus erythematosus (OR: 0.23, 95 % CI: 0.11–0.48, p < 0.001), but a higher risk of rheumatoid arthritis (OR: 2.99, 95 % CI: 1.15–7.83, p = 0.025) and ulcerative colitis (OR: 5.50, 95 % CI: 1.20–25.29, p = 0.028). Patients with a-ANCA had a better renal survival (OR: 0.14, 95 % CI: 0.08–0.24, p < 0.001) and lower mortality (OR: 0.31, 95 % CI: 0.16–0.60, p = 0.001) than patents in the typical ANCA group. The 5-year renal survival and mortality was 89.3 % and 8.8 %, respectively, in patients with a-ANCA. ConclusionPatients with a-ANCA had better renal survival and lower mortality rates compared to patients with typical ANCA. These real-world data provide evidence of the long-term outcome and shed light on avenues for the strategic management of patients with a-ANCA.

The association between dietary insulin index and dietary insulin load with rheumatoid arthritis.

This study was designed to assess the relationship between dietary insulin index (DII) and dietary insulin load (DIL) and rheumatoid arthritis (RA) risk in a case-control study. This study enrolled ninety-five newly diagnosed RA patients and 200 age- and sex-matched healthy controls. Dietary intakes were assessed using a validated 168-item semi-quantitative FFQ. DII and DIL were calculated using food insulin index values from previously published data. In the unadjusted model, individuals in the highest DIL tertile had the significantly higher odds of RA than those in the lowest tertile of the DIL scores (OR = 1·32, 95 % CI (1·15, 1·78), Pfor trend = 0·009). After adjusting for confounders, the risk of RA was 2·73 times higher for participants in the highest tertile of DIL than for those in the lowest tertile (OR = 2·73, 95 % CI (1·22, 3·95), Pfor trend < 0·001). In addition, patients in the highest DII tertile had higher risk of RA than those in the first tertile (OR = 2·22, 95 % CI (1·48, 3·95), Pfor trend = 0·008). This association persisted after adjusting for potential confounders (OR = 3·75, 95 % CI (3·18, 6·78), Pfor trend = 0·002). Our findings suggest that diets high in DII and DIL may increase the risk of developing RA, independent of other potential confounders. These findings can be verified by more research, particularly with a prospective design.

Genetic evidence for causal effects of leukocyte counts on risk for rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation of leukocytes and inflammatory mediators within the synovial tissue. Leukocyte counts are proposed to play a role in the pathogenesis of RA. However, the causality remains unclear. To investigate the causal relationship between various leukocytes and RA by implementing two-sample univariable Mendelian Randomization (MR) and multivariable MR. MR analysis was performed using respective genome-wide association study (GWAS) summary statistics for the exposure traits (eosinophil counts, neutrophil counts, lymphocyte counts, monocyte counts, basophil counts, and white blood cell counts) and outcome trait (RA). Summary statistics for leukocytes were extracted from the Blood Cell Consortium meta-analysis and INTERVAL studies. Public GWAS information for RA included 14,361 cases and 43,923 controls. Inverse variance weighted, weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier, and multivariable MR analyses were performed in MR analysis. Univariable MR found elevated eosinophil counts (OR 1.580, 95% CI 1.389–2.681, p = 1.30 × 10–7) significantly increased the risk of RA. Multivariable MR further confirmed that eosinophil counts were a risk factor for RA. Increased eosinophils were associated with higher risk of RA. Further elucidations of the causality and mechanisms underlying are likely to identify feasible interventions to promote RA prevention.

Longitudinal reciprocal association between rheumatoid arthritis and chronic obstructive pulmonary disease and mediation of inflammation.

To elucidate the longitudinal reciprocal association between rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD), and the mediating role of systemic inflammation in the association. 403045 participants from UK Biobank were enrolled in this study. A cross-lagged panel model was used to investigate the longitudinal reciprocal association between RA and COPD. Cox-proportional hazard regression and logistic regression models were also conducted to examine the association between baseline RA and COPD during follow-up, and vice versa. Causal mediation analysis was then performed to explore the mediating roles of 160 systemic inflammatory biomarkers in the bidirectional association. At baseline, 4755 (1.2%) and 6989 (1.7%) individuals were diagnosed with RA and COPD, respectively. After adjusting for the covariates, the result of cross-lagged panel model revealed a bidirectional association between RA and COPD (β = 0.018, P < 0.001 for RA→COPD path; β = 0.010, P < 0.001 for COPD→RA path). In the non-COPD population, the risk of future COPD was increased in RA patients (Cox: HR = 1.65, 95% CI, 1.50-1.83; logistic: OR = 1.85, 95% CI, 1.66-2.07). In the non-RA population, baseline COPD was associated with a higher risk of RA during follow-up (Cox: HR = 1.67, 95% CI, 1.44-1.92; logistic: OR = 1.70, 95% CI, 1.47-1.97). Five inflammatory factors mediated the RA→COPD path, and C-reactive protein mediated the COPD→RA path (FDR < 0.05). A significant bidirectional association exists between RA and COPD, and it is partially mediated by systemic inflammation.

Alteration of Gut Microbiota in Individuals at High-Risk for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance.

In this study, we aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis. Fecal samples were collected from 38 healthy individuals and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA) positivity (Pre-RA), 12 of 53 Pre-RA individuals developed RA within 5 years of follow-up. The differences in intestinal microbial composition between the healthy controls and Pre-RA individuals or among Pre-RA subgroups were identified by 16S ribosomal RNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice that received GM from the healthy control or Pre-RA groups were then evaluated for intestinal permeability, inflammatory cytokines, and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from Pre-RA individuals on arthritis severity in mice. Stool microbial diversity was lower in Pre-RA individuals than in healthy controls. The bacterial community structure and function significantly differed between healthy controls and Pre-RA individuals. Although there were differences to some extent in the bacterial abundance among the Pre-RA subgroups, no robust functional differences were observed. The metabolites in the serum of the Pre-RA group were dramatically different from those in the healthy controls group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the Pre-RA group increased intestinal permeability in FMT mice and zonula occludens-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving Pre-RA feces compared to healthy controls. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice. Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.

Implications of Peptidyl Arginine Deiminase 4 gene transcription and polymorphisms in susceptibility to rheumatoid arthritis in an Iranian population

BackgroundPeptidyl arginine deiminase 4 (PADI4) has been implicated in Rheumatoid arthritis (RA) pathogenesis. Here we aimed to evaluate the association of PADI4 gene rs11203367 and rs1748033 single nucleotide polymorphisms (SNPs) with RA proneness.MethodsThe mRNA expression of PADI4 was determined in the whole blood samples. The genotyping of PADI4 polymorphisms was conducted using allelic discrimination TaqMan genotyping Real-time PCR.ResultsThe alleles and genotypes of rs11203367 polymorphism were not associated with susceptibility to RA risk. The T allele (OR = 1.58, 95%CI: 1.21–2.04, P = 0.0005), TT genotype (OR = 2.79, 95%CI: 1.53–5.06, P = 0.0007), TC genotype (OR = 1.52, 95%CI: 1.04–2.23, P = 0.0291), dominant (OR = 1.72, 95%CI: 1.19–2.47, P = 0.0034) and recessive (OR = 2.19, 95%CI: 1.25–3.82, P = 0.0057) models of rs1748033 SNP were associated with higher risk of RA. There was a significant upregulation of PADI4 mRNA in the RA patients compared to controls. mRNA expression of PADI4 had significantly positive correlation with anti-CCP level (r = 0.37, P = 0.041), RF level (r = 0.39, P = 0.037), and CRP level (r = 0.39, P = 0.024).ConclusionPADI4 gene rs1748033 SNP was associated with increased RA risk. This polymorphism might affect the RA pathogenesis regardless of impressing the levels of PADI-4 in serum.

IL-21 (rs2055979 and rs2221903)/IL-21R (rs3093301) Polymorphism and High Levels of IL-21 Are Associated with Rheumatoid Arthritis in Mexican Patients.

Rheumatoid Arthritis (RA) is characterized by joint destruction, chronic inflammation, and autoantibody production. IL-21/IL-21R plays an essential role in the immunopathology of RA. Elevated IL-21 serum levels have been associated with RA and disease activity. Here, we evaluated the association of IL-21/IL-21R polymorphisms and IL-21 serum levels with RA. The study included 275 RA patients and 280 Control subjects (CSs). Single nucleotide polymorphisms IL-21 (rs2055979 and rs2221903) and IL-21R (rs3093301) were genotyped using PCR-RFLP. Clinical activity was evaluated by DAS28-ESR; IL-21 and anti-CCP serum levels were quantified by ELISA. The IL-21 rs2055979 AA genotype was higher in RA patients than in the CS group (p = 0.0216, OR = 1.761, 95% CI = 1.085-2.859); furthermore, RA patients showed anti-CCP elevated levels compared to the CA genotype (p = 0.0296). The IL21R rs3093301 AA genotype was also higher in RA patients than in the CS group (p = 0.0122, OR = 1.965, 95% CI = 1.153-3.348). The AT haplotypes of IL-21 rs2055979 and rs2221903 were more frequent (49%) in the RA group (p = 0.006). IL-21 serum levels were significantly elevated in the RA group, but without an association with IL-21 polymorphisms. In conclusion, IL-21 rs2255979 and IL-21R rs3093301 are associated with a higher risk of RA, and could be a genetic marker. Moreover, the elevated IL-21 levels in RA suggest that IL-21/IL-21R could be a therapeutic target in RA.

Prevention vs treatment of rheumatoid arthritis.

Whether a yet chronic and not curable disease like rheumatoid arthritis (RA) can be subject to prevention or whether available resources should be focused on treatment is a classical dilemma. Similar to the case in most other chronic diseases, the focus in research as well as in clinical practice has been on the treatment of established diseases, resulting in drugs that are efficient in eliminating most joint damage but not able to cure the disease or stop needs for continuous treatment of the disease. Less effort has been spent on identifying and implementing ways to prevent the disease. We argue in this review that knowledge concerning the longitudinal evolvement of the major, 'seropositive' subset of RA has now come to a stage where prevention should be a large part of the research agenda and that we should prepare for prevention as part of clinical practice in RA. We describe briefly the knowledge basis for broad public health-based prevention as well as for a 'precision prevention' strategy. In the latter, individuals at high risk for RA will be identified, monitored, and ultimately provided with advice on how to change lifestyle/environment or be given treatment with drugs able to delay and ultimately stop the development of RA. Whether this potential of precision prevention for RA will change the broader clinical practice will depend on whether specific and long-lasting interference with disease-inducing immunity, ultimately 'tolerance therapy', will become a reality.

A Mendelian randomization study on causal effects of leisure sedentary behaviour on the risk of rheumatoid arthritis.

The causal inference between leisure sedentary behaviour (LSB) and rheumatoid arthritis (RA) is still controversial because of potential residual confounding and reverse causality. The present study used publicly available large-scale genome-wide association studies (GWAS) of LSB (television watching, computer use, and driving) and RA to perform a two-sample Mendelian randomization (MR) study to evaluate the causal effect of LSB on the risk of RA. We detected significant causal associations using the multiplicative random effects-inverse variance weighted (MRE-IVW) method, the maximum likelihood, robust adjusted profile scores, the weighted median, MR-Egger regression, and several complementary sensitivity analyses. Risk factor analysis was also conducted to further investigate potential mediators linking causal inference. Increased genetic liability to leisure television watching was significantly associated with a higher risk of RA (MRE-IVW method; OR=2.46, 95% CI 1.77-3.41; p=8.35 × 10-8 ). MR estimates indicated that prolonged leisure computer use was causally associated with a lower risk of RA (MRE-IVW method; OR=0.23, 95% CI 0.12-0.46; p=2.19 × 10-5 ). However, we found no evidence for a causal effect of leisure driving on the risk of RA (MRE-IVW method; OR=0.59, 95% CI 0.10-3.41; p=0.557). No pleiotropy was detected by the sensitivity analysis. This study supports a causal association between prolonged leisure television watching and an increased risk of RA. Additionally, prolonged computer use might be a protective factor for RA.

Association of Gene Polymorphisms in CXC Chemokine Receptor 5 with Rheumatoid Arthritis Susceptibility.

Rheumatoid arthritis (RA) is caused by complicated interactions between genes and the environment. CXC chemokine receptor 5 (CXCR5) is required for B and T follicular helper cell migration and humoral immunity generation. Therefore, this study aimed to assess whether polymorphisms of the CXCR5 gene are implicated in RA development and progression. This case-control study enrolled 285 RA patients and 291 healthy controls. The polymerase chain reaction-ligase detection reaction method was used to genotype rs630923, rs497916, rs3922, and rs676925 in the CXCR5 gene. Epidemiological, clinical, and laboratory data were collected retrospectively. The rs630923 A allele was associated with a higher risk of RA (AOR [adjusted odds ratio]=2.00, 95% confidence interval [CI] =1.14-3.53). However, in the RA group, the frequency of the rs497916 T allele was lower (AOR=0.69, 95% CI=0.51-0.93). Regarding rs3922, AG+GG genotype carriers were at a significantly lower risk for RA than AA genotype carriers (AOR=0.70, 95% CI=0.49-0.99). In the RA group, we found that the different genotypes were significantly associated with specific laboratory values, including rheumatoid factor, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, and alkaline phosphatase. This is the first report indicating that CXCR5 polymorphisms were associated with RA susceptibility. These findings lead to a rising possibility of identifying RA-susceptible individuals based on genetic markers.

Adding Chinese Herbal Medicine to Routine Care is Associated With a Lower Risk of Rheumatoid Arthritis Among Patients With Asthma: A Population-Based Retrospective Cohort Study.

Objective: Due to the shared pathogenesis of asthma and rheumatoid arthritis (RA), patients with asthma were found to have a higher risk of RA. While the benefits and safety of Chinese herbal medicine (CHM) for asthma have been reported, the scientific evidence regarding its effect on RA is limited. This longitudinal cohort study aimed to determine the relation between CHM use and RA risk in patients with asthma. Methods: Using the nationwide claims data, we enrolled 33,963 patients 20–80 years of age who were newly diagnosed with asthma and simultaneously free of RA between 2000 and 2007. From this sample, we utilized propensity score matching to create sets of participants as treatment and control groups, which comprised 13,440 CHM users and 13,440 non-CHM users. The incidence rate and hazard ratio (HR) for RA between the two groups were estimated at the end of 2013. A Cox proportional hazards model was constructed to examine the impact of the CHM use on the risk of RA. Results: The cumulative incidence of RA was substantially lower in the CHM user group. In the follow-up period, 214 patients in the CHM user group (1.92 per 1,000 person-years) and 359 patients in the non-CHM user group (2.92 per 1,000 person-years) developed RA (adjusted HR = 0.63, 95% confidence interval: 0.54–0.75). Of the commonly-prescribed formulae, nine CHM products were associated with a lower RA risk: Xiao-Qing-Long-Tang, Ma-Xing-Gan-Shi-Tang, Ding-Chuan-Tang, Xin-Yi-Qing-Fei-Tang, Bei Mu, Jie Geng, Xing Ren, Da Huang, and San Chi. Conclusion: This study found that patients with asthma who received CHM treatment, in addition to the conventional therapy, had a lower risk of RA. Use of CHM treatment may be integrated into conventional therapy to reduce subsequent RA risk among asthma patients.

Correlation of CRP genotypes with serum CRP levels and the risk of rheumatoid arthritis in Chinese Han population.

C-reactive protein (CRP) is an important index for evaluating the disease activity of rheumatoid arthritis (RA). CRP may play a direct role in bone destruction in RA. Studies have demonstrated that serum CRP levels had a close correlation with tissue inflammation scores in patients with RA. In addition, genetic factors play a crucial role in the development of RA. In this study, we aimed to investigate the relationship between the CRP gene variants (rs1205 polymorphism) and the risk of RA in Chinese Han population. 502 RA patients and 581 controls were included in this study. The associations between CRP gene variants and CRP levels and RA risk were investigated. We found that TT/ TT + CT genotype was significantly related with an increased risk of RA (TT vs CC: OR, 1.56, 95%CI, 1.01-2.40, P = 0.045; TT + CT vs CC: OR, 1.30, 95%CI, 1.02-1.65, P = 0.032). In addition, T allele was shown to associate with an elevated risk of RA. After subgroup analysis, we found that rs1205 polymorphism was significantly related with an enhanced risk of RA among females, individuals lower than 60years, and subjects with a BMI > 25kg/m2. Furthermore, data showed that the CRP gene rs1205 polymorphism correlated with CRP and ESR levels. Furthermore, the TT genotype was significantly associated with a reduction of CRP levels compared with CT or CC genotype. To sum up, this study reveals that rs1205 polymorphism of the CRP gene is related with an increased risk of RA and CRP levels in Chinese Han population. Key Points • The CRP gene rs1205 polymorphism is related with a higher risk of RA. • The CRP gene rs1205 polymorphism correlates with CRP and ESR levels. • The TT genotype of rs1205 polymorphism is linked with a reduction of CRP levels.

Rheumatoid arthritis is a preventable disease: 11 ways to reduce your patients' risk.

New evidence shows that up to 40% of rheumatoid arthritis (RA) cases are attributable to exposure to potentially modifiable factors. We can now identify people at higher risk of RA (pre-RA) through their family history, risk factors, autoantibodies and symptoms. Counselling these patients to act to modify factors known to be associated with RA risk could prevent the development of RA, and evidence shows that informing individuals of their risk and of ways to reduce it leads to positive behavioural change and is not harmful. This consumer-focussed narrative review is targeted at primary care providers and physicians to describe 11 changes that can be made, based on current evidence linking potentially modifiable factors to RA risk. These evidence-based recommendations are: (i) cease smoking; (ii) reduce exposure to inhaled silica, dusts and occupational risks; (iii) maintain a healthy weight; (iv) increase leisure time physical activity; (v) maintain good dental hygiene; (vi) maximise breastfeeding if able; (vii) maximise dietary quality and avoid high-salt diets; (viii) consume high levels of omega-3 fatty acids and fish; (ix) reduce consumption of sugar-sweetened soft drinks; (x) consume moderate levels of alcohol; and (xi) remain vitamin D replete.

Urticaria and increased risk of rheumatoid arthritis: a two-sample Mendelian randomisation study in European population.

In recent years, a growing body of observational studies suggest that urticaria is associated with a higher risk of rheumatoid arthritis (RA). However, the causal association between urticaria and RA remains unknown. To investigate the causal relationship of urticaria and RA in European populations by Mendelian randomisation (MR) approach. We conducted two-sample MR analyses. Eleven single-nucleotide polymorphisms associated with urticaria were used as instrumental variables. The summary data on urticaria were derived from FinnGen Data Freeze 2. The summary data on RA were obtained from a published meta-analysis using European samples. Four MR methods were applied to the MR estimates. Three heterogeneity tests, including Cochran's Q test, single variant analysis, and leave-one-out variant analysis, were used. The pleiotropy and horizontal pleiotropy among instrumental variables were assessed with MR-Egger regression intercept, MR pleiotropy residual sum and outlier global test, and PhenoScanner. The MR analysis suggested that urticaria was causally associated with RA (odds ratio = 1.114, 95% confidence interval = 1.024-1.211, p = .011). No genetic pleiotropy or horizontal pleiotropy was revealed by MR-Egger regression intercept and MR pleiotropy residual sum and outlier global test. The sensitivity analysis results were relatively robust. The MR analysis suggested there was sufficient evidence to indicate urticaria is the cause of RA.

Early-life famine exposure and rheumatoid arthritis in Chinese adult populations: a retrospective cohort study

ObjectiveThis study aimed to explore the association between famine exposure in early life and the odds of rheumatoid arthritis (RA) in adulthood.DesignA population-based retrospective cohort study.SettingChina.ParticipantsA total of 111 706...

Alcohol Consumption and Risk of Rheumatoid Arthritis among Chinese Adults: A Prospective Study.

Alcohol consumption may be associated with the risk of rheumatoid arthritis (RA), but potential sex-related differences in this association have not been explored. Thus, we utilized 87,118 participants in the Kailuan Study, a prospective cohort initiated in 2006 to study the risk factors of cardiovascular disease in a Chinese population. We included those that did not have RA at baseline (2006), and performed cox proportional hazard modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to the levels of alcohol consumption (never or past, light or moderate (<1 serving/day for women, <2 servings/day for men), and heavy (>1 serving/day for women, >2 servings/day for men), adjusting for age, sex, body mass index, and smoking. Diagnoses of RA were confirmed via medical record review by rheumatologists. From 2006 to 2018, we identified 87 incident RA cases. After adjusting for potential confounders, the HR of RA was 1.26 (95% CI: 0.62, 2.56) for participants with light or moderate alcohol consumption and 1.98 (95% CI: 0.93, 4.22) for participants with heavy alcohol consumption) versus non-drinkers. The HR of each 10 g increase in alcohol consumption was 1.11 (95% CI: 0.98, 1.26) (p-trend = 0.09). A significant association between alcohol consumption and RA risk was observed in women, but not in men (p for interaction = 0.06). Among women, each 10 g increase in alcohol consumption was significantly associated with a high risk of RA (HR: 1.56; 95% CI: 1.06, 2.29). In contrast, each 10 g increase in alcohol consumption was not significantly associated with the risk of RA in men (HR: 1.10; 95% CI: 0.97, 1.25). Excluding past drinkers generated similar results. In this prospective Chinese cohort, increasing alcohol consumption was associated with an elevated risk of RA among women, but not in men. These findings highlight the importance of incorporating analysis of sex differences into future studies of alcohol consumption and RA risk.

Environment and Lifestyle: Their Influence on the Risk of RA.

Background: Rheumatoid arthritis (RA) is a complex disease in which environmental agents are thought to interact with genetic factors that lead to triggering of autoimmunity. Methods: We reviewed environmental, hormonal, and dietary factors that have been suggested to be associated with the risk of RA. Results: Smoking is the most robust factor associated with the risk of RA, with a clear gene–environment interaction. Among other inhalants, silica may increase the risk of RA in men. There is less evidence for pesticides, pollution, and other occupational inhalants. Regarding female hormonal exposures, there is some epidemiological evidence, although not consistent in the literature, to suggest a link between hormonal factors and the risk of RA. Regarding dietary factors, available evidence is conflicting. A high consumption of coffee seems to be associated with an increased risk of RA, whereas a moderate consumption of alcohol is inversely associated with the risk of RA, and there is less evidence regarding other food groups. Dietary pattern analyses (Mediterranean diet, the inflammatory potential of the diet, or diet quality) suggested a potential benefit of dietary modifications for individuals at high risk of RA. Conclusion: To date, smoking and silica exposure have been reproducibly demonstrated to trigger the emergence of RA. However, many other environmental factors have been studied, mostly with a case-control design. Results were conflicting and studies rarely considered potential gene–environment interactions. There is a need for large scale prospective studies and studies in predisposed individuals to better understand and prevent the disease and its course.

Patients with asthma have a higher risk of rheumatoid arthritis: A systematic review and meta-analysis

ObjectiveThis study aimed to investigate whether patients with asthma have a higher risk of incident rheumatoid arthritis (RA) using systematic review and meta-analysis technique. MethodsPotentially eligible studies were identified from Medline and EMBASE databases from inception to May 2020 using search strategy that comprised of terms for “Asthma” and “Rheumatoid arthritis”. Eligible cohort study must consist of one cohort of patients with asthma and another cohort of individuals without asthma. Then, the study must effect estimates with 95% confidence intervals (95% CIs) comparing incident RA between the groups. Eligible case-control studies must include cases with RA and controls without RA. Then, the study must explore their history of asthma. Odds ratio (OR) with 95% CIs of the association between asthma status and RA must be reported. Point estimates with standard errors were retrieved from each study and were combined together using the generic inverse variance method. ResultsA total of 22,442 articles were identified. After two rounds of independent review by three investigators, six cohort studies and fourteen case-control studies met the eligibility criteria and were included into the meta-analysis. Meta-analysis of cohort studies found that patients with asthma had a significantly higher risk of RA compared with individuals without asthma with the pooled hazard ratio of 1.42 (95% CI, 1.18 – 1.70). Meta-analysis of case-control studies revealed that patients with asthma had a higher risk of RA compared with individuals without asthma with the pooled odds ratio of 1.33 (95%CI, 0.97 – 1.83). Funnel plot for the meta-analysis of case-control studies was asymmetric, suggesting the presence of publication bias. ConclusionsThis systematic review and meta-analysis found a significant association between asthma and higher risk of incident RA.