Adult Rheumatoid Arthritis Research Articles

Interpreting Rheumatology Laboratory Tests

Interpreting Rheumatology Laboratory Tests

Interrogation of STAT3 activation in patients with polyarticular juvenile arthritis

Abstract Juvenile idiopathic arthritis (JIA) can cause pain and disability, but early disease control improves outcomes. The polyarticular JIA (polyJIA) subset is clinically similar to adult rheumatoid arthritis (RA), yet its pathogenesis remains incompletely understood. A pathway of interest in polyJIA is STAT3 signaling. STAT3 is a transcription factor critical to development of inflammatory Th17 cells and modulation of regulatory T cells. Elevated Th17s and activated STAT3 have been shown in RA. We aimed to profile T cell subsets and STAT3 activation in polyJIA. Blood from 13 patients with polyJIA was collected at initial diagnosis and serially until remission. Peripheral blood mononuclear cells were isolated and T cell subsets and STAT activation (phosphorylation) were evaluated using flow cytometry. Regulatory T cells from patients with polyJIA were found at similar levels as pediatric controls. However, treatment naïve polyJIA patients had increased Th17s compared to pediatric controls (0.15% v 0.44%, p=0.037). We identified IL-17 and IFN-γ dual+ helper T cells (non-classical Th1s) appearing in post-treatment samples from polyJIA patients. After stimulation (IL-6, IL-27 or IFN-α), a subset of polyJIA patients had highly activated STAT3, but not STAT1 or STAT5, in CD3+CD4+ T cells. A better understanding of the mechanisms underlying polyJIA is needed for more efficient and effective clinical care. Although multiple therapeutics to treat JIA exist, a biomarker-driven approach to treatment does not. Patients with polyJIA have increased Th17s and a subset have highly activated STAT3. These immunologic features may help identify patients that would benefit from upfront, tailored treatment with therapeutics targeting this pathway.

Tuberculin skin test before biologic and targeted therapies: does the same rule apply for all?

This study aimed to compare Tuberculin Skin Test (TST) and QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients scheduled for biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) in a Bacillus Calmette-Guérin-vaccinated population. Adult RA (n = 206) and SpA (n = 392) patients from the TReasure database who had both TST and QFT-GIT prior to initiation of biological and targeted synthetic DMARDs were included in the study. Demographic and disease characteristics along with pre-biologic DMARD and steroid use were recorded. The distribution of TST and performance with respect to QFT-GIT were compared between RA and SpA groups. Pre-biologic conventional DMARD and steroid use was higher in the RA group. TST positivity rates were 44.2% in RA and 69.1% in SpA for a 5mm cutoff (p < 0.001). Only 8.9% and 15% of the patients with RA and SpA, respectively, tested positive by QFT-GIT. The two tests poorly agreed in both groups at a TST cutoff of 5mm and increasing the TST cutoff only slightly increased the agreement. Among age, sex, education and smoking status, pre-biologic steroid and conventional DMARD use, disease group, and QFT-GIT positivity, which were associated with a 5mm or higher TST, only disease group (SpA) and QFT-GIT positivity remained significant in multiple logistic regression. TST positivity was more pronounced in SpA compared to that in RA and this was not explainable by pre-biologic DMARD and steroid use. The agreement of TST with QFT-GIT was poor in both groups. Using a 5mm TST cutoff for both diseases could result in overestimating LTBI in SpA.

P090 Clinical prediction models for methotrexate treatment outcomes in rheumatoid arthritis patients: a review of existing models and summary of their limitations

Abstract Background/Aims Methotrexate (MTX) is the preferred first line therapy for rheumatoid arthritis (RA), according to NICE guidelines. MTX has several advantages over other treatments including effectiveness and low cost; however, around 40% of patients are classed as non-responders after 6 months. Therefore, there is a clinical need to identify patients at high-risk of poor outcomes, such that patients could potentially be fast tracked onto alternative therapies to improve their clinical outcomes and quality of life. Such risk stratification is possible through prognostic prediction models, although models which have previously been developed appear to have had little impact on practice. This may be in part due to methodological features of their development and validation but, to date, no review has collated the evidence in this field. This review therefore aimed to (i) identify and summarise multivariable prediction models of MTX treatment outcomes in biologic-naïve adult RA patients, and (ii) appraise their methodological properties. Methods A systematic search was carried out using Medline Ovid to identify studies developing or validating prediction models of MTX outcomes in the population of interest, including demographic, disease-specific or treatment-related covariates, published between 2005 and 2020. Models were stratified by outcome definition, and information on predictors, predictor associations with the outcome, model performance, handling of missing data and model validation were extracted. Results Twenty-two studies (14 (64%) using data from observational studies and 8 (36%) from randomised controlled trials) were identified. Of these, 15 (68%) based their outcome on a state of disease activity, such as low disease activity or remission, 4 (18%) used the EULAR response criteria, and 3 (14%) predicted discontinuation due to adverse events (AEs). AEs were also incorporated into the composite outcome with disease activity in 3 (14%) studies, 1 (5%) investigated both outcomes in separate models, and only 1 (5%) accounted for potential competing risks to their primary outcome. Internal validation using cross sampling techniques, which is critical for reducing overfitting, was completed in only 5 (23%) studies. Only 4 (18%) studies carried out external validation in new data. Missing data was appropriately handled using multiple imputation in 5 (23%) studies, whilst others used single imputation (n = 1, 4%) or complete case analysis (n = 13, 59%), resulting in potentially biased risk estimates, or did not report how they handled missing data (n = 3, 14%). Conclusion This review summarises current prediction models of MTX treatment outcomes in RA. It highlights several methodological shortcomings that should be addressed in future model development and validation to improve accuracy of predictions. Without tackling these issues, prediction of MTX treatment outcomes will remain at high risk of bias and should not be recommended for informing risk stratification for RA treatment decisions. Disclosure C. Gehringer: None. G. Martin: None. K. Hyrich: None. S. Verstappen: None. J. Sergeant: None.

Per-/polyfluoroalkyl substance concentrations in human serum and their associations with immune markers of rheumatoid arthritis

Per-/polyfluoroalkyl substances (PFASs) are ubiquitous in the environment and have been proved to be immunotoxic to humans. However, it remains unclear whether exposure to PFASs affects the risk of rheumatoid arthritis (RA). In this study, nine PFASs were determined in human serum collected from 280 health populations and 294 RA patients in a cohort enrolled between 2018 and 2020 in Hangzhou, China, and were examined their correlations with immune marker levels. Perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were the predominant PFASs in human serum, with median (mean) concentrations of 5.4 (7.6), 2.8 (3.5), and 1.9 (2.5) ng/mL, respectively. Serum PFOA and 6:2 Cl-PFESA concentrations were positively correlated with anti-cyclic citrullinated peptide antibody (ACPA) (βPFOA = 0.59, 95% confidence interval (CI): 0.37, 0.81; β6:2 Cl-PFESA = 0.48, 95% CI: 0.29, 0.66), immunoglobulin G (βPFOA = 0.25, 95% CI: 0.21, 0.29; β6:2 Cl-PFESA = 0.16, 95% CI: 0.12, 0.19) as well as rheumatoid factors (RF) (βPFOA = 0.57, 95% CI: 0.34, 0.80; β6:2 Cl-PFESA = 0.54, 95% CI: 0.36, 0.72). The correlations between serum PFOS levels and RF (β = 0.52, 95% CI: 0.28, 0.77), ACPA (β = 0.48, 95% CI: 0.23, 0.73), as well as immunoglobulin M (β = −0.24, 95% CI: 0.64, 0.15) respectively were statistically stronger. We also found PFOA concentrations in serum were associated with the level of C-reactive protein (β = 0.52, 95% CI: 0.40, 0.65). To our knowledge, this is the first study reporting significant associations between several PFASs and change of specific immune marker levels, suggesting that PFAS exposure may increase the risk of RA in adults.

The association between rheumatoid arthritis and cardiovascular disease among adults in the United States during 1999–2018, and age-related effect modification in relative and absolute scales

To explore the rheumatoid arthritis (RA)-cardiovascular diseases (CVD) association in relative and absolute risk scales among US adults aged ≥20 years over time and the effect modification of the association by age. We analyzed aggregated data from all ten continuous National Health and Nutrition Examination Survey cycles. A sample of 35,062 complete-case subjects was considered. The design-based regressions were used to investigate the associations in relative and absolute scales. In relative scale, the CVD odds ratio was 2.32, 2.19, and 1.97 among adults with RA than no arthritis in 1999-2006, 2007-2012, and 2013-2018 cycles, respectively. This time trend was not statistically significant. The absolute risk estimates were 11, 10, and 9 per 100 CVD events. We also observed a significant effect modification by age; the higher relative risk among younger adults (<50 years) with RA and higher absolute risk in older adults (≥80 years) with RA were consistent across survey cycles. There is a significant association between RA and CVD among US adults in both relative and absolute risks. Moreover, age is a significant effect modifier for this association; but with opposing age-related trends in relative and absolute scales.

Prevalence of depressive symptoms in patients with rheumatoid arthritis at a regional hospital in KwaZulu-Natal, South Africa.

BackgroundDepression affects 14.8% – 38.8% of patients with rheumatoid arthritis (RA) in developed countries. The prevalence and risk factors for depression in patients with RA in sub-Saharan Africa is not well established.AimTo determine the prevalence of depressive symptoms in patients with RA.SettingPublic sector regional hospital in South Africa.MethodsA cross-sectional descriptive study was undertaken with 110 adult RA patients. A structured socio-demographic and clinical questionnaire, the modified health assessment questionnaire (mHAQ), the simplified disease activity index (SDAI) for RA, the patient health questionnaire (PHQ-9), and the Household Food Insecurity Access scale (HFIAS) for nutritional status, were used. Correlates of depressive symptomatology in participants with RA were identified using t-tests and regression analyses.ResultsMost of the participants were women (90.9%), 67% had moderate to severe RA disease on the SDAI score, 92.7% reported functional disability (HAQ score of ≥ 1), and 87.2% reported mild to severe depressive symptoms. Unemployment (p < 0.01), severe food insecurity (p < 0.01) and functional disability (p = 0.02), were significantly associated with the depressive symptoms, but not with disease activity (p = 0.8) or inflammatory markers (p = 0.63). Unemployment (adjusted β = −5.07, p < 0.01) and severe food insecurity (adjusted β = −4.47, p < 0.01) were significantly associated with depressive symptoms, based on the adjusted regression model.ConclusionAs RA effects functional status, with the impact of the resulting unemployment and food insecurity being associated with depression, affected people should be screened for depression and managed using a multidisciplinary approach, especially considering the role of social determinants in RA patients with depression.

A CD40 variant is associated with systemic bone loss among patients with rheumatoid arthritis.

Little is known about genes predisposing to systemic bone loss (SBL) in rheumatoid arthritis (RA). Therefore, we examined the association between SBL and variants of genes playing a critical role in both immune response and bone homeostasis among patients with RA. IRAK-1 rs3027898, IRAK-2 rs3844283, IRAK-2 rs708035, IFIH1 rs1990760, CD40 rs48104850, TNFAIP3 rs2230926, and miR146-a rs2910164 were genotyped in 176 adult RA patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Low BMD was observed in 116 (65.9%) patients. Among them, 60 (34.1%) had low femoral neck (FN) Z score, 72 (40.9%) had low total femur (TF) Z score, and 105 (59.6%) had low lumbar spine (LS) Z score. Among all the SNPs assessed, only CD40 rs4810485 was found to be associated with reduced TF Z score with the CD40 rs4810485 T allele protecting against reduced TF Z score (OR = 0.40, 95% CI = 0.23-0.68, p = 0.0005). This association was confirmed in the multivariate logistic regression analysis (OR = 0.31, 95% CI = 0.16-0.59, p = 3.84 × 10-4). Moreover, median FN BMD was reduced among RA patients with CD40 rs4810485 GG genotype compared to RA patients harbouring CD40 rs4810485 TT and GT genotypes (0.788 ± 0.136 versus 0.826 ± 0.146g/cm2, p = 0.001). IRAK-1 rs3027898, IRAK-2 rs3844283, rs708035, IFIH rs1990760, TNFAIP3 rs2230926, and miR146-a rs2910164 were not found to be associated with SBL. This study for the first time ever demonstrated an association between aCD40 genetic variant and SBL among patients with RA. • CD40 rs4810485 GG genotype is associated with decreased BMD among patients with RA. • CD40 rs4810485 might serve as a genetic marker for SBL in RA. • CD40 genetic variations might be integrated in future development of more effective therapeutic interventions for prevention of SBL in RA.

Association of tumor necrosis factor-α inhibitors and liver cirrhosis in patients with rheumatoid arthritis: A nationwide population-based nested case-control study.

Results from various studies are controversial regarding long-term hepatic effects of tumor necrosis factor (TNF)-α inhibitors. Here we aimed to investigate the development of liver cirrhosis with TNF-α inhibitors use in patients with rheumatoid arthritis (RA). This nested case-control study was based on the National Health Insurance Research Database (January 1, 2000 to December 31, 2008) of Taiwan. We identified 559 adult RA patients who developed liver cirrhosis, and 1055 matched control RA patients. TNF-α inhibitors of interest in the study period included adalimumab and etanercept. Multivariate logistic regression analysis for the development of liver cirrhosis with respect to use of TNF-α inhibitors was performed. The incidence rate of liver cirrhosis was 274 per 100000 person-years in newly diagnosed RA patients. We found the use of TNF-α inhibitors was not associated with the development of liver cirrhosis in RA patients (odds ratio 1.02, 95% confidence interval 0.61, 1.70) after adjustment for potential confounders. In addition, the finding was robust to an unobserved confounder. We found no association between the use of TNF-α inhibitors and development of liver cirrhosis in RA patients.

POSA370 Healthcare Resource Use By European Patients Enrolled in RA-be-Real: A Multinational, Prospective, Observational Study of the Effectiveness, Healthcare Resource Utilization and Costs in Patients with Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic or Biologic Disease Modifying Therapies

Baricitinib (BARI) is a JAK1/2 inhibitor approved for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). RA-BE-REAL is a 3-year, prospective, observational study of adult RA patients (pts). The overall study Objectives: are to report the proportion of pts that discontinue treatment and to report the extent of healthcare resource use (HRU) by pts following 6-months (M) of either BARI, biologic (b)DMARDs or any other targeted synthetic (ts)DMARDs (b/tsDMARDs) after starting that treatment for the first time.

The development and validation of a Patient-Perceived Methotrexate Intolerance Scale for use in adult rheumatoid arthritis patients.

To develop a scale to measure methotrexate intolerance for use in adult rheumatoid arthritis (RA) patients and to describe its psychometric properties. A three-phase study was conducted. During Phase 1, we conducted individual interviews with RA patients (n=14) to inform our item development process. During Phase 2, we asked for RA patients' (n=10) feedback on item readability, clarity and the scale's ability to measure methotrexate intolerance. During Phase 3, we had patients with RA (n=204) complete the scale to develop a final version and to describe the scale's internal validity (Cronbach's alpha), test-retest reliability (intra-class correlation coefficients), construct validity and discriminant validity and the ability of the scale to discriminate between past and present methotrexate users. The newly developed, weighted scale (Patient-Perceived Methotrexate Intolerance Scale [PPMIS]) includes four subscales: Methotrexate Benefits, Methotrexate Risks-Side Effect Considerations, RA Risks and Methotrexate Risks-Willingness to Take Methotrexate Despite Risks. Cronbach's alpha ranged from 0.79 to 0.94. Test-retest reliability at 2weeks was 0.73-0.88. Construct validity was supported with significant logical relationships between subscale scores and the existing methotrexate intolerance scale and past/present methotrexate use. The PPMIS was able to correctly classify RA patients as a past versus present methotrexate user 77% of the time. At the cut point of 3.29, the sensitivity of the PPMIS is 74% and specificity is 72% to correctly classify patients into past/present methotrexate use. This is the first known scale with favourable measurement properties to evaluate methotrexate intolerance using a patient-centred perspective.

AGER gene variant as a risk factor for juvenile idiopathic arthritis

The AGER gene encodes a cell surface multiligand receptor of advanced glycation end-products that is also capable of binding other molecules and is involved in numerous pathways related to inflammation, apoptosis, immunity and so on. In the present study, we aimed to investigate whether the AGER rs1035798 (G>A) intronic polymorphism, showing an association with multiple sclerosis and rheumatoid arthritis in adults, is related to juvenile idiopathic arthritis (JIA). Caucasian children from the Belarusian population were enrolled in the study. In total, there were 201 cases with JIA, 37 with juvenile systemic lupus erythematosus, 222 children with the articular syndrome of non-autoimmune etiology (positive control for JIA) and 365 negative controls (children without any autoimmune or inflammatory diseases). Genomic DNA samples from the patients and controls were genotyped by a real-time polymerase chain reaction. A marked association of the homozygous AA rs1035798 genotype with JIA (p = 5 × 10-4 ) was found. Allele A was also associated with JIA (p = 0.0058), as well as with the articular syndrome of non-autoimmune etiology (p = 0.0264). The highest frequencies of the AA genotype were found in the subgroups of JIA patients with polyarthritis or severe oligoarthritis. The AA genotype patients also had the smallest mean age of the JIA onset. Our results demonstrate that the AGER rs1035798 AA genotype is a risk factor for JIA in Belarusian children. They also suggest a link between the AGER AA genotype and the risk of JIA early onset and severity. However, the functional relevance of the rs1035798 polymorphism is still unclear.

Evaluation of a multidisciplinary care model to improve quality of life in rheumatoid arthritis: a randomised controlled trial.

Health-Related Quality of Life (HR-QOL) is an important patient-reported domain in patients with rheumatoid arthritis (RA). The uptake of multidisciplinary team (MDT) care in RA is generally low, due to initial high demand for resources. We hypothesised that whilst pharmacological treatments are effective in controlling disease activity, a multipronged intervention in an MDT may have a positive impact on HR-QOL. This was a single-centre randomized parallel group, single-blind controlled trial of MDT vs. usual care in an established RA clinic. Data were collected through face-to-face questionnaires, medical records review, and joint counts by a blinded assessor at 0, 3 and 6months. Adult RA patients were randomly assigned in a single visit to a 6-member MDT (rheumatologist, nurse, social worker, physiotherapist, occupational therapist, and podiatrist) or usual care. MDT providers prescribed medications and counselled patients on managing flares, medication adherence, coping, joint protection, exercise, footwear. The primary outcome was minimal clinically important difference (MCID) in HR-QOL (increase in European QOL-5-Dimension-3-Level, EQ-5D-3L by 0.1) at six months. 140 patients (86.3% female, 53.4% Chinese, median (IQR) age 56.6 (46.7, 62.4) years); 70 were randomized to each arm. Median (IQR) disease duration was 5.5 (2.4, 11.0) years and disease activity in 28 joints (DAS28) was 2.87 (2.08, 3.66). 123 patients completed the study. Twenty-six (40.6%) MDT vs. 23 (34.3%) usual care patients achieved an MCID in EQ-5D-3L, OR 1.3 (0.6, 2.7). In multivariable logistic regression, baseline EQ-5D-3L was the only predictor of achieving MCID. There was more disease modifying anti-rheumatic drug escalation in MDT (34.4% vs. 19.4%). Patients with high disease activity were more likely to achieve MCID in the MDT arm. A single visit by stable patients with low disease activity to an MDT failed to achieve MCID in the EQ-5D-3L; however, did achieve small but significant improvements in the EQ-5D-3L, DAS28, pain, coping and self-efficacy. To be sustainable, MDT care should be targeted at patients with high disease activity or those with a new diagnosis of RA. The study is registered on ClinicalTrials.gov, identifier: NCT03099668.

Subcutaneous Infliximab, CT-P13SC: A Profile of Its Use in the EU.

CT-P13 (Remsima®; Inflectra®), a biosimilar of reference infliximab (Remicade®), provides a useful alternative for patients requiring infliximab therapy and, as with other biosimilar agents, has the potential to reduce treatment costs. Furthermore, the availability of CT-P13 in a subcutaneous formulation (CT-P13SC), with the possibility (after adequate training) of self-administration at home, has the potential to both improve patient convenience and reduce the burden on the healthcare system. The initial approval of CT-P13SC, for use in the treatment of rheumatoid arthritis in adults, was based on the findings of a randomised, double-blind phase I/III trial which demonstrated the non-inferiority of CT-P13SC administered once every 2weeks to intravenous CT-P13 (CT-P13IV) administered once every 8weeks in reducing disease activity in patients with active rheumatoid arthritis. Subsequently, based on pharmacokinetic data in patients with inflammatory bowel disease, CT-P13SC has also been approved in the EU for use in the treatment of Crohn's disease, ulcerative colitis and, by extrapolation, ankylosing spondylitis, psoriatic arthritis and psoriasis, in adults.

Passive Smoking Throughout the Life Course and the Riskof Incident Rheumatoid Arthritis in Adulthood AmongWomen.

To investigate passive smoking throughout the life course and the risk of rheumatoid arthritis (RA), while accounting for personal smoking. We analyzed the Nurses' Health Study II prospective cohort, using information collected via biennial questionnaires. We assessed the influence of 1) maternal smoking during pregnancy (in utero exposure), 2) childhood parental smoking, and 3) years lived with smokers since age 18. Incident RA and serostatus were determined by medical record review. Using the marginal structural model framework, we estimated the controlled direct effect of each passive smoking exposure on adult incident RA risk by serologic phenotype, controlling for early-life factors and time-updated adulthood factors including personal smoking. Among 90,923 women, we identified 532 incident RA cases (66% seropositive) during a median of 27.7 years of follow-up. Maternal smoking during pregnancy was associated with RA after adjustment for confounders, with a hazard ratio (HR) of 1.25 (95% confidence interval [95% CI] 1.03-1.52), but not after accounting for subsequent smoking exposures. Childhood parental smoking was associated with seropositive RA after adjustment for confounders (HR 1.41 [95% CI 1.08-1.83]). In the controlled direct effect analyses, childhood parental smoking was associated with seropositive RA (HR 1.75 [95% CI 1.03-2.98]) after controlling for adulthood personal smoking, and the association was accentuated among ever smokers (HR 2.18 [95% CI 1.23-3.88]). There was no significant association of adulthood passive smoking with RA (HR 1.30 for ≥20 years of living with a smoker versus none [95% CI 0.97-1.74]). We found a potential direct influence of childhood parental smoking on adult-onset incident seropositive RA even after controlling for adulthood personal smoking.

Birthweight, body size, and growth during childhood and risks of rheumatoid arthritis: a large Danish cohort study

Objectives: Adult obesity may be positively associated with risks of rheumatoid arthritis (RA), but associations with early life body size are unknown. We examined whether birthweight, childhood body mass index (BMI), height, and changes in BMI and height were associated with risks of adult RA. Method: A cohort of 346 602 children (171 127 girls) from the Copenhagen School Health Records Register, born in 1930–1996, with measured weights and heights from 7 to 13 years of age, were included. Information on RA, including serological status, came from national registers from 1977 to 2017. Cox regressions were performed. Results: During a median of 35.1 years of observation time per person, 4991 individuals (3565 women) were registered with RA. Among girls, per BMI z-score, risks of RA and seropositive RA increased by 4–9% and 6–10%, respectively. Girls with overweight had higher risks of RA than girls without overweight. Girls who became overweight by 13 years of age had increased risks of RA compared to girls without overweight at 7 or 13 years (hazard ratio = 1.40, 95% confidence interval 1.19–1.66). For boys, associations between BMI and RA (including seropositive RA) were not statistically significant. Height was not associated with RA (any type) in girls. Taller boys had higher risks of RA, especially seropositive RA. Birthweight was not associated with RA. Conclusions: Among women, childhood adiposity was associated with increased risks of RA. Among men, childhood height was positively associated with risks of RA. These findings support the hypothesis that early life factors may be important in the aetiology of RA.

Emerging Value of Platelet-to-Hemoglobin Ratio and Monocyte-to-Hemoglobin Ratio in Assessment of Rheumatoid Arthritis Patients

Abstract Background: Rheumatoid arthritis (RA) is chronic au-toimmune disease associated with systemic inflammation that affects mainly synovial joints. Inflammation is the main reason of tissue destruction, physical disability and excess of mortality in RA. There is a need to find accurate inexpensive valuable inflammatory markers to be helpful in early diagnosis, prompt treatment and strict follow-up of RA patients. Aim of Study: To assess platelet-to-hemoglobin ratio (PHR) and monocyte-to-hemoglobin ratio (MHR) in RA patients. In addition to evaluate their associations with clinical and laboratory markers of RA disease activity and severity. Patients and Methods: The study included 175 adult RA patients and 186 age and gender healthy individuals were enrolled as control group. Disease activity score (DAS28) and RA medical records-based index of severity (RARBIS) were assessed in RA patients. PHR and MHR were measured in patients and controls. Results: They were 154 females and 21 males RA patients with a mean age of 45.43±10.5 years and disease duration of 9.3±0.47 years. PHR and MHR were significantly higher in patients (27.04±9.52, 0.03±0.02) than controls (21.58±5.6, 0.02±0.01) respectively, (p < 0.001). PHR and MHR had diag-nostic ability to discriminate RA patients from controls with sensitivity of 75%, 73.94% respectively and specificity of 53.23% in both. PHR had significant positive correlations with DAS28 (r=0.25, p=0.003), RARBIS (r=0.20, p=0.041), erythrocyte sedimentation rate (ESR) (r=0.41, p < 0.001), C-reactive protein (CRP) (r=0.4, p < 0.001) and anti-cyclic cit-rullinated peptide antibodies (anti-CCP abs) (r=0.3, p=0.001). MHR was only correlated with CRP (r=0.24, p=0.002). Mul-tivariate linear regression for the increase in PHR among RA patients revealed that ESR (b=0.100; p < 0.001, CI=0.05-0.145) and CRP (b=0.091; p=0.004, CI=0.02-0.152) were significant predictors. Conclusion: PHR and MHR were significantly increased in RA patients than controls. In addition, PHR and to lesser extent MHR were associated with RA disease activity and severity clinical as well as laboratory markers. This means they may serve as novel, inexpensive and easily obtainable inflammatory RA markers helping in evaluation and monitoring of RA patients disease activity and severity.

Assessing methotrexate intolerance and its prevalence in rheumatoid arthritis: Development and validation of the MISA questionnaire.

Methotrexate (MTX) intolerance refers to unpleasant symptoms that accompany use of MTX. Although a validated questionnaire on MTX intolerance exists for children with juvenile idiopathic arthritis, it is lacking for adult rheumatoid arthritis (RA) patients. A 10-item questionnaire called Methotrexate Intolerance and Severity assessment in Adults (MISA) was developed to assess MTX intolerance. On receiver operating characteristic analysis, its predictive ability was compared to Methotrexate Intolerance Severity Score (MISS), a validated questionnaire for children. Subsequently, prevalence and associations of intolerance were assessed in 414 RA patients. After 1year, discontinuation of MTX was compared between patients with and without MTX intolerance. MISA score had a good predictive ability (area under the curve [AUC] of 0.904), with sensitivity and specificity of 91.4% and 84.3% (cut-off ≥1) to correctly classify MTX intolerance and was better than MISS score (AUC of 0.823). Among 414 RA patients, 159 (38.4%) had MTX intolerance, with common symptoms being nausea, lethargy, irritability and loss of appetite. On multivariable analysis, age (odds ratio 0.972) and body mass index (odds ratio 1.061) were significant predictors of MTX intolerance. At 1year, a higher proportion of patients with intolerance than without intolerance had discontinued MTX (odds ratio 2.4, P=0.02). To classify severity of intolerance, another score, MISA-cross-product, was developed and validated, with an AUC of 0.899. The newly developed MISA questionnaire and score had good predictive ability to diagnose MTX intolerance. Intolerance to MTX was common, being found in one-third of RA patients. Patients with intolerance were twice more likely to discontinue MTX at 1year.

Outcomes of COVID-19 in patients with rheumatoid arthritis: A multicenter research network study in the United States

ObjectivesTo investigate outcomes of Coronavirus Disease-2019 (COVID-19) in patients with rheumatoid arthritis (RA) as compared to the general population. Additionally, outcomes were explored among RA patients stratified by sex, race, and medications use through sub-cohort analyses. MethodsThis comparative cohort study used a US multicenter research network (TriNetX) to extract data on all adult RA patients who were diagnosed with COVID-19, and adults without RA who were diagnosed with COVID-19 (comparative cohort) anytime from January 20, 2020 to April 11, 2021. COVID-19 outcomes were assessed within 30 days after its diagnosis. Baseline characteristics that included demographics and comorbidities were controlled in propensity score matching. ResultsA total of 9730 RA patients with COVID-19 and 656,979 non-RA with COVID-19 were identified. Before matching, the risk of all outcomes including mortality (RR: 2.11, 95%CI: 1.90 to 2.34), hospitalization (RR: 1.60, 1.55 to 1.66), intensive care unit-ICU admission (RR: 1.86, 1.71 to 2.05), mechanical ventilation (RR: 1.62, 1.44 to 1.82), severe COVID-19 (RR: 1.89, 1.74 to 2.06), acute kidney injury (RR: 2.13, 1.99 to 2.29), kidney replacement therapy/hemodialysis (RR: 1.40, 1.03 to 1.89), acute respiratory distress syndrome-ARDS (RR: 1.76, 1.53 to 2.02), ischemic stroke (RR: 2.62, 2.24 to 3.07), venous thromboembolism-VTE (RR: 2.30, 2.07 to 2.56), and sepsis (RR: 1.97, 1.81 to 2.13) was higher in RA compared to non-RA. After matching, the risks did not differ in both cohorts except for VTE (RR: 1.18, 1.01 to 1.38) and sepsis (RR: 1.27, 1.12 to 1.43), which were higher in the RA cohort. Male sex, black race, and glucocorticoid use increased the risk of adverse outcomes. The risk of hospitalization was higher in rituximab or interleukin 6 inhibitors (IL-6i) users compared to tumor necrosis factor inhibitors (TNFi) users, with no significant difference between Janus kinase inhibitors (JAKi) or abatacept users and TNFi users. ConclusionThis large cohort study of RA-COVID-19 found that the risk of all outcomes was higher in the RA compared to the non-RA cohort before matching, with no difference in the majority of outcomes after matching, implying the risk being attributed to adjusted factors. However, the risk of VTE and sepsis was higher in RA cohort even after matching, indicating RA as an independent risk factor. Male sex, black race, and glucocorticoid use were associated with adverse outcomes in RA with COVID-19. Rituximab or IL-6i users were associated with an increased risk of hospitalization compared to TNFi users.

Impact of using concomitant conventional DMARDs on adherence to biologic DMARD treatment in rheumatoid arthritis: Multi-centre, population-based cohort study

PurposeTo evaluate the impact of concomitant use of conventional synthetic DMARDs (csCMARD) on adherence, switching and dose of biologic disease modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis (RA) patients treated with bDMARDs. Patients and methodsThis was a population-based cohort study conducted in five provinces of Canada (Alberta, Manitoba, Ontario, Quebec, and Saskatchewan), and one American database (IBM® MarketScan® Databases). Adult RA patients entered the study after a 3-month initiation period of bDMARDs between 1 January 2007, and 30 March 2014. Concomitant csDMARD exposure was compared to non-csDMARD exposure on the following outcomes: discontinuation of bDMARD therapy, switching of bDMARDs, and percent change in dose of bDMARD compared to initial dose. The effect of the time-varying changes in csDMARD exposure was analyzed using marginal structural models. Dose change was analyzed using linear regression. Results from each participating site were combined using likelihood ratio meta-analysis. ResultsThe study population comprised 20,221 new users of bDMARDs: adalimumab (7609), etanercept (9809), abatacept (1024), infliximab (1779). Concomitant use of csDMARD therapy was not significantly associated with reduced discontinuation of bDMARD treatment (hazard ratio 0.90, 95% intrinsic confidence interval 0.79 to 1.02) or reduced switching of bDMARDs (hazard ratio 0.95, 95% intrinsic confidence interval 0.80 to 1.11), but was associated with a small increase in bDMARD dose compared to the mean dose over the first three months of treatment (mean percentage change in dose +0.56% mg/day, 95% intrinsic confidence interval +0.14% to +0.97%). ConclusionIn this large study of RA patients using bDMARDs in Canada and the United States, we found no clear evidence that patients who received concomitant csDMARD therapy were less likely to discontinue, switch or increase their dose of bDMARD.