Recent-onset Rheumatoid Arthritis Research Articles

Can Pharmacological Conditioning as an Add-On Treatment Optimize Standard Pharmacological Treatment in Patients with Recent-Onset Rheumatoid Arthritis? A Proof-of-Principle Randomized Clinical Trial.

Medication regimens using conditioning via variable reinforcement have shown similar or improved therapeutic effects as full pharmacological treatment, but evidence in patient populations is scarce. This proof-of-principle double-blind randomized clinical trial examined whether treatment effects in recent-onset rheumatoid arthritis (RA) can be optimized through pharmacological conditioning. After four months of standardized treatment (n = 46), patients in clinical remission (n = 19) were randomized to the Control group (C), continuing standardized treatment (n = 8), or the Pharmacological Conditioning (PC) group, receiving variable treatment according to conditioning principles (n = 11). After eight months, treatment was tapered and discontinued linearly (C) or variably (PC). Standard treatment led to large improvements in disease activity and HRQoL in both groups. The groups did not differ in the percentage of drug-free clinical remission obtained after conditioning or continued standard treatment. The PC group did show a larger decrease in self-reported disease activity (Cohen's d = 0.9) and a smaller increase in TNF-α levels (Cohen's d = 0.7) than the C group. During all phases, more differences between groups were found for the patients who followed protocol than for the intention-to-treat sample. Although the results are not conclusive, pharmacological conditioning may have some advantages in terms of disease progression and stability, especially during the conditioning phase, compared with standard clinical treatment. The effects may be particularly beneficial for patients who show a good initial response to increased medication dosages.

Repair of joint damage in patients with rheumatoid arthritis does not relate to previous suppression of inflammation: a subanalysis after 8 years treat-to-target in the BeSt-trial

ObjectivesTo investigate whether repair of erosions and joint space narrowing (JSN) in rheumatoid arthritis (RA) occurs and whether clinical variables predict this.MethodsEight-year follow-up data of the BeSt-study were used. Patients...

Bone mineral density status in patients with recent-onset rheumatoid arthritis.

Osteoporosis is a sizable comorbidity complication in Rheumatoid Arthritis (RA) sufferers. In the current study, the prevalence of osteopenia and osteoporosis in active RA sufferers and the association of disease-related factors of osteoporosis and reduced bone mineral density (BMD) have been examined. In this cross-sectional study, 300 new-onset symptoms (less than one year) RA patients without a history of glucocorticoids or DMARDs were selected. Biochemical blood measurements and BMD status were performed with dual-energy X-ray absorptiometry. According to the T-scores of the patients, they were divided into three groups: osteoporosis<-2.5, -2.5 < osteopenia <-1, and - 1 < normal. Also, the MDHAQ questionnaire, DAS-28, and FRAX criteria were calculated for all patients. Multivariate logistic regression was used to determine the associated factors of osteoporosis and osteopenia. The Prevalence of osteoporosis and osteopenia was 27% (95%CI:22-32) and 45% (95%CI:39-51), respectively. The multivariate regression analysis showed that age could play a role as an associated factor for spine/hip Osteoporosis and Osteopenia. The female gender is also a predictor of Spine osteopenia Patients with Total hip Osteoporosis were more likely to have higher DAS-28 (OR 1.86, CI 1.16-3.14) and positive CRP (OR 11.42, CI 2.65-63.26). recent-onset RA patients are at risk for osteoporosis and its complications, regardless of using glucocorticoids or DMARDs. Demographic factors (e.g. age and female gender), patients' MDHAQ scores, and disease-related factors(e.g., DAS-28, positive CRP were associated with reduced BMD levels. Therefore, it is recommended that clinicians investigate early BMD measurements to have a reasonable judgment for further interventions. The online version contains supplementary material available at 10.1007/s40200-023-01200-w.

Factors Associated With Household Work Limitations in Mexican Patients With Rheumatoid Arthritis: The Impact of the Disease on Women's Life.

Little attention has been given to the impact of rheumatoid arthritis (RA) on domestic work, which remains the domain of women, particularly in the Latin American region. The study identified factors associated with RA-related household work limitations (HOWL) in Mexican for women with long-standing disease. This cross-sectional study was performed between September 2020 and April 2022, in patients from the recent-onset RA cohort (initiated in 2004). At study entry, patients had standard rheumatic assessments and were administered the HOWL questionnaire, a survey to assess family responsibilities, household work characteristics, and the patient's economic dependency, and the family APGAR index to assess family function. Multiple logistic regression analysis identified variables associated with RA-related HOWL. Data from 114 female RA patients were analyzed. Overall, at cohort entry, patients were middle-aged (median, 37.5 years), with 12 years of education, and the minority (n = 42 [39.3%]) were married or living together. Patients were representative of typical patients with recent-onset disease and had significant disease activity. At study entry, the patients had 12 (7-16) years of disease duration, and their disease was under control. The median (interquartile range) HOLW-Q score was 0.67 (0-3.33), and 33 patients (28.9%) had RA-related HOWL. Receiving financial support for family living expenses, requiring assistance for activities of daily living, and DAS28 (Disease Activity Score, 28 joints evaluated) were associated with RA-related HOWL; meanwhile, a better Short-Form 36 score at disease onset was protective. Domestic work in Mexican RA women might be impacted by social determinants, health-related quality of life at disease onset, and current disease activity status.

Sleep quality and predictors of optimal sleep in patients with rheumatoid arthritis: data from a recent-onset cohort.

Sleep disorders are part of the symptomatology of rheumatoid arthritis (RA) patients and are related to disease characteristics and comorbidities. The study describes sleep quality among RA patients and identifies predictors of optimal sleep. Patients whose data were analysed were identified from the recent-onset RA cohort initiated in 2004. In 2010, the Medical Outcome Study Sleep Scale (MOS-SS) was incorporated into the patients' assessments. Up to December 2019, the cohort comprised 187 patients with at least one MOS-SS application (in 78 patients at cohort entry) and six months of outcomes behaviour (cumulative) previous to the MOS-SS application: DAS28-ESR, pain-VAS, fatigue, HAQ-DI, SF-36, treatment (corticosteroids, DMARDs/patient and adherence), Charlson score, and major depressive episodes. A trained data abstractor retrospectively reviewed their charts. Multiple logistic regression analysis estimated odds ratios (95% confidence interval) to define baseline and cumulative variables predictive of optimal sleep (dichotomised variable derived from the quantity of sleep dimension of the MOS-SS). At the first MOS-SS application, patients were primarily middle-aged women with short disease duration and low disease activity. They scored higher on the "snoring" and "sleep non-adequacy" MOS-SS dimensions. There were 96 patients (51.3%) with optimal sleep. Lower baseline BMI, better baseline fatigue score, longer follow-up at the clinic, and better SF-36 physical summary score were predictors of optimal sleep (mental summary score also remained in the model when switched to the physical summary score). Optimal sleep is achieved by half of the RA patients and predicted by BMI, patient-reported outcomes, and follow-up.

Exhaled nitric oxide in early rheumatoid arthritis and effects of methotrexate treatment

Patients with established rheumatoid arthritis (RA) and disease modifying treatments have lower nitric oxide (NO) levels in the alveolar compartment (CANO) and in the airway wall (CawNO), but also higher diffusion capacities for NO in the airways (DawNO) compared to matched controls. The aim of the present study was to investigate the NO lung dynamics in patients with recent onset RA before and after immune suppression with methotrexate therapy. Patients with early RA and antibodies against anticitrullinated peptides (ACPA) were recruited. Measurement of exhaled NO and inflammatory markers in serum were performed. Clinical disease activity was evaluated with Disease Activity Score for 28 joints. Healthy individuals were used as matched controls. Data are presented as median (lower quartile, upper quartile) values. RA patients (n = 44) had lower exhaled NO (FENO50) 16 (10–24) ppb compared to controls 21 (15, 29) ppb, p = 0.013. In NO-dynamics, CANO was lower in RA patients 1.6 (1.0, 2.2) ppb compared to the control subjects 2.3 (1.3, 3.1) ppb, p = 0.007. CawNO was also lower in the RA patients 55 (24, 106) ppb compared to control subjects 124 (110, 170) ppb, p < 0.001, but DawNO was higher 17 (8, 30) mL/s and 9 (5, 11) mL/s respectively, p < 0.001. Methotrexate treatment for three months reduced disease activity, but did not change the NO dynamics. In conclusion, the altered NO dynamics of the lung in ACPA-positive RA patients are already present in the early stages of the disease before any treatments and do not change after methotrexate therapy suggesting a role in the pathogenesis.

Extramucosal Formation and Prognostic Value of Secretory Antibodies in Rheumatoid Arthritis.

To investigate levels and possible extramucosal formation of secretory Ig, including anti-citrullinated protein antibodies (ACPAs), in rheumatoid arthritis (RA). Three patient groups were studied: 1) ACPA-positive patients with musculoskeletal pain without clinical arthritis, 2) patients with recent-onset RA, and 3) patients with established RA. In baseline serum samples (groups 1 and 2) and paired synovial fluid samples (group 3), we analyzed total secretory IgA, total secretory IgM, free secretory component (SC), and SC-containing ACPA. Extramucosal formation of SC-containing ACPA was investigated by preincubating RA sera and affinity-purified ACPA with recombinant free SC. Compared to healthy controls, serum levels of total secretory IgA and total secretory IgM were increased both in patients with early RA and at-risk patients (P < 0.05). Patients with early RA with elevated total secretory Ig had significantly higher disease activity during the 3-year follow-up period compared to those without increased levels. At-risk patients who developed arthritis during follow-up (39 of 82) had higher baseline total secretory IgA levels compared to those who did not (P = 0.041). In established RA, total secretory IgA and total secretory IgM levels were higher in serum than in synovial fluid (P < 0.0001), but SC-containing ACPAs adjusted for total secretory Ig concentration were higher in synovial fluid (P < 0.0001). Preincubation with recombinant free SC yielded increased SC-containing ACPA reactivity in sera as well as in affinity-purified IgA and IgM ACPA preparations. Circulating secretory Ig are elevated before and at RA onset. In the presence of free SC, secretory Ig may form outside the mucosa, and SC-containing ACPAs are enriched in RA joints. These findings shed important new light on the mucosal connection in RA development.

Early persistence on therapy impacts drug-free remission: a case-control study in a cohort of Hispanic patients with recent-onset rheumatoid arthritis

BackgroundMedication adherence is suboptimal in rheumatoid arthritis (RA) patients and impacts outcomes. DMARD-free remission (DFR) is a sustainable and achievable outcome in a minority of RA patients. Different factors have been associated with DFR, although persistence in therapy (PT), a component of the adherence construct, has never been examined. The study’s primary aim was to investigate the impact of PT’s characteristics on DFR in a cohort of Hispanic patients with recent-onset RA.MethodsA single data abstractor reviewed the charts from 209 early (symptoms duration ≤ 1 year) RA patients. All the patients had prospective assessments of disease activity and PT and at least 1 year of follow-up, which was required for the DFR definition. DFR was defined when patients achieved ≥ 1 year of continuous Disease Activity Score-28 joints evaluated ≤ 2.6, without DMARDs and corticosteroids. PT was defined based on pre-specified criteria and recorded through an interview from 2004 to 2008 and thereafter through a questionnaire. Cases (patients who achieved ≥ 1 DFR status) were paired with controls (patients who never achieved DFR during their entire follow-up) according to ten relevant variables (1:2). Cox regression analysis estimated hazard ratios (HRs) for DFR according to two characteristics of PT: the % of the patient follow-up PT and early PT (first 2 years of patients’ follow-up).ResultsIn March 2022, the population had 112 (55–181) patient/years follow-up. There were 23 patients (11%) with DFR after 74 months (44–122) of follow-up, and the DFR status was maintained during 48 months (18–82). Early PT was associated with DFR, while the % of the patient follow-up PT was not: HR = 3.84 [1.13–13.07] when the model was adjusted for cumulative N of DMARDs/patient and 3.16 [1.14–8.77] when also adjusted for baseline SF-36 physical component score. A lower N of cumulative DMARDs/patient was also retained in the models. Receiving operating curve to define the best cutoff of patient follow-up being PT to predict DFR was 21 months: sensitivity of 0.739, specificity of 0.717, and area under the curve of 0.682 (0.544–0.821).ConclusionsDFR status might be added to the benefits of adhering to prescribed treatment.

Influence of glucocorticoid treatment on trabecular bone score and bone remodeling regulators in early rheumatoid arthritis

BackgroundGlucocorticoids (GC) modulate several regulators involved in the pathogenesis of bone changes in rheumatoid arthritis (RA). Trabecular bone score (TBS) allows the indirect assessment of bone quality. The aim of this study was to investigate the effects of GC on TBS and serum levels of bone turnover regulators in patients with recent-onset RA.Materials and methodsForty-seven subjects with recent-onset RA (< 6 months) were classified in two groups, low (lGC) and high (hGC) glucocorticoids, according to glucocorticoid dose regimens. Bone mineral density (BMD), TBS, and circulating Dickkopf-1 (Dkk1), sclerostin, osteoprotegerin (OPG), and RANK-L were evaluated at baseline and 6 and 12 months.ResultsBMD significantly declined after 12 months with no significant difference between the lGC and hGC group, whereas TBS decreased in the hGC group only. Circulating OPG decreased during the follow-up period, the reduction being significantly greater in hGC group; conversely, sclerostin and RANK-L serum increased, in a significantly greater extent in the hGC group. TBS inversely correlated with sclerostin, RANK-L, and Dkk1 circulating levels whereas directly correlated with OPG circulating levels. GC cumulative dose showed an inverse relationship with BMD in both the hGC and lGC groups; TBS values showed an inverse relationship with GC cumulative dose in the hGC group only. GC cumulative dose was associated to higher sclerostin and lower OPG serum levels. TBS did not correlate with disease activity whereas BMD was inversely related to disease activity.ConclusionsIn early RA, GC exposure contributes to the reduction of BMD and affects bone quality depending on dose regimens. TBS could be a useful tool to evaluate the negative effect of GC on bone microarchitecture.Trial registrationThis study was ancillary to a parallel-group observational prospective study which was approved by the medical local ethics committee (protocol number DDG 334/19-06-2019).

Impact of Anti-Citrullinated Protein Antibodies on Progressive Systemic Bone Mineral Density Loss in Patients With Early Rheumatoid Arthritis After Two Years of Treat-to-Target.

ObjectivesTo investigate the association of anti-citrullinated protein antibodies (ACPA) with changes in systemic bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) after two years of treat-to-target.MethodsBMD was measured at the lumbar spine (LS) and femoral neck (FN) in 100 patients with recent onset RA at baseline and after 24 months of treatment aimed at low disease activity (LDA) according to the 28-joints disease activity score (DAS28 <3.2). Multivariable regression analyses were performed to determine independent associations between autoantibodies and other disease and treatment-related parameters with BMD loss.ResultsAfter 24 months, the majority of the patients were at least in LDA (78%), with slightly more ACPA-positive subjects achieving the target. The BMD had significantly decreased at both the LS (mean [SD] percent loss -1.8 [6.2], p=0.03) and the FN (-2.4 [7.3], p=0.03) in ACPA-positive but not in ACPA-negative patients. Consequently, the proportion of patients with reduced BMD (Z score ≤-1) after 24 months was significantly higher among ACPA-positive patients at both the spine (39.5% vs 19.3%, p=0.05) and the hip (37.2% vs 12.2%, p=0.007). The association between ACPA and BMD loss was independent of other variables including age, gender, disease activity, cumulative dose of glucocorticoids and duration of therapy with bisphosphonates at the LS but not the FN.ConclusionsACPA are associated with ongoing BMD loss at the spine despite suppression of inflammation and adoption of prophylactic measures. ACPA-positive RA patients should be therefore strictly monitored for the development of osteoporosis.

High disease activity is associated with higher blood pressure in recent onset rheumatoid arthritis patients, post-hoc analyses of IMPROVED study

Abstract Funding Acknowledgements Type of funding sources: None. Background Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high prevalence of cardiovascular morbidity and mortality. Purpose: purpose of our project was to investigate the association between disease activity and systolic and diastolic blood pressure (SBP, DBP) in patients with recent-onset rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) who were treated to target disease activity score (DAS)&amp;lt;1.6 in the IMPROVED study. Methods: The associations between disease activity and SBP/DBP were tested for 610 patients (364 RA, 246 UA), cross-sectionally and over time. GEE analyses were performed with both SBP and DBP as outcome measures and disease activity categories (DAS&amp;lt;1.6;&amp;gt;1.6 but ≤2.4; &amp;gt;2.4), CRP level, treatment arms or the number of visits on a certain drug as potential predictors in separate analyses. Separate analyses tested potential contributions of gender, anti-cyclic citrullinated peptide antibodies (ACPA) status, and fulfilling the 2010 ACR/EULAR (American college of rheumatology/ European league against rheumatism) classification criteria. In addition association of BP with various levels of disease activity was tested with T-test. Results: At the baseline mean (SD) SBP was 133 (20) and DBP mean (SD) was 80 (10).  SBP &amp;gt; 140mm Hg was observed in 40% of patients and DBP &amp;gt; 90 mm Hg  in 21% of patients. SBP and DBP statistically significantly decreased during 5 years follow up (mainly during year 1), but the difference in mm Hg was small. Estimates from GEE analysis showed that patients with high DAS &amp;gt;2.4 (HDAS) had a statistically significantly higher SBP (average 3 mm Hg higher, 95% CI 1.7; 4.2, p &amp;lt; 0.01), than the patients in with DAS ≤2.4. ANOVA analyses showed a statistically significant association between SBP and DAS. In addition, post hoc analyses showed that patients with HDAS had a statistically significantly higher  SBP (mean (SD) 132 (19) than the patients with DAS &amp;lt; 1.6 (remission) (mean (SD) 129 (20), p &amp;lt; 0.01), and patients in LDAS but DAS≥1.6 had a statistically significantly higher SBP (mean (SD) 131 (19) than the patients in remission (mean (SD)  129 (20), p = 0.02) (Figure 1), whereas no association was found between DAS category and DBP. Gender, ACPA status or fulfilling the 2010 classification criteria did not influence the relation between DAS and blood pressure. Conclusions: In patients with RA or UA, a higher DAS is associated with higher blood pressure, but the clinical impact is unclear. Abstract Figure 1

Clinical management and discontinuation of treatment in patients with recent onset rheumatoid arthritis in a rheumatology consultation

IntroductionThe treatment of Rheumatoid Arthritis (RA) has changed dramatically in recent years, especially with the use of disease modifying drugs (DMARDs). Data on the management of this disease in clinical trials are abundant, but not so in real life. The aim of our study is to describe the management of an early RA cohort in daily clinical practice, especially DMARD discontinuations and reasons. MethodsA retrospective observational study of patients with RA diagnosed between 01/07 and 12/14 followed up to 01/17, using >1 DMARD ≥ 3 months. Variables: sociodemographic, clinical, treatment, DMARD discontinuation and reason. Descriptive analysis of sociodemographic, clinical and treatment characteristics. Discontinuation incidence rate (DIR) due to survival techniques, expressed in 100 patients*year with 95% confidence interval. Results814 patients were included with 2388 courses of treatment, 77% women, mean age 57.5 years. First course: monotherapy (92.75%), especially Methotrexate (56.06%). In later courses there was increased combined therapy and use of biologicals (mainly Etanercept). There were 1094 discontinuations (29.5 [27.8–31.3]). The DIR was higher for adverse events (15.9 [14.7–17.3]), biologicals (49.6 [43.1–57.2]) and combined therapy. The DMAR with the lowest DIR was MTX (25.8 [23.8–28.1]). ConclusionMethotrexate was the most used drug, biologicals increased throughout the follow-up, the most frequent being Etanercept. The DMARD DIR was 29*100 patients per year, mainly due to adverse events. It seems to be higher in the therapies that include biologicals and combined therapies. MTX is the drug with the lowest DIR.

Tocilizumab can efficiently prevent bone destruction in patients with recent-onset rheumatoid arthritis

Objectives To assess whether tocilizumab (TCZ) can prevent bone destruction in patients with recent-onset rheumatoid arthritis (RA). Methods DAS28-ESR and van der Heijde-modified Sharp score (mTSS) were evaluated in 50 patients who received TCZ within 1 year from the onset of RA. TCZ was consecutively administered during the observation period within the first 2 years. In 15 patients, mTSS could be evaluated at 5 years. Results The mean DAS28-ESR at baseline, 1, 2, and 5 years was 4.86, 1.29, 1.19, and 1.18, respectively. The change in mTSS (ΔmTSS) between baseline and 2 years was −0.33. The structural remission rates (ΔmTSS/year ≤0.5) were 91.8% and 92.7% during the first and second years, respectively. Only one increase in erosion score was observed in the first year in 2 patients and the erosion score of all patients did not increase in the second year. In 15 patients, the ΔmTSS over 5 years was 0.80, corresponding to 0.16 per year. The structural remission rate at 5 years (ΔmTSS ≤2.5) was 93.3%. The erosion score was 0 in all 15 patients at 5 years, indicating that bone destruction did not become apparent. Conclusion TCZ can efficiently prevent bone destruction in patients with recent-onset RA.

Subjective sleep disturbances at the time of diagnosis in patients with polymyalgia rheumatica and in patients with seronegative elderly-onset rheumatoid arthritis. A pilot study.

ObjectivesTo investigate subjective sleep disturbances in patients with recent-onset polymyalgia rheumatica (PMR) and in patients with recent-onset seronegative elderly-onset rheumatoid arthritis (SEORA).Material and methodsThe study involved patients consecutively referred to two outpatient clinics from January to June 2018, with a diagnosis of PMR according to 2012 European League Against Rheumatism and American College of Rheumatology provisional criteria, and patients with a diagnosis of SEORA according to 1987 American Rheumatism Association criteria + age + absence of rheumatoid factor and anti-citrullinated peptide antibodies. All patients were naive to glucocorticoid (GC) therapy. After informed consent, we asked the patients to fill out a questionnaire including the Medical Outcomes Study – Sleep Scale (MOS-SS), pain Visual Analogic Scale (VAS), Cumulative Illness Rating Scale (CIRS), Neuropsychiatric Inventory (NPI), and how many minutes their morning stiffness (MS) lasted, at baseline and after 1 (T1) and 12 (T2) months. Differences between groups were calculated with the t-test; all p-values were two-sided and p < 0.05 was used to determine statistical significance. The study was approved by the local ethics committee and carried out in accordance with the Helsinki Declaration.ResultsThe MOS-SS scores and MS duration were the only variables to show at T0 a significant difference between the two groups. In particular, MOS-SS scores were 47.6 ±8.4 (PMR) and 28.26 ±12.4 (SEORA), with p-values = 0.000. The MS duration was 90 ±9.9 minutes and 45 ±5.5 minutes, with p-value = 0.000. At T1 and T2, MOS-SS scores and MS duration decreased in the two groups, and no significant differences were found.ConclusionsThe study suggests that the assessment of subjective sleep disturbances can be useful in the differential diagnosis between recent-onset PMR and SEORA.

Association of a Type 2-Polarized T Cell Phenotype With Methotrexate Nonresponse in Patients With Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated through complex immunologic pathways. Among RA patients receiving low-dose methotrexate (MTX) monotherapy, approximately one-half exhibit a meaningful clinical response within the first 6 months of starting treatment. Whether baseline immune phenotypes differ between subsequent MTX responders and nonresponders is unknown. This study utilized comprehensive T cell immunophenotyping to identify specific immunologic pathways associated with MTX-nonresponsive joint inflammation in patients with RA. In total, 32 patients with recent-onset RA were treated with MTX therapy. After 6 months, 15 patients were categorized as responders and 17 as nonresponders. Comprehensive blood T cell immunophenotyping, using multiparameter immunofluorescence flow cytometry analyses, was performed at baseline and following 6 months of treatment. Baseline measures of disease activity (Disease Activity Score in 28 joints [DAS28], C-reactive protein level, and erythrocyte sedimentation rate) did not differ between MTX responders and nonresponders following MTX treatment. Frequencies of CD4+ and CD8+ T cells were skewed to favor higher CD4:CD8 T cell ratios in MTX responders compared to nonresponders (P < 0.05). The proportion of inducible costimulator-expressing Treg cells was significantly greater among MTX nonresponders. Interleukin-13 (IL-13)-producing, but not interferon-γ- or IL-17-producing, CD4+ effector memory T (Tem) cells were significantly more frequent in MTX nonresponders (P < 0.05). The ratio of IL-13+:IL-17+ Tem cells among CD4+ Tem cells was 1.9-fold higher in MTX nonresponders compared to responders (P < 0.05). Both the CD4:CD8 T cell ratio and the frequency of IL-13+CD4+ Tem cells correlated with changes in the DAS28 score following MTX treatment, whereas T cell expression of immune checkpoint inhibitor markers (CTLA-4, programmed death 1, and T cell immunoglobulin and mucin domain-containing protein 3) did not differ between MTX responders and nonresponders. We observed a bias toward type 2-polarized T cell inflammatory responses in the peripheral blood of MTX-nonresponsive RA patients. Targeting the IL-13+CD4+ T cell pathway could be a new therapeutic strategy in RA patients whose disease remains resistant to MTX.

Pharmacological conditioning in the treatment of recent-onset rheumatoid arthritis: a randomized controlled trial study protocol

BackgroundIn pharmacological conditioning associations are formed between the effects of medication and contextual factors related to the medication. Pharmacological conditioning with placebo medication can result in comparable treatment effects and reduced side effects compared to regular treatment in various clinical populations, and may be applied to achieve enhanced drug effects. In the current study protocol, pharmacological conditioning is applied to achieve enhanced treatment effects in patients with recent-onset rheumatoid arthritis (RA). The results from this study broaden the knowledge on the potential of pharmacological conditioning and provide a potential innovative treatment option to optimize long-term pharmacological treatment effectiveness for patients with inflammatory conditions, such as recent-onset RA.MethodsA multicenter, randomized controlled clinical trial is conducted in patients with recent-onset RA. Participants start on standardized pharmacological treatment for 16 weeks, which consists of methotrexate (MTX) 15 mg/week and a tapered schedule of prednisone 60 mg or 30 mg. After 4 months, participants in clinical remission (based on the rheumatologist’s opinion and a targeted score below 1.6 on a 44-joint disease activity score (DAS44)) are randomized to 1 of 2 groups: (1) the control group (C), which continues with a standardized treatment schedule of MTX 15 mg/week or (2) the pharmacological conditioning group (PC), which receives an MTX treatment schedule in alternating high and low dosages. In the case of persistent clinical remission after 8 months, treatment is tapered and discontinued linearly in the C group and variably in the PC group. Both groups receive the same cumulative amount of MTX during each period. Logistic regression analysis is used to compare the proportion of participants with drug-free clinical remission after 12 months between the C group and the PC group. Secondary outcome measures include clinical functioning, laboratory assessments, and self-reported measures after each 4-month period up to 18 months after study start.DiscussionThe results from this study broaden the knowledge on the potential of pharmacological conditioning and provide a potential innovative treatment option to optimize long-term pharmacological treatment effectiveness in patients with inflammatory conditions, such as recent-onset RA.Trial registrationNetherlands Trial Register, NL5652. Registered on 3 March 2016.

Factors Associated With Low Lean Mass in Early Rheumatoid Arthritis: A Cross- Sectional Study.

Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical activity. Materials and Methods: 91 patients with early rheumatoid arthritis (ERA) (72% female) and 328 control subjects (54% female) were studied. BC-lean and fat mass parameters were measured with a Lunar Prodigy Dual Energy X-Ray Absorptiometry (DXA) machine. The prevalence, age and gender adjusted odds ratios of having low lean mass and overfat, associations between nutrition, physical activity, and ERA disease specific parameters and the presence of low lean mass were evaluated. Results: We found that the BC of patients with recent onset RA differs from control subjects—ERA patients had a higher mean body fat percentage (BFP) and lower appendicular lean mass (ALM). 41.8% of the ERA patients and 19.8% of the controls were classified as having low lean mass adjusted OR 3.3 (95% C.I. 1.9–5.5, p < 0.001). 68.1% of the ERA subjects and 47.3% of the controls were overfat (adjusted OR 1.9 (95% C.I. 1.1–3.3, p = 0.02)) and the adjusted odds of having both low lean mass and overfat were 4.4 times higher (26.4% vs. 7.0% 95% C.I. 2.3–8.4, p < 0.001) among the ERA group. Higher ESR (OR 1.03, C.I. 1.002–1.051, p = 0.03), CRP (OR 1.03, C.I. 1.002–1.061, p = 0.04), lower protein intake (OR 0.98 C.I. 0.96–0.99, p = 0.04), corticosteroid usage (OR 3.71 C.I. 1.4–9.9, p < 0.01) and lower quality of life (higher HAQ score OR 2.41 C.I. 1.24–4.65, p < 0.01) were associated with having low lean mass in the ERA group (adjusted to age and gender). Conclusions: Patients with early RA have lower appendicular lean mass and higher body fat percentage compared to healthy controls. Loss of lean mass in early RA is associated with elevated inflammatory markers inducing catabolism, lower protein intake and also with GCS treatment.

Cardiovascular risk factors' behavior during the early stages of the disease, in Hispanic rheumatoid arthritis patients: a cohort study.

Rheumatoid arthritis (RA) patients from Latin America present distinctive characteristics relevant when assessing their cardiovascular (CV) risk. The objective was to monitor CV risk factor behavior in the early stages of the disease and to identify predictors of major CV outcomes (MACE). A recent-onset RA cohort was initiated in 2004; data from 185 patients with ≥ 1year of follow-up were analyzed. Patients underwent prospective assessments of CV risk factors. Incident MACE were confirmed according to standardized definitions. Appropriated statics was used based on the distribution of the variables. At baseline, patients were primarily middle-aged females (87.6%), with active disease (69.7%). Most prevalent CV risk factors were C-reactive-protein > 1mg/L (90.3%), Castelli ratio > 3 (83.8%), and low-high-density lipoprotein levels (73.5%). The number of patients with an incident CV risk factor after 1year was higher for a Castelli ratio > 3 (23%), low-high-density lipoprotein serum cholesterol (16.3%), high total serum cholesterol (10.6%), and BMI ≥ 30kg/m2 (10%). A minority of patients met the age-range criteria for the application of ACC/AHA 2013 criteria and Reynolds Risk Score (45.8% and 34.1%, respectively). Fifteen patients were classified with high-CV risk during the first year of follow-up, according to ACC/AHA 2013 criteria. Until June 2018, the cohort underwent 1358 patient/years follow-up; six patients developed incidental MACE; high-CV risk at baseline failed to predict MACE. Recent-onset RA Hispanic patients present a distinctive pattern and first-year behavior of CV risk factors. During follow-up, few patients developed incidental MACE.

The epidemiology of established rheumatoid arthritis.

No published epidemiological study has specifically focused on the prevalence of established rheumatoid arthritis (RA), as epidemiologists do not study established RA separated from RA as a whole; especially no incidence studies can be found, as incidence refers to new cases (early RA). Such a study, if it existed, would find a prevalence much larger than that of recent-onset RA, and should be planned based on clear definitions that currently do not exist in epidemiology. As a result, any study addressing RA as a whole, leaving aside early arthritis, would be actually studying established RA. This work reviews the epidemiology of RA, in contraposition of early RA, and tried to highlight epidemiological characteristics of established RA in published studies as well as methodological issues, including differences between recent-onset and established RA regarding the prevalence of comorbidities and other characteristics, and differences across countries. The global epidemiology of established RA teaches us that long-term outcomes could largely depend on health care models and are modifiable.

Early clinical response and long-term radiographic progression in recent-onset rheumatoid arthritis: Clinical remission within six months remains the treatment target.

The primary objective was to evaluate the correlation between 5-year radiographic structural disease progression and early clinical remission in recent-onset rheumatoid arthritis (RA). The secondary objective was to assess the correlation between erosion development in joints free of damage at baseline and early clinical remission. A single-center retrospective study was performed in 133 patients meeting ACR criteria for RA of recent onset. Two radiologists independently quantified radiographic structural lesions at the hands and forefeet using the Sharp van der Heijde (SVdH) Score at the diagnosis then 5 years later. The patients were divided into two groups based on whether the lesions were stable (SVdH Score increase ≤ 10 points, Xray-STAB group) or had worsened (SVdH Score increase > 10 points, Xray-PROG group). The clinical response was assessed after 3, 6, and 12 months. Clinical remission was defined based on the DAS28-CRP, SDAI, CDAI, and ACR/EULAR Boolean remission criteria. Of the 133 patients, 90 were in the Xray-STAB group (mean SVdH score increase, 2.4 ± 2.9) and 43 in the Xray-PROG group (22.9 ± 13.4). The 6-month disease activity indices were higher in the Xray-PROG group (P < 0.05). Achieving a 6-month clinical remission had 58.6%, 39.1%, 40.0%, and 32.2% sensitivity for predicting 5-year radiographic stability when the DAS28-CRP, SDAI, CDAI, and Boolean definition were used, respectively; corresponding values for specificity were 73.8%, 85.7%, 83.7%, and 90.5%. Achieving a clinical remission within 6 months is key to preventing radiographic structural progression in patients with recent-onset RA.