Low Disease Activity In Rheumatoid Arthritis Research Articles

Cross-sectional association between social and demographic factors and disease activity in rheumatoid arthritis

BackgroundThis study aimed to assess the association between social factors, demographic parameters, and disease activity among rheumatoid arthritis (RA) patients.MethodsThe University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry was used for this study and included patients meeting 1987 ACR criteria for RA enrolled between 2010–2015. The registry collected clinical and laboratory data at each visit, permitting the calculation of disease activity measures that included Disease Activity 28-C Reactive Protein (DAS28-CRP). The current study was conducted as a cross-sectional study in which baseline data were used to construct multiple logistic regression models assessing the relationship between disease activity measures (DAS28-CRP), functional capacity (health assessment questionnaire (HAQ)), selected demographic and social factors (occupation, education, income, marital status, race, gender, age, and BMI), and clinical/laboratory variables.ResultsThe analyses included 729 patients with baseline DAS28-CRP and social/demographic data. The mean age at enrollment was 59.5 (Standard Deviation (SD) = 12.7) years, 78% were female, and the median RA disease duration was 9.8 (Interquartile Range (IQR): 3.7, 19.1) years. We dichotomized the DAS28-CRP score and defined scores above or below 3.1 as high versus low RA disease activity. Most patients with high RA disease activity (N = 326, 45%) had less than a college degree (70%), were not working/retired/disabled (71%), and had an annual income under $50 K (55%). We found that higher body mass index (BMI) (Odds Ratio (OR) = 1.04, 95% CI: 1.01—1.08), longer disease duration (> 2 and < 10 years versus ≤ 2 years of disease) (OR = 0.45, 95% CI: 0.25—0.78), and being retired (OR = 1.74, 95% CI: 1.02—2.98) were associated with RA disease activity.ConclusionIncreased RA activity may be associated with various social factors, potentially leading to more severe and debilitating disease outcomes. These findings provide evidence to support efforts to monitor disparities and achieve health equity in RA.

Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients.

Within rheumatoid arthritis (RA) patients treated with intravenous tocilizumab (IV-TCZ), it is unclear if power Doppler ultrasonography (PDUS) can predict future clinical response. This study sought to determine if baseline PDUS or its early changes can predict 12-week and 24-week disease activity outcomes, and quantify the need for dose escalation (4 to 8mg/kg). Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24weeks using 34-joint PDUS (US34-PDUS), clinical disease activity index (CDAI), 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR), ACR 20/50/70, health assessment questionnaire-disability index (HAQ-DI), and PDUS 20/50/70, a novel measure. Logistic regression models evaluated the predictive utility of US34-PDUS of DAS28-ESR response after adjusting for covariates. Ninety-four percent of patients required dose escalation to 8mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24weeks (p < 0.001). Baseline PDUS and 12-week PDUS change correlated with CDAI at 24weeks (p < 0.05). Logistic regression demonstrated baseline US34-PDUS was independently associated with DAS28-ESR ≥ 1.2 response, even after adjusting for baseline DAS28-ESR (p = 0.03). CDAI, DAS28-ESR, and their components increased across PDUS 20/50/70 categories; however, HAQ-DI did not. RA patients treated with IV-TCZ for 24weeks demonstrated significant improvement, and baseline/early changes in PDUS were predictive of later clinical response. The PDUS 20/50/70 measure is a novel metric of response. This study suggests that IV-TCZ 4mg/kg may not be sufficient to attain low RA disease activity at 12weeks, in RA patients with moderate to severe disease (DAS28 ≥ 4.4 and US34-PDUS ≥ 10). ClinicalTrials.gov NCT01717859 Key Points • Over 90% of RA patients with baseline DAS28-ESR ≥ 4.4 and PDUS34 ≥ 10 required intravenous tocilizumab dose escalation from 4 to 8mg/kg at 12weeks. • Reduction in power Doppler ultrasonography (US34-PDUS) scores correlate with DAS28-ESR and CDAI over 24weeks in rheumatoid arthritis patients with moderate to severe disease activity. • Baseline US34-PDUS predicts future improvements in clinical disease activity outcomes, independent of baseline DAS28-ESR. • Clinical response measures, DAS28-ESR and CDAI, improved across US34-PDUS 20/50/70 categories, while patient-reported outcomes did not.

Clinicopathological characteristics of lymphoproliferative disorders in 232 patients with rheumatoid arthritis in Japan: A retrospective, multicenter, descriptive study.

To describe the clinicopathological characteristics of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA). In this multicenter case series, we retrospectively reviewed the medical records of RA patients who were newly diagnosed as having LPDs with or without biopsy confirmation between 2000 and 2017 in eight hospitals in Japan. We included 232 patients with LPDs. The median age was 67 years (interquartile range [IQR], 60-73 years), and 77.1% were female. At the time of LPD diagnosis, 94.8% and 62.6% of the patients were methotrexate users and in remission or had low RA disease activity, respectively; lymphadenopathy and extranodal involvement were present in 77.1% and 51.9%, respectively. Major extranodal sites were the lungs and oral/oropharyngeal mucosa. The most common LPD pathological subtype was diffuse large B-cell lymphoma (40.5%), followed by classic Hodgkin lymphoma (10.8%), Epstein-Barr virus-positive mucocutaneous ulcer (7.7%), and reactive lymphoid hyperplasia (6.2%). The clinical and laboratory characteristics varied across the pathological subtypes. LPD occurred mainly in methotrexate users, while RA disease activity did not seem to be associated with LPD development. Although the clinical manifestations vary among pathological subtypes, manifestations of LPD in patients with RA can include lymphadenopathy, extranodal mass, and mucocutaneous ulcer.

Association among periodontitis severity, anti-agalactosyl immunoglobulin G titer, and the disease activity of rheumatoid arthritis.

The aim of the present study was to evaluate the association between the periodontal and serological parameters and the disease activity of rheumatoid arthritis (RA) and between the anti-agalactosyl immunoglobulin G (IgG) titer and periodontitis severity. The objective was also to assess the effect of supragingival scaling on the serological parameters in patients with RA. The periodontal and serological parameters in relation to the autoimmune inflammatory response have been linked to RA disease activity. However, the association of the anti-agalactosyl IgG titer with RA disease activity and periodontitis severity has not been elucidated. The periodontal, rheumatologic, and serological data were collected from 127 patients with RA in a retrospective cohort study. Of the 127 patients, 21 had been randomly assigned to receive oral hygiene instruction and supragingival scaling. The anti-agalactosyl IgG titer was determined by an electrochemiluminescence immunoassay. The patients with a moderate to high RA disease activity showed significantly higher levels of probing depth (PD), clinical attachment level, anti-cyclic citrullinated peptide IgG, and anti-agalactosyl IgG titer and greater mean percentages of severe periodontitis than those with a low RA disease activity (p<.05 for all). Both univariate and multivariate analyses revealed a significantly positive correlation between the PD and RA disease activity (p=.009 and p=.001), between the anti-agalactosyl IgG titer and RA disease activity (p=.002 and p<.001), and between the anti-agalactosyl IgG titer and PD (p<.001 for both). Supragingival scaling significantly decreased the anti-agalactosyl IgG titer (p=0.03). The PD and anti-agalactosyl IgG titer are positively interrelated, both of which are correlated positively with RA disease activity and influenced by supragingival scaling in patients with RA.

TIPE2 and PCNP expression abnormalities in peripheral blood mononuclear cells associated with disease activity in rheumatoid arthritis: a meta-analysis.

Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease posing a considerable burden on both individuals and society. Tumor necrosis induced protein 8-like 2 (TIPE2), closely related to PEST-containing nuclear protein (PCNP) expression, is an immune-related protein potentially involved in the pathogenesis of autoimmune diseases. In this study, we aimed to assess differential expressions of TIPE2 and PCNP in peripheral blood mononuclear cells (PBMCs) between active and inactive RA patients. Relevant studies were selected from Medline, Google Scholar, Web of Science, and China National Knowledge Infrastructure (CNKI). Only observational studies (irrespective of publication status, language, or blinding), which compared patients in high disease activity, irrespective of the sample size, with patients in low disease activity of RA were evaluated. Four studies were included with 248 patients, 138 in the active group and 110 in the inactive group. Three studies provided data on TIPE2 expression levels, where 106 patients were divided into the active group and 88 patients were divided into the inactive group. The pooled analysis revealed a statistically significant difference between the two groups (WMD: 5.60; 95% CI: 5.02-6.18). Two studies provided data on PCNP expression levels, where 64 patients were divided into the active group and 44 patients were divided into the inactive group. The pooled analysis revealed a statistically significant difference between the two groups (WMD: 7.76; 95% CI: 3.09-12.43). The expression levels of TIPE2 and PCNP are significantly increased in PBMCs of active RA patients.

Association between vitamin D and fatigue in patients with rheumatoid arthritis: a cross-sectional study

ObjectivesIn rheumatoid arthritis (RA), fatigue is an important complaint with a significant impact on quality of life. Vitamin D has modulatory effects on cells of the immune system and may...

Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study.

Background: Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA). Methods: All RA-ILD patients treated with ABA for at least six months were retrospectively evaluated. Serology, previous and concurrent therapies, chest high-resolution computer tomography (HRCT), forced vital capacity (FVC), and lung diffusion of carbon monoxide (CO, DLCO) were collected. Results: Forty-four patients were included; HRCT, FVC, and DLCO were analyzed at baseline, at one year, and at the end of follow-up. A remission or a low disease activity of RA was reached in 41/44 patients. Overall, FVC and DLCO remained stable or increased in 86.1% and 91.7% of patients, respectively, while HRCT was stable or improved in 81.4% of them. Previous and concurrent treatments, in particular, methotrexate, serology, age, sex, joint and lung disease duration were not associated with the outcome at univariate analysis. Conclusion: The management of RA-ILD patients remains a critical unmet medical need. Waiting for prospective controlled studies, ABA has shown a good safety profile in our cohort of Italian RA-ILD patients.

Effects of tofacitinib on the clinical features of periodontitis in patients with rheumatoid arthritis: two case reports

BackgroundThe pathobiology of rheumatoid arthritis (RA) is similar to that of periodontitis in that proinflammatory cytokines play an important pathologic role. There is evidence to suggest that inhibitors of tumor necrosis factor (TNF) and interleukin-6 (IL-6) receptor for the treatment of RA ameliorated periodontal inflammation. However, no study has evaluated the effect of tofacitinib, an oral Janus kinase inhibitor for the treatment of RA, on periodontitis.Case presentationThe present report cases are 51- and 43-year-old non-smoking women with RA who demonstrated localized moderate chronic periodontitis. Both cases showed improvement in the periodontal inflammatory condition after 3 months of tofacitinib therapy, although the teeth count and supragingival bacterial plaque level were relatively unchanged. Improvements were also observed in the serum levels of IL-6 in both cases as well as in the serum levels of TNF-α and anti-cyclic citrullinated peptide immunoglobulin G in one case and of rheumatoid factor and matrix metalloproteinase-3 in the other case. Patients who received tofacitinib exhibited an inconsistent clinical response, likely due to the low disease activity of RA at the start of the administration.ConclusionsThese are the first reported cases in which tofacitinib may have a beneficial effect on periodontitis. However, more research is required to understand the relationship between periodontitis and tofacitinib therapy.

Parvovirus B19 infection modulates the levels of cytokines in the plasma of rheumatoid arthritis patients

BackgroundParvovirus B19 (B19V) infection is associated with various autoimmune diseases. We investigated the levels of pro-inflammatory (IFNᵧ, TNFα, IL-2, IL-12) and anti-inflammatory (IL-4, IL-10) cytokines in the plasma of B19V DNA positive (B19+) and negative (B19−) rheumatoid arthritis (RA) patients in comparison with the control group (healthy persons). MethodsBlood samples were collected from 118 patients with RA and 49 healthy voluntaries. B19V sequence was determined in whole blood and cell-free plasma DNA by nested PCR. The levels of cytokines in the plasma and cell culture medium from Concanavalin A (ConA) or B19V VP1 protein stimulated PBMC were determined by ELISA. ResultsThe levels of IL-4, IL-10, IL-12, IL-2 and TNFα were higher in plasma of RA patients in comparison with control persons. B19+ controls and RA patients had lower levels of IFNᵧ in comparison with B19− controls and RA patients.Within RA patients the plasma levels of IFNᵧ were lower in patients with low RA disease activity or remission. Plasma level of IL-4 was increased and IL-10 level was decreased in B19+ RA patients in comparison with B19− RA patients and did not differ between B19+ and B19− controls. B19V infection did not affect plasma levels of IL-12, IL-2, and TNFα.ConA and B19 VP1 protein stimulated PBMC from RA patients produced less IFNᵧ than stimulated PBMC from the healthy controls. ConclusionsB19V infection could differently modulate the amount of cytokines in the plasma of healthy persons and RA patients. Decreased production of IFNᵧ and raised level of plasma IL-4 in RA patients could lower antiviral clearance.

Multifactorial intervention to prevent cardiovascular disease in patients with early rheumatoid arthritis: protocol for a multicentre randomised controlled trial

IntroductionCardiovascular morbidity is a major burden in patients with rheumatoid arthritis (RA). In this study, we compare the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment...

Intensive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate (MTX), a synthetic disease-modifying anti-rheumatic drug (sDMARD) and biological DMARDs (bDMARDs) has revolutionized treatment of RA and clinical remission or low disease activity (LDA) are now realistic targets, achieved by a large proportion of RA patients. We are now in a position to evaluate if it is possible to maintain remission or LDA while at the same time reducing the burden of treatment on the patient and healthcare system. Data are emerging from large, well-conducted studies designed to answer this question, shedding light on which patient populations and treatment algorithms can survive treatment discontinuation or tapering with low risk of disease flare. For early RA, approximately half of early RA patients could discontinue TNF-targeted bDMARDs without clinical flare and functional impairment after obtaining clinical remission by bDMARDs with MTX. In contrast, for established RA, fewer patients sustained remission or LDA after the discontinuation of bDMARDs and “deep remission” at the discontinuation was a key factor to maintain the treatment holiday of bDMARDs. Thus, this article provides a brief outline on withdrawing or tapering bDMARDs once patients have achieved remission or LDA in RA.

Design characteristics of the CORRONA CERTAIN study: a comparative effectiveness study of biologic agents for rheumatoid arthritis patients

BackgroundComparative effectiveness research has recently attracted considerable attention. The Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) is an ongoing prospective cohort study of adult patients with Rheumatoid Arthritis (RA).Methods/DesignCERTAIN uses the existing Consortium of Rheumatology Researchers of North America (CORRONA) network of participating private and academic sites in order to recruit patients fulfilling the 1987 ACR criteria that have at least moderate disease activity. Patients starting or switching biologic agents either anti-TNF therapy or a non anti-TNF biologic are eligible for enrollment, depending on the treatment selected by their physician. Enrollment is expected to be completed by March of 2014, and 2711 patients will participate in the study. As of October 7th 2013, 2234 patients have been enrolled. Patient visits and laboratory blood work are mandated every three months for one year. Safety data is collected through one year and beyond. The primary comparative effectiveness endpoint is attainment of low RA disease activity at one year among patients who have been exposed to at least one prior TNF-α inhibitor agent prior to enrollment. Multiple secondary effectiveness and safety endpoints will be addressed by investigating the entire population enrolled (naïve and biologic experienced).DiscussionThe unique design features of CERTAIN will inform comparative effectiveness and safety questions for choosing biologic agents for the management of RA.

Treatment with Rituximab in a Patient with Refractory Felty Syndrome and Low Rheumatoid Arthritis Disease Activity: A Case Report

Felty syndrome (FS) is a rare manifestation in rheumatoid arthritis (RA) characterized by neutropenia and splenomegaly. Treatment for FS is not well established because there has been no randomized controlled study. A few recent reports found rituximab effective in patients with refractory FS. According to those reports, most patients with RA and FS had active arthritis. Here we report a case of a patient with glucocorticoid dependent and disease-modifying anti-rheumatic drugs (DMARDs) refractory FS and quiescent RA who was successfully treated with rituximab.

Outcome Assessments in Rheumatoid Arthritis

Increasing evidence suggests low disease activity or remission is achievable in rheumatoid arthritis (RA). Using a treat to target strategy (T2T) has been shown to achieve these targets of remission or low disease activity in RA. In order to successfully treat to target, rheumatologists need reliable measures of disease activity to switch and/or escalate therapy to achieve or maintain therapeutic targets. Multiple disease-activity measures have been developed for both research and clinical practice. For clinical practice, the American College of Rheumatology (ACR) has recommended the PAS, PAS II, RAPID 3, CDAI, DAS 28, and SDAI for measuring disease activity in rheumatoid arthritis. Each of these measures has strengths and limitations, but they all accurately reflect disease activity, discriminate well between disease states, and are feasible to perform in the clinical setting. Implementation in the clinical setting can be optimized through leveraging technology and systems redesign. Tools such as web-based and smartphone applications have been developed to increase the ease with which these measures can be deployed. Disease-activity measurement in rheumatoid arthritis is included in the rheumatoid arthritis quality measures group in the Centers for Medicare and Medicaid Services' incentive-based Physician Quality Reporting System.

Clinical and Radiological Results of Radiolunate Arthrodesis for Rheumatoid Arthritis: 22 Wrists Followed for an Average of 7 Years

To evaluate the clinical and radiological results of radiolunate (RL) arthrodesis for rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs and/or biologicals with an average of 7 years of follow-up. In addition, we compared the results in advanced stages with those in less advanced stages in patients with comparatively low disease activity of RA. This study included RL arthrodesis for 22 wrists in 19 patients with comparatively low disease activity of RA. The mean follow-up period was 7 years (range, 2-16 y). Fourteen wrists with Larsen classification grade III and 8 wrists with grade IV were included in this study. The range of motion was calculated, and clinical scores were graded using the Mayo wrist score and the Stanley classification. The carpal height ratio (CHR) and ulnar translation (UT) were determined from the radiographs. All wrists achieved radiographic fusion. Clinical scores were markedly improved, although there was a decrease in flexion. The Larsen grade did not deteriorate during follow-up. CHR and UT improved immediately after operation and remained good through the final follow-up. Although the flexion/extension range of motion of the grade IV wrists was smaller than that of the grade III wrists at follow-up, both groups obtained good clinical results. Our results for RL arthrodesis were clinically and radiologically better than those of previous reports. Control of the disease activity of RA could theoretically be a factor in obtaining good long-term clinical and radiographic outcomes. RL arthrodesis is our recommended procedure for the RA wrist even in the advanced stage. Therapeutic IV.

Post-menopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin levels.

Serum undercarboxylated osteocalcin (ucOC) is a biochemical bone marker of vitamin K insufficiency. It had been reported that bone resorption inhibitors tend to decrease the serum ucOC level in patients with primary osteoporosis. In rheumatoid arthritis (RA) patients, these results have never been reported. We investigated risk factors which could change serum ucOC level in post-menopausal women with RA (no.=100). Twenty patients received no bone resorption inhibitor (control), 30 received raloxifene (RLX), while 50 received alendronate (ALN). This cross-sectional study was limited to patients with low RA disease activity (Disease Activity Score-28 ≤3.2). We measured serum ucOC, and the data were analyzed by multivariable analysis, including ucOC and the other variables. Scheffe's F test demonstrated a significant difference in serum ucOC levels between controls and the RLX group (p<0.01), and between controls and the ALN group (p<0.01). Serum ucOC levels were low in both treated groups. An adjusted multivariate analysis was performed for the variables: bone resorption inhibitor use, serum alkaline phosphatase, glucocorticoid dose, age, estimated glomerular filtration rate and matrix metalloproteinase 3. As a result, serum ucOC inversely correlated with bone resorption inhibitor use (p<0.01) and oral glucocorticoid dose (p<0.01), which were independent risk factors of lowering ucOC. Bone resorption inhibitors and glucocorticoids were independent risk factors for lowering serum ucOC levels in post-menopausal RA patients.

Cytokines and Pregnancy in Rheumatic Disease

Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy-related disorders. Studies at the level of the maternal-fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study.