Mild Rheumatoid Arthritis Research Articles

Sema4D as a biomarker for Predicting rheumatoid arthritis disease activity.

The semaphorins are membrane or secreted proteins first identified in neural development. Semaphorin 4D (Sema4D) is the first family member found to have immune properties. We evaluated the potential of Sema4D as a marker for rheumatoid arthritis (RA) disease activity, singly and in combination with other known biomarkers including rheumatoid factor (RF) and C-reactive protein (CRP). Three hundred and eleven RA patients were enrolled. The patients were divided into three groups based on their disease activity in 28 joints (DAS28): mild, moderate, and severe. The healthy group included 40 healthy individuals. SerumSema4D was measured by quantitative ELISA and the specificity and sensitivity of biomarkers were evaluated by generating a receiver operating characteristic (ROC) curve to analyze their diagnostic accuracy. Serum Sema4D levels in the moderate and severe RA groups were elevated significantly above those of the controls (P < 0.01), while levels in the mild RA and control groups did not differ significantly (P > 0.05). The Sema4D cutoff threshold was 15.7ng/ml when the DAS28 was applied as a reference. Compared to the erythrocyte sedimentation rate (ESR and CRP, Sema4D had the highest specificity (96.8%) and area under the curve (0.80) for diagnosing RA activity. The highest specificity (100%) for the biomarker combinations was obtained when Sema4D was combined with CRP and anti-CCP, the combination of the Sema4D combined with ESR and anti-CCP had the highest sensitivity (99.35%). According to this result, a new model for jointly calculating RA activity of Sema4D,anti-CCP and CRP was constructed. Meanwhile another model is established by using the method of multivariate analysis.Model comparison results showed the the multiple regression algorithm method fitted the patients' disease activity better. The serum Sema 4D level effectively reflects moderate to severe RA activity. Sema4D levels can be used together with conventional RA biomarkers to increase the diagnostic power of RA activity. The multiple regression algorithm method is promising in disease activity calculation.

Patients’ satisfaction with treatment using anti rheumatic drugs, and their adherence to medication: A non interventional, cross sectional study among some Chinese outpatients

Purpose: To determine satisfaction with treatment and adherence to medication amongst Chinese patients with rheumatoid arthritis.&#x0D; Methods: This cross-sectional study enrolled 398 rheumatoid arthritis (RA) patients who filled out questionnaire during outpatient consultation. The Chinese version of the Treatment Satisfaction Questionnaire (C-TSQM-II) was used to evaluate treatment satisfaction, while the Chinese Compliance Questionnaire for Rheumatology (threshold ≤ 80) and the medication possession ratio (MPR) were used for the assessment of adherence to medication.&#x0D; Results: In all medications, treatment satisfaction was higher in the mild subgroup and the moderate subgroup than in the severe subgroup (p &lt; 0.05). Treatment satisfaction scores with respect to biological disease-modifying anti-rheumatic drugs (bDMARDs) were significantly lower in patients in the severe subgroup than in those in the moderate subgroup, with respect to convenience and global satisfaction (p &lt; 0.05). Moreover, for bDMARDs therapies, treatment satisfaction was higher in the moderate subgroup than in the severe subgroup in all four areas examined (p &lt; 0.05). The Chinese Compliance Questionnaire score showed that 156 patients (39 %) were adherent to medication, while 242 patients (61 %) were not. Results from MPR indicate that 310 patients (78 %) were adherent to medication, while 68 patients (22 %) were not. In the mild group, 96.5 % of patients were adherent to all medications, and 94.4 % were adherent to bDMARDs. &#x0D; Conclusion: Patients were most likely unable to distinguish amongst disease progression, disease-induced damage, and other causes of pain or discomfort. Treatment satisfaction and medication adherence were higher in patients with mild rheumatoid arthritis.

Mortality and immune-related adverse events after immune checkpoint inhibitor initiation for cancer among patients with pre-existing rheumatoid arthritis: a retrospective, comparative, cohort study.

Patients with pre-existing rheumatoid arthritis initiating immune checkpoint inhibitors for cancer might be at risk of increased mortality, rheumatoid arthritis flares, and other immune-related adverse events (AEs). We aimed to determine whether pre-existing rheumatoid arthritis was associated with higher mortality and immune-related AE risk in patients treated with immune checkpoint inhibitors. This retrospective, comparative cohort study was conducted at the Mass General Brigham Integrated Health Care System and the Dana-Farber Cancer Institute in Boston (MA, USA). We searched data repositories to identify all individuals who initiated immune checkpoint inhibitors from April 1, 2011, to April 21, 2021. Patients with pre-existing rheumatoid arthritis had to meet the 2010 American College of Rheumatology-European Alliance of Associations for Rheumatology (ACR-EULAR) criteria. For each pre-existing rheumatoid arthritis case, we matched up to three non-rheumatoid arthritis comparators at the index date of immune checkpoint inhibitor initiation by sex (recorded as male or female), calendar year, immune checkpoint inhibitor target, and cancer type and stage. The coprimary outcomes were time from index date to death and time to the first immune-related AE, measured using an adjusted Cox proportional hazards model. Deaths were identified by medical record and obituary review. Rheumatoid arthritis flares and immune-related AE presence, type, and severity were determined by medical record review. We identified 11 901 patients who initiated immune checkpoint inhibitors for cancer treatment between April 1, 2011, and April 21, 2021; of those, 101 met the 2010 ACR-EULAR criteria for rheumatoid arthritis. We successfully matched 87 patients with pre-existing rheumatoid arthritis to 203 non-rheumatoid arthritis comparators. The median age was 71·2 years (IQR 63·2-77·1). 178 (61%) of 290 participants were female, 112 (39%) were male and 268 (92%) participants were White. PD-1 was the most common immune checkpoint inhibitor target (80 [92%] of 87 patients with rheumatoid arthritis vs 188 [93%] of 203 comparators). Lung cancer was the most common cancer type (43 [49%] vs 114 [56%]), followed by melanoma (21 [24%] vs 50 [25%]). 60 (69%) patients with rheumatoid arthritis versus 127 (63%) comparators died (adjusted hazard ratio [HR] of 1·16 [95% CI 0·86-1·57]; p=0·34). 53 (61%) patients with rheumatoid arthritis versus 99 (49%) comparators had any all-grade immune-related AE (adjusted HR 1·72 [95% CI 1·20-2·47]; p=0·0032). There were two (1%) grade 5 immune-related AEs (deaths) due to myocarditis, both in the comparator group. Rheumatoid arthritis flares occurred in 42 (48%) patients with rheumatoid arthritis, and inflammatory arthritis occurred in 14 (7%) comparators (p<0·0001). Those with rheumatoid arthritis were less likely to have rash or dermatitis (five [6%] vs 28 [14%]; p=0·048), endocrinopathy (two [2%] vs 22 [11%]; p=0·0078), colitis or enteritis (six [7%] vs 28 [14%] comparators; p=0·094), and hepatitis (three [3%] vs 19 [9%]; p=0·043). Patients with pre-existing rheumatoid arthritis initiating immune checkpoint inhibitors had similar risk of mortality and severe immune-related AEs as matched comparators. Although patients with pre-existing rheumatoid arthritis were more likely to have immune-related AEs, this finding was mostly due to mild rheumatoid arthritis flares. These results suggest that this patient population can safely receive immune checkpoint inhibitors for cancer treatment. None.

Hubungan Nyeri Rheumatoid Arthritis dengan Kemandirian ADL pada Lansia

Abstract: Purpose: The research objective was to determine the correlation between rheumatoid arthritis pain with the independent activity of daily living on the elderly at the Kalibalangan Village of South Abung District in North Lampung Regency 2022. Method: The research objective was to determine the correlation between rheumatoid arthritis pain with the independent activity of daily living on the elderly at the Kalibalangan Village of South Abung District in North Lampung Regency 2022. Results: The results showed that most of the 54.2% (39 people) were elderly with mild rheumatoid arthritis pain levels. Most of the respondents have an independent level of 56.9% (41 people). There is a correlation between rheumatoid arthritis pain with the independent activity of daily living in the elderly at the Kalibalangan Village of North Lampung Regency in 2022. The statistical test results obtained a p-value of 0.003 (&lt;0.05) and an odd ratio/risk factor (OR) of 5.075. Contribution: By conducting this research, researchers expect that health care workers can improve the quality of services, especially for the elderly. Keywords: 1. Rheumatoid Arthritis Pain 2. Independence Level 3. Elderly

Impact of photodynamic therapy as an adjunct to non-surgical periodontal treatment on clinical and biochemical parameters among patients having mild rheumatoid arthritis with periodontitis

PurposeTo evaluate the efficacy of photodynamic therapy (PDT) as an adjunct to non-surgical periodontal therapy on the clinical periodontal and biochemical parameters among patients with rheumatoid arthritis (RA) having periodontitis. MethodsA total of 50 RA patients with periodontitis were included. The subjects were equally divided into two groups: Group A – scaling and root planning (SRP) + PDT; Group B – SRP only, respectively. Plaque score (PS), bleeding on probing (BOP), and pocket depth (PD) were estimated. The biochemical parameters included the assessment of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and rheumatoid factors (RFs). ResultsPlaque scores and BOP significantly reduced in both the groups at both 6 and 12 weeks with significant difference between both the groups at 6 weeks follow up (p<0.05). On inter-group comparison, there was a statistically significant reduction seen for BOP in Group A at 12 weeks (p<0.001). PD significantly reduced in both the groups at both time points; however, significant reduction was noted for Group A compared to Group B (p<0.01). IL-6 and TNF-α significantly reduced in both the groups at 6 and 12 weeks follow up. However, the proinflammatory cytokine levels significantly reduced in group A as compared to group B at both 6 and 12 weeks (p<0.05). GCF levels of RF did not show any change in either of the groups at either time point or between the groups (p>0.05). ConclusionPDT significantly reduced the proinflammatory burden in terms of periodontal attachment level and bleeding on probing within the periodontal inflammatory pockets in patients having RA.

Interleukin – 6 Serum Level and Single Nucleotide Gene -174 G/C promoter Polymorphism in Patients with Rheumatoid Arthritis / Iraq

Objective: To 1) assess IL-6 levels in the serum of patients with rheumatoid arthritis (RA). 2) study IL-6 promoter -174 G>C “single nucleotide polymorphism (SNP)” as an imminent factor for the disease development. 3) find any relation between the level of serum IL-6 cytokine and other parameters such as age, gender, clinical severity of diseases and “disease activity scores (DAS28)”. Materials & methods: This research was carried out through a case – control approach at “Ibn – Senna Teaching Hospital” in Mosul city between November 2020 and July 2021. It included 61 RA patients diagnosed according to “ACR / EULAR 2010 criteria” and 50 healthy individuals. IL-6 serum levels were ascertained by ELISA and genotyping of IL-6 promoter was accomplished by “sequence-specific primer-polymerase chain reaction (SSP-PCR)”. Results: Mean IL-6 level in RA (69.42 ng /l ± 62.99) was elevated in comparison to healthy people (14.66 ng /l ± 23.58), P < 0.001. No age or gender effects on IL-6 concentration were noted. The ideal cut-off of IL-6 for discrimination of RA with best discriminative utility compared to healthy controls was 22.80 ng/l. At this value the IL-6 sensitivity was 91.8%, specificity 82.0% and accuracy rate 73.80%. G/G genotype was the most pervasive genotype in both RA patients and controls (70.5% in RA and 64% in healthy controls). However, it did not seem to be a risk factor for RA development compared to G/C or C/C genotypes “(OR = 1.3438, 95% CI=0.605-2.984,P=0.469)”. The mean IL-6 level in patients with GG genotype was (73.70 ng / l ± 71.09) compared to (58.37 ng /l ± 37.86) in patients with GC genotype. There was no significant difference in the IL-6 level between patients with GG and patients with GC genotypes (P = 0.2375). Although higher IL-6 mean concentration was reported in severe RA, however, no significant difference was found between patients with mild, moderate and severe RA respectively. No correlation of serum levels of IL-6 with genetic promoter polymorphism, clinical severity of diseases or DAS 28 score were reported. Conclusion: The concentration of serum IL-6 was elevated in RA in regard to healthy controls which confirmed its pivotal role in RA pathogenesis. Our data did not support the role of IL-6 promoter -174 G> C polymorphism as a risk factor for RA, nor seem to play a major role in the increase of IL-6 level among our patients with RA.

Effects of the COVID-19 pandemic on psychology and disease activity in patients with ankylosing spondylitis and rheumatoid arthritis

Background/aim The COVID-19 outbreak is known to increase stress levels of most patients with chronic diseases. Patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are highly susceptible to environmental stress. In the current study, we aimed to determine how the COVID-19 pandemic psychologically affected patients with chronic progressive diseases such as AS and RA and the effects of these psychological factors on disease activity. Materials and methods Age and sex-matched patients with AS (n = 80), RA (n = 80), and healthy controls (n = 80) were included in the study. All participants were evaluated with the “Perceived COVID-19 Threat Form (PCTF)”, “Suicide-Ideation Scale (SIS)”, “Hospital Anxiety and Depression Scale (HADS)”, “The Ability to Cope with Trauma (PACT)”, and “Psychological General Well-Being Index (PGWB)” scales. BASDAI was used in patients with AS, and DAS28 was used in patients with RA to assess disease severity.Results Compared to healthy individuals, patients with RA and AS had lower PGWB scores and higher HADS depression and anxiety subscale scores. Almost all psychometric assessment test scores were worse in AS patients with high-disease activity compared to those in low-disease activity. PACT scores were higher in patients with moderate RA compared to patients with mild RA (p = 0.006). While a positive correlation was identified between BASDAI and most of the psychometric assessment test scores (r = 0 .36 for PCTF, r = 0.53 for depressive scores, r = 0.54 for anxiety scores, r = 0.57 for suicidal ideation), DAS28 scores were found to be associated only with PACT total and PACT perceived forward-focused subscale scores (r = –.26 and r = .33, respectively). Conclusion Psychologically, AS and RA patients were found to be worse off compared to healthy controls. The perceived COVID threat and psychological status were associated with disease activity in AS, but not RA patients. Patients with chronic illnesses may be more vulnerable to the psychological effects of the pandemic, which can worsen disease activity.

Genetic association of interleukin-4 VNTR polymorphism with susceptibility to rheumatoid arthritis in South Gujarat population

Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease, which causes swelling and severe pain within joints. The variable number tandem repeats (VNTR) polymorphism of interleukin-4 (IL4) gene has been associated with autoimmune diseases including RA. The study investigated the association of IL4 VNTR (IVS3; R1 > R2) polymorphism with RA susceptibility in South Gujarat population of India. Polymerase chain reaction (PCR) method was used for genotyping of IL4 VNTR polymorphism in 302 RA patients and 334 controls and ELISA was used for estimation of plasma IL-4 levels. The genotype and allele frequencies of the polymorphism were significantly differed between RA patients and control population (p < 0.0001), suggesting that IL4 VNTR polymorphism is associated with RA susceptibility in South Gujarat population. The susceptible ‘R2’ allele was prevalent in RA group as compared to the control group (79.4% vs 64.00%; p < 0.0001). Moreover, both the genotype and allele frequencies were significantly differed between severe and mild RA patients (p = 0.0039 & p = 0.0005 respectively). The plasma IL-4 levels (p = 0.0216) and genotype-phenotype correlation revealed significant increased IL-4 levels for R2R2 genotype in RA patients compared to controls (p = 0.0265). The IL-4 levels were significantly higher in R2R2 genotype when compared to R1R1 and R1R2 genotypes in RA patients (p = 0.007 & p = 0.03 respectively). Furthermore, IL-4 levels were significantly increased in severe RA patients compared to mild (p = 0.0293). Both, IL-4 levels and R2R2 genotypes were positively correlated with rheumatoid factor (r = 0.49, p = 0.0009 & r = 0.41, p = 0.035 respectively). Overall, the study for the first time suggests that IL4 VNTR R2 allele may be associated with susceptibility to RA in South Gujarat population and it is likely to play a role in increased IL-4 levels thereby contributing to RA pathogenesis.

High Prevalence of Depressive Symptoms Among Ugandan Patients with Rheumatoid Arthritis.

BackgroundThere is a scarcity of data on the burden of depression among Ugandans with rheumatoid arthritis (RA) patients. We aimed to screen for symptoms of depression, their severity and associated factors among patients with RA in Uganda.Patients and MethodsA descriptive, cross-sectional study was conducted between September and December 2020 at Mulago National Referral Hospital (MNRH) and Nsambya Hospital. Patients with RA were enrolled consecutively. Data on demographics, disease course and comorbidities and depression symptomatology were collected through an interviewer administered questionnaire. Symptoms of depression were screened for using the depression/anxiety dimension of the EuroQoL questionnaire.ResultsForty-eight patients with a median age of 52 (IQR: 43.5–60.5) years were recruited in the study. The majority of the patients were female (91.7%, n=44). Twenty-nine patients (60.4%) had comorbidities with a median Charlson comorbidity score of 3 (IQR: 2–4). Overall, 70.8% (n=34) had depressive symptoms. Patients attending MNRH were more likely to have depressive symptoms (p=0.025). Significantly, patients with depressive symptoms were younger (p=0.027), had lower health index value (p<0.001), and lower overall self-reported health status (p=0.013). At binary logistic regression, patients at MNRH (crude odds ratio (COR): 4.32, 95% confidence interval (CI): 1.16–16.15, P=0.030), patients aged <52 years (COR: 5.24, 95% CI: 1.23–22.28, P=0.025) and those with mild RA (COR: 5.71, 95% CI: 1.15–28.35, P=0.033) were significantly more likely to have depressive symptoms. Increase in age (COR: 0.94, 95% CI: 0.89–0.99, P=0.025), and high visual analogue score (COR: 0.94, 95% CI: 0.89–0.99, P=0.013) were protective.ConclusionDepressive symptoms were common among RA patients in Uganda. Routine screening, diagnosis and management of depression is recommended among young patients to improve quality of life and patient outcomes.

Microscopic Hematuria Associated with Rheumatoid Arthritis: Review of Literature.

Microscopic hematuria is common manifestation in patients with mild rheumatoid arthritis (RA). It has not been extensively addressed, to our knowledge, by scholars. In this review, we discussed in detail the epidemiological aspect of this problem from the clinical point of view. We reviewed many articles from different electronic databases on the web such as PubMed, LILACS, CINAHL, and PSYCH INFO to get up with a narrative review. Twenty-eight studies entailed the issue regarding etiology, pathology, clinical picture, prognosis complications, and treatment. This clinical sign must be addressed by clinical staff treating patients with RA. Also, further studies should be done to discover the hidden areas in this topic.

C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis

Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to the critical form of the coronavirus disease − 19 (COVID-19). On the other side, RA patients have been found not to have an increased risk of COVID-19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID-19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side. In this research, we used the in silico approach to investigate the transcriptomic profile of RA synovium to identify shared molecular pathways with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted a possible mechanism through which HCQ, which can be used as a monotherapy in mild RA or as one of the triple-DMARDs therapy (tDMARDs; methotrexate, sulphasalazine, and HCQ), might interfere with the COVID-19 infection. This might be achieved through the ability of HCQ to upregulate specific immune cell populations like activated natural killer (NK) cells, which were found to be significantly reduced in COVID-19 infection. In addition to its ability to block CCR5 rich immune cell recruitment that also was upregulated in the SARS-COV-2 infected lungs. This might explain some of the reports that showed beneficial effects.

Treatment satisfaction with rheumatoid arthritis in patients with different disease severity and financial burden: A subgroup analysis of a nationwide survey in China.

BackgroundDespite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patient-assessed) and proportions of treatment cost to household income.MethodsThis was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10–30%, 31–50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients’ treatment satisfaction.ResultsWhen considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 13.183, P = 0.004). For biological disease-modifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups (F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 8.794, P = 0.032).ConclusionHigher disease severity and higher financial burden were associated with lower patient satisfaction.

Establishment of anti-C1q monoclonal antibodies to measure serum C1q levels discriminating disease severity subsets of rheumatoid arthritis within 5 years of onset

Objectives: To establish anti-C1q monoclonal antibodies which can measure serum C1q levels discriminating disease severity subsets of rheumatoid arthritis (RA) within 5 years of onset.Methods: In this multi-centre, longitudinal, observational study, 122 RA patients [102 females, baseline age 58.5 years, rheumatoid factor (RF) positivity 78.7%, serum C-reactive protein (CRP) 1.2 mg/dl, and concomitant methotrexate (MTX) 4.9 mg/week (29.5%)] within 5 years of onset (disease duration 21.0 months) were enrolled from 1985 to 2000. Patients were not treated by more than 8 mg/week of MTX or biologics which may strongly affect the course of joint destruction. Disease severity at 10–15 years of onset was classified according to the number of destructed joints of overall 68 joints on plain radiographs (36 patients were mild RA group involving only peripheral joints and 86 were severe RA group involving large axial joints). Baseline serum C1q levels were evaluated by ELISA with newly developed 4 monoclonal anti-C1q antibodies, and compared between two groups as well as conventional RA disease activity markers.Results: There were no significant differences between two groups in baseline conventional RA disease activity markers such as RF, erythrocyte sedimentation rate, CRP, and matrix metalloproteinase-3. However, compared to mild RA group, severe RA group showed higher baseline serum C1q levels (μg/ml) evaluated by anti-C1q monoclonal antibodies of no.33 (104.8 ± 22.3 vs. 118.3 ± 19.3; p = .0024), no. 40 (102.6 ± 21.9 vs 121.2 ± 22.3; p = .000069), no. 54 (102.1 ± 22.5 vs. 119.3 ± 26.9; p = .00052), and no. 76 (105.6 ± 21.8 vs. 122.6 ± 26.4; p = .00043). Receiver operating characteristic curve analysis revealed that in patients with serum C1q levels of ≥110.5 μg/ml (measured by antibody no. 40), 78.9% (75/95) belonged to severe RA group.Conclusion: Measuring serum C1q levels of RA within 5 years of onset by newly developed anti-C1q antibodies may be useful in predicting the prognosis of disease severity evaluated by the extent of joint destruction.

The outcome of patients with rheumatoid arthritis: a cross-sectional study

Background: Rheumatoid arthritis (RA) is an autoimmune disorder that affects human joints. The disease also can destroy others body systems, including skin, eyes, lungs, blood vessels, and heart. The aim of the current study was to investigate the effectiveness of RA concerning disease activity and the rate of remission, quality of life, and employment as measured by the disease activity score (DAS 28). Methodology: This cross-sectional study was conducted during the period from October to November 2018. Two RA patient cohorts were created based on the physician-reported DAS28; adequately controlled (DAS28 &amp;#8804; 3.2) and inadequately controlled (DAS28 &amp;gt;3.2). We used descriptive statistics to compare the two groups. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) software (version. 22). A p-value of &amp;#8804;0.05 was considered statistically significant. Results: A quarter (24.5%) of the inadequately controlled cohort were currently in remission less than 70% of those with adequately controlled RA. Also, 31% of the inadequately controlled group had mild RA which was less than those with adequately controlled RA (83.3%; p = 0.001) and fewer patients were found to be with stable disease status (38% vs 65%; p = 0.001). Patients in the inadequately controlled cohort had a lower quality of life, employment (0.49 vs 0.72; p = 0.001), and had higher rates of work impairment(37 vs 18.4; p = 0.04). Conclusion: Inadequately controlled RA patients (DAS28 &amp;gt; 3.2) were in less remission than those with inadequately controlled RA (DAS28 &amp;#8804; 3.2) and there were fewer patients with stable disease status. Patients in the inadequately controlled group had a lower quality of life and employment compared to the adequately controlled cohort who had higher rates of work impairment.

Testing the construct validity of a health transition question using vignette-guided patient ratings of health

BackgroundA single-item transition question is often used to assess improvement or worsening in health, but its validity has not been tested extensively. The purpose of this study was to test the construct validity of a transition question by relating it to qualitative changes in patient’s self-rating of health guided by clinical vignettes.MethodsWe studied 169 patients with active rheumatoid arthritis (RA) before and after treatment escalation. At both assessments, patients scored their current health on a rating scale after first rating three vignettes describing mild, moderate, or severe RA. We classified patients into one of these three RA categories using a nearest-neighbor match. We then related the change in these self-rated categories between visits to responses to a transition question on visit 2.ResultsSixty patients improved their RA vignette category after treatment, 86 remained in the same vignette category, and 23 worsened categories. On the transition question, 101 patients reported improvement, 48 reported no change, and 20 reported worsening, representing a modest association with changes in RA vignette categories (polychoric correlation r = 0.19). The association was stronger if patients who were in the mild RA category at both visits were also classified as improved if their self-rating changed from below to above their mild vignette rating (r = 0.23) and when incorporating the importance of changes on the transition question (r = 0.26).ConclusionChanges in health states, guided by clinical vignettes, support the construct validity of the transition question.

Conserved 33-kb haplotype in the MHC class III region regulates chronic arthritis

Genome-wide association studies have revealed many genetic loci associated with complex autoimmune diseases. In rheumatoid arthritis (RA), the MHC gene HLA-DRB1 is the strongest candidate predicting disease development. It has been suggested that other immune-regulating genes in the MHC contribute to the disease risk, but this contribution has been difficult to show because of the strong linkage disequilibrium within the MHC. We isolated genomic regions in the form of congenic fragments in rats to test whether there are additional susceptibility loci in the MHC. By both congenic mapping in inbred strains and SNP typing in wild rats, we identified a conserved, 33-kb large haplotype Ltab-Ncr3 in the MHC-III region, which regulates the onset, severity, and chronicity of arthritis. The Ltab-Ncr3 haplotype consists of five polymorphic immunoregulatory genes: Lta (lymphotoxin-α), Tnf, Ltb (lymphotoxin-β), Lst1 (leukocyte-specific transcript 1), and Ncr3 (natural cytotoxicity-triggering receptor 3). Significant correlation in the expression of the Ltab-Ncr3 genes suggests that interaction of these genes may be important in keeping these genes clustered together as a conserved haplotype. We studied the arthritis association and the spliceo-transcriptome of four different Ltab-Ncr3 haplotypes and showed that higher Ltb and Ncr3 expression, lower Lst1 expression, and the expression of a shorter splice variant of Lst1 correlate with reduced arthritis severity in rats. Interestingly, patients with mild RA also showed higher NCR3 expression and lower LST1 expression than patients with severe RA. These data demonstrate the importance of a conserved haplotype in the regulation of complex diseases such as arthritis.

Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of SBI-087, a CD20-Directed B-cell Depleting Agent: Phase 1 Dose Escalating Studies in Patients With Either Mild Rheumatoid Arthritis or Systemic Lupus

PurposeSBI-087 is a Small Modular Immunopharmaceutical Protein™(SMIP™) drug that binds to CD20 and has been reported to deplete B cells in murine/primate studies. The safety, tolerability and pharmacokinetic/pharmacodynamic properties of SBI-087 were evaluated in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). MethodsSingle-dose SBI-087 was evaluated in 2 Phase I, open-label, escalating-dose studies in patients with RA or SLE. The studies included 6 IV/4 SC escalating doses (RA) and 1 IV/4 SC escalating doses (SLE). Escalation was determined by tolerability/rate of B-cell depletion. Serum was collected for analyses of pharmacokinetic and pharmacodynamic (CD19+ B cells) properties and immunogenicity. Patients were followed until B-cell counts were normalized or stabilized. Safety, tolerability was evaluated from adverse events, physical examinations, vital sign measurements, ECG, and clinical laboratory results. FindingsSixty patients with RA (IV, 28; SC, 32) and 30 patients with SLE (6 per cohort) were enrolled. Mild to moderate infusion reactions occurred in several patients at the top doses in the RA study despite a pretreatment regimen of IV doses. Unanticipated reactions after SC administration of SBI-087 included fever, chills, and malaise, seen on the day of dosing in the lowest-dose cohorts in both studies. These events were abrogated in subsequent cohorts by a pre/postdose treatment regimen consisting of oral corticosteroids, acetaminophen, and an antihistamine. SBI-087 clearance (IV) ranged from 22 to 229 mL/h; volume of distribution at steady state ranged from 5 to 12 L. Apparent clearance (SC) ranged from 44.7 to 105 mL/h; volume of distribution ranged from 14.3 to 32.1 L. Overall, PK properties were similar at equivalent doses between IV/SC administrations in patients with RA/SLE. Mean t½ (IV) ranged from 2.1 to 10.7 days (less at lower doses). SBI-087 concentration and B-cell depletion were generally dose proportional across IV and SC cohorts. However, the extent of B-cell depletion was less, and rate of repletion was faster, in patients with SLE versus RA. In both studies, B-cell repletion to baseline did not occur in the majority of patients by the end of the observation period. Overall, the prevalence and type of adverse events were similar to those seen with other anti-CD20–depleting agents. ImplicationsIn patients with mild RA/SLE, SBI-087 was well tolerated when administered intravenously or subcutaneously with pre- and posttreatment regimens. B-cell depletion is long lasting, and the duration and extent of depletion may be greater in RA compared with SLE. SBI-087 exhibited slow elimination and low distribution in both populations. Clinicaltrials.gov identifiers: NCT00641225 (RA) and NCT00714116 (SLE).

Parameters of the assessment of voice quality and clinical manifestation of rheumatoid arthritis

PurposeThe aim of the study was to investigate the voice quality parameters in 72 rheumatoid arthritis (RA) patients and their relationships with the clinical manifestations and disease activity. The control group consisted of 30 healthy subjects. Material and methodsAll RA patients were evaluated by extensive clinical, laboratory and radiographic studies. The phoniatric assessment included the analysis of vocal folds vibrations by digital stroboscopy (DS) of the larynx using HRES ENDOCAM 5562 system, digital kymography (DKG) and High-Speed Digital Imaging (HSDI) technique. The acoustic voice analysis was conducted using DiagnoScope Specialist program. ResultsVoice quality disorders were registered in 32 (44.44%) RA patients and observed more frequently in patients with moderate and severe activity (DAS28≥3.2) than in mild RA. In digital stroboscopy, confirmed by digital kymography, the hypofunctional dysphonia was observed especially in patients with DAS28≥3.2. Outcomes of the subjective assessment of voice quality were in accordance with the objective parameters and acoustic voice examination. ConclusionsIn RA patients the most frequent voice quality disorders with hypofunctional dysphonia were registered. The relationships between voice quality disorders, clinical activity and radiographic progression of RA patients were observed. Digital stroboscopy, digital kymography, High-Speed Digital Imaging and acoustic voice analysis used in the complex diagnosis of RA confirmed the presence of pathological changes in the larynx. There is a need of cooperation between rheumatologists and phoniatricians in the diagnosis and treatment of dysphonia in RA patients.

Patients with regular physical activity before onset of rheumatoid arthritis present with milder disease

ObjectivesPhysical activity has been shown to decrease inflammatory markers; here we investigate the effect on the clinical presentation of rheumatoid arthritis (RA).MethodsWe used the cases from the population-based EIRA study...

HLA-DR/DQ Genotypes in Kurd Patients with Rheumatoid Arthritis: Relation to Disease Activity.

Specific alleles present at the HLA-DR/DQ loci seem to be associated with disease activity of rheumatoid arthritis. In the present study, our aim was to investigate the distribution of HLA-DR/DQ alleles among Kurd patients with rheumatoid arthritis and to ascertain their relationship with disease activity. Sixty five patients with rheumatoid arthritis (RA) and 65 apparently healthy subjects participated in the study. Diagnosis and disease activity were confirmed. Blood analyses, including those of laboratory markers of disease activity, were done. The 28 joint disease activity score (DAS-28) was calculated. HLA-DR/DQ typing was performed by polymerase chain reaction (PCR).The association between HLA-DR/DQ genotypes and disease activity was determined. The most frequent alleles which were identified in RA patients were HLA-DRBI*01(23.1%) and HLA-DQBI*6(34.6%), whereas in healthy subjects, they were HLA-DRBI*11(17.7%) and HLA-DQBI*03(35.4%). Patients with active disease had high frequencies of HLA-DQBI*6 (40.0%) as compared to those with moderate disease activity (16.7%); OR=3.33. Patients with severe RA had increased frequencies of HLA-DQBI*6 (56.3%) as compared to those with mild RA (10.0%); OR = 11.57. Patients with positive rheumatoid factor (RF) and positive Anti-citrullinated peptide antibody (Anti-CCP), also had high frequencies of HLA-DQBI*06 (38.4% and 39.4%) as compared to frequencies of 11.1% and 15.4% which were seen in patients with negative rheumatoid factor and negative anti-CCP (OR= 4.98 and3.10) respectively. HLA-DQBI*06 was found to be more common in Kurd patients and it was significantly associated with disease activity; this may indicate a high risk for developing a more progressive type of the disease.