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ID PMID Title PublicationDate abstract
28706330 Effects of co-treatment with pioglitazone and methotrexate on experimentally induced rheum 2017 Mar OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting the synovial joints of the body. Methotrexate (MTX) is considered as a mainstay in the management of RA. However, monotherapy with MTX in RA is often limited by potential long-term toxicity. The present study was conducted to evaluate if MTX-pioglitazone combination therapy has an add-on benefit over monotherapy with MTX or pioglitazone on disease activity in male Wistar rats in adjuvant-induced arthritis model. MATERIALS AND METHODS: Arthritis was induced by single subcutaneous injection of complete Freund's adjuvant (CFA) in thirty male Wistar albino rats. They were then divided into five equal groups, which included two control groups (arthritic and nonarthritic), pioglitazone-treated (1.35 mg/kg daily), MTX-treated (0.225 mg/kg daily), and MTX + pioglitazone-treated. The disease-modifying action of the drugs was assessed by various physiological, hematological, and biochemical parameters along with histopathological and radiological analysis of affected joints. The experimental data were statistically assessed by one-way ANOVA. RESULTS: There was a significant reduction of disease activity in the MTX monotherapy group when compared with disease control. However, pioglitazone monotherapy group failed to demonstrate any significant effect on disease activity. The MTX-pioglitazone combination group demonstrated greater suppression of disease activity as compared to MTX and pioglitazone monotherapy and disease control group (P < 0.05). CONCLUSION: The present study demonstrates that the combination therapy of MTX with pioglitazone offers better control of disease activities in RA as compared to MTX or pioglitazone monotherapy.
28608433 Performances of Clinical Disease Activity Index (CDAI) and Simplified Disease Activity In 2018 Nov BACKGROUND/PURPOSE: To compare the performance of Disease Assessment Score of 28 joints - C-reactive protein (DAS-28-CRP), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) composite measures to assess status of patients with rheumatoid arthritis (RA) on methotrexate, versus DAS-28 CRP as the gold standard. METHODS: One hundred and thirty-five patients with RA as per the 2010 American College of Rheumatology/European League Against Rheumatism criteria were included in the prospective study. The disease activity was assessed at baseline and at every 6 weeks for 24 weeks, by DAS-28-CRP, CDAI and SDAI. Patients were divided into groups of remission, low, moderate and high activity on the basis of predefined cut-offs for DAS-28-CRP, CDAI and SDAI. A Spearman correlation between composite measures and inter-group comparison of the measures was performed. RESULTS: There was an excellent positive correlation between DAS-28-CRP and CDAI (linear weighted κ baseline - 0.545), DAS-28 CRP and SDAI (linear weighted κ - 0.689) at baseline. There was moderate agreement between DAS-28-CRP and CDAI (linear weighted κ final visit - 0.458) at final visit. There was moderate correlation between SDAI and DAS-28-CRP at final visit (linear weighted κ - 0.470). However, correlation between CDAI versus SDAI remained excellent at baseline and final visit. Patients in remission as per DAS-28-CRP had significantly more residual disease activity compared to SDAI and CDAI remission criteria. CONCLUSION: The study shows an excellent strong positive correlation between DAS-28-CRP, CDAI and SDAI at initial evaluation but not at final visit. SDAI- and CDAI-based remission criteria seem to be better than DAS-28-CRP-based remission criteria.
24716863 Risk factors of adverse events during treatment in elderly patients with rheumatoid arthri 2017 Mar OBJECTIVES: The risk factors of adverse events during a number of currently used treatments for rheumatoid arthritis (RA) in elderly patients were examined. METHODS: A retrospective observational study was conducted for 300 elderly RA patients registered in December 2009 at Sasebo Chuo Hospital, Japan, and the adverse events during the treatments for RA were assessed. RESULTS: The average age of the patients was 74.3 ± 5.8 years. The Steinbrocker stage was IV in almost one-half of the patients. Methotrexate (MTX) was used in 54.0% of patients and biologics in 23.0% of patients. Adverse events occurred in 103 patients (34.3%). The most common adverse events were infections (46.6%), including pneumonia (21.4%). Multiple logistic analyses revealed that the factors significantly related to infection were advanced Steinbrocker stage and the existence of respiratory diseases, and that of pneumonia was the existence of diabetes mellitus (DM). CONCLUSIONS: The elderly RA patients with advanced stage, respiratory diseases or DM should be monitored for infections, including pneumonia, carefully during treatment.
28474138 Effects of iguratimod on the levels of circulating regulators of bone remodeling and bone 2017 Jun This study aims to investigate the effect of iguratimod, a novel disease-modifying antirheumatic drug, alone or combined with methotrexate (MTX), on the serum levels of regulators of bone remodeling (receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and Dickkopf-1 (DKK-1)) and bone remodeling markers (C-telopeptide of type I collagen (CTX-I) and procollagen type I N-terminal propeptide (PINP)) in patients with rheumatoid arthritis (RA). Patients with RA were treated with iguratimod, MTX, or their combination for 12 months. Serum samples were collected before treatment and 6 and 12 months afterwards. RANKL, OPG, DKK-1, CTX-I, and PINP levels were measured, and radiographic progression was assessed. The serum RANKL levels decreased after treatment for 6 and 12 months with iguratimod (median: baseline 565.00 pmol/L vs. 6 months 411.00 pmol/L vs. 12 months 212.00 pmol/L), MTX (median: baseline 562.50 pmol/L vs. 6 months 399.50 pmol/L vs. 12 months 163.50 pmol/L), and their combination (median: baseline 971.00 pmol/L vs. 6 months 272.50 pmol/L vs. 12 months 241.50 pmol/L). Combination therapy showed greater effects 6 months post-treatment compared to single-drug therapy. PINP levels increased significantly 12 months post-treatment with all therapies, but only the combination therapy led to decreased CTX-I levels. OPG and DKK-1 levels showed no significant changes. The three treatments showed no significant differences in radiographic progression. Iguratimod could stimulate bone formation and regulate the RANKL/RANK/OPG system rather than DKK-1levels. Its effects are comparable to those of MTX, and combination therapy showed stronger effects.
24725498 Translation and validation of the Turkish language version of the Rheumatoid Arthritis Dis 2017 Dec AIM: The purpose of this study was to translate the Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), which is a tool for measuring disease activity in rheumatoid arthritis (RA) patients, into Turkish language and prove its validity, reliability and sensitivity to changes. METHODS: Translation from the original German version was performed according to the standardized methods. One hundred and two patients with RA completed in the Turkish RADAI-5 twice within 3 days interval. Internal consistency and test-retest reliability was investigated by calculating Cronbach's alpha and intra-class correlation coefficients (ICC), respectively. Validity was assessed by analyzing the correlations between the Turkish RADAI-5 and some measurement tools evaluating the disease activity, functional status and quality of life. To test the scale's responsiveness to the changes, another 23 patients with uncontrolled disease activity and three newly diagnosed RA patients completed the RADAI-5 before and after a biologic agent or methotrexate treatment. RESULTS: There were no floor or ceiling effects. Cronbach's alpha (0.91) and ICC (0.997) values certified the Turkish version's reliability. Strong correlations between the Turkish questionnaire and Disease Activity Score-28 (DAS28), DAS28-CRP, DAS28-three variables, Health Assessment Questionnaire, Rheumatoid Arthritis Quality of Life questionnaire, patient's and doctor's global assessments, tender joint count proved the convergent validity of the scale. Effect size (3.08) demonstrated that the Turkish RADAI-5 is sensitive to the changes. CONCLUSION: The Turkish RADAI-5 is a feasible, reliable and valid questionnaire and sensitive to changes; thus it can be used to monitor disease activity in Turkish RA patients.
27974101 Response to methotrexate predicts long-term mortality of patients with rheumatoid arthriti 2017 May OBJECTIVES: To assess if there is a correlation between the degree of response to treatment with methotrexate (MTX) and long-term mortality in a cohort of patients with rheumatoid arthritis (RA) established in Germany in the early eighties. METHODS: RA patients who had started MTX treatment between 1980 and 1987 were included. One year after baseline, the treatment response was evaluated. Responders were defined as patients with at least 20% decline in the swollen joint count (out of 32 joints) and the ESR with a prednisone dosage <5 mg/day. Thereafter, assessments were performed at 10, 18, and 30 years after baseline. Standardised mortality ratios (SMR) were calculated, Cox regression and logistic regression were performed. RESULTS: The cohort comprised 271 patients. In 2015, about 30 years after the initiation of MTX therapy, 185 patients (68%) were deceased, 52 (19%) lost to follow-up and 34 alive. The response after the first year of MTX treatment was the strongest predictor of survival with a hazard ratio of 0.44 (95% confidence interval [CI]: 0.30-0.65). However, even responders still had an SMR of 1.37 (95% CI 1.31-1.65), but this was much worse for non-responders who had an SMR of 4.22 (95% CI 3.13-5.56). Using Cox regression analysis no difference was detected between responders with more than 50% improvement (38% of all patients) and those with 20-50% improvement (28%). CONCLUSIONS: The predictive value of a response to one year of MTX therapy for long-term mortality of RA patients is independent of the degree of response.
28725981 Certolizumab pegol was effective for treating residual synovitis after total knee arthropl 2018 Apr We present the case of a 59-year-old female who developed rheumatoid arthritis in 2007. Right total knee arthroplasty (TKA) was performed in 2008. Although she was treated with methotrexate (MTX) after the operation, this treatment was insufficient. Infliximab (IFX) was introduced in 2001, and she achieved clinical remission. Left TKA was performed in October 2014. Because active synovitis was not detected by ultrasound after the operation, IFX was discontinued. She had been treated with MTX 8 mg weekly. However, arthralgia of the bilateral knees developed in March 2015. Ultrasound showed synovial hypertrophy with vascular signals representing postoperative residual synovitis. She was given certolizumab pegol. According to ultrasound, the synovitis had improved after 3 months.
28072731 Focal segmental glomerulosclerosis lagged behind the onset of rheumatoid arthritis by 7 ye 2017 Jan INTRODUCTION: The co-existence of focal segmental glomerulosclerosis (FSGS) and rheumatoid arthritis (RA), presenting either together or in succession, is very rare. A variety of histopathological features in the clinical renal disease may occur in RA. Only 8 studies have previously reported this poorly understood connection. CLINICAL FINDINGS/DIAGNOSES: A case of a 54-year-old male with RA lasting for more than 7 years developed cheirarthritis as the first signs. Symmetric polyarthralgia and multiple swollen joints throughout the body were followed, accompanied with morning stiffness. Gradually, he suffered from albuminuria, hypoalbuminemia, edema, and hyperlipidemia in 2014. The patient had the history of administering loxoprofen, celecoxib, leflunomide, and methotrexate. He was diagnosed as RA, nephrotic syndrome. Renal biopsy confirmed FSGS. CONCLUSION: Our case and the review of the literature indicate that FSGS is one of the causes of nephrotic syndrome in RA. It strongly suggested that RA patients with the abnormal kidney functions should be routinely screened for FSGS to guide the therapy, achieve both RA and FSGS remission, determine a prognosis, and avoid end-stage renal lesion.
28349270 Effect of thymidylate synthase (TYMS) gene polymorphisms with methotrexate treatment outco 2017 Jun Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease causing joint damage and significant functional impairment. Methotrexate (MTX) remains the mainstay for the treatment of RA. MTX inhibits several enzymes of the folate and nucleotide pathways. Thymidylate synthase (TYMS) is an important enzyme in the de novo pyrimidine pathway responsible for DNA replication. The two common gene polymorphisms analyzed in TYMS are 28-bp tandem repeat polymorphism and a 6-bp insertion/deletion polymorphism. The present study was carried out to find the role of these TYMS gene polymorphisms with clinical phenotype, treatment response, and MTX adverse events in 254 patients with RA of south Indian Tamil ethnicity. TYMS gene polymorphisms were analyzed by PCR. The allele frequencies of TYMS gene polymorphisms did not differ between good and non-responders. However, the TYMS 28-bp tandem repeat 3R allele was higher in non-responders than in patients undergoing remission [64 vs 51.11%, p = 0.06, OR 0.58, 95% CI (0.34-1.00)]. The TYMS 6-bp deletion allele was higher in non-responders than good responders [78.20 vs 64.92%, p = 0.06, OR 0.51 95% CI (0.27-0.98)]. TYMS 3R allele and TYMS 6-bp deletion allele may favor non-response to MTX in south Indian Tamils. TYMS gene polymorphisms did not influence MTX adverse events.
28758827 Lymphoproliferative disorders in patients with rheumatoid arthritis in the era of widespre 2018 Jan Lymphoproliferative disorders (LPD) in patients receiving methotrexate (MTX) have gained strong attention. In this article, I reviewed the basic and clinical findings of this issue. Patients with RA possess a high risk of lymphoma, but epidemiological evidence showing an association between the use of MTX and lymphoma is still limited. Rapid regression of LPD after stopping MTX in patients with RA strongly suggests that there is a causative relationship. Genetic predisposition, accumulated inflammation, impaired generation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes, effects of MTX on the regulation of EBV genes, and low hypermethylation of apoptosis-related genes are relevant to the development of LPD and rapid regression after cessation of MTX. The clinical and histological characteristics of LPD in RA patients who are treated with MTX have been established, and recent data indicate that initial cessation of MTX and watchful waiting to observe an increase in peripheral lymphocyte counts have a therapeutic value. In advanced cases, various chemotherapy regimens are used, and consultation with hematologists is recommended to select the optimal treatment. There is no consensus on the treatment of RA after development of LPD, and long-term observation is necessary to investigate the safety of disease-modifying antirheumatic drugs in these patients.
28403797 Is the Treatment with Biological or Non-biological DMARDS a Modifier of Periodontal Condit 2017 BACKGROUND AND OBJECTIVE: Experimental models suggest the use of different therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal condition. This study evaluated the effects of conventional drug treatment and anti-TNF therapy in patients with RA on microbiological and periodontal condition, establishing the association of markers of periodontal infection with indexes of rheumatic activity. MATERIALS AND METHODS: One hundred seventy nine individuals with RA were evaluated (62 with anti-TNF-. and 115 with only DMARDs). The periodontal evaluation included plaque and gingival indexes, bleeding on probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival plaque samples for microbiological analysis. Rheumatologic evaluations included a clinical examination, rheumatoid factor (RF), antibodies against cyclic-citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). RESULTS: Anti-TNF-alpha therapy influenced periodontal microbiota with a higher frequency of T. denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher extension of CAL (p=0.005), and anti-TNF-alpha therapy with methotrexate was associated with a lower extension of CAL (p=0.05). The use of corticosteroids exerted a protective effect on the number of teeth (p=0.027). The type of DMARD affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs titers were associated with the presence of red complex periodontal pathogens (p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05), and ESR was associated with a greater PD (p=0.044) and presence of red complex (p=0.030). CONCLUSION: Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.
29141665 Matrix metalloproteinase-3 and the 7-joint ultrasound score in the assessment of disease a 2017 Nov 15 BACKGROUND: This study aimed to investigate the reliability and validity of serum matrix metalloproteinase-3 (MMP-3) levels and articular ultrasound (US) scores in assessing disease activity and therapeutic response in rheumatoid arthritis (RA) patients. METHODS: A total of 151 RA patients were enrolled, of whom 22 were treated with certolizumab pegol (Cimzia, CZP). The RA patients were divided into the following four subgroups according to their disease activity score in 28 joints (DAS28): stable, mild activity, moderate activity, and high activity. Forty-three healthy controls were simultaneously studied. The serum MMP-3 levels and 7-joint US (US7) scores of all subjects were determined. The patients who were treated with CZP were subsequently followed for 6 months. RESULTS: The serum MMP-3 levels of all the RA patients were significantly higher than those of healthy controls, and those of patients with moderate and severe RA were significantly higher than those of patients with stable RA. The US7 scores of patients with severe RA were significantly higher than those of patients in other groups. Using the DAS28 as a reference standard, the corresponding cutoff value of MMP-3 was 70.5 ng/ml. After CZP treatment, the MMP-3 levels and US7 scores were significantly decreased at week 2, and the mean changes in US7 scores at weeks 12 and 24 were significantly higher in both groups with American College of Rheumatology 50% positive response (ACR50) and ACR 70% positive response (ACR70) than in the negative groups. CONCLUSION: Serum MMP-3 and the US7 scores could both effectively reflect disease activity and therapeutic responses in patients with moderate to severe RA. TRIAL REGISTRATION: CTR20140405 (RA0044), CTR20140405: A phase 3, Multicenter, Double-blind, Placebo Controlled, Parallel Group, Randomized, 24-Week Study to Evaluate the Safety and Efficacy of Certolizumab Pegol as Additional Medication to Methotrexate in Chinese Subjects With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate, Registered on 13 June 2014. CTR20140412 (RA0078), CTR20140412: A phase 3, Multicenter, Open-label Extension Study to Assess the Safety and Efficacy of Certolizumab Pegol as Additional Medication to Methotrexate in Chinese Subjects With Active Rheumatoid Arthritis Who Participated in RA0044, Registered on 02 July 2014.
28266606 Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients w 2017 Mar 7 Methotrexate (MTX) is widely used and considered a first-line disease modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX effectiveness in RA patients, although inconsistent results have been reported. A systematic review and meta-analysis were performed to identify genetic variants associated with MTX efficacy. A total of 30 publications that included 34 genes and 125 SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the systematic review (SR), and 21 studies were included in 9 meta-analyses. Associations between MTX response in RA patients in MTHFR 1298A > C (rs1801131), ATIC 347C > G (rs2372536), RFC-1 80G > A (rs1051266), SLC19A1 A > G (rs2838956) and SLC19A1 G > A (rs7499) genetic polymorphisms were found, but not observed between the MTHFR 677C > T (rs1801133), TYMS 28 bp VNTR (rs34743033), MTRR 66A > G (rs1801394), and ABCB1 3435C > T (rs1045642). However, for the polymorphisms not being associated following meta-analysis could still be associated if larger cohorts were used, and studies of other polymorphisms are necessary in large cohorts and a rigorous way, which may provide more accurate results for the effect of the gene polymorphisms on the MTX response.
29185111 Factors influencing spinal sagittal balance, bone mineral density, and Oswestry Disability 2018 Feb PURPOSE: To identify the factors influencing spinal sagittal alignment, bone mineral density (BMD), and Oswestry Disability Index (ODI) outcome measures in patients with rheumatoid arthritis (RA). METHODS: We enrolled 272 RA patients to identify the factors influencing sagittal vertical axis (SVA). Out of this, 220 had evaluation of bone mineral density (BMD) and vertebral deformity (VD) on the sagittal plane; 183 completed the ODI questionnaire. We collected data regarding RA-associated clinical parameters and standing lateral X-ray images via an ODI questionnaire from April to December 2012 at a single center. Patients with a history of spinal surgery or any missing clinical data were excluded. Clinical parameters included age, sex, body mass index, RA disease duration, disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR), serum anti-cyclic citrullinated peptide antibody, serum rheumatoid factor, serum matrix metalloproteinase-3, BMD and treatment type at survey, such as methotrexate (MTX), biological disease-modifying anti-rheumatic drugs, and glucocorticoids. We measured radiological parameters including pelvic incidence (PI), lumbar lordosis (LL), and SVA. We statistically identified the factors influencing SVA, BMD, VD, and ODI using multivariate regression analysis. RESULTS: Multivariate regression analysis showed that larger SVA correlated with older age, higher DAS28-ESR, MTX nonuse, and glucocorticoid use. Lower BMD was associated with female, older age, higher DAS28-ESR, and MTX nonuse. VD was associated with older age, longer disease duration, lower BMD, and glucocorticoid use. Worse ODI correlated with older age, larger PI-LL mismatch or larger SVA, higher DAS28-ESR, and glucocorticoid use. CONCLUSIONS: In managing low back pain and spinal sagittal alignment in RA patients, RA-related clinical factors and the treatment type should be taken into consideration.
28420837 Clinical Characteristics of Rheumatoid Arthritis Patients Achieving Functional Remission w 2017 Objective Although previous studies have reported the prognostic factors for functional remission, no reports have cited the predictive factors. Our aim was to study the predictive factors for functional remission, which is a treatment goal in rheumatoid arthritis (RA), after receiving biological disease-modifying antirheumatic drugs (bDMARDs) treatment for six months. Methods The study consisted of 333 RA patients treated with bDMARDs for six months. The following patient characteristics were investigated: age, gender, disease duration, type of bDMARDs, baseline steroid and methotrexate dosage, and levels of serum rheumatoid factor, matrix metalloprotease, anti-cyclic citrullinated peptides antibody, tumor necrosis factor-α, and interleukin-6. In our evaluation, we used the Simplified Disease Activity Index (SDAI) for RA disease activity, health assessment questionnaire disability index (HAQ-DI) for activity of daily living, Short Form (SF)-36 for quality of life, and Hamilton Depression Rating Scale (HAM-D) or Self-rating Depression Scale (SDS) to determine the patients' depression status. The subjects were divided into two groups: patients with HAQ-DI≤0.5 and HAQ-DI>0.5 at 6 months. Results A univariate analysis comparing a group of RA patients without functional remission (n=68) showed that the patients with functional remission (n=164) had the following in common compared with those without remission: younger age, shorter disease duration, lower baseline steroid dosage, lower SDAI, lower HAQ-DI, higher SF-36, and lower HAM-D. Only lower HAQ-DI scores and "mental health" score on the SF-36 were detected using a logistic regression analysis. Conclusion These findings suggested that RA patients with lower HAQ-DI and lower depression scores at baseline were more likely to achieve functional remission using bDMARDs treatment than those without these variables.
28919284 MMP-8 and TIMP-1 are associated to periodontal inflammation in patients with rheumatoid ar 2019 Jun BACKGROUND: Aim of this cross-sectional study was the investigation of associations between different rheumatoid arthritis (RA)-related blood parameters and periodontal condition as well as selected periodontal pathogenic bacteria in RA patients under methotrexate (MTX) immunosuppression. METHODS: Periodontal probing depth (PPD), bleeding on probing (BOP) and clinical attachment loss (CAL) were assessed. Periodontal condition was classified into: no/mild and moderate or severe periodontitis (P). Prevalence of selected periodontal pathogenic bacteria and concentration of matrix metalloproteinase 8 (MMP-8) was assessed from the gingival crevicular fluid (GCF) using PCR and ELISA, respectively. Blood samples were analyzed for the concentration of selected rheumatoid parameters. STATISTICAL ANALYSIS: t-test, Mann-Whitney-U-Test, exact Fisher tests or chi square test (p < 0.05). RESULTS: Fifty-six patients (mean age 55.07 years, 34 P, 22 no P) were included. While prevalence of periodontal pathogenic bacteria was higher in P patients, no substantial association of bacteria with blood parameters was found. In periodontal diseased participants, MMP-8 concentration in GCF (6.22 ± 7.01 vs. 15.99 ± 13.49; p < 0.01) and blood (2.60 ± 3.57 vs. 5.52 ± 5.92; p < 0.01) was increased, while no correlation between GCF and blood was found (Spearman's rho: 0.175; p = 0.23). Furthermore, higher blood concentrations of MMP-8 and tissue inhibitor of MMP (TIMP-1) were detected in patients with increased periodontal inflammation (BOP positive, p < 0.01). CONCLUSION: Periodontal inflammation appears associated to MMP-8 and TIMP-1 in blood. Thereby, clinical interaction between periodontal conditions, periodontal pathogenic bacteria and RA-related cytokines remain unclear.
29247126 Preference phenotypes to facilitate shared decision-making in rheumatoid arthritis. 2018 May OBJECTIVE: Implementing treat-to-target (TTT) strategies requires that patients with rheumatoid arthritis (RA) and their rheumatologists decide on how best to escalate care when indicated. The objective of this study was to develop preference phenotypes to facilitate shared decision-making at the point of care for patients failing methotrexate monotherapy. METHODS: We developed a conjoint analysis survey to measure the preferences of patient with RA for triple therapy, biologics and Janus kinase (JAK) inhibitors. The survey included seven attributes: administration, onset, bothersome side effects, serious infection, very rare side effects, amount of information and cost. Each choice set (n=12) included three hypothetical profiles. Preference phenotypes were identified by applying latent class analysis to the conjoint data. RESULTS: 1273 participants completed the survey. A five-group solution was chosen based on progressively lower values of the Akaike and Bayesian information criteria. Members of the largest group (group 3: 38.4%) were most strongly impacted by the cost of the medication. The next largest group (group 1: 25.8%) was most strongly influenced by the risk of bothersome side effects. Members of group 2 (11.2%) were also risk averse, but were most concerned with the risk of very rare side effects. Group 4 (6.6%) strongly preferred oral over parenteral medications. Members of group 5 (18.0%) were most strongly and equally influenced by onset of action and the risk of serious infections. CONCLUSIONS: Treatment preferences of patients with RA can be measured and represented by distinct phenotypes. Our results underscore the variability in patients' values and the importance of using a shared decision-making approach to implement TTT.
29141716 Hansen's Disease and Rheumatoid Arthritis Crossover of Clinical Symptoms: A Case Series of 2017 Dec Hansen's Disease (HD) is a rare, chronic granulomatous infection of the skin and peripheral nerves caused by the noncultivable organism Mycobacterium leprae. Arthritis is the third most common symptom of HD. Subjects with both confirmed HD on skin biopsy and chronic arthritis were identified at the National Hansen's Disease Program (NHDP). We conducted a series of medical chart reviews and extracted and logged personally deidentified data into a database and carried out descriptive analyses. Eighteen of 261 subjects presented to the NDHP with both HD and chronic arthritis between 2001 and 2015. Among these, 16 were male, 16 were white, and 15 were residents of Louisiana. The median age at diagnosis of HD was 67 years. Ten of these subjects were diagnosed with borderline lepromatous leprosy, seven were diagnosed with lepromatous, and one was diagnosed with borderline tuberculoid leprosy. Patients were symptomatic with arthritis for a median of 5.3 years before HD diagnosis. Sixty-two percent of patients (11) were diagnosed with rheumatoid arthritis (RA) before HD diagnosis, and 10 of which were seronegative RA. Hands, feet, wrists, and elbows were most commonly reported as affected joints. Over half of the patients (61%) had completed HD multidrug therapy at the time of review, and 73% of these subjects had persistent joint pain requiring steroids or methotrexate for symptomatic control. Chronic arthritis in HD patients is present in a series of US-acquired cases of HD. Arthritis did not resolve with successful treatment of HD in most cases.
28117352 IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combinati 2017 Jan 24 T cells are key players in immune-mediated rheumatoid arthritis (RA). We previously reported that interleukin (IL)-22(+)CD4(+)T helper (IL-22(+) Th) cells and IL-22 critically control the pathogenesis of RA. Here we monitored circulating levels of different IL-22(+) Th cell subsets and measured plasma levels of IL-22, IL-17, and interferon (IFN)-γ in 60 patients with active RA following 12-week combination methotrexate (MTX) and leflunomide (LEF) therapy (MTX+LEF) and 20 healthy individuals. We found the frequencies of circulating IFN-γ(-)IL-17(-)IL-22(+) (Th22), IFN-γ(-)IL-17(+) (total Th17), IFN-γ(+)IL-17(-)IL-22(+) (IL-22(+)Th1) cells, and IFN-γ(-)IL-17(+)IL-22(+) (IL-22(+)Th17) cells, as well as the plasma levels of IL-22, IL-17 and IFN-γ to be significantly reduced in RA patients that responded to treatment, but not in non-responders. Reductions in plasma IL-22 level significantly correlated with percentage of circulating Th22 cells and the decrease of plasma IL-22 level correlated with the reduction of DAS28 in responders. Our data suggests that circulating Th22 cells and plasma IL-22 level play a detrimental role in RA. The combination MTX+LEF therapy, by targeting Th22 cells and reducing IL-22 level, relieves the immune defects and ameliorates symptoms of RA. This study provides novel mechanistic understanding of the pathogenesis of RA, which may promote a design of better therapies for RA.
28144917 Impact of Adalimumab on Work Productivity and Activity Impairment in Japanese Patients wit 2017 Mar INTRODUCTION: The Adalimumab Non-interventional Trial for Up-verified Effects and Utility (ANOUVEAU) was a large-scale, multicenter, prospective, observational, single-cohort study that evaluated the effects of adalimumab (ADA) on rheumatoid arthritis (RA)-related work productivity and activity impairment (RA-related WPAI) and disease activity in routine rheumatology care in Japan. METHODS: Patients with RA were categorized as paid workers (PWs, ≥35 h/week), part-time workers (PTWs, <35 h/week), or homemakers (HMs, unemployed) and were administered the WPAI for RA (WPAI/RA) questionnaire. All patients who received ADA were followed for 48 weeks to evaluate safety and effectiveness. RESULTS: Of the 1808 patients analyzed, 825, 243, and 740 patients were PWs, PTWs, and HMs, respectively. WPAI/RA domain scores significantly improved at weeks 12, 24, and 48 in all groups, with maximum improvement observed for PWs (p < 0.05). Additionally, remission rates (according to Disease Activity Score 28, erythrocyte sedimentation rate, Simplified Disease Activity Index, or Health Assessment Questionnaire-Disability Index scores) and EuroQol 5-Dimension 3-Level scores significantly increased from baseline to 48 weeks in all groups (p < 0.0001). Analysis of patient subgroups revealed better WPAI/RA outcomes for patients who were biologic-naïve, treated with concomitant methotrexate, or with RA duration of ≤2 years (p < 0.05). The rate of serious adverse events over 48 weeks of ADA treatment was 5.23%. CONCLUSIONS: Treatment with ADA provided sustained improvement in WPAI and had an acceptable safety profile in patients with RA. FUNDING: AbbVie GK and Eisai Co., Ltd. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01346488.