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ID PMID Title PublicationDate abstract
29961161 Joint longitudinal model development: application to exposure-response modeling of ACR and 2018 Oct Exposure-response modeling is important to optimize dose and dosing regimen in clinical drug development. The joint modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript presents the results of joint modeling of continuous and ordered categorical endpoints in the latent variable IDR modeling framework through the sharing of model parameters, with an application to the exposure-response modeling of sirukumab. Sirukumab is a human anti- interleukin-6 (IL-6) monoclonal antibody that binds soluble human IL-6 thus blocking IL-6 signaling, which plays a major role in the pathophysiology of rheumatoid arthritis (RA). A phase 2 clinical trial was conducted in patients with active RA despite methotrexate therapy, who received subcutaneous (SC) administration of either placebo or sirukumab of 25, 50 or 100 mg every 4 weeks (q4w) or 100 mg every 2 weeks (q2w). Major efficacy endpoints were the 20, 50, and 70% improvement in the American College of Rheumatology (ACR20, ACR50, and ACR70) disease severity criteria, and the 28-joint disease activity score using C-reactive protein (DAS28). The ACR endpoints were treated as ordered categorical and DAS28 as continuous. The results showed that, compared with the common approach of separately modeling the endpoints, the joint model could describe the observed data better with fewer parameters through the sharing of random effects, and thus more precisely characterize the dose-response relationship. The implications on future dose and dosing regimen optimization are discussed in contrast with those from landmark analysis.
30105374 Tumor Necrosis Factor Inhibitors and Cancer Recurrence in Swedish Patients With Rheumatoid 2018 Sep 4 BACKGROUND: Use of tumor necrosis factor inhibitors (TNFi) in patients with a history of cancer remains a clinical dilemma. OBJECTIVE: To investigate whether TNFi treatment in rheumatoid arthritis (RA) is associated with increased risk for cancer recurrence. DESIGN: Population-based cohort study based on linkage of nationwide registers. SETTING: Sweden. PARTICIPANTS: Patients with RA who started TNFi treatment between 2001 and 2015, after being diagnosed with cancer, and matched patients with RA and a history of the same cancer who had never received biologics. MEASUREMENTS: The primary outcome was the first recurrence of cancer. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs), taking into account time, cancer type, and whether the cancer was invasive or in situ (or tumor, node, metastasis [TNM] classification system stage in a subset of patients). RESULTS: Among 467 patients who started TNFi treatment (mean time after cancer diagnosis, 7.9 years), 42 had cancer recurrences (9.0%; mean follow-up, 5.3 years); among 2164 matched patients with the same cancer history, 155 had recurrences (7.2%; mean follow-up, 4.3 years) (HR, 1.06 [95% CI, 0.73 to 1.54). Hazard ratios were close to 1 in analyses of patient subsets matched on cancer stage or with similar time from index cancer diagnosis to the start of TNFi treatment, as well as in unmatched analyses. Several CIs had upper limits close to 2. LIMITATION: The outcome algorithm was partly nonvalidated, and channeling bias was possible if patients with a better index cancer prognosis were more likely to receive TNFi. CONCLUSION: The findings suggest that TNFi treatment is not associated with increased risk for cancer recurrence in patients with RA, although meaningful risk increases could not be ruled out completely. PRIMARY FUNDING SOURCE: ALF (an agreement in Stockholm County Council concerning medical education and research in health and medical care), the Swedish Cancer Society, the Swedish Foundation for Strategic Research, and the Swedish Research Council.
27958380 Influence of IL6R gene polymorphisms in the effectiveness to treatment with tocilizumab in 2018 Jan In the present study, we aimed to investigate the influence of clinical parameters and single-nucleotide polymorphisms of interleukin-6 receptor (rs12083537, rs2228145, rs4329505 and rs11265618) on response to tocilizumab, TCZ (European League Against Rheumatism (EULAR) response, remission, low disease activity (LDA) and improvement of DAS28). We performed a retrospective cohort study in patients with Rheumatoid Arthritis (RA) treated with TCZ for 12 months. Multivariable analysis showed that the only variable independently associated to satisfactory EULAR response (odds ratio (OR): 0.61; 95% of confidence interval (CI)(95%): 0.42, 0.88; P=0.008), remission (OR: 0.51; CI(95%): 0.35, 0.75; P=0.001), LDA (OR: 0.41; CI(95%): 0.24, 0.72; P=0.002) and improvement in DAS28 (B=-0.32; CI(95%)): -0.47, -0.17; P=7.5 × 10(-5)) at 12 months was lower number of previous biological therapy (BT). High baseline DAS28 was also associated with a greater decrease in DAS28 at 12 months of treatment (B=0.99; CI(95%): 0.79, 1.20; P=1.5 × 10(-14)). Those patients who were carriers of AA genotypes for rs12083537 (OR: 13.0; CI(95%): 2.31, 72.91; P=0.004) and CC for rs11265618 (OR: 12.15; CI(95%): 2.18, 67.81; P=0.004) had better LDA response at 12 months of treatment with TCZ. In conclusion, RA patients treated with TCZ showed better EULAR response, remission, LDA and DAS28 improvement rates when a lower number of BT were previously administered. The AA genotype for rs12083537 and CC for rs11265618 polymorphisms for may act as predictors of good response LDA.
28432580 Corneal melting in rheumatoid arthritis patients treated with a tectonic reinforcing corne 2018 Jun PURPOSE: Corneal melting with perforation is a severe ophthalmic complication of autoimmune disorders such as rheumatoid arthritis. It requires urgent medical management in order to maintain the integrity of the globe and preserve vision. Treating this complication by penetrating keratoplasty is problematic due to the high rate of recurrence of corneal melting as well as other complications. We describe the use of a tectonic fresh-tissue corneolimbal covering graft. METHODS: An interventional case series including three patients that presented to our tertiary center between 2000 and 2015 with corneal melting and perforation, secondary to rheumatoid arthritis. Emergency surgery included suturing of a 13.00- to 13.50-mm full-thickness fresh-tissue corneolimbal covering graft to the patient's posterior limbal zone. RESULTS: The corneolimbal graft maintained the integrity of the cornea in all cases, by sealing the perforation and promoting the creation of a fibrovascular scar at the area of corneal melting. There were no complications, recurrences of host corneal melting, or perforation during the follow-up period. CONCLUSION: Fresh-tissue full-thickness corneolimbal grafts may be used to cover emergency corneal melting and perforations secondary to rheumatoid arthritis.
29631228 Region-specific foot pain and plantar pressure in people with rheumatoid arthritis: A cros 2018 Jun BACKGROUND: It is unclear whether region-specific foot pain may influence plantar pressure in people with established rheumatoid arthritis. The aim was to determine the association between region-specific foot pain and region-specific plantar pressure. METHODS: Twenty-one people with rheumatoid arthritis and 19 age- and sex-matched controls participated in this study. Self-reported foot pain in the toes, forefoot, midfoot and rearfoot was assessed using foot diagrams. Peak pressure and pressure time integrals for the toes, forefoot, midfoot and rearfoot were calculated using a pressure mat system. Differences in foot pain and pressure between the groups were calculated using appropriate regression models. To determine associations between region-specific pain and pressure, linear regression models were used while adjusting for body mass and participant group. FINDINGS: Participants with rheumatoid arthritis were primarily elderly female with long disease duration. Compared to controls, participants with rheumatoid arthritis had higher odds of foot pain at the toes (Odds Ratio (OR) = 10.4, P = 0.001), forefoot (OR = 6.3, P = 0.006) and rearfoot (OR = 10.1, P = 0.011). Participants with RA had higher peak pressure at the rearfoot (P = 0.003) and higher pressure time integrals at the forefoot (P = 0.005), midfoot (P = 0.016) and rearfoot (P < 0.001). After adjusting for body mass and participant group, peak pressure was significantly higher at the toes in those with midfoot pain and rearfoot pain. INTERPRETATION: People with rheumatoid arthritis experience region-wide foot pain and demonstrate differences in pressure distribution compared to people without rheumatoid arthritis. Foot pain at the midfoot and rearfoot is also associated with increases in plantar pressure at the toes.
29804386 [Standard treatment of autoimmune hepatitis: experience from rheumatoid arthritis]. 2018 Feb 20 The treatment of autoimmune hepatitis is similar to that of rheumatic immune disease, which requires the use of hormones and immunosuppressive agents to induce and maintain remission therapy. As one of the most common diseases of rheumatology, rheumatoid arthritis has a definite treatment strategy and gradually becomes a new concept of rheumatoid disease. However, the current treatment of autoimmune hepatitis is still lack of standard compliance treatment strategies, and for the disease activity and immunosuppressive treatment of the efficacy of no uniform standard evaluation criteria, there is no clear evidence of the need to increase the hormone dose or the timing of treatment for patients with substandard treatment, so we consider the standard treatment of autoimmune hepatitis from the experience of rheumatoid arthritis of rheumatism, in order to provide reference for perfecting the standardized treatment of autoimmune hepatitis.
30580359 Calculation of free and bioavailable vitamin D and its association with bone mineral densi 2018 Dec INTRODUCTION: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women. MATERIALS AND METHODS: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzyme-linked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae. RESULTS: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH)D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD. CONCLUSION: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.
27574922 Effect of Electroacupuncture in "Zusanli" and "Kunlun" Acupoints on TLR4 Signaling Pathway 2018 May/Jun BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Previous study suggested that toll-like receptor (TLR) signaling pathway contributes to the development and progression of RA. In recent years, acupuncture has become one of the most vital treatments of arthralgia. But little is known about the mechanisms of improving RA by acupuncture. STUDY QUESTION: The study studied the effect of electroacupuncture in "Zusanli" and "Kunlun" acupoints on the expression of TLR4, myeloid differentiation factor 88 (MYD88), and NF-κB in adjuvant arthritis rats to clarify the molecular mechanism of acupuncture of RA. STUDY DESIGN: A rat model of adjuvant arthritis was established with injection of 0.1 mL Freund complete adjuvant in the right hindlimb footpad. We next punctured the Zusanli and Kunlun acupoints with 0.25 × 40-mm acupuncture needles to 5-mm depth. Then, we performed electroacupuncture treatment for 28 days with frequency of 2 Hz and intensity of 2 mA, once a day and 30 minutes each time. MEASURES AND OUTCOMES: Arthritis index and paw swelling were measured every week. FQ-PCR and western blot were used to detect the expression of TLR4, MYD88, and NF-κB. RESULTS: Paw swelling of rats injected with Freund complete adjuvant was more serious than that of the normal rats, which illustrated the successful establishment of adjuvant arthritis rat model. After treatment for 14 days, the paw swelling and joint symptoms score decreased, paw tissue inflammation eased in the rats of treatment group compared with the model group during the same period. After treatment for 28 days, the expression of TLR4, MYD88, and NF-κB in the ankle bone tissues decreased at both mRNA and protein levels. CONCLUSIONS: Stimulation with electric needle in Zusanli and Kunlun acupoints can reduce the expression of TLR4, MYD88, and NF-κB, which play an important role in treatment of adjuvant arthritis.
30030103 Succinate induces synovial angiogenesis in rheumatoid arthritis through metabolic remodeli 2018 Oct BACKGROUND AND PURPOSE: In response to hypoxic succinate accumulates in arthritis synovium, however, the implication is little known. This study aims to investigate whether succinate could act as a metabolic signal linking metabolic alternation with angiogenesis in arthritis synovium. EXPERIMENTAL APPROACH: The interaction between elevated succinate and VEGF production was examined in endothelial cells. Succinate production, HIF-1α induction and angiogenesis in the hypoxic synovium of collagen-induced arthritis rats were also investigated. KEY RESULTS: Intracellular succinate promoted VEGF production and induced angiogenic response dependent on HIF-1α induction in endothelial cells. Luciferase reporter assay showed that succinate increased VEGF expression through gene promoter activation dependent on HIF-1α induction. Intracellular succinate released into intercellular space, where extracellular succinate activated succinate receptor G-protein-coupled receptor 91 (GPR91) and induced VEGF production, further exacerbating angiogenesis. In addition, TGF-β1 treatment increased succinate production due to the reversal of succinate dehydrogenase (SDH) activation, and consistently, SDH inhibitor dimethyl malonate reduced angiogenesis in the arthritis synovium. CONCLUSION AND IMPLICATIONS: More than an intermediate, succinate functioned as a signaling molecule to link metabolic reprograming with angiogenesis. Intracellular succinate induced angiogenesis through HIF-1α induction, while extracellular succinate acted on GPR91 activation, working together to disturb energy metabolism and exacerbate inflammation and angiogenesis in arthritis synovium. Our work suggested that suppression of SDH could prevent succinate accumulation and inhibit angiogenesis via blocking HIF-1α/VEGF axis. This finding not only provides a novel insight into angiogenesis, but also reveals a potential therapeutical strategy to attenuate revascularization in arthritis.
30061164 Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis. 2018 Nov OBJECTIVES: Recent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage. METHODS: HK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 10(8) particles of ad-HK2 or ad-GFP were injected into the knee of wild-type mice. K/BxN serum transfer arthritis was induced in HK2(F/F) mice harbouring Col1a1-Cre (HK2(Col1)), to delete HK2 in non-haematopoietic cells. RESULTS: HK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and colocalises with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2(Col1) mice significantly showed decreased arthritis severity, bone and cartilage damage. CONCLUSION: HK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment.
29463015 Association between Bone Mineral Density of Femoral Neck and Geriatric Nutritional Risk In 2018 Feb 18 Treatment of rheumatoid arthritis (RA) with biological disease-modifying anti-rheumatic drugs (bDMARDs) induces rapid remission. However, osteoporosis and its management remains a problem. The Geriatric Nutritional Risk Index (GNRI) evaluates the risk of malnutrition-related complications in elderly patients and has been shown to be a significant predictor of many diseases. We evaluated the correlation between GNRI and RA activity. In addition, risk factors for femoral neck bone loss were evaluated in RA patients treated with bDMARDs. We retrospectively examined the medical records of 146 patients with RA, collecting and recording the patients' demographic and clinical characteristics. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Inverse correlations were observed between GNRI and disease duration, disease activity score-28 joint count serum C-reactive protein (CRP), simple disease activity index, modified health assessment questionnaire score and CRP. GNRI showed correlation with femoral neck BMD and femoral neck BMD ≤ 70% of young adult men (YAM). Multiple regression analysis showed that female sex, increased age and lower GNRI were risk factors for lower BMD of the femoral neck. Multivariate binomial logistic regression analysis showed that female sex (odd ratio: 3.67) and lower GNRI (odd ratio: 0.87) were risk factors for BMD ≤ 70% of YAM. Because the GNRI is a simple method, it might be a simple predictor for RA activity and BMD status in RA patients. Complementary nutritional therapies might improve RA activity and osteoporosis in RA patients who have undergone treatment with bDMARDs.
28395581 A case-control study of rheumatoid arthritis revealed abdominal obesity and environmental 2018 Mar BACKGROUND: The aim of this study was to evaluate new and previously hypothesized environmental risk factors and their interaction with rheumatoid arthritis (RA). METHODS: Four hundred patients recently diagnosed with RA and 400 controls frequency-matched by gender and birth year using Propensity Score Matching (PSM) were selected from northern China. Investigation was performed using self-reported data from interviewer-administered surveys. Associations between exposure variables and risk of RA were evaluated using multifactor non-conditional logistic regression. RESULTS: It showed that damp localities, draft indoor, abdominal obesity (AO), and family history of RA among first-degree relatives were independent risk factors and drinking of milk was independent protective factors for RA. Besides these risk factors, in women, infrequent delivery times, early age at menopause, and late age at menarche were also independent risk factors for RA. Both the additive model and the multiplication model suggested that there was an interaction relationship between AO and damp localities (p < .001), and only the additive model suggested that there was interaction relationship between AO and no milk drinking (p < .001) in our study population. In women, there was interaction relationship between AO and damp localities (p < .001) and between AO and age at menopause (p < .001). CONCLUSIONS: In northern China, damp localities, draft indoor, AO, family history of RA among first-degree relatives, and no milk drinking may be important risk factors of RA patients.
30518319 A statistical measure for the skewness of X chromosome inactivation based on family trios. 2018 Dec 5 BACKGROUND: X chromosome inactivation (XCI) is an important gene regulation mechanism in females to equalize the expression levels of X chromosome between two sexes. Generally, one of two X chromosomes in females is randomly chosen to be inactivated. Nonrandom XCI (XCI skewing) is also observed in females, which has been reported to play an important role in many X-linked diseases. However, there is no statistical measure available for the degree of the XCI skewing based on family data in population genetics. RESULTS: In this article, we propose a statistical approach to measure the degree of the XCI skewing based on family trios, which is represented by a ratio of two genotypic relative risks in females. The point estimate of the ratio is obtained from the maximum likelihood estimates of two genotypic relative risks. When parental genotypes are missing in some family trios, the expectation-conditional-maximization algorithm is adopted to obtain the corresponding maximum likelihood estimates. Further, the confidence interval of the ratio is derived based on the likelihood ratio test. Simulation results show that the likelihood-based confidence interval has an accurate coverage probability under the situations considered. Also, we apply our proposed method to the rheumatoid arthritis data from USA for its practical use, and find out that a locus, rs2238907, may undergo the XCI skewing against the at-risk allele. But this needs to be further confirmed by molecular genetics. CONCLUSIONS: The proposed statistical measure for the skewness of XCI is applicable to complete family trio data or family trio data with some paternal genotypes missing. The likelihood-based confidence interval has an accurate coverage probability under the situations considered. Therefore, our proposed statistical measure is generally recommended in practice for discovering the potential loci which undergo the XCI skewing.
29956820 Increased rate of lumbar spondylolisthesis in rheumatoid arthritis: A case-control study. 2018 Sep OBJECTIVE: The aim of this study was to compare the prevalence of lumbar spondylolisthesis (SPL) in patients suffering from low back pain (LBP) with or without rheumatoid arthritis (RA) and to identify potential factors associated with SPL in patients with RA. METHODS: We performed a case-control study. Cases and control patients had chronic LBP (more than 4 weeks). Patient with RA fulfilled the 2010 ACR/EULAR criteria. The main outcome was the presence of lumbar SPL on lumbar X-ray. The prevalence of SPL between RA and control patients was compared using chi-squared test. Potential factors associated with SPL in patients with RA were investigated by univariate and multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 67 cases and 83 controls were included. Median [interquartile range] age of patients with RA was 60.0 years [51.0-72.0]; 80.6% were females; and 92.5% and 83.6% were positive for anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor, respectively. Mean RA disease duration was 11.2 ± 8.7 years. SPL was more frequent in patients with RA than controls (41.8% versus 18.1%, P = 0.001). Adjusted to gender, RA was associated with increased prevalence of SPL (OR 3.15 [95% CI 1.48-6.70], P = 0.003). Among patients with RA, SPL was mainly Grade 1 (85.7%). Multivariate analysis revealed SPL is associated with increased age in patients with RA (OR 1.06 [1.02-1.11], P = 0.004). CONCLUSION: In a population of patients with chronic LBP, the prevalence of lumbar SPL was higher with than without RA. SPL might be explained by synovitis of lumbar facet joints.
29157669 The combination of IL-6 and its soluble receptor is associated with the response of rheuma 2018 Jun BACKGROUND: IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses. METHODS: Heparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients. RESULTS: Three statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90-183)pg/ml, in g2 12.3(4.4-24)pg/ml, and in g3 60.1(30-146)pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5-15), g2 = 12(8-20), and g3 23(16-26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups. CONCLUSIONS: RA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.
29717989 [Screening for tuberculosis before TNFα treatment in routine rheumatic care in Iceland. R 2018 Mai INTRODUCTION: Treatment with TNFα inhibitors (TNFαi) greatly increases the risk of reactivation of tuberculosis in rheumatic patients. Therefore, it is recommended to screen patients for tuberculosis before initiating TNFαi treatment. Iceland has a low prevalence of tuberculosis and BCG vaccination is not routine praxis. The purpose of this study was to review the results from TB-screening in routine praxis and to analyze whether changes in the screening process are to be recommended. MATERIAL AND METHODS: All patients with RA, PsA and AS who were registered in ICEBIO (1999-2014) due to TNFαi treatment were included. Data collection consisted of age, sex, start date of TNFαi treatment and results from a tuberculin skin test (TST) and chest x-ray. The data were then crosschecked with the Berkill registry, a nationwide database for TB. RESULTS: 756 individuals (58% female, mean-age of 54 years) were included. TST was negative in 614 cases (81%), 41 positive (5.4%), 9 false positives (1.2%) and 92 were missing (12%). 119 patients were registered in Berkill whereof 72 had a history of positive TST and 55 had been vaccinated, while 14 patients had been diagnosed with tuberculo-sis (where of 7 had negative TST on screening). Three patients were diagnosed with tuberculosis after the TNFi treatment. CONCLUSION: These results illustrate the importance of tuberculosis screening before initiating TNFαi treatment. Improvement in registration of TST results is necessary and whether interferon gamma release assays (IGRA) should be added to the screening process remains to be discussed.
28649878 Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients wi 2018 Jan OBJECTIVES: Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. RESULTS: Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. CONCLUSIONS: TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.
28471034 Ultrasonography-detected subclinical inflammation in patients with hand osteoarthritis and 2018 Mar OBJECTIVES: A recent review of ultrasound (US) studies in osteoarthritis (OA) showed very limited data about hand OA. Previous US studies in patients with OA described a degree of overlap between the US appearance of rheumatoid arthritis (RA) and OA joints. The present study aimed to assess the US features of subclinical inflammation in RA and hand OA, using the same US examination protocol. METHODS: A retrospective, cohort study compared patients with established RA (n = 224) and hand OA (n = 73), with respect to several demographic, clinical, laboratory and US parameters. We used a 22-hand joint US examination protocol (wrists, metacarpophalangeal and proximal interphalangeal joints bilaterally - Outcome Measures in Rheumatology Clinical Trials [OMERACT] scoring system) for all patients. RESULTS: Subclinical joint inflammation in the context of equivocal clinical examination was found in 9.6% of OA patients compared with 46.4% of RA patients (p = 0.0001), despite the fact that there was no significant difference between the degree of chronic joint swelling (synovial hypertrophy grades 2 and 3; p = 0.75 and p = 0.11, respectively). The presence of osteophytes was more common in patients with hand OA, as expected (p = 0.0001). CONCLUSIONS: Our study findings reflected differences between the incidence and characteristics of subclinical inflammation in patients with RA and OA, which could be helpful in patients with an equivocal clinical examination or history of both diseases. Almost one in 10 patients with hand OA had active synovitis, while almost one in two patients with RA had uncontrolled inflammation in at least one joint.
30210649 Anti-Inflammatory and Antioxidant Actions of Methyl Jasmonate Are Associated with Metaboli 2018 Methyl jasmonate (MeJA) is a fatty acid-derived cyclopentanone which shares structural similarities with prostaglandins and has been under study as a promising anti-inflammatory agent. This study investigated the actions of MeJA on systemic inflammation and oxidative status in rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. MeJA (75 to 300 mg·kg(-1)) was administrated orally during 18 days after arthritis induction with Freund's adjuvant. Articular and systemic inflammation was greatly increased in arthritic rats, likewise the oxidative stress in plasma and liver. The hepatic glucokinase activity and glycolysis were increased in arthritic rats. MeJA decreased most inflammatory parameters and abolished the increased protein carbonylation in plasma and liver, diminished the increased hepatic ROS content, and restored the hepatic GSH/GSSG ratio in arthritic rats. However, the MeJA treatment decreased the hepatic glucokinase activity and glycolysis and stimulated mitochondrial ROS production in healthy and arthritic rats. Oxygen uptake was increased by MeJA only in livers from treated arthritic rats. This action may bear relation to the increased activity of mitochondrial NADP(+)-dependent enzymes to provide reducing equivalents for the glutathione cycle. These beneficial effects, however, are associated with a decreased glucose flux through the glycolysis in the liver of arthritic and healthy rats.
29797175 Combining online and in-person methods to evaluate the content validity of PROMIS fatigue 2018 Sep PURPOSE: Fatigue is frequent and often severe and disabling in RA, and there is no consensus on how to measure it. We used online surveys and in-person interviews to evaluate PROMIS Fatigue 7a and 8a short forms (SFs) in people with RA. METHODS: We recruited people with RA from an online patient community (n = 200) and three academic medical centers (n = 84) in the US. Participants completed both SFs then rated the comprehensiveness and comprehensibility of the items to their fatigue experience. Cognitive debriefing of items was conducted in a subset of 32 clinic patients. Descriptive statistics were calculated, and associations were evaluated using Pearson and Spearman correlation coefficients. RESULTS: Mean SF scores were similar (p ≥ .61) among clinic patients reflecting mild fatigue (i.e., 54.5-55.9), but were significantly higher (p < .001) in online participants. SF Fatigue scores correlated highly (r ≥ 0.82; p < .000) and moderately with patient assessments of disease activity (r ≥ 0.62; p = .000). Most (70-92%) reported that the items "completely" or "mostly" reflected their experience. Almost all (≥ 94%) could distinguish general fatigue from RA fatigue. Most (≥ 85%) rated individual items questions as "somewhat" or "very relevant" to their fatigue experience, averaged their fatigue over the past 7 days (58%), and rated fatigue impact versus severity (72 vs. 19%). 99% rated fatigue as an important symptom they considered when deciding how well their current treatment was controlling their RA. CONCLUSIONS: Results suggest that items in the single-score PROMIS Fatigue SFs demonstrate content validity and can adequately capture the wide range of fatigue experiences of people with RA.