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ID PMID Title PublicationDate abstract
28605351 The Potential of Circadian Realignment in Rheumatoid Arthritis. 2016 In this short review, we discuss evidence supporting the modulation of peripheral circadian systems as a therapeutic strategy for rheumatoid arthritis (RA). We first review the role of proinflammatory cytokines and oxidative stress, two of the primary mediators of chronic inflammation in RA, and their regulation by circadian clock machinery. We further highlight the role of environmental and metabolic signals in regulating the central and peripheral circadian clocks, with an emphasis on seasonal variations in photoperiod and rhythmic metabolic input, respectively. Finally, we hypothesize that the entrainment and realignment of peripheral clock rhythms have the ability to modulate these mediators, improving clinical outcomes in RA patients. Our discussion emphasizes the use of light therapy and time-restricted feeding for entraining peripheral clocks either via the entrainment of the central circadian clock in suprachiasmatic nuclei (SCN) or directly by uncoupling the peripheral circadian clocks from SCN. In doing so, we highlight the use of nonpharmacologic interventions as a potential strategy for improving clinical outcomes in chronic inflammatory conditions such as RA.
25650053 Combined use of fenestrated-type artificial dermis and topical negative pressure wound the 2016 Feb We report a case of circumferential venous leg ulcer in a rheumatoid arthritis patient. Mesh skin grafting was performed in another hospital, but the graft failed and the patient was referred to our hospital. This ulcer was treated by the combination therapy of a fenestrated-type artificial dermis with negative pressure wound therapy (NPWT) and secondary mesh grafting using our 'grip tape technique'. NPWT was started at -100 mmHg and continued until the formation of dermis-like tissue. A section stained using haematoxylin and eosin and an anti-αSMA (α smooth muscle actin) immunohistological section of the biopsy from dermis-like tissue showed an abundant infiltration of fibroblasts and capillary formation beneath the fenestration of the silicone sheet. Threefold mesh skin grafting was subsequently performed and it was taken up completely. The fenestrated-type artificial dermis in combination with NPWT produced good results without infection in the treatment of complex wounds. In addition, our 'grip tape technique' was useful to apply polyurethane foam to the entire surface of the lower leg.
27291096 Presepsin and procalcitonin as biomarkers of systemic bacterial infection in patients with 2018 Jul AIM: To assess the diagnostic values of presepsin and procalcitonin in patients with rheumatoid arthritis (RA) by identifying those with bacterial infection METHOD: During June 2014-September 2015, 126 patients with RA and 25 healthy controls were enrolled. RA patients were divided into an infection group and a non-infection group. Infection was diagnosed by clinical symptoms, microbiological or radiographic methods, and good response to antibiotics. Concentrations of plasma presepsin, serum procalcitonin, C-reactive protein (CRP), and white blood cell counts (WBC) were measured and compared in each group. The correlations with the Sequential Organ Failure Assessment (SOFA) Score and these markers were calculated. RESULTS: RA patients included 26 patients in the infection group, 45 patients in the CRP-positive non-infection group (CRP > 0.3 mg/dL), and 55 patients in the CRP-negative non-infection group (CRP < 0.3 mg/dL). Levels of presepsin and procalcitonin in the infection group were highest and significantly higher than those in the CRP-positive non-infection group (presepsin 682.8 ± 158.1 pg/mL vs. 192.0 ± 12.0 pg/mL [P < 0.0001]; procalcitonin 4.052 ± 1.637 ng/mL vs. 0.120 ± 0.032 ng/mL [(P < 0.0001]). According to receiver operating characteristic curve (ROC) analysis, presepsin and procalcitonin levels appeared to have a higher diagnostic accuracy for infection than CRP or WBC. For the infection group, the SOFA Score positively correlated with the concentration of presepsin but not with that of procalcitonin. CONCLUSION: Presepsin and procalcitonin may be useful to identify infection in RA patients. Presepsin may better reflect infection severity than procalcitonin.
25729035 More than Just Minutes of Stiffness in the Morning: Report from the OMERACT Rheumatoid Art 2015 Nov OBJECTIVE: Stiffness was endorsed within the rheumatoid arthritis (RA) flare core domain set at the previous Outcome Measures in Rheumatology meeting (OMERACT 11). Two stiffness breakout groups at the present OMERACT 12 RA flare workshop discussed results of new qualitative studies in RA stiffness. METHODS: Results from 2 independent studies of RA stiffness were presented to breakout group participants, followed by group discussions about stiffness measurement. RESULTS: Both studies identified stiffness as complex, variable with the level of disease activity, and as encompassing concepts of impact, intensity, timing, location, and duration. That stiffness has an effect on multiple dimensions of health was a common finding. Participants agreed that stiffness is an important aspect of RA flare. Whether measuring only morning stiffness duration, the traditional approach in RA, was sufficient in coverage of the concept was unclear. Groups agreed that more research on stiffness measurement is needed considering the importance patients place on the effect of stiffness. CONCLUSION: Results from independent studies highlight stiffness effect as an important feature of RA, in addition to intensity, timing, location, and duration. Additional work is needed to identify optimal ways to assess stiffness in RA and other rheumatologic diseases.
26078491 Characterization of the Hypercitrullination Reaction in Human Neutrophils and Other Leukoc 2015 Autoantibodies against citrullinated proteins are diagnostic for rheumatoid arthritis. However, the molecular mechanisms driving protein citrullination in patients with rheumatoid arthritis remain poorly understood. Using two independent western blotting methods, we report that agents that trigger a sufficiently large influx of extracellular calcium ions induced a marked citrullination of multiple proteins in human neutrophils, monocytes, and, to a lesser extent, T lymphocytes and natural killer cells, but not B lymphocytes or dendritic cells. This response required 250-1,000 μM extracellular calcium and was prevented by EDTA. Other neutrophil activating stimuli, such as formyl-peptides, GM-CSF, IL-6, IL8, TNFα, or phorbol ester, did not induce any detectable increase in protein citrullination, suggesting that receptor-induced calcium mobilization is insufficient to trigger hypercitrullination. We conclude that loss of membrane integrity and subsequent influx of high levels of calcium, which can be triggered by perforin released from cytotoxic cells or complement mediated formation of membrane attack complexes in the joints of rheumatoid arthritis patients, are sufficient to induce extensive protein citrullination in immune cells, notably neutrophils. This mechanism may provide the citrullinated autoantigens that drive autoimmunity in this devastating disease.
25801886 Fingerprinting of anti-citrullinated protein antibodies (ACPA): specificity, isotypes and 2015 Apr Anti-citrullinated protein antibodies (ACPA) are a family of rheumatoid arthritis (RA)-specific autoantibodies that recognize the amino acid citrulline, resulting from the post-translational modification of arginine. Peptidyl arginine deiminase, the enzyme responsible for citrullination, is present in humans in different isoforms with different tissue distribution, enzymatic activity and target specificity; nonetheless, the number of proteins citrullinated in physiological or pathological conditions is wide, but not every citrullinated protein is a target for antibodies. In pre-RA patients the immune response to citrullinated antigens is initially restricted, expands with time and, after the onset of the disease, is relatively stable. ACPA are heterogeneous in terms of not only fine specificity but also isotype and IgG subclasses usage. This heterogeneity may be relevant for the immunopathogenesis of RA, conditioning the interaction of antibodies with complement and Fc receptors.
26286534 Investigation of the relationship between the onset of arthritis and uveitis in geneticall 2015 Aug 19 INTRODUCTION: Systemic rheumatic conditions are often accompanied by intraocular inflammatory disease (termed uveitis). Despite the frequent manifestation of uveitis with arthritis, very little is understood of the underlying mechanisms that mediate the eye's susceptibility to disease. The genetically susceptible SKG mouse strain develops arthritis that arises from an inherent mutation that disrupts T-cell antigen receptor signal transduction and thymic selection. The ensuing T-cell-mediated disease is further modulated through exposure to microbial triggers. The purpose of this study was to elucidate how a genetically determined shift in the T-cell repertoire toward self-reactive T cells that drive arthritis influences uveitis in SKG mice. METHODS: SKG mice (BALB/c mice that harbor the W163C point mutation in zeta-chain-associated protein kinase 70 [i.e., ZAP-70]) were housed under arthritis-resistant, specific pathogen-free conditions. Arthritis was induced by intraperitoneal injection with fungal glucans (zymosan or curdlan). Arthritis onset and severity were evaluated by clinical scoring, histopathology and infrared imaging within the joints. Periocular traits involving blepharoconjunctivitis were evaluated by clinical scoring and histology. Eyes were evaluated for signs of anterior uveitis using intravital videomicroscopy to document cell-trafficking responses within the iris vasculature and stroma and by histology to detect inflammatory infiltrate and tissue damage within the anterior and posterior eye segments. RESULTS: Exposure to zymosan resulted in the predicted arthritic, sexually dimorphic phenotype in SKG mice. The eyes of SKG mice exhibited episodic intravascular cellular responses to zymosan or curdlan as indicated by significant increases in leukocyte-endothelium interactions akin to ocular vasculitis. However, despite the significant increase in early cell-trafficking responses, cellular infiltration into the iris stroma was not observed and histopathological signs indicative of a sustained uveitis were absent. Instead, eyes of SKG mice developed blepharoconjunctivitis that coincided with arthritis and exhibited sexual dimorphism. CONCLUSIONS: This study underscores the complexity surrounding the pathogenesis of uveitis and its relationship with arthritis. The findings suggest that distinct mechanisms exist by which pathogenic autoimmune T cells target the eyes versus joints, which likely involves the environmental context but nonetheless should be taken into account in the identification and development of effective therapies for each organ.
27376404 Economic impact of expanded use of biologic therapy for the treatment of rheumatoid arthri 2016 Dec OBJECTIVES: To estimate economic impact resulting from increased biologics use for treatment of rheumatoid arthritis (RA) and Crohn's disease (CD) in Argentina, Brazil, Colombia, and Mexico. METHODS: The influence of increasing biologics use for treatment of RA during 2012-2022 and for treatment of CD during 2013-2023 was modeled from a societal perspective. The economic model incorporated current and projected medical, indirect, and drug costs and epidemiologic and economic factors. Costs associated with expanded biologics use for RA were compared with non-expanded use in Argentina, Brazil, Colombia, and Mexico. A similar analysis was conducted for CD in Brazil, Colombia, and Mexico. RESULTS: Accounting for additional costs of biologics and medical and indirect cost offsets, the model predicts that expanded use of biologics for patients with RA from 2012 to 2022 will result in cumulative net cost savings of ARS$2.351 billion in Argentina, R$9.004 billion in Brazil, COP$728.577 billion in Colombia, and MXN$18.02 billion in Mexico; expanded use of biologics for patients with CD from 2013 to 2023 will result in cumulative net cost savings for patients with CD of R$0.082 billion in Brazil, COP$502.74 billion in Colombia, and MXN$1.80 billion in Mexico. Indirect cost offsets associated with expanded biologics use were a key driver in reducing annual per-patient net costs for RA and CD. LIMITATIONS: Future economic projections are limited by the potential variance between projected and actual future values of biologic prices, wages, medical costs, and gross national product for each country. CONCLUSIONS: Increasing biologics use to treat RA and CD may limit cost growth over time by reducing medical and indirect costs. These findings may inform policy decisions regarding biologics use in Argentina, Brazil, Colombia, and Mexico.
26677127 Cancellous and Cortical Bone Microarchitectures of Femoral Neck in Rheumatoid Arthritis an 2016 May This study investigated the 3D microarchitecture of cancellous and cortical bones of the femoral neck in rheumatoid arthritis (RA), osteoarthritis (OA) and donor controls. 26 femoral necks (including heads) were harvested during total hip replacement surgeries in 11 patients with RA (mean age 66.7 ± 12.8 years) and 15 patients with OA (67.3 ± 8.4 years). Femoral heads/necks were also harvested from 8 donors (74.9 ± 10.2 years). Bone samples of 10 mm thickness were prepared from each femoral neck and scanned with micro-CT to evaluate microarchitectural parameters. The RA and OA samples showed no significant differences in microarchitectural parameters in cancellous or cortical bone. Compared with the donor controls, bone volume fraction in RA and OA cancellous bone was significantly greater, the structure model index in OA was significantly lower, and the surface density in RA was significantly greater. The RA bone tissues showed erosion and marked osteophyte formation. This study demonstrated that RA and OA have similar trends of overall microarchitectural degeneration in the femoral neck, despite marked erosion in RA bone and osteophyte formation in OA bone. However, we could not eliminate the possibility of local differences between RA and OA bone. The age-related bone loss in RA and OA was less severe than those of normal ageing and osteoporosis, suggesting a compensatory effect of the diseases to increase bone density.
26845700 A Feedback Loop between Inflammation and Zn Uptake. 2016 OBJECTIVE: Zinc (Zn) has major effects on the immune system and inflammation is associated with systemic Zn deficiency. The aim of this work was to investigate how inflammation modifies Zn metabolism at the cellular level. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation. Osteoarthritis (OA) synoviocytes were used as control. METHODS: Zn levels were measured in medium and inside cells by Induced Coupled Plasma-Mass Spectrometry (ICP-MS), in the presence of minute quantities of stable spike 70Zn isotope and the addition or not of the pro-inflammatory cytokines interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α). Gene expression of ZIP-8 importer, ZnT1 exporter and the homeostasis regulators metallothioneins (MTs) was evaluated after pre-exposure to cytokines, with or without exogenous Zn addition at increasing concentrations. IL-6 production was used as a marker of inflammation and measured by ELISA. RESULTS: Exposure to IL-17 and TNF-α enhanced expression of the Zn-importer ZIP-8, regardless of the concentration of Zn in the culture medium. In contrast, the expression of the Zn-exporter ZnT1 and of the MTs was primarily dependent on Zn levels. Addition of Zn also increased the production of IL-6, thus further stimulating the inflammatory response. CONCLUSION: IL-17/TNF-mediated inflammation enhanced the intracellular Zn uptake by synoviocytes, further increasing inflammation. These observations document the existence of a feedback loop between inflammation and Zn uptake. Based on these results, a mathematical model was developed to represent the cytokine-mediated Zn homeostasis alterations.
26151628 Role of Polymer Architecture on the Activity of Polymer-Protein Conjugates for the Treatme 2015 Aug 10 Polymers of similar molecular weights and chemical constitution but varying in their macromolecular architectures were conjugated to osteoprotegerin (OPG) to determine the effect of polymer topology on protein activity in vitro and in vivo. OPG is a protein that inhibits bone resorption by preventing the formation of mature osteoclasts from the osteoclast precursor cell. Accelerated bone loss disorders, such as osteoporosis, rheumatoid arthritis, and metastatic bone disease, occur as a result of increased osteoclastogenesis, leading to the severe weakening of the bone. OPG has shown promise as a treatment in bone disorders; however, it is rapidly cleared from circulation through rapid liver uptake, and frequent, high doses of the protein are necessary to achieve a therapeutic benefit. We aimed to improve the effectiveness of OPG by creating OPG-polymer bioconjugates, employing reversible addition-fragmentation chain transfer polymerization to create well-defined polymers with branching densities varying from linear, loosely branched to densely branched. Polymers with each of these architectures were conjugated to OPG using a "grafting-to" approach, and the bioconjugates were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The OPG-polymer bioconjugates showed retention of activity in vitro against osteoclasts, and each bioconjugate was shown to be nontoxic. Preliminary in vivo studies further supported the nontoxic characteristics of the bioconjugates, and measurement of the bone mineral density in rats 7 days post-treatment via peripheral quantitative computed tomography suggested a slight increase in bone mineral density after administration of the loosely branched OPG-polymer bioconjugate.
27174398 Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical 2017 Mar OBJECTIVES: To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. METHODS: We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). RESULTS: The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. CONCLUSIONS: Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates.
26517829 Combination of B cell biomarkers as independent predictors of response in patients with rh 2015 Nov OBJECTIVES: Identification of B cell biomarkers predictive of response prior to therapy with rituximab (RTX) and evaluation of the efficacy of long-term treatment in patients with rheumatoid arthritis (RA). METHODS: 302 RA patients failing one TNFi were treated with two applications of 1000 mg RTX (FIRST study). During the follow-up study (ReFIRST) the patients were treated for up to three more courses if they showed measurable clinical response but RA was still active. In a substudy on 154 RA patients peripheral B cell subsets were determined by flow cytometry before starting RTX. Rheumatoid factor (RF), RF-isotypes and anti-citrullinated protein antibodies (ACPA) were also measured. RESULTS: Based on multivariate analyses patients with positive RF and normal (>lower limit) levels of CD19⁺ B cells (RF⁺CD19⁺) showed better treatment effects compared to patients who had only one or none of those parameters. Considering the RF status of the patients, analysis of B cell subpopulations yielded a correlation between higher ER rates and "double negative" CD19+CD27⁻IgD⁻ B cells. Lowest ER rates were observed for RF negative patients in combination with low numbers of CD19⁺CD27⁻IgD⁻ B cells as independent risk factors, thus defining a group with lower responses. Conversely, higher CD19⁺CD27⁻IgD⁻ B cells identified a responder group within RF negative patients. CONCLUSIONS: The data of this large biomarker study suggest that beyond RF positivity, normal levels of CD19⁺ B cells together with increased CD19⁺CD27⁻IgD⁻ B cells predict response to RTX in RA, in particular when all parameters were present.
25642940 Inactivation of DAP12 in PMN inhibits TREM1-mediated activation in rheumatoid arthritis. 2015 Rheumatoid arthritis (RA) is an autoimmune disease characterized by dysregulated and chronic systemic inflammatory responses that affect the synovium, bone, and cartilage causing damage to extra-articular tissue. Innate immunity is the first line of defense against invading pathogens and assists in the initiation of adaptive immune responses. Polymorphonuclear cells (PMNs), which include neutrophils, are the largest population of white blood cells in peripheral blood and functionally produce their inflammatory effect through phagocytosis, cytokine production and natural killer-like cytotoxic activity. TREM1 (triggering receptor expressed by myeloid cells) is an inflammatory receptor in PMNs that signals through the use of the intracellular activating adaptor DAP12 to induce downstream signaling. After TREM crosslinking, DAP12's tyrosines in its ITAM motif get phosphorylated inducing the recruitment of Syk tyrosine kinases and eventual activation of PI3 kinases and ERK signaling pathways. While both TREM1 and DAP12 have been shown to be important activators of RA pathogenesis, their activity in PMNs or the importance of DAP12 as a possible therapeutic target have not been shown. Here we corroborate, using primary RA specimens, that isolated PMNs have an increased proportion of both TREM1 and DAP12 compared to normal healthy control isolated PMNs both at the protein and gene expression levels. This increased expression is highly functional with increased activation of ERK and MAPKs, secretion of IL-8 and RANTES and cytotoxicity of target cells. Importantly, based on our hypothesis of an imbalance of activating and inhibitory signaling in the pathogenesis of RA we demonstrate that inhibition of the DAP12 signaling pathway inactivates these important inflammatory cells.
26755797 Do RA or TNF inhibitors increase the risk of cervical neoplasia or of recurrence of previo 2016 Jul OBJECTIVES: To examine screening patterns and the risk of cervical neoplasia in women with rheumatoid arthritis (RA) treated or not with tumour necrosis factor inhibitors (TNFi). METHODS: We performed a nationwide register-based cohort study in Sweden of women with RA who started a first TNFi (n=9629), biologics-naive women with RA (n=34 984) and general population comparators (matched 1:10, n=300 331), followed up from 1999 to 2012. Outcomes were first cytology screening with normal outcome, first ever cervical intraepithelial neoplasia (CIN) grade 1, first ever CIN 2-3 or adenocarcinoma in situ and first ever invasive cervical cancer during follow-up. HRs were assessed through Cox regressions adjusted for age, educational level, prior cervical screens, comorbidities, marital status and prior hospitalisations. RESULTS: Biologic-naive women with RA had more screenings (HR 1.08, 95% CI 1.06 to 1.10), were at greater risk of CIN 1 (HR 1.53, 1.23 to 1.89) and CIN 2-3 (HR 1.39, 1.16 to 1.66), but not of invasive cervical cancer (HR 1.09, 0.71 to 1.65) compared with the general population. Patients who initiated TNFi therapy had similar screening patterns (HR 1.01, 0.98 to 1.05), were not at increased risk of CIN 1 (HR 1.23, 0.87 to 1.74), but were at increased risk of CIN 2-3 (HR 1.36, 1.01 to 1.82) and invasive cervical cancer (HR 2.10, 1.04 to 4.23) compared with biologics-naive women with RA. Estimates varied little with successive adjustments, but were attenuated/absent in sensitivity analyses restricted to 2006-2012 and a disease-modifying antirheumatic drugs-treated comparator. CONCLUSIONS: Women with RA in general are at elevated risk of cervical dysplasia. Compared with biologics-naive patients, women treated with TNFi are at increased risk of cervical cancer. Whether this increase is causally linked with TNFi could not be fully disentangled.
25536168 Assessment of the effectiveness of golimumab 50-mg and 100-mg regimens in patients with rh 2015 Jul OBJECTIVES: To assess the effectiveness of the golimumab (GLM) 50-mg and 100-mg regimens in patients with rheumatoid arthritis (RA) in daily practice. METHODS: We retrospectively analyzed RA patients who started GLM between September 2011 and July 2012. Patients were divided into three groups: a 50-mg group; a 50/100-mg group (had a dose increase to 100 mg); and a 100-mg group (started GLM at 100 mg). We assessed Disease Activity Score 28 (DAS28) and treatment continuation rate. Risk factors associated with time to discontinuation of the 50-mg regimen were determined with proportional hazards analysis. RESULTS: We analyzed 74 patients: 43 in the 50-mg group, 23 in the 50/100-mg group, and 8 in the 100-mg group. DAS28 improved from 4.0 ± 1.0, 4.8 ± 1.0, and 4.7 ± 1.9, respectively, at baseline to 2.4 ± 1.2, 3.3 ± 1.5, and 2.5 ± 0.7, respectively, at week 52. Treatment continuation rates at week 52 were 73.7%, 60.9%, and 87.5%, respectively. In the 50/100-mg group, the mean DAS28 improved significantly from 4.4 ± 1.2 before to 3.6 ± 1.3 12 weeks after the dose increase. Oral corticosteroid therapy ≥ 5 mg/day, previous use of two biologic agents, and DAS28 > 5.1 at initiation of GLM were significantly associated with discontinuation of the 50-mg regimen. CONCLUSIONS: Both GLM 50-mg and 100-mg regimens are effective in patients with RA in daily practice.
25403996 Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis. 2015 Aug Psoriasis is a prevalent autoimmune disease of the skin that causes significant psychological and physical disability. Tumor necrosis factor (TNF)-blocking agents have proven to be highly efficacious in the management of moderate-to-severe psoriasis. However, a significant percentage of patients do not respond to this treatment. Recently, variation at the PDE3A-SLCO1C1 (phosphodiesterase 3A-SoLute Carrier Organic anion transporter family member 1C1) locus has been robustly associated with anti-TNF response in rheumatoid arthritis. Using a cohort of 130 psoriasis patients treated with anti-TNF therapy, we sought to analyze the association of this locus with treatment response in psoriasis. We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (P=0.0031). Importantly, the allele that was previously associated with the lack of response to rheumatoid arthritis (G allele, single-nucleotide polymorphism rs3794271) was associated with a higher anti-TNF efficacy in psoriasis. The results of this study are an important step in the characterization of the pharmacogenetic profile associated with anti-TNF response in psoriasis.
27368035 Diffuse alveolar damage in a patient with rheumatoid arthritis under prolonged leflunomide 2016 Jun Patients with rheumatoid arthritis (RA) often have pulmonary involvement, and interstitial lung disease (ILD) is the primary manifestation, in which diffuse alveolar damage (DAD) is a rare histopathologic pattern. Leflunomide (LEF) is a frequently prescribed disease-modifying antirheumatic drug for treating RA. LEF-related ILD in the form of DAD has been reported in patients with RA, with the duration of LEF treatment before symptom onset ranging from 6 to 1204 days.We present a case of elderly woman with RA under prolonged LEF treatment for >9 years (3291 days), who had acute respiratory failure with the initial presentation of exertional dyspnea, fever, chills, and productive cough for 2 days. The histopathologic result of surgical lung biopsy was compatible with DAD. She was diagnosed as having LEF-related ILD, based on correlated clinical history, compatible histopathologic examination and excluding possible infection after extensive survey.Although the causative role of LEF cannot be confirmed, this case still hints that LEF-related DAD may occur even if LEF has been prescribed for a prolonged period.
24833784 Fertility in women with rheumatoid arthritis: influence of disease activity and medication 2015 Oct OBJECTIVES: Many female rheumatoid arthritis (RA) patients attempting to conceive have a time to pregnancy (TTP) of >12 months. During this period RA often cannot be treated optimally. We sought to identify clinical factors associated with prolonged TTP in female RA patients. METHODS: In a nationwide prospective cohort study on pregnancy in RA patients (PARA study), women were included preconceptionally or during the first trimester. Cox regression analysis was used to study the association of disease characteristics and medication use with TTP. RESULTS: TTP exceeded 12 months in 42% of 245 patients. Longer TTP was related to age, nulliparity, disease activity (DAS28), and preconception use of non-steroidal anti-inflammatory drugs (NSAIDs) and prednisone. These variables were independently associated with TTP, with HRs for occurrence of pregnancy of 0.96 (95% CI 0.92 to 1.00) per year of age, 0.52 (0.38 to 0.70) for nulliparity, 0.81 (0.71 to 0.93) per point increase in DAS28, 0.66 (0.46 to 0.94) for NSAIDs and 0.61 (0.45 to 0.83) for prednisone use. The impact of prednisone use was dose dependent, with significantly longer TTP when daily dose was >7.5 mg. Smoking, disease duration, rheumatoid factor, anti-citrullinated protein antibodies, past methotrexate use, and preconception sulfasalazine use did not prolong TTP. CONCLUSIONS: TTP in RA is longer if patients are older or nulliparous, have higher disease activity, use NSAIDs or use prednisone >7.5 mg daily. Preconception treatment strategies should aim at maximum suppression of disease activity, taking account of possible negative effects of NSAIDs use and higher prednisone doses.
26792597 Prevalence of hypothyroidism in rheumatoid arthritis and its correlation with disease acti 2017 Jan OBJECTIVES: To analyse the prevalence of hypothyroidism in rheumatoid arthritis (RA) patients and to elucidate its correlation with disease activity. METHODS: A total of 52 RA patients were enrolled in this study. All patients were assessed fully clinically and underwent routine laboratory investigation including thyroid function testing. RESULTS: Hypothyroidism (defined as having a TSH level >4.20 μIU/mL) was observed in 20/52 (38.4%). Erythrocyte sedimentation rates (ESR) were found significantly elevated in patients with hypothyroidism compared to those without (36.3 ± 24.2 vs. 24.6 ± 9.0 mm/h). Disease activity parameters such as DAS-28-ESR, tender joint count; VAS scores were also significantly higher in the former. A significant correlation with serum TSH levels was observed with ESR and DAS-28-ESR. CONCLUSION: Thyroid function test should be included in clinical evaluation of RA patients.