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ID PMID Title PublicationDate abstract
29504319 Anti-Arthritic Effect Of Thymoquinone In Comparison With Methotrexate On Pristane Induced 2018 Jan BACKGROUND: Rheumatoid arthritis inflammatory joint disease which is chronic in nature. Since long various researches are carried out to find the remedy of this disease but still a lot of work needed to be done. METHODS: This comparative study was performed from March to August 2013 at Postgraduate Medical Institute, Lahore. A total of thirty-two female Sprague-Dawley rats were randomly divided into four equal groups (n=8); group A was kept as healthy control, group B was kept as positive control, group C was treated with thymoquinone and group D was treated with methotrexate. Arthritis developed within two weeks in group B, group C and group D after giving a single shot of pristane intradermally. Treatment was started on day 15. At day 30 (time of dissection) paw weight and histopathological sections of ankle joints of all the animals were taken. RESULTS: The results shown significant rise in paw weight and score of histopathological parameters in group B, group C and group D when compared with healthy control rats. Thymoquinone and methotrexate treated groups shown reduction in paw weight and score of histopathological parameters when compared to positive control rats with p-value 0.001each. The difference between groups C and D was insignificant (p-value 0.062). CONCLUSIONS: Study results supported the anti-inflammatory and disease modifying activities of thymoquinone as it significantly reduces both paw weight and histological parameters of joint inflammation.
26457478 Progression of palindromic rheumatism to juvenile idiopathic arthritis in a Japanese girl 2018 Mar Palindromic rheumatism (PR), a rare disease in children, is characterized by recurrent arthritis or periarthritis and asymptomatic interval. We report evolution of PR to juvenile idiopathic arthritis in a Japanese girl with heterozygous complex L110P-E148Q allele of MEFV gene. Poor response to colchicine alone suggests that the MEFV substitution could increase the susceptibility to arthritis rather than caused arthritis associated with atypical Familial Mediterranean Fever. Weekly methotrexate is a choice for such cases.
27604908 New inflammatory markers in early rheumatoid arthritis. 2018 Mar BACKGROUND: Rheumatoid arthritis (RA) is the most common chronic inflammatory disorder and is associated with progressive destruction of synovial joints and physical disability. Therapies with known benefits include disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, as well as more recent biologic agents, such as tumor necrosis factor inhibitors (anti-TNF therapy). METHOD: This was a retrospective study, which included 205 RA and 112 early RA (ERA) patients from the Rheumatology Clinic at Gaziantep University School of Medicine Research Center as well as 104 healthy controls. RESULTS: The mean neutrophil to lymphocyte ratio (NLR) was found to be 3.15 ± 2.64 in the patient group and 2.03 ± 0.94 in the control group. The mean platelet to lymphocyte ratio (PLR) was 162.39 ± 107.76 in the patient group and 131.23 ± 48.09 in the control group. There was a significant difference in both the NLR and PLR between the patient and control groups (both p < 0.01). There was a significant difference in both the NLR and PLR between patients with active disease and remission (both p < 0.001) in RA, including anti-TNF therapy and DMARDs groups. There was a significant difference in NLR (p = 0.001) but not in PLR (p = 0.051) between active disease and remission in ERA. CONCLUSION: The results of the present study suggest that the NLR may be considered a useful marker of disease activity in RA and one that can aid the diagnosis of ERA. The PLR can be used in the assessment of disease activity in RA patients undergoing anti-TNF therapy but is not suitable for diagnosing ERA.
30128641 Efficacy of Monotherapy with Biologics and JAK Inhibitors for the Treatment of Rheumatoid 2018 Oct Despite recommendations suggesting that biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) should be used in combination with methotrexate in the treatment of rheumatoid arthritis (RA), up to one-third of patients with RA are treated with monotherapy. The objective of the systematic literature review reported here was to evaluate the clinical evidence regarding the efficacy of b/tsDMARDs as monotherapy in the treatment of RA. MEDLINE(®), Embase(®), and the Cochrane Central Trials Register (to April 11, 2017) and the American College of Rheumatology and European League Against Rheumatism conference proceedings (2010-2016) were searched for randomized controlled trials evaluating the efficacy of b/tsDMARDs as monotherapy for RA in adults. Forty-four monotherapy studies of abatacept, adalimumab, baricitinib, certolizumab pegol, etanercept, sarilumab, sirukumab, tocilizumab, and tofacitinib reported in 71 publications were identified. Tocilizumab had the most studies (14), followed by etanercept (10) and adalimumab (9). These b/tsDMARDs were consistently shown to be efficacious treatments, regardless of whether patients were intolerant of or had never used conventional synthetic (cs) DMARDs. However, better treatment outcomes were usually achieved with combination therapy, and this was observed for all b/tsDMARDs assessed by this review. Only a few studies provided a head-to-head comparison between b/tsDMARD treatments or between b/tsDMARD monotherapy and combination therapy, and as many were initial RA treatments they were not generalizable to usual care. In conclusion, evidence from randomized trials suggests that the b/tsDMARDs studied are effective as monotherapy. In general, some patient responses seem better with combination therapy and the durability of monotherapy is less than combination therapy. There is, however, a need for longer-term head-to-head trials to establish positioning of these interventions in the treatment algorithm for RA. FUNDING: Pfizer.Plain Language Summary: Plain language summary available on the journal website.
29057725 Prevalence of Nasal Colonization with Staphylococcus aureus in Patients with Rheumatoid Ar 2018 Apr 20 Objetive: Patients with Rheumatoid Arthritis (RA) and nasal carriers of Staphylococcus aureus have an increased risk of developing infections caused by S. aureus. Our objective was to determine the prevalence of S. aureus nasal colonization in patients with RA and its relationship to RA treatments. METHODS: Two hundred and seven patients with RA and 37 healthy controls were prospectively included in a cross-sectional study. A nasal secretion sample was collected by swab from both anterior nostrils and was referred to the hospital's microbiology department for culturing. RESULTS: The mean age of the patients (168 women, 78%) was 61 ± 12 years old. The mean disease duration was 13 ± 10 years. Seventy-six percent of the patients were positive for Rheumatoid Factor (RF), and 71% were positive for Anti-citrullinated Peptides Antibodies (ACPA). Seventy percent had joint erosions. The mean DAS28 was 3.1 ± 2.2. S. aureus nasal colonization was found in 36% of the RA patients and 35% of the controls. Three patients and no controls were resistant to oxacilin/ mupirocin. The patients who were positive for ACPA had a higher prevalence of S. aureus colonization (43% vs. 17%; p < 0.05). The colonization prevalence in the patients treated with glucocorticoids was 32% (n: 133); methotrexate and/or leflunomide, 37% (n: 167); anti-TNF agents, 46% (n: 54), p < 0.05 versus patients not treated with anti-TNF agents; rituximab, 22% (n: 18); tocilizumab, 39% (n: 18). CONCLUSION: The prevalence of S. aureus nasal colonization in patients with RA does not appear to be greater than that of the general population. Anti-TNF agents might confer a higher prevalence of colonization.
29380036 TYMS polymorphisms and responsiveness to or toxicity of methotrexate in rheumatoid arthrit 2018 Nov OBJECTIVE: The aim of this study was to investigate whether the thymidylate synthase (TYMS) 2R/3R and 6 bp I/D polymorphisms can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: We conducted a meta-analysis of studies on the association between the TYMS 2R/3R and 6 bp I/D polymorphisms and non-responsiveness to or toxicity of MTX in RA patients. RESULTS: A total of 11 studies involving 1613 patients were considered. Meta-analysis showed no association between the TYMS 2R/3R 3R allele and non-responsiveness to MTX therapy (odds ratio [OR] = 1.087, confidence interval [CI] = 0.682-1.731, p = 0.726). The meta-analysis indicated that there was no association between the TYMS 6 bp I/D D allele and non-responsiveness to MTX therapy (OR = 0.688, 95% CI = 0.281-1.683, p = 0.413). Meta-analysis revealed that the TYMS 2R/3R polymorphism was not associated with MTX toxicity, except for in a co-dominant model, and the TYMS 6 bp I/D polymorphism was not associated with MTX toxicity in all genetic models. CONCLUSIONS: This meta-analysis demonstrates that the TYMS 2R/3R and 6 bp I/D polymorphisms may not be associated with non-responsiveness to or toxicity of MTX therapy in RA patients.
30146748 CD39 positive regulatory T cell frequency as a biomarker of treatment response to methotre 2018 Aug AIM: Nearly one-third of patients with rheumatoid arthritis (RA) do not respond to Methotrexate (MTX), the first-line therapy in RA. CD39, an ectonucleotidase highly expressed on regulatory T cells (Tregs), is responsible for production of adenosine, an important anti-inflammatory mediator of MTX action. Higher expression of CD39 on Tregs improves their suppressive capacity. Therefore, we aimed to study the role of CD39(+) Treg frequency as a biomarker for MTX treatment response in RA. METHODS: Patients with active RA who were naive to disease-modifying anti-rheumatic drugs were enrolled. Frequencies of CD39(+) Tregs (CD4(+) CD25(+) FoxP3(+) CD39(+) cells) and CD4(+) CD25(+) CD39(+) cells were determined by flow cytometry in peripheral blood before the start of therapy. After 4 months of MTX monotherapy, patients were classified into responders (European League Against Rheumatism [EULAR] good/moderate response) and non-responders (EULAR no response). All samples were genotyped for single nucleotide polymorphisms (SNPs) rs11188513 and rs7071836 in the ENTPD1 (CD39) gene. RESULTS: After 4 months of MTX monotherapy, 54 patients were classified as responders and 16 as non-responders. The baseline CD39(+) Treg and CD4(+) CD25(+) CD39(+) cell frequencies were significantly higher in the responder group as compared with the non-responder group (P < 0.05 and P < 0.01, respectively). AA genotype at SNP rs7071836 was associated with poor response to MTX (P < 0.05; odds ratio = 5.67; 95% CI = 1.12-28.75). CONCLUSION: Higher frequencies of CD39(+) Tregs and CD4(+) CD25(+) CD39(+) cells in the peripheral blood are associated with response to MTX in RA and hence, these could be considered as potential biomarkers for prediction of response to MTX treatment.
29998824 Prevention of the progressive biochemical cartilage destruction under methotrexate therapy 2019 Mar OBJECTIVES: The aim of the study was to investigate biochemical cartilage composition under methotrexate (MTX) therapy and to intra-individually assess the impact of inflammation severity on cartilage composition by using dGEMRIC MRI in patients with early rheumatoid arthritis (eRA). METHODS: dGEMRIC of MCP joints of the index and middle finger of 28 patients from the AthroMark cohort were examined prior to MTX-therapy as well as after 3 and 6 month. OMERACT RA MRI score and clinical parameters (CRP and DAS28) were registered at any time point. Each patient's second and third MCP joints were dichotomised into the joint with more severe synovitis versus the joint with less severe synovitis according to the RAMRIS synovitis subscore. RESULTS: MCP joints with more severe synovitis ('bad joints') demonstrated significantly lower dGEMRIC values compared to MCP joints with less severe synovitis ('good joints') at time-points 0 and 3 months (p=0.002; p=0.019, respectively). After 6 months of MTX therapy no significant difference of dGEMRIC index was found between good and bad joint (p=0.086). CONCLUSIONS: Under MTX therapy, biochemical cartilage integrity remains stable; no further cartilage destruction occurred if patients were treated early in the course of the disease. In addition, six months of MTX therapy triggered an alignment of dGEMRIC index of MCP joints with initially severe synovitis and less severe synovitis in an intra-individual assessment. This underlines the importance of an early treatment in eRA to reduce further cartilage damage of the inflamed joints.
29341936 Rheumatic manifestations among cancer patients treated with immune checkpoint inhibitors. 2018 Mar BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. AIM: To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts. RESULTS: Rheumatic manifestations were encountered in 14 of 400 patients (3.5%) who had received immunotherapy between January 1st 2013 and April 30th, 2017. The most common rheumatic manifestation was inflammatory arthritis (85%) for which a third (4/11) had a clear cut predisposing factor such as a personal or family history of psoriasis, a prior episode of uveitis or ACPA positivity. Pulmonary sarcoidosis and biopsy-proven eosinophilic fasciitis were diagnosed in two additional patients. Treatment with NSAIDS was mostly unsuccessful while steroid therapy was beneficial in doses ≥20 mg/d. Methotrexate enabled steroid tapering without an excess of side effects or tumor progression in the short follow-up available. Overall, rheumatic manifestations tended to occur later in the course of immunotherapy as compared to other iAE. CONCLUSIONS: Our findings underscore that rheumatic iAE are part of the side effect profile of ICIs and require heightened awareness as these therapies are becoming the standard of care for various malignancies. We show that these appear later in the course of iAEs and respond preferentially to high dose steroids. MTX appears effective as a steroid sparing agent.
30075744 Serum metabolomic profiling predicts synovial gene expression in rheumatoid arthritis. 2018 Aug 3 BACKGROUND: Metabolomics is an emerging field of biomedical research that may offer a better understanding of the mechanisms of underlying conditions including inflammatory arthritis. Perturbations caused by inflamed synovial tissue can lead to correlated changes in concentrations of certain metabolites in the synovium and thereby function as potential biomarkers in blood. Here, we explore the hypothesis of whether characterization of patients' metabolomic profiles in blood, utilizing (1)H-nuclear magnetic resonance (NMR), predicts synovial marker profiling in rheumatoid arthritis (RA). METHODS: Nineteen active, seropositive patients with RA, on concomitant methotrexate, were studied. One of the involved joints was a knee or a wrist appropriate for arthroscopy. A Bruker Avance 700 MHz spectrometer was used to acquire NMR spectra of serum samples. Gene expression in synovial tissue obtained by arthroscopy was analyzed by real-time PCR. Data processing and statistical analysis were performed in Python and SPSS. RESULTS: Analysis of the relationships between each synovial marker-metabolite pair using linear regression and controlling for age and gender revealed significant clustering within the data. We observed an association of serine/glycine/phenylalanine metabolism and aminoacyl-tRNA biosynthesis with lymphoid cell gene signature. Alanine/aspartate/glutamate metabolism and choline-derived metabolites correlated with TNF-α synovial expression. Circulating ketone bodies were associated with gene expression of synovial metalloproteinases. Discriminant analysis identified serum metabolites that classified patients according to their synovial marker levels. CONCLUSION: The relationship between serum metabolite profiles and synovial biomarker profiling suggests that NMR may be a promising tool for predicting specific pathogenic pathways in the inflamed synovium of patients with RA.
30112846 Intravenous Infusion of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Rheumatoid 2018 Sep Based on immunomodulatory actions of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), in vitro or preclinical studies of hUCB-MSCs have been conducted extensively in rheumatoid arthritis (RA). However, few human trials have investigated the outcomes of hUCB-MSC infusions. The CURE-iv trial was a phase I, uncontrolled, open label trial for RA patients with moderate disease activity despite treatment with methotrexate. The patients received a single intravenous infusion of 2.5 × 10(7) , 5 × 10(7) , or 1 × 10(8) cells of hUCB-MSCs for 30 minutes, three patients in each cluster, with an increment of cell numbers when there was no dose-limited adverse event. Clinical and safety assessments were performed during the study period, and serum cytokines were measured at baseline and 24 hours after the infusion. Out of 11 screened RA patients, 9 were enrolled. The participants were predominantly female (78%) and the mean age was 57.4 years. The mean disease duration was 9.5 years, and baseline 28-joint disease activity score (DAS28; using erythrocyte sedimentation rate) was 4.53. There was no major toxicity in all clusters up to 4 weeks after the infusion. Serum erythrocyte sedimentation rate changes at 4 weeks (n = 9) were -7.9 ± 10.4 (p = .0517) and DAS28 changes were -1.60 ± 1.57 (p = .0159). Reduced levels of IL-1β, IL-6, IL-8, and TNF-α at 24 hours were observed in the cluster infused with 1 × 10(8) MSCs. This phase Ia hUCB-MSC infusion trial for established RA patients revealed no short-term safety concerns. Stem Cells Translational Medicine 2018.
30418117 The VICM biomarker is released from activated macrophages and inhibited by anti-GM-CSFRα- 2019 Jan OBJECTIVES: Macrophages possess widespread pro-inflammatory, destructive, and remodelling capabilities that can critically contribute to acute and chronic diseases, such as rheumatoid arthritis (RA). Continuous monitoring and measurement of selective counteraction of macrophage activity in patients require a sensitivity and non-invasive marker. We characterised the VICM (citrullinated and MMP degraded vimentin fragment) biomarker by investigating the release from in vitro activated macrophages and by monitoring the change in serum levels after treatment with the anti-GM-CSFRα-mAb (mavrilimumab). METHODS: Peripheral blood mononuclear cells were isolated, and lipopolysaccharide (LPS) was used to activate the macrophages and calcium chloride (CaCl2) was used to facilitate the citrullination process of vimentin. Supernatants, cell lysates, was collected and analysed by ELISA, and western blotting. RA patients were treated with mavrilimumab+methotrexate or methotrexate alone in a phase 2b study (NCT01706926) once every two weeks for 24 weeks. Serum levels of VICM were measured at baseline and multiple time points post-treatment. In addition, whole blood expression of peptidylarginine deiminase-2 (PAD-2) and matrix metalloproteinase-9 (MMP-9) transcripts were tested by quantitative reverse transcriptase PCR assays at day 0 and day 169 post-treatment. RESULTS: VICM levels were significantly higher at day 5 and 8 in supernatants of activated macrophages compared to controls (p<0.01), which was confirmed by Western blot. In RA patients, VICM correlated with disease activity (DAS28), modified total sharp score (mTSS), joint space narrowing (JSN), joint erosions and CRP at baseline. VICM was dose-dependently and significantly (p<0.01) inhibited by mavrilimumab. This suppression of VICM serum levels was supported by a decreased expression of PAD2 and MMP9 transcripts in patients treated with mavrilimumab. CONCLUSIONS: These data verified that VICM is released by activated macrophages. Treatment of RA patients with mavrilimumab significantly reduced release of VICM and peptidylarginine deiminases-2 (PAD-2) gene expression indicating that mavrilimumab indeed is targeting activated macrophages and that VICM may be a novel blood-based marker of anti-GM-CSF response.
29713747 The prognostic value of positron emission tomography/computed tomography in rheumatoid art 2018 Sep Recently, methotrexate-associated lymphoproliferative disorders (MTX-LPDs) in rheumatoid arthritis (RA) have been found to commonly occur in association with iatrogenic immunodeficiency. Several factors have been reported to be related to the prognosis. We herein investigate the efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting the prognosis of MTX-LPD. We performed a retrospective analysis of the clinical features, characteristics, and outcomes of 18 patients with MTX-LPDs who were treated from 2004 to 2015. All of the patients were diagnosed with MTX-LPD based on the histological examination of biopsy specimens. Spontaneous regression was detected after the cessation of MTX in 5 of 18 cases (28%). The maximum standardized uptake value (SUVmax) of the FDG uptake on PET/CT was significantly lower, and the maximum size of the LPD-associated tumor was significantly smaller among the patients who showed spontaneous regression (p = 0.01, p = 0.04, respectively). Both the SUVmax and the maximum tumor size were related to better overall survival (p = 0.02, p = 0.04, respectively). Thus, PET/CT can be used to predict spontaneous regression and the prognosis at the diagnosis of MTX/LPD. Cases that showed spontaneous regression never relapsed during the follow-up period, despite the usage of several anti-rheumatoid arthritis drugs, including biological agents. The early detection of LPDs and the early cessation of MTX are important for the management of RA patients. An evaluation by F-FDG-PET/CT can be useful for predicting spontaneous regression and the prognosis.
30227223 Circadian rhythms and rheumatoid arthritis. 2019 May Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities, embracing sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of pro-inflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night. In chronic inflammatory conditions such as RA, the amplitude of the circadian rhythm of the anti-inflammatory endogenous cortisol availability is not increased as expected and requested, which indicate a reduced night cortisol secretion under the adrenal chronic stress induced by the disease. Therefore, the prevention/treatment of the immune cell night hyperactivity, with related flare of cytokine synthesis and morning RA clinical symptoms, has been shown more effective when the availability of the exogenous glucocorticoids is obtained in the middle of the night (night release). The impressive positive results observed in RA patients treated with modified-night release prednisone with a low-dose chronotherapy, seem applicable even for other agents such as conventional NSAIDs and DMARDs, including the positive experimental and clinical results obtained by the night time daily administration of methotrexate. Interestingly, a very recent study showed that methotrexate upregulates important cell circadian genes, resulting in induction of apoptosis in synovial fibroblasts. The link between the circadian rhythms of the disease and the chronotherapy of RA is promising.
30168274 Influence of methotrexate on gastrointestinal symptoms in patients with rheumatoid arthrit 2019 Feb AIM: This study aimed to determine the influence of methotrexate (MTX) on gastrointestinal (GI) symptoms in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study examined 529 consecutive patients with RA receiving oral MTX in our department between April 1 and September 30, 2017. GI symptoms were evaluated by the Gastrointestinal Symptom Rating Scale (GSRS); a score of ≥2 was considered "symptomatic." Prevalence of GI symptoms was compared between patients receiving ≤8 mg/wk (low-dose) vs >8 mg/wk (high-dose) of MTX. RESULTS: Of our study population, 313 (59%) received low-dose MTX at a median (interquartile range) dose of 6 (6-8) mg/wk, whereas 216 (41%) received high-dose MTX at a median dose of 12 (10-12) mg/wk. Relative to the low-dose MTX group, the high-dose MTX group exhibited a higher prevalence of reflux (32% vs 24%, P = 0.043) and abdominal pain (28% vs 18%, P = 0.007). There was no significant group-dependent difference in the prevalence of indigestion, diarrhea or constipation. Multivariate logistic regression analysis revealed that high-dose MTX (>8 mg/wk) was independently associated with reflux (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.07-2.43) and abdominal pain (OR: 1.60, 95% CI: 1.04-2.43), and that the ORs for reflux and abdominal pain among those receiving high-dose MTX (>8 mg/wk) were similar to those using nonsteroidal anti-inflammatory drugs. CONCLUSION: High-dose MTX is independently associated with the prevalence of upper GI symptoms in Japanese patients with RA.
30411174 Should a patient with rheumatoid arthritis be a kidney donor? 2019 Jan We cared for a woman with sero-positive rheumatoid arthritis (RA), in clinical remission on oral methotrexate (MTX) and hydroxychloroquine, who wished to donate a kidney to a brother with end-stage renal disease (ESRD). We could find scant literature about this unusual clinical circumstance, and therefore review pertinent aspects of renal disease in RA, perioperative medical management, maintenance of disease remission, outcomes for RA patients who have donated kidneys, and relevant ethical issues. Renal complications in RA are not uncommon, with as many as 50% of patients at risk of reduced eGFR. This reflects anti-rheumatic and analgetic medication use (non-steroidal anti-inflammatory drugs, acetaminophen, DMARDs [cyclosporine and, historically, D-penicillamine and gold compounds], and others), glomerulitis, interstitial nephritis, complicating Sjogren's syndrome, vasculitis, or amyloidosis, and/or emergence of an "overlap" syndrome or other rheumatic disorder. The literature suggests that MTX need not be interrupted for surgery. The risk of perioperative infection to our patient would be low and remission should be sustained. We are aware of one study of six patients with RA who donated kidneys; they experienced no complications, ESRD, or deaths after a median follow-up of 8.2 years. Our ethical responsibilities are to balance patient autonomy of decision-making while assuring clinical beneficence and minimizing potential maleficence. Our perspective was that it would not be unreasonable to support this patient donating a kidney if, when fully informed, that remained her wish.
29859543 Accelerated subcutaneous nodulosis in patients with rheumatoid arthritis treated with toci 2018 Jun 3 BACKGROUND: Tocilizumab is a monoclonal antibody directed against the interleukin-6 receptor, which is approved for the treatment of moderate-to-severe rheumatoid arthritis. Authors have found that it prevents lung and subcutaneous nodulosis in patients with rheumatoid arthritis but, to the best of our knowledge, there are no data concerning the acceleration of subcutaneous nodulosis during tocilizumab therapy. CASE PRESENTATION: We report for the first time a small case series of five patients with rheumatoid arthritis: a 46-year-old white woman, a 70-year-old white woman, a 63-year-old white woman, a 69-year-old white man, and a 72-year-old white woman (mean age 64 ± 10.6 years); they experienced worsening subcutaneous nodulosis during treatment with intravenously administered tocilizumab. Four of the five patients were positive for rheumatoid factor and five for anti-citrullinated peptide antibodies. All of the patients had previously been treated with various conventional and biological drugs; at the time of our observation, three were taking methotrexate, two hydroxychloroquine, and four were taking prednisone. Tocilizumab 8 mg/kg was administered intravenously every 4 weeks for a mean of 43.4 ± 32.4 months, and led to good disease control in three cases. All of the patients had a history of subcutaneous nodulosis, which considerably worsened during tocilizumab treatment, with the development of new nodules on their fingers, elbows, or in the inframammary fold, tending to ulcerate. The management of this medical event included discontinuation of methotrexate, the administration of steroids, the addition of hydroxychloroquine or colchicine, the use of antibiotics, and surgery. However, neither pharmacological nor surgical treatment was completely effective, as the nodules tended to recur and increased in number and size. CONCLUSIONS: To the best of our knowledge, this is the first report describing accelerated subcutaneous nodulosis in a small case series of patients with rheumatoid arthritis treated with tocilizumab.
30246572 The time-sequential changes of risk factors for adult T-cell leukemia development in human 2019 Sep Objective: This study aimed to investigate the time-sequential changes of risk factors for adult T-cell leukemia (ATL) development in human T-cell leukemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Methods: HTLV-1 infection was screened using particle agglutination assay and confirmed via western blotting in 365 RA patients. Twenty-three HTLV-1-positive RA patients were included in the study cohort. Blood samples were obtained from these patients at each observation time point. The values of HTLV-1 proviral load (PVL) and serum soluble IL-2 receptor (sIL2-R), which are risk factors for ATL development, were measured using real-time PCR and enzyme immunoassay, respectively. Results: The study cohort comprised 79 person-years. The median HTLV-1 PVL and sIL2-R values of the HTLV-1-positive RA patients were 0.44 copies per 100 white blood cells (WBCs) and 406 U/mL, respectively. Three HTLV-1-positive RA patients showed a high PVL value. No remarkable changes were observed in the PVL and sIL2-R values during the observation period. However, one elderly HTLV-1-positive RA patient who had a high PVL value developed ATL during treatment with methotrexate and infliximab. Conclusion: A thorough clinical assessment of the risk factors for ATL development may be necessary in daily clinical practice for RA patients in HTLV-1-endemic areas in Japan.
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.
29745885 Explorative analyses of protein biomarkers in patients with early rheumatoid arthritis ach 2018 Nov OBJECTIVES: Previously, we identified networks of co-expressed genes related to achieving sustained drug-free remission (sDFR). The aim of the present exploratory analysis was to identify inflammatory proteins associated with achieving sDFR and their enriched biological pathways, and compare these pathways with those found in the previous transcriptomic analyses. METHODS: Serum samples were used from 60 patients who participated in the U-Act-Early trial and were treated-to-target with tocilizumab plus methotrexate, or tocilizumab or methotrexate; 37 achieved sDFR (≥3 months drug-free) and 23 did not (controls). Luminex® multi-analyte profiling (xMAP)® was used to measure 85 proteins. Partial least square discriminant analyses (PLSDA) identified proteins associated with achieving sDFR within each strategy arm, which were thereafter used for pathway analyses. RESULTS: PLSDA identified 9, 14 and 13 relevant proteins in the tocilizumab plus methotrexate, tocilizumab and methotrexate arm, respectively and pathway analyses thereafter identified respectively 49, 88 and 117 significantly enriched gene ontology (GO) terms. When comparing these terms with those previously found in the transcriptomic analyses, corresponding pathways were related in the tocilizumab arm to activity of leukocytes; in the methotrexate arm to response of stimuli and regulation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. In the tocilizumab plus methotrexate arm, no corresponding enriched pathways were found. CONCLUSIONS: Multiple proteins were associated with achieving sDFR and several biological pathways corresponded, mainly in the methotrexate arm, with our previous transcriptomic findings potentially providing further insights into gene expression and protein translation in newly diagnosed RA patients.