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ID PMID Title PublicationDate abstract
31410787 Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthriti 2019 Dec INTRODUCTION: Peficitinib is a novel orally bioavailable, once-daily Janus kinase (JAK) inhibitor approved in Japan for the treatment of rheumatoid arthritis (RA). This 2-year extension study of two global phase IIb trials investigated the long-term safety and effectiveness of peficitinib. METHODS: All eligible patients with moderate-to-severe RA including patients in the placebo group who participated in one of two global phase IIb trials ('with methotrexate' or 'without methotrexate') were included in this 2-year open-label extension study and were converted to peficitinib 100 mg once daily. The primary objective was to evaluate an additional 2 years of safety by assessing treatment-emergent adverse events (AEs) and clinical laboratory evaluations for 105 weeks. Evaluation of an additional 2 years of effectiveness using American College of Rheumatology (ACR) 20/50/70 responses was the exploratory objective. RESULTS: Overall, 611 patients were enrolled in the extension study: 319 (52.2%) patients completed the study and 292 (48%) discontinued treatment, including for withdrawal of patient consent (n = 96), failure to achieve low disease activity (n = 62), and AE not including death (n = 41). AEs were reported in 463 (76%) patients. The most common AEs (per 100 patient-years) were upper respiratory tract infections (9.9) and urinary tract infections (7.2). Serious AEs were reported in 80 (13%) patients, with incidences per 100 patient-years of serious infections 2.7, herpes zoster 1.5 (including one herpes zoster ophthalmic), and malignancies 0.6 (most frequently basal cell carcinoma). At week 105, 269 (44%) patients demonstrated an ACR20 response relative to their respective phase IIb trial baselines. CONCLUSION: Among 319 patients who completed this 2-year extension of two global phase IIb studies, peficitinib 100 mg once daily demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01711814. Registered 19 October 2012. FUNDING: Astellas Pharma Global Development, Inc.
31068560 [Sarcoidosis-lymphoma syndrome showing abnormal FDG uptake in lymph nodes and muscles upon 2019 A 65-year-old woman was diagnosed with rheumatoid arthritis in 2010 and was treated with methotrexate (MTX). In 2012, she was diagnosed with sarcoidosis and underwent a follow-up therapy for mild peripheral neuropathy due to neurosarcoidosis. In 2018, she experienced primary splenic diffuse large B-cell lymphoma (DLBCL) and was diagnosed with sarcoidosis-lymphoma syndrome (SLS). MTX was discontinued, and six cycles of rituximab were administered combined with chemotherapy. Positron emission tomography combined with computed tomography performed 18 weeks after the last cycle of chemotherapy showed new abnormal fluoro-2-deoxy-D-glucose (FDG) uptake in the mediastinal and hilar lymph nodes and skeletal muscles. Sarcoidosis was suspected because of increased serum angiotensin-converting enzyme levels and magnetic resonance imaging findings in the lower limb muscles. However, pathological findings of DLBCL and sarcoidosis were not confirmed in the hilar lymph node biopsy. Therefore, malignant lymphoma can be distinguished from sarcoidosis using abnormal FDG uptake after chemotherapy for SLS.
31750337 Methotrexate-related lymphoproliferative disorders in the liver: Case presentation and min 2019 Nov 6 BACKGROUND: Immunosuppression is effective in treating a number of diseases, but adverse effects such as bone marrow suppression, infection, and oncogenesis are of concern. Methotrexate is a key immunosuppressant used to treat rheumatoid arthritis. Although it is effective for many patients, various side effects have been reported, one of the most serious being methotrexate-related lymphoproliferative disorder. While this may occur in various organs, liver involvement is rare. Information on these liver lesions, including clinical characteristics, course, and imaging studies, has not been summarized to date. CASE SUMMARY: We present a case of 70-year-old woman presented with a 2-wk history of fever and abdominal pain. She had had rheumatoid arthritis for 5 years and was being treated with medication including methotrexate. Contrast-enhanced computed tomography revealed multiple low density tumors in the liver and the histological analyses showed significant proliferation of lymphocytes in masses that were positive on immunohistochemical staining for CD3, CD4, CD8, and CD79a but negative for CD20 and CD56. Staining for Epstein-Barr virus-encoded RNA was negative. And based on these findings, the liver tumors were diagnosed as Methotrexate-related lymphoproliferative disorders. A time-dependent disappearance of the liver tumors after stopping methotrexate supported the diagnoses. CONCLUSION: The information obtained from our case and a review of 9 additional cases reported thus far assist physicians who may face the challenge of diagnosing and managing this disorder.
31168413 Low rates of radiographic progression of structural joint damage over 2 years of baricitin 2019 OBJECTIVES: To evaluate radiographic progression of structural joint damage over 2 years in patients with rheumatoid arthritis from baricitinib clinical trials who were disease-modifying antirheumatic drug (DMARD)-naïve or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR). METHODS: Patients had completed one of three phase III studies and entered a long-term extension (LTE) study, continuing on the same baricitinib dose as at originating study completion. At 52 weeks, DMARD-naïve patients receiving methotrexate (MTX) or combination therapy (baricitinib 4 mg+MTX) were switched to baricitinib 4 mg monotherapy (±MTX per investigator opinion); MTX-IR patients receiving adalimumab were switched to baricitinib 4 mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo were switched to baricitinib 4 mg on background csDMARD. Radiographs at baseline, year 1 and year 2 were scored using the van der Heijde modified Total Sharp Score. Linear extrapolation was used for missing data. RESULTS: Of 2573 randomised patients, 2125 (82.6%) entered the LTE, of whom 1893 (89.1%) entered this analysis. At year 2, progression was significantly lower with initial baricitinib (monotherapy or combination therapy) versus initial MTX in DMARD-naïve patients (proportion with non-progression defined by ≤smallest detectable change (SDC): 87.3% baricitinib 4 mg+MTX; 70.6% MTX; p≤ 0.001). In MTX-IR patients, progression with initial baricitinib was significantly lower than with initial placebo and similar to initial adalimumab (≤SDC: 82.7% baricitinib 4 mg; 83.5% adalimumab; 70.6% placebo; p≤0.001). In csDMARD-IR patients, significant benefit was seen with baricitinib 4 mg (≤SDC: 87.2% vs 73.2% placebo; p≤0.01). CONCLUSIONS: Treatment with once-daily baricitinib resulted in low rates of radiographic progression for up to 2 years.
31849542 Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc 2019 BACKGROUND: In rheumatoid arthritis (RA), little is known about clinical responses to treatment as predictors of patient-reported outcome (PRO) changes. In this post hoc analysis, we examined the relationship between clinical outcomes at week 12 and PRO changes at week 24 in patients with RA. METHODS: In an open-label study, Latin American patients with moderate-to-severe RA and an inadequate response to methotrexate (MTX) were randomized to receive etanercept 50 mg/week plus MTX (ETN+MTX; n=281) or an additional conventional disease-modifying anti-rheumatic drug (DMARD) plus MTX (DMARD+MTX; n=142) for 24 weeks. The PROs included Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form (SF-36), Physician and Patient Global Assessment scores (PGA, PtGA), Physician and Patient Satisfaction, and an activity impairment assessment. PRO changes at week 24 were calculated by week-12 improvements using the American College of Rheumatology criteria (ACR <20, ≥20 to <50, ≥50 to <70, and ≥70) and the 28-joint Disease Activity Scores (DAS28 ≥3.2, ≥2.6 to <3.2, and <2.6). Observed-cases data were analyzed using an ANCOVA model with linear contrast, adjusted for baseline PRO and ACR/DAS28 values. RESULTS: For both ETN+MTX- and DMARD+MTX-treated patients, there was a significant linear trend between week-12 changes in ACR and DAS28 responses and week-24 changes in HAQ-DI (P<0.001 for all), with numerical improvements generally favoring ETN+MTX. Similar relationships were observed for SF-36, PGA, PtGA, Physician Satisfaction, Patient Satisfaction, and activity impairment. CONCLUSIONS: In patients with RA, clinical response after 12 weeks of treatment with ETN+MTX or DMARD+MTX could be a predictor of week-24 response for several PROs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00848354.
30721326 Correction to: On-drug and drug-free remission by baseline symptom duration: abatacept wit 2019 May The article "On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis", written by Vivian P.Bykerk, was originally published Online First without open access.
31489783 Risk of cutaneous herpes zoster in patients with spondyloarthritis treated with convention 2020 Feb OBJECTIVES: To investigate the risk of cutaneous herpes zoster (HZ) in spondyloarthritis (SpA) compared with that in rheumatoid arthritis (RA), and in disease-modifying antirheumatic drugs (DMARDs) used in SpA. METHOD: A total of 727 patients with an expert diagnosis of SpA were identified retrospectively from four rheumatology centers in Hong Kong. Electronic medical records from 1995 to 2018 were reviewed for incidence of cutaneous HZ and demographic data including age, sex, comorbidities, smoking and drinking status. DMARDs used included sulphasalazine, methotrexate, leflunomide, steroids, etanercept, infliximab, adalimumab, golimumab, secukinumab and ustekinumab. Cox regression models were used to evaluate hazard ratios (HRs) of different DMARDs in patients with SpA. Propensity score was used for matching and comparison with 857 patients with RA. RESULTS: There were 23 cases of cutaneous HZ in patients with SpA and 59 cases in patients with RA. Among patients with SpA, 7 cases of cutaneous HZ may be attributed to sulfasalazine treatment, 7 to methotrexate, 2 to leflunomide, 2 to infliximab, 1 to etanercept, 2 to adalimumab, and 1 to secukinumab. Risks of cutaneous HZ were the same in SpA (stratified HR 0.97; 95% CI 0.58; 1.61; P = .89) and RA. Methotrexate (adjusted HR 3.47; 95% CI 1.25; 9.63; P = .02) and infliximab (adjusted HR 10.67; 95% CI 1.37; 82.88; P = .02) were found to be associated with HZ after adjustments for traditional risk factors. CONCLUSION: Risk of cutaneous HZ in SpA was not lower than in RA. Methotrexate and infliximab were associated with cutaneous HZ in SpA.
31564885 Clinical evaluation of the safety, efficacy and tolerability of sarilumab in the treatment 2019 Rheumatoid arthritis (RA) is an autoimmune disease that is characterised by synovial inflammation and progressive joint disorder with significant pain and stiffness, which lead to functional disability and systemic complications if left untreated. Although methotrexate (MTX) is the cornerstone in the RA therapy, it is ineffective or intolerable in up to 50% of patients. In addition, tumour necrosis factor (TNF) inhibitors which are regarded as the standard of care for those patients, have not been proven a panacea creating a therapeutic gap. In this direction, other cytokines such as the interleukin (IL)-6 in combination with MTX or as monotherapy have been approved. Sarilumab has already been approved for the treatment of moderate to severe RA, but more studies are on their way including polymyalgia rheumatica, giant cell arteritis, juvenile idiopathic arthritis, and indolent systemic mastocytosis. On the other hand, a study was prematurely discontinued after approximately 1.5 years, when the ankylosing spondylitis development program was discontinued due to lack of efficacy. Regarding safety, efficacy and tolerability of the molecule, three pivotal clinical trials have established sarilumab as one of the safe and efficacious choices for the treatment of RA (mobility, target and monarch trials). Significant decreases in progression of structural damage have been demonstrated. Infections and neutropenia are two of the most common adverse events. Sarilumab is beyond any doubt another molecule that can be added to the clinicians' armamentarium for the treatment of patients with moderate to severe RA with a good safety and efficacy profile.
35382152 Inflammatory arthritis in systemic sclerosis: What to do? 2019 Feb Musculoskeletal involvement, including arthritis and tendinopathy, is a common and important determinant of disability and impaired quality of life in systemic sclerosis. However, the treatment of arthritis in systemic sclerosis has not been studied as a primary outcome in randomized controlled trials, and arthritis-specific outcome measures for systemic sclerosis have not been sufficiently validated to date. Rheumatologists caring for patients with systemic sclerosis must address these complaints regularly despite the fact that the level of evidence for the treatment of systemic sclerosis-related inflammatory arthritis is limited. Consensus statements, based on treatments for related musculoskeletal aspects of rheumatoid arthritis, systemic lupus erythematosus, and other autoimmune diseases, support the use of methotrexate and hydroxychloroquine. Newer biologics, which have efficacy in the treatment of other autoimmune conditions, may show promise in the treatment of arthritis in systemic sclerosis. In this article, we review the current literature on the assessment and treatment of systemic sclerosis arthritis in order to address management considerations.
30991730 How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patien 2019 Apr 15 Methotrexate (MTX) is a remarkable drug with a key role in the management of rheumatoid arthritis (RA) at every stage of its evolution. Its attributes include good overall efficacy for signs and symptoms, inhibition of structural damage and preservation of function with acceptable and manageable safety, a large dose-titratable range, options for either an oral or parenteral route of administration, and currently unrivalled cost-effectiveness. It has a place as a monotherapy and also as an anchor drug that can be safely used in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or used concomitantly with biological DMARDs or targeted synthetic DMARDs. MTX is not without potential issues regarding toxicity, notably hepatotoxicity and bone marrow toxicity, as well as tolerability problems for some, but not all, patients. But many of these issues can be mitigated or managed. In the face of a welcome expansion in available targeted therapies for the treatment of RA, MTX looks set to remain at the foundation of pharmacotherapy for the majority of people living with RA and other inflammatory rheumatic diseases. In this article, we provide an evidence-based discussion as to how to achieve the best outcomes with this versatile drug in the context of a treat-to-target strategy for the management of RA.
30678235 Patients with Rheumatoid Arthritis Were Associated with a Risk of Rotator Cuff Diseases. 2019 Jan 22 Rheumatoid arthritis (RA) commonly causes inflammation in the joints and periarticular structures. The association between RA and rotator cuff (RC) has been reported; however, epidemiological studies on RA and RC tendons are scant. Therefore, we investigated RC disease (RCD) risk and analyzed the effects of RA medication, steroids, and methotrexate, on the risk of RCD for patients with RA. We conducted a retrospective cohort study with a 6-year longitudinal follow-up in Taiwan. Patients who received RA diagnoses between 2004 and 2008 were enrolled in the study cohort. The non-RA control cohort comprised age- and sex-matched controls. Propensity score matching was used for other comorbidities and treatments. The hazard ratios (HRs) and adjusted HRs (aHRs) were estimated after confounders were adjusted for. Effects of steroid and methotrexate use on RCD risk were also analyzed. We enrolled 4521 RA patients (study cohort) and 22,605 matched controls. RCD incidence was 145 and 91 per 100,000 person-years in the RA and control cohorts, respectively. In the RA cohort, the crude HR for RCD was 1.62 (95% confidence interval (CI), 1.41⁻1.86, p < 0.001), and the aHR was 1.56 (95% CI, 1.36⁻1.79, p < 0.001). The methotrexate nonusers exhibited an aHR (vs. controls) of 1.61 (95% CI, 1.40⁻1.85, p < 0.001), but the methotrexate users did not have a significantly higher aHR than the controls. The steroid nonusers had an aHR (vs. controls) of 1.69 (95% CI, 1.46⁻1.96, p < 0.001), but the aHR of the steroid users was not significantly higher than the control aHR. Patients with RA had a higher risk for RCD compared with the non-RA control cohort. Steroids or methotrexate use significantly reduces the risk of RCD occurrence in patients with RA. Treatment for RCD symptoms and controlling inflammatory process are important to ensure high-quality care for patients with RA.
32743504 Subcutaneous abatacept in rheumatoid arthritis: A real-life experience. 2019 Dec OBJECTIVES: To assess the effectiveness, safety, and drug survival of subcutaneous (SC) abatacept (ABA) in a cohort of rheumatoid arthritis (RA) patients in a real-world setting. METHODS: This was a retrospective cohort study from 2014 to 2018 in which patients with RA (1987 ACR criteria) were included. Patients were evaluated at a single rheumatology outpatient center in Bogotá, Colombia. The patients were classified according to their treatment background: biological-naïve (n = 65), switched from IV to SC ABA administration (125 mg-wk) (n = 32), and inadequate response to biological DMARD (n = 62). The primary endpoint was a change in DAS28-CRP and RAPID3 from baseline to 12 months. A linear mixed effect model was used to correlate repeated measures. Adverse events were assessed and recorded during each visit to the rheumatology center. Several Cox proportional hazard regression models were used to test if there were any differences in drug survival curves based on seropositivity for rheumatoid factor (RF), and anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP). Statistical analysis was done using software R version 3.4.4. RESULTS: A total of 159 patients were included. Baseline characteristics of patients were as follows: female gender 84%, median age of 54 years (IQR 16), median disease duration 10 years (11), RF positive 96%, anti-CCP positive 89%, erosive disease 55%, median DAS28-CRP 5.0 (2), and median RAPID3 17 (10). Concomitant use of methotrexate and SC ABA monotherapy were reported at 52% and 30% respectively. Demographics and disease characteristics were similar for all groups, except for baseline DAS28-CRP, and RAPID3 in the group that switched route of administration. The interaction between time and group was significant (p = 0.0073) for RAPID3. Infections, constitutional symptoms, and headaches were the most frequent AEs. Retention rate corresponded to 60% at 48 months. The most frequent reason for drug suspension was loss of efficacy. Median time of treatment for SC ABA was 31 months (IQR 30). The only association that reached statistical significance was anti-CCP concentration [Q1-Q4] (p = 0.005). According to the Cox proportional hazard regression model, there were significant differences between survival curves for Q1 (HR 0.15; 0.03-0.64 95% CI; p = 0.0096), and Q2 (HR 0.28; 0.08-0.92 95% CI; p = 0.0363) compared to the seronegative group. CONCLUSIONS: The results showed an improvement in RA disease activity and physical function in patients under SC ABA treatment. Patients switching from IV to SC administration of ABA had lower activity and functional impairment at baseline. SC ABA demonstrated a good safety profile consistent with previously published data. Patients with baseline levels of anti-CCP antibody concentrations had better drug survival than seronegative patients.
30923795 Incidence and predictors of dyspnea on exertion in a prospective cohort of patients with r 2019 Mar OBJECTIVE: To investigate the incidence and predictors of dyspnea on exertion among subjects with rheumatoid arthritis (RA). METHODS: We investigated dyspnea on exertion using a prospective cohort, the Brigham RA Sequential Study (BRASS). Clinically significant dyspnea on exertion was defined as a score of ≥3 (unable to ambulate without breathlessness or worse) on the validated Medical Research Council (MRC) scale (range 0-5). We analyzed subjects with MRC score <3 at BRASS baseline and ≥1 year of follow-up. The MRC scale was administered annually. We determined the incidence rate (IR) of dyspnea on exertion. We used Cox regression to estimate the HR for dyspnea on exertion occurring one year after potential predictors were assessed. RESULTS: We analyzed 829 subjects with RA and no clinically significant dyspnea on exertion during mean follow-up of 3.0 years (SD 1.9). At baseline, mean age was 55.7 years (SD 13.6), 82.4% were female, and median RA duration was 8 years. During follow-up, 112 subjects (13.5%) developed incident dyspnea on exertion during 2,476 person-years of follow-up (IR 45.2 per 1000 person-years). Independent predictors of incident dyspnea on exertion were: older age (HR 1.03 per year, 95%CI 1.01-1.04), female sex (HR 2.22, 95%CI 1.14-4.29), mild dyspnea (HR 2.62, 95%CI 1.60-4.28), and worsened MDHAQ (HR 2.36 per unit, 95%CI 1.54-3.60). Methotrexate use, RA disease activity, and seropositivity were not associated with incident dyspnea on exertion. CONCLUSION: Dyspnea on exertion occurred commonly in patients with RA. Older women with impaired physical function were especially vulnerable to developing dyspnea on exertion.
31662761 Demographic and Clinical Patterns of Rheumatoid Arthritis in an Emirati Cohort from United 2019 This retrospective cohort study aimed to assess the demographic and clinical characteristics of rheumatoid arthritis (RA) in Emirati patients attending Cleveland Clinic Abu Dhabi, a large tertiary center in the Middle East. In this study, 414 Emirati patients with RA were evaluated over a 3-year period from April 2015 to April 2018. All patients fulfilled the 2010 RA ACR/EULAR criteria and were assessed for demographic and clinical characteristics. The estimated RA prevalence rate in our population cohort was 2.72%. Females showed predominance (80%) with a higher body mass index (31.4 ± 6.61, P = 0.0001) compared to males (28.8 ± 6.03, P = 0.0001). The most frequent comorbidity observed was dyslipidemia (43.5%) followed by hypertension (37.9%), diabetes mellitus (34.5%), and gastroesophageal reflux disease (33.1%). Xerophthalmia was the most frequent extra-articular manifestation. Rheumatoid factor and anti-citrullinated peptide were detected in 63.3% and 41.5% patients, respectively, while both were present in 33.3% of patients. Methotrexate, adalimumab, and rituximab were the most frequently prescribed disease modifying agents. In this study, we describe disease features that are unique to United Arab Emirates (UAE) patients and demonstrate that RA has a significant disease burden. Our findings highlight the need for a RA national registry to improve the quality of care of these patients in UAE.
31007935 Inflammatory variant of pachydermoperiostosis responding to methotrexate: a report of two 2019 Apr Pachydermoperiostosis is a rare genetic disorder characterized by skin thickening, digital clubbing and periostitis. The pathogenesis is incompletely understood and there are no proven treatments for its manifestations. Although arthritis has been reported in 20-40% cases, most are non-inflammatory in nature and usually treated symptomatically with steroids or NSAIDs. We report two cases of pachydermoperiostosis with inflammatory variant of arthritis and raised inflammatory markers who were treated with tapering dose of prednisolone for 6 weeks and maintained on long-term low dose methotrexate like rheumatoid arthritis and followed for 2 years. In both cases, methotrexate was well tolerated and helped in maintaining symptomatic improvement and slowed the disease progression with significant steroid and NSAID sparing effect. We concluded that there exists an inflammatory subtype of disease where methotrexate can be beneficial.
31087133 [Biologics in the treatment of juvenile idiopathic arthritis : A comparison of mono- and c 2019 Sep In polyarticular juvenile idiopathic arthritis, methotrexate (MTX) is still used as first-line treatment. In case of insufficient response or intolerance, a number of biologics are now available. This faces physicians with challenging choices. Biologics are often combined with MTX, although in JIA there is little evidence and inconsistent results from various studies. In rheumatoid arthritis, combination therapy with tumor necrosis factor (TNF) inhibitors has been associated with higher efficacy. Tocilizumab appears to be highly effective as a monotherapy. MTX has a protective effect on the formation of anti-drug antibodies, which is particularly important for the use of anti-TNF antibodies. This could also be observed in children. For golimumab, combination with MTX is mandatory according to its approval, as is the cause for abatacept. With regard to tolerability, apart from the classic side effects of MTX, there are no other significant differences concerning the combination of MTX and biologics. In case of MTX intolerance, leflunomide may be considered as an (unapproved) alternative.
31612088 Hemophagocytic Syndrome-Associated Variant of Methotrexate-Associated Intravascular Large 2019 A 59-year-old man was treated for rheumatoid arthritis (RA) for 12 years with methotrexate (MTX) and prednisolone. After MTX-associated interstitial pneumonia developed, he was treated with cyclophosphamide and prednisolone for 7 months. Arthritis worsened, and tacrolimus was added to the treatment regimen. One month later, he had fever, loss of appetite, and dyspnea on exertion. Blood tests showed pancytopenia with large, atypical lymphocytes. Computed tomography showed mild splenomegaly. Bone marrow examination demonstrated CD20-positive, EBER-positive atypical lymphocytes, and hemophagocytosis. Random skin biopsy led to the diagnosis of intravascular large B-cell lymphoma (IVLBCL). The final diagnosis was a hemophagocytic syndrome-associated variant of IVLBCL. Complete remission was achieved after seven courses of R-CHOP. However, within a month, he complained of dizziness. Magnetic resonance imaging revealed focal infarctions in the cerebellum and around the left lateral ventricle. Central nervous system relapse was suspected. Although salvage chemotherapy (CHASER), whole brain irradiation, and intrathecal injection of cytarabine and prednisolone were temporarily effective, he died. Autopsy revealed infiltration of lymphoma cells in the brain and adrenal glands. To the best of our knowledge, this is the sixth case of IVLBCL and the first case of the hemophagocytic syndrome-associated variant of IVLBCL in RA patients in the literature.
31267867 Influence of the OATP Polymorphism on the Population Pharmacokinetics of Methotrexate in C 2019 BACKGROUND: The Pharmacokinetics of Methotrexate (MTX) has been reported to show significant intersubject variability. MTX is metabolized by SHMT1 and transported by OATP1B1 and OATP1B3 both of which show genetic polymorphisms. The non-genetic and genetic factors may influence the pharmacokinetics of MTX. OBJECTIVE: This study aimed to determine the pharmacokinetic parameters of MTX in Chinese patients and to investigate the effect of various non-genetic factors and genetic variants of OATP1B1, OATP1B3 on MTX's pharmacokinetics. METHODS: MTX concentration and clinical characteristics data were collected from 71 rheumatoid arthritis patients. For each patient, SLC19A1, SHMT1, OATP1B1, and OATP1B3 genotyping were tested. Population pharmacokinetic analysis was performed by Nonlinear Mixed-Effect Modeling (NONMEM). MTX pharmacokinetic properties analysis was executed using the one-compartment pharmacokinetic model which incorporated first-order conditional estimation methods with interaction. Besides, the impact of genetic factors and demographic factors on MTX disposition were explored. RESULTS: All the genotypes of steady-state plasma concentrations and OATP1B1 rs4149056, OATP1B1 rs2306283, and OATP1B3 rs7311358 were determined. The detected blood drug concentration reached the standard. Genotypes were all measured. At the same time, the population pharmacokinetic model of methotrexate was obtained CL(L·h-1) =8.25× e0.167× SNP (SNP: SLCO1B1 388A/A=3; SLCO1B1 388A/G=2; SLCO1B1 388G/G=1); V(L)= 32.8; Ka(h- 1)=1.69. CONCLUSION: In our study, it was showed that OATP1B1-388 G>A SNP had a significant effect on CL/F. The factor should be considered when determining MTX dosing. However, prospective studies with a large number of participants are needed to validate the results of this study.
28532741 Coexistence of sarcoidosis and adult onset Still disease. 2019 Sep Sarcoidosis is a chronic, inflammatory disease with unknown cause characterized by non-caseating granuloma formations. It can be presented with bilateral hilar lymphadenopathy, skin lesions, eye involvement and locomotor system findings. Adult onset Still disease (AOSD) is a chronic inflammatory disease which presents with fever, arthritis and typical skin rashes. The disease is rare and can be misdiagnosed due to the absence of typical clinical and laboratory findings. The association of sarcoidosis and AOSD has not been previously reported in the literature. Herein we reported the development of AOSD in a patient followed by the diagnosis of sarcoidosis. The patient did not respond to high-dose corticosteroids and methotrexate therapy, and the disease was under control with anti-IL-6 (Tocilizumab) drug.
31169840 Remotely controlled nanofluidic implantable platform for tunable drug delivery. 2019 Jun 25 Chronic diseases such as hypertension and rheumatoid arthritis are persistent ailments that require personalized lifelong therapeutic management. However, the difficulty of adherence to strict dosing schedule compromises therapeutic efficacy and safety. Moreover, the conventional one-size-fits-all treatment approach is increasingly challenged due to the intricacies of inter- and intra-individual variabilities. While accelerated technological advances have led to sophisticated implantable drug delivery devices, flexibility in dosage and timing modulation to tailor precise treatment to individual needs remains an elusive goal. Here we describe the development of a subcutaneously implantable remote-controlled nanofluidic device capable of sustained drug release with adjustable dosing and timing. By leveraging a low intensity electric field to modify the concentration driven diffusion across a nanofluidic membrane, the rate of drug administration can be increased, decreased or stopped via Bluetooth remote command. We demonstrate in vitro the release modulation of enalapril and methotrexate, first-line therapeutics for treatment of hypertension and rheumatoid arthritis, respectively. Further, we show reliable remote communication and device biocompatibility via in vivo studies. Unlike a pulsatile release regimen typical of some conventional controlled delivery systems, our implant offers a continuous drug administration that avoids abrupt fluctuations, which could affect response and tolerability. Our system could set the foundation for an on-demand delivery platform technology for long term management of chronic diseases.