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ID PMID Title PublicationDate abstract
32911290 Racial and ethnic differences in medication use among beneficiaries of social security dis 2020 Oct OBJECTIVE: To determine racial/ethnic differences in the use of conventional synthetic or biologic disease-modifying anti-rheumatic drugs (csDMARDs or bDMARDs, respectively) and long-term glucocorticoids (GC) or opioids among beneficiaries of the Social Security Disability Insurance (SSDI) with rheumatoid arthritis (RA) and <65 years old. METHODS: Serial cross-sectional analyses of Centers for Medicare and Medicaid Services claims data (2007, 2011, and 2014) for individuals <65 years old with RA receiving SSDI Medicare and Medicaid, no longer working because they were considered disabled. Generalized estimating equation models were used to determine whether the proportion of patients who used csDMARD, bDMARD, long-term GC, and long-term opioids differed by race/ethnicity. RESULTS: There were 12,931; 15,033; and 15,599 participants in 2007, 2011, and 2014, respectively. The overall use of csDMARD without bDMARD among beneficiaries of the SSDI were 31.1%, 30.3%, and 29.2%; 50.2%, 51.7%, and 53.8% used bDMARDs; 37.6%, 36.1%, and 34.4% used long-term GC; and 61.1%, 63.8%, and 63.7% used long-term opioids in years 2007, 2011, and 2014 respectively. The use of csDMARDs without bDMARDs was higher and the use of bDMARDs was lower among Blacks compared to Whites (adjusted absolute difference: +3.0%, +5.0%, and +3.3% for csDMARDs without bDMARDs and -4.6%, -5.7%, and -4.0% for bDMARDs in 2007, 2011, and 2014, respectively; all p<0.05). The use of bDMARDs was higher among Hispanics compared to Whites (adjusted absolute difference: +7.1%, +7.3%, and +7.5% in 2007, 2011, and 2014, respectively; all p<0.05). Long-term GC use was lower among Hispanics than among Whites only in year 2014 (absolute percentage point difference of -4.2%); no other difference in long-term GC use was identified. Whites were the patients with the highest use of long-term opioids (more than two third in each calendar year). CONCLUSION: Racial and ethnic differences exists in regards to the treatment of RA among beneficiaries of the SSDI. These findings suggest that this already vulnerable population of patients with RA can also have a racial and ethnic disparity that can contribute to additional disease burden and that should be examined in order to inform future interventions or even inform future policy changes to the SSDI.
33008951 IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators. 2020 Nov 15 IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK-, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.
32009093 Hemophagocytic Lymphohistiocytosis in a Patient with Rheumatoid Arthritis on Pembrolizumab 2020 Apr 15 Immune checkpoint inhibitors have changed the landscape of classic cancer treatment. However, their use is associated with the emergence of new adverse events. An elderly man with rheumatoid arthritis was started on pembrolizumab for newly diagnosed advanced lung cancer. He subsequently developed hemophagocytic lymphohistiocytosis (HLH), which is potentially fatal but has not been properly established as an immune checkpoint inhibition-induced event. We herein report the case of a patient with pembrolizumab-induced HLH.
33323533 Impact of Comorbid Conditions on Healthcare Expenditure and Work-related Outcomes in Patie 2021 Aug OBJECTIVE: To evaluate the effect of comorbid conditions on direct healthcare expenditure and work-related outcomes in patients with rheumatoid arthritis (RA). METHODS: This is a retrospective analysis of the Medical Expenditure Panel Survey from 2006 to 2015 in 4967 adults with RA in the United States. Generalized linear models were used for healthcare expenditure and income, logistic models for employment status, and zero-inflated negative binomial models for absenteeism. Thirteen comorbid conditions were included as potential predictors of direct cost- and work-related outcomes. The models were adjusted for sociodemographic factors including sex, age, region, marital status, race/ethnicity, income, education, and smoking status. RESULTS: Patients with RA with heart failure (HF) had the highest incremental annual healthcare expenditure (US$8205, 95% CI $3683-$12,726) compared to those without the condition. Many comorbid conditions including hypertension (HTN), diabetes, depression, chronic obstructive pulmonary disease, cancer, stroke, and HF reduced the chance of patients with RA aged between 18-64 years being employed. Absenteeism of employed patients with RA was significantly affected by HTN, depression, disorders of the eye and adnexa, or stroke. On average, RA patients with HF earned US$15,833 (95% CI $4435-$27,231) per year less than RA patients without HF. CONCLUSION: Comorbid conditions in patients with RA were associated with higher annual healthcare expenditure, lower likelihood of employment, higher rates of absenteeism, and lower income. Despite its low prevalence, HF was associated with the highest incremental healthcare expenditure and the lowest likelihood of being employed compared to other common comorbid conditions.
31203225 Rituximab Therapy for Systemic Rheumatoid Vasculitis: Indications, Outcomes, and Adverse E 2020 Apr OBJECTIVE: To characterize the indication, outcomes, and adverse effects of rituximab (RTX) treatment in a large single-center cohort of patients with systemic rheumatoid vasculitis (RV). METHODS: We retrospectively reviewed the medical charts of 17 patients treated with RTX for systemic RV from 2000 to 2017. Clinical characteristics, outcomes, and adverse effects were analyzed. RESULTS: At RV diagnosis, mean age was 59 years, 59% were female, 94% were white, and 82% had positive rheumatoid factor. At the time of initiating RTX, median Birmingham Vasculitis Activity Score for rheumatoid arthritis was 4.0 (interquartile range 2.0-7.5). RV presented in the skin in 8 patients (47%), as mononeuritis multiplex in 2 (12%), inflammatory ocular disease in 2 (12%), and affected multiple organ systems in 5 (29%). RTX was used for induction therapy in 8 patients (47%), relapsing RV in 4 (24%), second-line therapy in 2 (12%), and salvage therapy or in combination with another agent in 3 (18%). At 3 months, 2 (13%) of 15 patients with available followup information achieved complete remission (CR), and 10 (67%) achieved partial response (PR). At 6 months, 6 patients (40%) achieved CR, 8 (53%) achieved PR, and one had no response. At 12 months, 8 of 13 patients with available records (62%) had CR and 5 patients (38%) had PR. CONCLUSION: Systemic RV is difficult to treat effectively. CR of RV was achieved in 62% and PR in 38% of patients within 12 months of RTX use. Further evidence is needed to inform treatment for patients with RV.
31787605 Reasons for Biologic and Targeted Synthetic Disease-modifying Antirheumatic Drug Cessation 2020 Aug 1 OBJECTIVE: To provide real-world evidence about the reasons why Australian rheumatologists cease biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) when treating patients with rheumatoid arthritis (RA), and to assess (1) the primary failure rate for first-line treatment, and (2) the persistence on second-line treatments in patients who stopped first-line tumor necrosis factor inhibitors (TNFi). METHODS: This is a multicenter retrospective, noninterventional study of patients with RA enrolled in the Australian Optimising Patient outcome in Australian RheumatoLogy (OPAL) dataset with a start date of b/tsDMARD between August 1, 2010, and June 30, 2017. Primary failure was defined as stopping treatment within 6 months of treatment initiation. RESULTS: Data from 7740 patients were analyzed; 6914 patients received first-line b/tsDMARD. First-line treatment was stopped in 3383 (49%) patients; 1263 (37%) were classified as primary failures. The most common reason was "lack of efficacy" (947/2656, 36%). Of the patients who stopped first-line TNFi, 43% (1111/2560) received second-line TNFi, which resulted in the shortest median time to stopping second-line treatment (11 months, 95% CI 9-12) compared with non-TNFi. The longest second-line median treatment duration after first-line TNFi was for patients receiving rituximab (39 months, 95% CI 27-74). CONCLUSION: A large proportion of patients who stopped first-line TNFi therapy received another TNFi despite evidence for longer treatment persistence on second-line b/tsDMARD with a different mode of action. Lack of efficacy was recorded as the most common reason for making a switch in first-line treatment of patients with RA.
31958273 Glucocorticoids in rheumatoid arthritis: current status and future studies. 2020 Jan Since their first use for treating rheumatoid arthritis (RA) in the late 1940s, glucocorticoids (GCs) have been representing a substantial part of the therapeutic arsenal for RA. However, even if GCs are still widely prescribed drugs, their toxicity is discussed controversially, so obtaining consensus on their use in RA is difficult. Hence, the most recent European League Against Rheumatism and American College of Rheumatology recommendations on early arthritis and RA management advocate the use of GCs as adjunct treatment to conventional synthetic disease-modifying antirheumatic drugs, at the lowest dose possible and for the shortest time possible. However, the recommendations remain relatively vague on dose regimens and routes of administration. Here, we describe literature data on which the current recommendations are based as well as data from recent trials published since the drafting of the guidelines. Moreover, we make proposals for daily practice and provide suggestions for studies that could help clarifying the place of GCs in RA management. Indeed, numerous items, including the benefit/risk ratio of low-dose and very low-dose GCs and optimal duration of GCs as bridging therapy, remain on the research agenda, and future studies are needed to guide the next recommendations for RA.
33080751 Development of severe thrombocytopenia with TAFRO syndrome-like features in a patient with 2020 Oct 16 RATIONALE: Thrombocytepenia, anasarca, fever, renal insufficiency, and organomegaly (TAFRO) syndrome is a novel disease entity characterized by a constellation of symptoms (thrombocytopenia, anasarca, fever, renal insufficiency, and organomegaly). Here, we describe the development of TAFRO syndrome-like features during the treatment of rheumatoid arthritis with a Janus kinase (JAK) inhibitor. PATIENT CONCERNS: In this report, a 74-year-old woman treated with a JAK inhibitor (tofacitinib) for rheumatoid arthritis was admitted because of fever and thrombocytopenia. DIAGNOSES: On laboratory examination, marked thrombocytopenia and elevated creatinine and C-reactive protein levels were present. A computed tomography scan revealed lymphadenopathy, hepato-splenomegaly, and anasarca. A left axillary lymph node biopsy revealed Castleman's disease-like features. These clinical features satisfied the proposed diagnostic criteria for TAFRO syndrome. Since autoimmune disorders should be excluded when diagnosing TAFRO syndrome, it is not strictly correct to diagnose her as TAFRO syndrome. Therefore, we diagnosed her as rheumatoid arthritis complicated by TAFRO syndrome-like features. INTERVENTIONS: The patient was treated with high-dose glucocorticoid, tacrolimus, eltrombopag, intravenous immunoglobulin, and rituximab. OUTCOMES: Her condition was refractory to the above-mentioned treatment, and she eventually died because of multi-organ failure 6 months after the first admission. LESSONS: TAFRO syndrome-like features can develop during treatment with a JAK inhibitor for rheumatoid arthritis. Patients with autoimmune diseases complicated by TAFRO syndrome-like features can follow a fatal clinical course, and thus, an intensive combined treatment is warranted for such patients, especially in cases refractory to glucocorticoid.
31980382 Grading of Ultrasonography in Rheumatoid Arthritis of Wrist and Hand Joints. 2020 Jul RATIONALE AND OBJECTIVES: To evaluate the role of musculoskeletal ultrasound (MSUS) in the grading of rheumatoid arthritis (RA) wrist and hand joints and correlate it with clinical, laboratory, and radiological data. MATERIALS AND METHODS: A cross-sectional study recruited 50 patients in a tertiary care hospital. RA activity was assessed by DAS28. MSUS dorsal longitudinal scan was performed on the wrists, MCPs, and PIPS joints using high frequency (18 MHZ) linear transducer. 100 wrists in three different views, 500 MCPs, 500 PIPs were evaluated using the grayscale ultrasound and power Doppler ultrasound semiquantitative scale and scores ranging from 0-3. The results were correlated with clinical, laboratory and radiological data. All patients' wrist and hand joints X-rays were evaluated using the Larsen score. RESULTS: The mean age of the patients (49 females and one male) was 44.58 ± 10.07 years, and their mean disease duration was 16.26 ± 1.07 years. The mean DAS28 was 5.19 ± 0.95. 97.5% of joints had grade I Larsen score, 11.07% of the joints had erosions, 9.2% of the joints had effusions, 23.8% of the joints had synovial thickening, 11.9% of the joints showed PD signals and 3.5% of the joints were accompanied with tenosynovitis. Significant relations (p < 0.05) found among DAS28 and (PD signals, synovial thickening, tenosynovitis, effusion, and Larsen score). A nonsignificant relation (p > 0.05) among DAS28 and erosions detected by MSUS and X-ray. CONCLUSION: MSUS is powerful in the detection of early RA regarding synovitis, joint effusion, tenosynovitis, and bone erosions, which were correlated with clinical and laboratory parameters.
31292313 Validating an Empirical Mathematical Model for Dynamic Contrast-enhanced MR Imaging of Han 2020 Aug 3 PURPOSE: To evaluate the feasibility of an empirical mathematical model (EMM) to fit dynamic contrast-enhanced MRI (DCE-MRI) data of hand and wrist synovitis and whether parameters of EMM are significantly correlated with clinical disease activity in patients with rheumatoid arthritis (RA). METHODS: Thirty-one consecutive patients with RA prospectively underwent Institutional Review Board (IRB)-approved DCE-MRI scans with temporal resolution of 20 s using a 1.5T system. ROIs were placed where the highest signal increase was observed and the kinetic curves were analyzed using an EMM: ΔS(t) = A(1 - e(-α t)) e(-βt), where ΔS is relative enhancement, t is time from when the signal increase was first observed, starting from baseline (ΔS = 0), A is the upper limit of signal intensity, α (s(-1)) is the rate of signal increase, and β (s(-1)) is the rate of signal decrease during washout. The initial slope of the kinetic curve (Aα), the initial area under the curve (AUC30), the time at which the kinetic curve reached its peak (T(peak)) and the signal enhancement ratio (SER) defined as the change in signal intensity between the initial and delayed time points (t = 60 and 300 s, respectively) were calculated. RA magnetic resonance imaging scores (RAMRIS) with and without contrast media were evaluated. These parameters or scores were compared with the Disease Activity Score (DAS) 28-erythrocyte sedimentation rate (ESR). RESULTS: A showed a significant correlation with DAS28-ESR (r = 0.58; P = 0.0005). β, AUC30 and T(peak) were also significantly correlated with DAS28-ESR with a lesser degree (r = 0.49; P = 0.0051, r = 0.50; P = 0.0038 and r = -0.51; P = 0.0028, respectively), whereas α, Aα, SER and RAMRIS were not. CONCLUSION: EMM could fit the DCE-MRI data of hand and wrist synovitis. AUC30 obtained from the uptake phase of the kinetic curve as well as A, β and T(peak) obtained throughout the kinetic curve might be effective to predict the clinical disease activity.
32101306 Use of Magnetic Resonance Imaging to Identify Immune Checkpoint Inhibitor-Induced Inflamma 2020 Feb 5 IMPORTANCE: Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for an ever-increasing number of cancers. However, their use has also led to the emergence of immune-related adverse events, such as ICI-induced inflammatory arthritis. A reproducible, reliable, and accessible modality is needed to assess and distinguish early ICI-induced inflammatory arthritis and help in management. Magnetic resonance imaging (MRI) of joints may be helpful for early diagnosis, guiding therapeutic decision-making, and identifying patients at high risk for erosive disease. OBJECTIVE: To assess the role of MRI of joints in patients with ICI-induced inflammatory arthritis. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series included patients enrolled at the National Institutes of Health Clinical Center in Bethesda, Maryland. Patients were evaluated by the rheumatology consultation service between December 27, 2016, and May 28, 2019. A retrospective health record review was performed to determine demographic characteristics, clinical characteristics of inflammatory arthritis and malignant tumors, and imaging findings. Inclusion criteria were patients who were enrolled on various institutional review board-approved protocols of ICIs, developed joint-related symptoms, and had MRI data for at least 1 joint. Data were analyzed from June 1, 2019, to September 1, 2019. EXPOSURES: Undergoing MRI of at least 1 joint. MAIN OUTCOMES AND MEASURES: All MRIs were reviewed for synovitis, tenosynovitis, bone marrow edema, and soft tissue conditions. RESULTS: A total of 8 patients (mean [SD] age, 58.8 [5.2] years; 6 women and 2 men) between the ages of 50 and 65 years who were undergoing ICI therapy for a variety of malignant tumors were included in this study. Only 1 patient was receiving combined ICI therapy. The results of 13 separate MRI examinations were reviewed. The most commonly performed MRIs were of the hands and wrists (9 MRIs), followed by knee examinations (3 MRIs). Tenosynovitis and synovitis were frequently seen in the hands and wrists. Bone marrow edema and erosions were also found in 3 patients, suggesting early damage. In larger joints (ie, knees and ankles), joint effusions and synovial thickening were characteristic. Most patients (5 patients) were treated with corticosteroids and had good responses. In patients with high-risk features on MRI imaging (eg, bone marrow edema, erosions), disease-modifying antirheumatic drug therapy was also discussed as a treatment option. CONCLUSIONS AND RELEVANCE: These findings suggest that advanced imaging may help to distinguish ICI-induced inflammatory arthritis from other causes of joint pain, aid in identifying patients at increased risk of joint damage, and provide utility in monitoring inflammatory arthritis treatment response in patients receiving ICI therapy.
32787514 C3 Gene Functional Polymorphisms and C3 Serum Levels in Patients with Rheumatoid Arthritis 2021 Nov The complement system is a key component of the innate immunity that plays a significant role in the development and clinical presentation of Rheumatoid arthritis (RA). Complement protein C3 is a central molecule in the activation of complement with a significant role in the inflammatory processes of RA. Nevertheless, the impact of C3 gene polymorphisms in the development of RA is still unknown. The current study aimed to investigate the possible influence of C3 gene polymorphisms in the susceptibility and clinical expression of RA. Three C3 polymorphisms (rs2250656:A > G, intron 2; rs2230199:C > G [p.Arg102Gly], exon 3 and rs1047286:C > T [p.Pro314Leu], exon 9) were assessed by sequence-specific PCR in a total of 156 RA patients and 270 healthy controls from Southern Brazil. In addition, C3 levels were measured in 60 patients and 60 controls by immunoturbidimetry and clinical features were collected from medical records. The frequency of rs2230199 G allele and GG genotype was significantly higher in RA patients than controls (p(adj) = 0.012 OR = 1.57 [1.11-2.31]; p(adj) = 0.008, OR = 1.60 [1.35-2.33]) as well as the rs1047286 T and TT (p(adj) = 0.010, OR = 1.67 [1.12-2.40]; p(adj) = 0.001, OR = 1.83 [1.27-2.65] and the C3 AGT haplotype (p(adj) = 0.0007 OR = 1.92 [1.32-2.80]). Moreover, C3 serum levels were higher in patients than controls (median: 169 mg/dl vs.155 mg/dl; p(adj) = 0.022), as well as in RF seronegative compared with seropositive patients (172 mg/dl vs. 165 mg/dl; p(adj) = 0.007). Our results suggest that the rs2230199 G (p.102Gly) and rs1047286 T (p.314Leu) alleles play a role in the pathophysiology of RA, possibly impacting complement activation by the alternative pathway.
32035098 Activation of GPR43 suppresses TNF-α-induced inflammatory response in human fibroblast-li 2020 May 15 Although rheumatoid arthritis (RA) has long posed a major threat to global health, the mechanisms driving the development and progression of RA remain incompletely understood. In the present study, we investigated the effects of G protein-coupled receptor 43 (GPR43/FFAR2) in various aspects of the pathogenesis of RA. To our knowledge, this is the first study to demonstrate that GPR43 is expressed on human fibroblast-like synoviocytes (FLS). Furthermore, we show that GPR43 is upregulated in FLS exposed to tumor necrosis factor-α (TNF-α). Importantly, our findings demonstrate that activation of GPR43 using its specific agonist significantly suppressed expression of the following key factors of RA: cytokines, such as interleukin-6 (IL-6), IL-8, high mobility group protein 1 (HMG-1); chemokines, such as monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cellular adhesion molecule 1 (VCAM-1); markers of oxidative stress, such as production of reactive oxygen species (ROS) and 4-hydroxynoneal (4-HNE); degradative enzymes, such as matrix metalloproteinase-3 (MMP-3) and MMP-13; and activation of the nuclear factor-κB (NF-κB) inflammatory signaling pathway. These results suggest a promising potential role for GPR43 as a specific target in the treatment and prevention of RA.
32648248 Does Older Age have an Impact on Rituximab Efficacy and Safety? Results from the NOR-DMARD 2020 Aug OBJECTIVE: The objective of this study was to compare the efficacy and safety of rituximab in older vs younger patients with rheumatoid arthritis. METHODS: Data on 367 patients with rheumatoid arthritis treated with rituximab in the Norwegian Disease-Modifying Antirheumatic Drug (NOR-DMARD) register were analysed, comparing patients aged ≥ 65 years (n = 91) with patients aged < 65 years (n = 276). Drug survival was compared using a Kaplan-Meier analysis and Cox proportional hazard models. Disease activity, as assessed by the Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR) and the Simplified Disease Activity Index, was analysed with linear mixed models. The occurrence of adverse events was analysed by quasi-Poisson regression models. RESULTS: Drug survival was similar in the two age groups. The proportion of patients who remained taking rituximab over 2 years was 72% in those under aged 65 years vs 74% in those aged ≥ 65 years. No statistically significant association with age was found for drug survival in either the unadjusted (hazard ratio 1.13, p = 0.65) or adjusted Cox proportional hazard analyses for the model with DAS28-ESR as a confounder (effect size 1.11, p = 0.73). Models including the Simplified Disease Activity Index instead of DAS28-ESR yielded similar results. Age was furthermore not significantly associated with disease activity over time, although there was a tendency towards a poorer response in older patients. In the older age group, there was a higher incidence of pneumonia (107 vs 51 per 1000 patient-years) and other serious infections (142 vs 66 per 1000 patient-years). CONCLUSIONS: Rituximab is a reasonable therapeutic option for older patients with rheumatoid arthritis although vigilance is needed with regard to the infection profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01581294.
32539713 JAK inhibitors impair GM-CSF-mediated signaling in innate immune cells. 2020 Jun 15 BACKGROUND: Innate immune cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via release of cytokines. Small-molecule inhibitors of Janus kinases (JAKi) are clinically efficacious in patients with RA. However, the isoform-specific action of each JAKi is difficult to assess, since JAKs form heterodimeric complexes with cytokine receptors. We assessed the effects of several JAKi on GM-CSF-primed human innate immune cells. RESULTS: Treatment with JAKi (tofacitinib, baricitinib, upadacitinib) prevented GM-CSF-induced JAK2/STAT5 phosphorylation at higher concentrations (400 nM) in THP-1 cells. Whereas compared with baricitinib or upadacitinib, the inhibitory effects of tofacitinib on the GM-CSF-induced JAK2/STAT5 phosphorylation were weak at lower concentrations (≤ 100 nM). All JAKi inhibited GM-CSF-induced IL-1β production by human neutrophils. However, the inhibitory effects of baricitinib on IL-1β production were larger compared to those of tofacitinib or upadacitinib at lower concentrations (≤ 100 nM). Similarly, all JAKi inhibited GM-CSF-induced caspase-1(p20) production by human neutrophils. CONCLUSION: We conclude that incubation with JAKi prevents GM-CSF-mediated JAK2/STAT5 activation in human innate immune cells. Although baricitinib and upadacitinib almost completely blocked GM-CSF-mediated JAK2/STAT5 signaling, the inhibitory effects of tofacitinib were weaker at lower concentrations suggesting that variation exists among these JAKi in the inhibition of JAK2 signaling pathways.
32852139 Immunogenicity of an adalimumab biosimilar, FKB327, and its reference product in patients 2020 Nov AIM: This study, FKB327-003, is a phase 3, open-label extension (OLE) study comparing the long-term immunogenicity of an adalimumab biosimilar, FKB327 (F), with the reference product (RP). METHODS: In the OLE, patients completing 24 weeks of an initial randomized, double-blind (DB) study (Period 1) with clinical response and no safety concerns were rerandomized to F or RP, so that two-thirds of patients remained on the same treatment and one-third switched to the alternate treatment for weeks 24 through 54 (OLE weeks 0-30; Period 2), then all received F through week 100 (OLE week 76; Period 3). Treatment sequences were F-F-F (no switch), RP-F-F and RP-RP-F (single switch), and F-RP-F (double switch). Patients who entered the OLE study were evaluated for immunogenicity across switching sequences. RESULTS: The proportion of patients with positive antidrug antibody (ADA) status at the end of Period 1 was 61.7% and 60.0% for F and RP, respectively. The proportion of patients with positive ADA status did not increase throughout Period 1, and was similar for F and RP at all time points. At the end of Period 3, the proportion of patients with positive ADA status was lower in all treatment sequences, at 51.1%, 54.4%, 48.1%, and 42.5% for F-F-F, F-RP-F, RP-F-F, and RP-RP-F, respectively. CONCLUSION: The RP and F showed comparable immunogenicity characteristics after long-term administration. Development of ADAs with the RP and F was similar, and was not impacted by switching and double switching between F and RP treatment.
32205219 Low but Long-lasting Risk of Reversal of Seroconversion in Patients With Rheumatoid Arthri 2020 Oct BACKGROUND & AIMS: In patients who have resolved hepatitis B virus (HBV) infection, treatment of rheumatoid arthritis (RA) can result in reappearance of hepatitis B surface antigen (HBsAg), called reverse seroconversion. We investigated clinical features and outcomes of reverse seroconversion in patients who received immunosuppressant or biologic therapy for RA. METHODS: We identified 1494 patients with RA (925 who resolved HBV infection) and available data on levels of antibody to HB core antigen and HBsAg who had attended Taipei Veterans General Hospital from January 2007 through December 2017. We identified 17 cases (median age, 66 years) who were negative for HBsAg before treatment of RA and reverse seroconversion (HBsAg reappearance) after glucocorticoid treatment (n = 13) and/or biologic therapy (adalimumab, n = 2; etanercept, n = 1; rituximab, n = 9; or abatacept, n = 4). Four patients were positive for antibodies against HBsAg (seroconverted) before the immunosuppressive treatment. RESULTS: The median time from immunosuppressive treatment to reverse seroconversion was 120 months (range, 20-264 months), whereas the time from biologic therapy treatment to reverse seroconversion was 66 months (range, 10-105 months). After reverse seroconversion, 8 individuals (47.1%) were positive for HB e antigen; 9 cases (52.9%) did not have a flare of alanine transaminase. However, 3 patients (17.6%) developed liver decompensation. CONCLUSIONS: In patients who resolved HBV infection and received immunosuppressant treatment of RA, risk of reversal of seroconversion is low but persists for up to 10 years. Patients with RA who previously resolved HBV infections should be monitored for levels of HBsAg and HBV DNA once immunosuppressive treatment of RA begins.
32576440 Does Preparation of the Subtalar Joint for Primary Union Affect Clinical Outcome in Patien 2020 Sep This study aimed to evaluate whether preparation of the subtalar joint affects the clinical outcomes after tibiotalocalcaneal arthrodesis using an intramedullary nail with fins for rheumatoid ankle/hindfoot deformity. Fifty-three joints in 51 patients who underwent tibiotalocalcaneal arthrodesis using an intramedullary nail with fins for rheumatoid arthritis at 2 institutions were included. Ten patients were male and 41 were female, with a mean age at surgery and follow-up period of 61.3 years and 71.6 months, respectively. Radiographic bone union was evaluated at the most recent visit. Univariate and multivariable analyses were performed to determine the risk factors associated with nonunion. The mean postoperative Japanese Society for Surgery of the Foot ankle/hindfoot scale was 65.3 (range, 5-84). The tibiotalar nonunion rate was 0%, whereas the subtalar nonunion rate was 43.3% (23 joints). Revision surgery was performed in 5, all of which were due to painful subtalar nonunion. Absence of subtalar curettage and earlier postoperative weightbearing were significantly associated with subtalar nonunion (p = .0451 and p = .0438, respectively). Subtalar nonunion after tibiotalocalcaneal arthrodesis for rheumatoid hindfoot is associated with higher revision rate. To decrease the risk of subtalar nonunion after tibiotalocalcaneal arthrodesis with an intramedullary nail in rheumatoid patients, curettage for the subtalar joint should be performed, and full weightbearing should be delayed until at least 26 days postoperatively.
31894253 Humulus japonicus extract ameliorates collagen‑induced arthritis in mice through regulat 2020 Feb Humulus japonicus (HJ) is a widely used herbal medicine in Asia with anti‑oxidative, anti‑microbial, and anti‑inflammatory effects. We investigated the potential therapeutic effects of HJ in rheumatoid arthritis (RA) using a mouse model of collagen‑induced arthritis (CIA) and a lipopolysaccharide‑stimulated murine macrophage cell line (RAW 264.7). The CIA mice were administered 300 mg/kg HJ orally starting 3 days prior to second immunization. The clinical and histopathological findings were assessed in the paw of CIA mice. The levels of autoantibodies and inflammatory markers were determined in the plasma and cell culture supernatant, respectively. The expression at mRNA and protein levels was analyzed by reverse transcription quantitative‑PCR and western blot analysis, respectively. HJ significantly decreased the gross arthritic scores and paw swelling in CIA mice. Furthermore, synovial inflammation, cartilage destruction, and bone erosion were markedly reduced by HJ. It also decreased the expression of inflammatory enzymes in both the paw of mice and RAW 264.7 cells. Moreover, the expression of genes related to all macrophages and pro‑inflammatory M1 macrophage were significantly decreased, whereas the expression of anti‑inflammatory M2 macrophage marker was markedly increased in the paw of HJ‑treated CIA mice. In addition, HJ suppressed the levels of plasma anti‑type II collagen antibody following the decreased expression of T helper type 1 (Th1) and Th2 cell‑associated surface markers and cytokines in the paw. HJ also significantly inhibited the expression of IL‑6 both in vitro and in vivo, followed by reduced STAT3 phosphorylation and expression in the paw of CIA mice. Finally, the expression of osteoclast‑related genes was decreased in the paw of HJ‑treated CIA mice. These findings suggest that HJ can play a role in suppressing the development of CIA by overall regulation of articular inflammation. This study should provide new insights into the use of HJ as a therapeutically effective natural product against RA.
32088800 Effects of rituximab therapy on B cell differentiation and depletion. 2020 May Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell‑mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38(++)CD24(++)IgD(+/-) immature B cells and IgD(-)CD38(+/-) memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4(+)CD25(+)CD127(-/low) Treg cells and CD19(+)CD24(hi)CD38(hi) Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19(+/-)CD27(++)CD38(++) preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders.