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ID PMID Title PublicationDate abstract
31174962 Trabecular Bone Score Is a Useful Parameter for the Prediction of Vertebral Fractures in P 2020 Jul INTRODUCTION: Polymyalgia rheumatica (PMR), a benign rheumatic disorder, requires long-term glucocorticoid therapy, which could be associated with osteoporosis. In the present study, we compared bone mineral density (BMD), trabecular bone score (TBS) and frequencies of vertebral fracture (VF) among patients with PMR or rheumatoid arthritis (RA) and controls. METHODS: Fifty-three postmenopausal women with PMR aged 50 yr or older were eligible for inclusion in this study. Subjects in RA (n = 106) and control (n = 106) groups were selected by propensity score matching with controlling age, body mass index and use of anti-osteoporotic agents. RESULTS: The frequency of VF in patients with PMR (30.2%) was significantly higher than those in patients with RA (13.2 %) and controls (13.2%, p = 0.017). The mean TBS of patients with PMR (1.317 ± 0.092) was significantly lower than those of patients with RA (1.336 ± 0.089) and the controls (1.373 ± 0.073, p < 0.001). In receiver operating characteristic analysis for VF in patients with PMR, the area under the curve (AUC) was 0.759 (95% confidence interval [CI] = 0.601-0.918, p < 0.001) for TBS and 0.618 (95% CI = 0.442-0.795, p < 0.001) for L-spine BMD. The AUCs were 0.760 (95% CI = 0.630-0.891, p ≤ 0.001) and 0.767 (95% CI 0.627-0.907, p < 0.001) for femur neck and total hip BMD, respectively. Multivariate analysis identified the factor associated with VF of patients with PMR as a lower TBS (Odds ratio: 0.000, 95% CI: 0.000, 0.754, p = 0.043). CONCLUSION: TBS could be a supplementary tool for discriminating osteoporotic fractures in postmenopausal patients with PMR.
33280072 Analysis of a single-institution cohort of patients with Felty's syndrome and T-cell large 2021 Jan T-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder characterized by a persistent increase in the number of large granular lymphocytes (LGLs), neutropenia, and splenomegaly. Clinical manifestations of T-LGLL in the setting of rheumatoid arthritis (RA) are often identical to those in which one would suspect Felty's syndrome (FS). These disorders are distinguished by the presence of T-cell clonality, which is present in T-LGLL but not in FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) and 5b (STAT5b) genes can be used as molecular markers of T-LGLL, but their prevalence in FS is unknown.Eighty-one patients with RA and unexplained neutropenia or/and an increase in the number of LGLs above 2 × 10(9)/L were stratified into RA-associated T-LGLL (N = 56) or FS (N = 25) groups based on the presence or absence of T-cell clonality. STAT3 and STAT5b gene mutations were assessed in each group by means of allele-specific polymerase chain reaction assays. Clinical, immunological, laboratory data and the results of immunophenotyping of blood and bone marrow lymphocytes were also evaluated.Mutations of the STAT3 gene and an increase in the number of LGLs above 2 × 10(9)/L were detected in RA-associated T-LGLL, but not in FS (39% vs 0% and 21% vs 0%, respectively). Mutations in the STAT5b gene were not observed in either group. Expression of CD57, CD16, and CD5(-/dim) on CD3(+)CD8(+) T-lymphocytes was observed in both RA-associated T-LGLL and FS.STAT3 gene mutations or LGL counts over 2 × 10(9)/L in RA patients are indicative of T-LGLL.
33219307 Chronic exposure to TNF reprograms cell signaling pathways in fibroblast-like synoviocytes 2020 Nov 20 Fibroblast-like synoviocytes (FLS) play a critical role in the pathogenesis of rheumatoid arthritis (RA). Chronic inflammation induces transcriptomic and epigenetic modifications that imparts a persistent catabolic phenotype to the FLS, despite their dissociation from the inflammatory environment. We analyzed high throughput gene expression and chromatin accessibility data from human and mouse FLS from our and other studies available on public repositories, with the goal of identifying the persistently reprogrammed signaling pathways driven by chronic inflammation. We found that the gene expression changes induced by short-term tumor necrosis factor-alpha (TNF) treatment were largely sustained in the FLS exposed to chronic inflammation. These changes that included both activation and repression of gene expression, were accompanied by the remodeling of chromatin accessibility. The sustained activated genes (SAGs) included established pro-inflammatory signaling components known to act at multiple levels of NF-kappaB, STAT and AP-1 signaling cascades. Interestingly, the sustained repressed genes (SRGs) included critical mediators and targets of the BMP signaling pathway. We thus identified sustained repression of BMP signaling as a unique constituent of the long-term inflammatory memory induced by chronic inflammation. We postulate that simultaneous targeting of these activated and repressed signaling pathways may be necessary to combat RA persistence.
32584674 Indications for Rituximab Use in an Integrated Health Care Delivery System. 2020 Jul BACKGROUND: Rituximab is a top-selling biologic that was first approved by the FDA in 1997 for a non-Hodgkin lymphoma orphan indication. It has since been approved for additional orphan indications, with rheumatoid arthritis as the only FDA-approved, nonorphan indication. Evidence suggests that rituximab is frequently used off-label, but information on its use over time and indications for use in the United States is limited. OBJECTIVE: To assess incident rituximab use over time in an integrated health care delivery system. METHODS: This was a cross-sectional, retrospective study. Data were collected from administrative databases and manual chart reviews. Patients who received their first rituximab infusion between October 1, 2009, and December 31, 2017, and who were not a part of a clinical trial were included. Indication for use (FDA-approved orphan/nonorphan, off-label) was determined. Proportions of use were assessed over time. Multivariable logistic regression modeling was performed to assess factors associated with receiving rituximab for an FDA-approved indication. RESULTS: A total of 1,674 patients were included. The majority (66.4%) of patients had an FDA-approved indication, with lymphoma being the most common approved indication (66.4%). The most common indication for off-label use was neurologic conditions (72.7%), predominantly demyelinating diseases. Off-label indication use increased from 1.2% in 2009 to 55.6% in 2017. Factors associated with rituximab use for an FDA-approved indication included increased age (adjusted odds ratio [AOR] = 1.05, 95% CI = 1.04-1.07) and increased burden of chronic disease (chronic disease score: AOR = 1.07, 95% CI = 1.02-1.12; Charlson Comorbidity Index score: AOR = 3.52, 95% CI = 3.03-4.10). CONCLUSIONS: Off-label use of rituximab grew dramatically over the course of the study. With the recent FDA approval of the rituximab biosimilar and its expected lower price, off-label use will likely continue to rise. Opportunities for cost savings and to ensure appropriate use of these medications should be evaluated. DISCLOSURES: This study was funded by Kaiser Permanente. All authors except Hansen are employed by Kaiser Permanente. Hansen has nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors in May 2019 in Salt Lake City, UT, and at an encore presentation October 2019 at the American College of Clinical Pharmacy Annual Meeting in New York, NY.
32907801 Two-year cost effectiveness between two gradual tapering strategies in rheumatoid arthriti 2020 Dec OBJECTIVE: The aim of the current study was to evaluate the 2-year cost-utility ratio between tapering conventional synthetic disease-modifying antirheumatic drugs (csDMARD) first followed by the tumour necrosis factor (TNF)-inhibitor, or vice versa, in patients with rheumatoid arthritis (RA). METHODS: Two-year data of the Tapering strategies in Rheumatoid Arthritis trial were used. Patients with RA, who used both a csDMARD and a TNF-inhibitor and had a well-controlled disease (disease activity score ≤2.4 and swollen joint count≤1) for at least 3 months, were randomised into gradual tapering the csDMARD first followed by the TNF-inhibitor, or vice versa. Quality-adjusted life years (QALYs) were derived from the European Quality of life questionnaire with 5 dimensions. Healthcare and productivity costs were calculated with data from patient records and questionnaires. The incremental cost-effectiveness ratio and the incremental net monetary benefit were used to assess cost effectiveness between both tapering strategies. RESULTS: 94 patients started tapering their TNF-inhibitor first, while the other 95 tapered their csDMARD first. QALYs (SD) were, respectively, 1.64 (0.22) and 1.65 (0.22). Medication costs were significantly lower in the patients who tapered the TNF-inhibitor first, while indirect cost were higher due to more productivity loss (p=0.10). Therefore, total costs (SD) were €38 833 (€39 616) for tapering csDMARDs first, and €39 442 (€47 271) for tapering the TNF-inhibitor (p=0.88). For willingness-to-pay (WTP) levels <€83 800 tapering, the csDMARD first has the highest probability of being cost effective, while for WTP levels >€83 800 tapering the TNF-inhibitor first has the highest probability. CONCLUSION: Our economic evaluation shows that costs are similar for both tapering strategies. Regardless of the WTP, tapering either the TNF-inhibitor or the csDMARD first is equally cost effective. TRIAL REGISTRATION NUMBER: NTR2754.
33067400 Development of a Flow Cytometry-Based Functional Assay to Study Anti-TNF Mechanisms of Act 2020 Oct 16 TNF is a key cytokine in autoimmune diseases like rheumatoid arthritis, and TNF antagonists are commonly prescribed therapeutics. Although anti-TNF drugs have enabled a very significant progress in this field, disease heterogeneity remains and causes diversity in patient response. These challenges increase the need for anti-TNF characterization tools that may open perspectives toward the development of personalized medicine. In this study, we present a novel whole blood-based flow cytometry functional assay that allows, within a given whole blood sample, the characterization of an anti-TNF molecule mechanisms of action. Whole blood from healthy human donors was employed to mimic the physiological state but also to streamline experimental workflows. Samples were incubated with LPS alone or in combination with various anti-TNF molecules such as adalimumab (ADA), etanercept (ETA), and infliximab. A 10-color flow cytometry panel including CD69, transmembrane TNF, CD16, CD62L, CD66b, CD11b, and CD54 as activation markers was used following a centrifugation-free protocol. CD69 expression decreased on NK, NKT, and T cells upon treatment with ADA, ETA, and IFX as a direct indication of forward signaling neutralization. Percentages of transmembrane TNF(+) monocytes increased after incubation when using ADA or IFX but not ETA, revealing the potential of the two first molecules to trigger reverse signaling. Ab-dependent cell cytotoxicity was informed by CD16 and CD69 expressions in some donors that showed increasing levels of CD16(-) CD69(+) NK cells when incubated with anti-TNFs. This study proposes a novel approach to assess anti-TNF mechanisms of action and provides a path toward capturing donor heterogeneity.
32641448 Increased primary care use for musculoskeletal symptoms, infections and comorbidities in t 2020 Jul OBJECTIVES: Little is known about relevant events in the at-risk phase of rheumatoid arthritis before the development of clinically apparent inflammatory arthritis (IA). The present study assessed musculoskeletal symptoms, infections and comorbidity in future IA patients. METHODS: In a nested case-control study using electronic health records of general practitioners, the frequency and timing of 192 symptoms or diseases were evaluated before a diagnosis of IA, using the International Classification of Primary Care coding system. Cases were 2314 adults with a new diagnosis IA between 2012 and 2016; controls were matched 1:2. The frequency of primary care visits was compared using logistic regression. RESULTS: The frequency of visits for musculoskeletal symptoms (mostly of shoulders, wrists, fingers and knees) and carpal tunnel syndrome was significantly higher in IA patients vs controls within the final 1.5 years before diagnosis, with ORs of 3.2 (95% CI 2.8 to 3.5), 2.8 (95% CI 2.5 to 3.1) and 2.5 (95% CI 2.2 to 2.8) at 6, 12 and 18 months before diagnosis, respectively. Also, infections (notably of the genital and urinary tracts), IA-comorbidities and chronic diseases were more prevalent in cases than controls, but more evenly spread out over the whole 6-year period before IA. A decision tree was created including all symptoms and diseases. CONCLUSION: There was an increased frequency of primary care visits for musculoskeletal symptoms, infections and comorbidities prior to the diagnosis of IA. This diverging trend is present for 4-6 years, but becomes statistically significant 1.5 years before the diagnosis. Validation of these results is warranted.
33030631 A multimodal intervention increases influenza vaccine uptake in rheumatoid arthritis. 2021 Feb Annual influenza vaccination is recommended for patients with rheumatoid arthritis (RA), but coverage is suboptimal. We assessed the impact of an implementation strategy in enhancing vaccination uptake in RA. We evaluated a multimodal implementation strategy at rheumatology clinics that included 3 approaches: patient recalls, a nurse providing vaccines, and physician reminders. We compared patient-reported vaccination rates after implementation with those reported before the implementation strategy in a nonequivalent control group. In multivariate analyses, we assessed factors potentially associated with influenza vaccine uptake. One hundred and sixteen RA patients were vaccinated during the intervention. The influenza vaccination rate in RA increased from 48.5% (65/136) before implementation to 62.6% (67/107) after implementation (difference of 14.1, 95% CI 1.5, 26.1). In multivariate analyses, older age, biologics use, and physician recommendation for vaccination were associated with influenza vaccine uptake. A multimodal intervention was associated with increased influenza vaccine coverage among RA patients. Older patients and those on biologics were more likely to be immunized against influenza. Physician's recommendations are important to promote vaccine coverage. Key Points • Despite current recommendations, influenza vaccine uptake among rheumatoid arthritis (RA) patients is suboptimal. • A multimodal implementation strategy facilitating access to influenza vaccine and raising awareness through vaccination reminders improved immunization uptake in RA. • Physicians play a key role in promoting annual seasonal influenza vaccination. • The reasons for vaccine hesitancy in RA should be addressed to reach a vaccination target of 80% required to reduce the burden of this preventable infection.
31820135 A quality improvement intervention failed to significantly increase pneumococcal and influ 2020 Mar OBJECTIVES: Pneumococcal and influenza vaccination rates have been suboptimal in studies of immunosuppressed patients. We aimed to assess barriers to and increase rates of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influenza vaccination in this group. The primary endpoint was a statistically significant increase in adequate PPSV23 and influenza vaccination. METHODS: In 2017, rheumatology outpatients completed an anonymous questionnaire recording vaccination knowledge, status, and barriers. Simultaneously, a low-cost multifaceted quality improvement (QI) intervention was performed. All outpatients on oral steroids, immunosuppressant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologics disease-modifying antirheumatic drugs (bDMARDs) were included in the study. In 2018, post-intervention, the clinic was re-assessed. Demographics, diagnosis, medications, smart phone access, and willingness to use this for vaccination reminders were assessed for independent vaccination predictors using binary logistic regression analysis. RESULTS: Four hundred twenty-five patients were included (72.6% rheumatoid arthritis, 74% women, 45.6% ≥ 60 years old). From 2017 to 2018, PPSV23 vaccination rates changed from 41.0 to 47.2% (P = 0.29) and influenza from 61.8 to 62.1% (P = 0.95). The most common reason for non-vaccination was lack of awareness. Following the intervention, this changed for influenza (36.7 to 34.2%) and PPSV23 (82.1 to 76.4%). General practitioners performed most vaccinations, only 3.6% were delivered in the hospital. Significant predictors of PPSV23 vaccination were older age {≥ 80 years had an OR 41.66 (95% CI 3.69-469.8, P = 0.003), compared with ≤ 39 years}, bDMARD use (OR 2.80, 95% CI 1.24-6.32, P = 0.013), and adequate influenza vaccination (OR 9.01, 95% CI 4.40-18.42, P < 0.001). Up-to-date PPSV23 vaccination (OR 8.93, 95% CI 4.39-18.17, P < 0.001) predicted influenza vaccination. CONCLUSIONS: PPSV23 and influenza vaccination rates were suboptimal. The intervention did not cause a statistically significant change in vaccination rates. Point-of-care vaccination may be more effective.Key Points• Low vaccination rates amongst immunosuppressed inflammatory arthritis outpatients• Less than 5% of vaccinations occurred in hospital• There was no statistically significant difference in the rates of adequate PPSV23 (41.0 to 47.2%) or influenza (61.8 to 62.1%) vaccination following our intervention.
32271590 Microparticles-in-Thermoresponsive/Bioadhesive Hydrogels as a Novel Integrated Platform fo 2020 Jun 1 Intra-articular (IA) injection of thermoresponsive hydrogels coupled with microparticles (MPs) possess the benefit of sustaining the anti-inflammatory drug effect within the joint cavity for rheumatoid arthritis treatment. Star-shaped thermoresponsive poly(polyethylene glycol) methacrylate [Poly(PEGMA)] copolymers were synthesized using free radical polymerization technique and fully characterized. Triamcinolone acetonide (TA)-loaded PLA/mPEG-PDL MPs, previously optimized, were integrated into the synthesized copolymer solutions at various concentrations and tested for their gelation temperatures. The MPs-in-hydrogel formulations were characterized using scanning electron microscope (SEM), viscosity measurements, ex vivo bioadhesion, and in vitro release studies. The anti-inflammatory effect of integrated systems was assessed in adjuvant-induced monoarthritic rat knee joints and compared to Kenacort and TA-loaded MPs. Two copolymers were successfully synthesized; G-1 = poly(PEGMA(188)-ME-co-PEGMA(475)-ME) and G-2 = poly(PEGMA(246)-EE-co-PEGMA(475)-ME). Using the tube inversion technique, the gel formation was found dependent on copolymer concentration. An irreversible aggregation was obtained at copolymer concentrations ≤10% (w/v), while a gel was formed at 20 and 30% (w/v) of both copolymers upon increasing temperature. The MP-hydrogel formulations were optimized at 20 and 30% (w/v) of G-1 and G-2 with gelation temperatures of 33 and 37 °C, respectively. SEM images revealed the porous microstructures of hydrogels and their adsorption on MP surfaces. The integrated formulas showed pseudoplastic behaviors, while the bioadhesion study confirmed their bioadhesiveness on excised cartilage. The in vitro release study confirmed drug sustainment from MPs-hydrogels compared to MPs. In vivo studies proved the superiority of MP-in-hydrogels in treatment of induced arthritis, relative to Kenacort and MPs alone, suggesting the applicability of this integrated platform in IA drug delivery.
32782226 Total ankle arthroplasty and ankle arthrodesis in rheumatic disease patients: An analysis 2021 Apr INTRODUCTION: Rheumatoid arthritis (RA), can manifest as an inflammatory arthropathy in the ankle. As a result, this study sought to examine the role of RA with respect to complications in patients undergoing either total ankle arthroplasty or ankle arthrodesis by utilizing the National Inpatient Sample to assess for correlations. METHODS: Admissions for TAA and AA were extracted from the National Inpatient Sample using primary ICD-9-CM diagnosis codes. Patients aged 18-65 years with a duration of hospital stay of >3 days and isolated complications were included. Multivariable regression was then performed within matched groups to determine differences. RESULTS: There was decreased risk of myocardial infarction, pulmonary embolism, surgical site infection, and urinary tract infection in patients with RA. Postoperative development of pneumonia was seen at a higher rate in patients with RA. CONCLUSION: RA is not associated with a markedly increased complication burden in the appropriately chosen surgical candidate for ankle arthrodesis and ankle arthroplasty.
31523041 Reliability of Magnetic Resonance Imaging (MRI) Scoring of the Metatarsophalangeal Joints 2020 Aug 1 OBJECTIVE: The Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is validated for hand MRI. Its reliability applied to metatarsophalangeal (MTP 1-5) joints is unknown and was studied in early arthritis and clinically suspect arthralgia. METHODS: Patients underwent 1.5 Tesla MRI of MTP, metacarpophalangeal (MCP 2-5), and wrist joints. Two paired readers scored bone marrow edema (BME), synovitis, tenosynovitis, and erosions. Interreader reliability was assessed of 441 consecutive early arthritis patients at baseline, 215 by 2 readers, and the remaining 226 by 2 different readers. Two readers scored baseline MRI of 82 consecutive patients with clinically suspect arthralgia, and 40 randomly selected patients by 9 readers. Intrareader reliability was determined on a random set of 15 early arthritis patients, scored twice by 2 readers. For change scores, 30 early arthritis patients with baseline and 1-year followup MRI were scored by 2 readers. Intraclass correlation coefficients (ICC), Bland-Altman (BA) plots, and smallest detectable change (SDC) were determined. MRI data of MTP joints were compared to wrist and MCP joints. RESULTS: Interreader ICC and mean scores in early arthritis were BME ICC 0.91-0.92 (mean 1.5 ± SD 2.6), synovitis 0.90-0.92 (1.3 ± 1.7), tenosynovitis 0.80-0.85 (1.1 ± 1.8), and erosions 0.88-0.89 (0.7 ± 1.0). In patients with clinically suspect arthralgia, ICC were comparable. Intrareader ICC for inflammatory MRI features were 0.84-0.98, for erosions 0.71 (reader 1), and 0.92 (reader 2). Change score ICC were ≥ 0.90, except erosions (0.77). SDC were ≤ 1.0. BA plots showed no systematic bias. Reliability scores of MTP joints were similar to MCP and wrist joints. CONCLUSION: Status and change MRI scores of BME, synovitis, tenosynovitis, and erosions of MTP joints can be assessed reliably by RAMRIS.
32609446 A case of new-onset vitiligo in a patient on tofacitinib and brief review of paradoxical p 2020 Mar 15 With recent advancements in the understanding of vitiligo pathogenesis, Janus kinase (JAK) inhibitors have emerged as a promising new treatment modality, but their effects remain incompletely elucidated. Tofacitinib, an oral JAK 1/3 inhibitor approved for the treatment of rheumatoid arthritis, has previously been shown to induce significant re-pigmentation in vitiligo. However, as with other novel targeted therapies, cutaneous adverse effects have been observed. We report a 36-year-old woman with a history of rheumatoid arthritis, refractory to multiple pharmacotherapies, who was initiated on tofacitinib and subsequently developed progressive depigmented patches consistent with new-onset vitiligo. Although definitive causation cannot be established in this case without additional studies, it is important to note that many targeted therapies have the potential to induce paradoxical effects, that is, the occurrence or exacerbation of pathologic conditions that have been shown to respond to these medications. Paradoxical findings with other targeted therapies include the occurrence of melanoma during treatment with BRAF inhibitors, keratoacanthomas with PD-1 inhibitors, vitiligo and psoriasis with TNF-alpha inhibitors, and hidradenitis suppurativa with various biologic agents. Although JAK inhibitors hold therapeutic promise in the treatment of inflammatory skin disorders, further research is warranted to more fully comprehend their effects.
32945021 SARS-CoV-2 infection in an advanced rheumatoid arthritis patient. 2020 Dec In late 2019, pneumonia due to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in Wuhan, China, which has immediately spread around the world. The major clinical manifestations of COVID‐19 include a range from asymptomatic presentation to acute respiratory distress syndrome (ARDS) [1]. Rheumatoid Arthritis (RA) patients usually managed with immunosuppressive agents, hence, they are at a higher risk of infections [2]. However, limited data are available about the severe case of COVID‐19 in RA patients [3‐7]. Here we present a complicated case of SARS‐CoV‐2 infection in a female RA patient.
31782014 Symptomatic elevation creatine kinase following treatment of rheumatoid arthritis with bar 2020 Feb The aim of RA treatment is to achieve reduction of disease activity and prevent joint damage and disability. Baricitinib is a synthetic small molecule which targets the JAK/STAT pathway which is implicated in the inflammatory response in RA. Baricitinib selectively targets JAK1 and JAK2 and has been shown to have efficacy in treating patients with RA. Common adverse effects reported during baricitinib therapy includes infection, asymptomatic changes in laboratory parameters including changes in neutrophil, lymphocyte, platelet counts, alanine aminotransferase, cholesterol, creatinine and creatine kinase (CK). We report the first two documented cases in Australia of baricitinib-induced symptomatic elevation of CK.
31393189 Investigation of the predictors of the response to Iguratimod therapy: A post-hoc analysis 2020 Jul Objectives: The treatment response according to patient disease activity during Iguratimod therapy for rheumatoid arthritis has not been sufficiently assessed. A post-hoc analysis of post-marketing surveillance was performed. The treatment effect was evaluated using the European League against Rheumatism (EULAR) response criteria.Methods: Disease Activity Score (DAS) 28 was assessed at various time points. Patients showing a moderate or good response according to the EULAR response criteria at 24 weeks after the start of Iguratimod therapy were considered Responders. Propensity score matching was also performed, after which the factors with the greatest effect on the treatment evaluation were investigated.Results: The mean DAS28 at the start of administration and after 24 weeks was 4.31 and 2.52, respectively, in the Responder and 3.48 and 3.48, respectively, in the Non-responder. After propensity score matching for patient characteristics, the primary factors found to be related to being a Responder were concomitant use of methotrexate (MTX) with Iguratimod, and prior treatment with MTX before the start of Iguratimod.Conclusion: As factors related to the treatment effect, the concomitant use of MTX may contribute to achieving a better effect, and this study has shown that real-world are consistent with the results of clinical trials.
31580454 Influence of prior antibiotic use on risk of rheumatoid arthritis: case control study in g 2020 Jun 1 OBJECTIVES: To test the hypothesis that prior antibiotics influences the risk of developing RA. METHODS: A case-control study was conducted over 15 years using the UK's Royal College of General Practitioners Research and Surveillance Centre database. The frequency and type of antibiotic prescription for patients who subsequently developed RA were compared with antibiotic prescriptions in a control group of patients who remained free of RA. Cases, defined as patients with a new diagnosis of RA made between 2006 and 2018, were matched with up to four RA-free controls on practice, age, gender and date of diagnosis. Exposure was measured by the number and type of prescriptions for antibiotics prior to the RA diagnosis or to the index date in controls. RESULTS: A total of 8482 patients with a new diagnosis of RA between 2006 and 2018 were compared with 22 661 controls. There was a higher likelihood of an RA diagnosis after antibiotic prescriptions within 1 year, 5 years and ever with a strong dose-response. Patients receiving >10 antibiotics in a 5 year period were more than twice as likely to receive an RA diagnosis as controls [adjusted odds ratio 2.65 (CI 2.40, 2.93)]. CONCLUSION: Exposure to antibiotics prior to the diagnosis was a significant risk factor for RA. This could reflect an immunological response to a compromised microbiome. Alternatively, patients with pre-symptomatic or early undiagnosed RA may have been more likely to present to their general practitioner with infections due to an unrecognized effect of RA.
33107629 Cy3-tilmanocept labeling of macrophages in joints of mice with antibody-induced arthritis 2021 Apr γ-Tilmanocept ((99m) Tc-tilmanocept) is a receptor-directed, radiolabeled tracer that is FDA-approved for guiding sentinel lymph node biopsy. Tilmanocept binds the C-type lectin mannose receptor (MR, CD206) on macrophages. In this study, nonradioactive, fluorescently-labeled Cy3-tilmanocept was used to detect CD206(+) mononuclear cells in the cartilage of mice with antibody-induced arthritis and in the synovial fluid and tissue of human subjects with rheumatoid arthritis (RA) for comparison with osteoarthritis (OA), and healthy volunteer (HV) controls. Murine arthritis was induced by injection of monoclonal anti-cartilage antibody followed by injection of Escherichia coli lipopolysaccharide. Post-arthritis development (7-11 days), the mice were injected intravenously with Cy3-tilmanocept followed by in vivo and ex vivo epifluorescence imaging. Two-photon imaging, immunofluorescence, and immunohistochemistry were used to identify articular and synovial macrophages (CD206, F4/80, and Cy3-tilmanocept binding) in murine tissues. Cy3-tilmanocept epifluorescence was present in arthritic knees and elbows of murine tissues; no radiographic changes were noted in the skeletons. However, inflammatory arthritic changes were apparent by histopathology and immunohistochemistry (F4/80), immunofluorescence (CD206) and Cy3-tilmanocept binding. In human RA synovial fluid, Cy3-tilmanocept staining correlated with CD206(+) /CD16(+) cells; negligible labeling was observed in OA samples. Cy3-tilmanocept colocalized with CD206 and staining was significantly higher in RA synovial tissue compared to OA or HV. Our results demonstrate that imaging with Cy3-tilmanocept can detect in vivo inflammatory, CD206(+) macrophages in an early arthritis animal model and in human RA patients. These data establish a novel tool for preclinical research of early arthritis and have implications for early RA detection and monitoring of therapeutic efficacy in humans.
32833085 Certain perspectives about the use of corticosteroids for managing hospitalized patients w 2020 Oct The administration of cortisone to a bedridden patient with rheumatoid arthritis (RA) 70 years ago was a transformative event in modern medicine. We have since struggled to balance the near-miraculous anti-rheumatic with the yet all-too-frequent devastating side effects of glucocorticoids (GC). With the current availability of newer disease-modifying and biologic anti-rheumatic agents, we were rather surprised to note that 94% of sick hospitalized patients with systemic rheumatic diseases at our medical center were on corticosteroids during a 3-month observation period. Comparing contemporary with past practices from historical references, we confirmed a perhaps paradoxical trend of increasing steroid usage in certain contexts over the years. Sixty-seven percent of our hospitalized lupus patients were started on GC of greater than 30 mg prednisone equivalent compared with 50% in the 1950s. Seventy-five percent of our RA inpatients had their GC dose increased on discharge. Both (2/2) our new RA patients were started on GC, compared with 69% in the 2000s and just 36% in the 1990s. This likely reflects both improved abilities to keep sick patients alive and inability of other anti-rheumatic therapies to consistently induce or sustain disease remission compared with the usually highly efficacious yet inexpensive GC in these particular patients. Administration of glucocorticoids to ill, often infected, patients with systemic rheumatic diseases remains more art than science. Current perspectives view glucocorticoids as considerably less salutary than previously thought; we are still challenged to keep our patients from developing preventable complications. These observations emphasize the need for more and better therapeutic alternatives to glucocorticoids. There are now several examples-disease-modifying and biologic medications for RA and biologics for lupus and vasculitis-that suggest the possibility of caring for our patients without the historical reliance on corticosteroids. We have made enormous progress since steroids were first offered to a patient with RA in 1948. We are hopeful the future will bring us interventions of comparable or better efficacy that are safer.
32791850 Radiographic and Clinical Outcomes of the Salto Talaris Total Ankle Arthroplasty. 2020 Dec BACKGROUND: The Salto Talaris is a fixed-bearing implant first approved in the US in 2006. While early surgical outcomes have been promising, mid- to long-term survivorship data are limited. The aim of this study was to present the survivorship and causes of failure of the Salto Talaris implant, with functional and radiographic outcomes. METHODS: Eighty-seven prospectively followed patients who underwent total ankle arthroplasty with the Salto Talaris between 2007 and 2015 at our institution were retrospectively identified. Of these, 82 patients (85 ankles) had a minimum follow-up of 5 (mean, 7.1; range, 5-12) years. The mean age was 63.5 (range, 42-82) years and the mean body mass index was 28.1 (range, 17.9-41.2) kg/m(2). Survivorship was determined by incidence of revision, defined as removal/exchange of a metal component. Preoperative, immediate, and minimum 5-year postoperative AP and lateral weightbearing radiographs were reviewed; tibiotalar alignment (TTA) and the medial distal tibial angle (MDTA) were measured to assess coronal talar and tibial alignment, respectively. The sagittal tibial angle (STA) was measured; the talar inclination angle (TIA) was measured to evaluate for radiographic subsidence of the implant, defined as a change in TIA of 5 degrees or more from the immediately to the latest postoperative lateral radiograph. The locations of periprosthetic cysts were documented. Preoperative and minimum 5-year postoperative Foot and Ankle Outcome Score (FAOS) subscales were compared. RESULTS: Survivorship was 97.6% with 2 revisions. One patient underwent tibial and talar component revision for varus malalignment of the ankle; another underwent talar component revision for aseptic loosening and subsidence. The rate of other reoperations was 21.2% (n = 18), with the main reoperation being exostectomy with debridement for ankle impingement (n = 12). At final follow-up, the average TTA improved 4.4 (± 3.8) degrees, the average MDTA improved 3.4 (± 2.6) degrees, and the average STA improved 5.3 (± 4.5) degrees. Periprosthetic cysts were observed in 18 patients, and there was no radiographic subsidence. All FAOS subscales demonstrated significant improvement at final follow-up. CONCLUSIONS: We found the Salto Talaris implant to be durable, consistent with previous studies of shorter follow-up lengths. We observed significant improvement in radiographic alignment as well as patient-reported clinical outcomes at a minimum 5-year follow-up. LEVEL OF EVIDENCE: Level IV, retrospective case series.