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ID PMID Title PublicationDate abstract
33322318 Efficacy of Spice Supplementation in Rheumatoid Arthritis: A Systematic Literature Review. 2020 Dec 11 BACKGROUND: Spices, i.e., curcumin, ginger, saffron, and cinnamon, have a thousand-year history of medicinal use in Asia. Modern medicine has begun to explore their therapeutic properties during the last few decades. We aimed to perform a systematic literature review (SLR) of randomized controlled trials (RCTs) assessing the effect of spice supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis, or psoriatic arthritis). METHODS: An SLR of RCTs, reviews, and meta-analyses was performed, searching for articles in MEDLINE/PubMed. Abstracts from international rheumatology and nutrition congresses (2017-2020) were also scrutinized. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration's tool and the Jadad scale. RESULTS: Altogether, six studies, assessing the use of spice supplementation only in RA patients, were included: one on garlic supplementation, two on curcumin, one on ginger, one on cinnamon, and one on saffron supplementation. Garlic, ginger, cinnamon, or saffron supplementation was associated with a decrease in RA clinical activity. However, several points limit the external validity of these studies. No conclusion on the impact of curcumin supplementation on RA activity could be drawn due to low-quality studies. CONCLUSIONS: Garlic, ginger, cinnamon, and saffron supplementation could have a beneficial effect on RA activity, but the risk of bias of these studies is difficult to assess and data are too limited to recommend them in daily practice.
32396523 Prognosis of pneumonia in patients with rheumatoid arthritis: the role of medication and d 2020 Feb OBJECTIVE: Patients with rheumatoid arthritis (RA) experience an increased risk of infections, but the prognosis of infections is unclear. We examined if patients with RA have worse outcomes from pneumonia than non-RA individuals. METHODS: In a population-based cohort study, we computed 90-day mortality rates and crude and adjusted HRs comparing pneumonia patients with and without RA. Among patients with RA, we evaluated prognostic effects of RA medications including prednisolone and disease activity as assessed by C reactive protein (CRP) or platelet levels measured 30-180 days before admission to avoid any influence from the subsequent infection. RESULTS: Among 52 577 patients hospitalised for the first time with pneumonia, 1220 (2.3%) had RA. The 90-day mortality was 19.9% for patients with RA and 18.9% for non-RA patients (adjusted 90-day HR of 1.05 (95% CI 0.92 to 1.19)). Compared with CRP levels <8 mg/L, CRP levels ≥20 mg/L predicted increased mortality in patients with RA with adjusted 90-day HRs of 4.98 (95% CI 2.19 to 11.36). Compared with methotrexate monotherapy, both prednisolone (HR 1.43 (95% CI 0.91 to 2.22)) and no RA therapy (HR 1.35 (95% CI 0.85 to 2.14)) tended to increase 90-day mortality. Compared with patients who used prednisolone and had low CRP levels, high CRP predicted increased mortality both in patients who used prednisolone (HR 3.09, 95% CI 1.25 to 7.65) and those who did not (HR 2.35, 95% CI 0.94 to 5.87). CONCLUSIONS: Overall, RA does not increase mortality following hospitalisation for pneumonia. However, high RA disease activity prior to admission predicts increased pneumonia mortality in patients regardless of prednisolone use.
32648642 Identification of Clinically and Pathophysiologically Relevant Rheumatoid Factor Epitopes 2020 Dec OBJECTIVE: Rheumatoid factors (RFs), which are anti-IgG autoantibodies strongly associated with rheumatoid arthritis (RA), are also found in other diseases and in healthy individuals. RFs bind to various epitopes in the constant (Fc-) domain of IgG. Therefore, disease-specific reactivity patterns may exist. This study was undertaken in order to develop a new approach to dissecting RF epitope binding patterns across different diseases. METHODS: We analyzed RF reactivity patterns in serum from patients with seropositive arthralgia, patients with RA, and patients with primary Sjögren's syndrome (SS) using bioengineered, natively folded IgG-Fc targets that demonstrated selective RF binding toward several distinct regions of the IgG-Fc domain. RESULTS: Rheumatoid factor responses primarily bound the Fc Elbow region, with a smaller number of RFs binding the Fc Tail region, while the Fc receptor binding region was hardly targeted. A restricted reactivity against the IgG-Fc Tail region was associated with less positivity for anti-citrullinated protein antibodies (ACPAs) and less arthritis development in arthralgia, whereas combined reactivity toward IgG-Fc Tail and Elbow regions was associated with more arthritis development. Reactivity toward the IgG-Fc Tail region was observed far more frequently in RA than in primary SS. CONCLUSION: Bioengineered IgG targets enable serologic characterization of RF reactivity patterns, and use of this approach appears to reveal patterns associated with ACPA detection and arthritis development in patients with arthralgia. These patterns are able to distinguish RA patients from primary SS patients. This new methodology improves the clinical value of RFs and our understanding of their pathophysiologic processes.
33161375 Hydroxychloroquine and the risk of respiratory infections among RA patients. 2020 Nov OBJECTIVES: To determine the effect of hydroxychloroquine on the incidence of new respiratory infections in a large registry of rheumatoid arthritis (RA) patients compared with a matched cohort receiving other conventional disease-modifying antirheumatic drugs (csDMARDs). METHODS: We reviewed physician-reported infections including upper respiratory infections (URI), bronchitis and pneumonia in the Corrona RA registry from June 2008 to February 2020 with the goal of comparing infections in biologic/targeted synthetic (b/ts) DMARDs naive HCQ starts compared with starts of other csDMARDs and no HCQ. Patients on different interventions were compared using time-varying adjusted Cox models adjusting for age, sex, duration of RA, BMI, disease activity, smoking status, concurrent medications, season of the year, year of onset and history of serious infections, diabetes or cardiovascular disease (CVD). A secondary analysis in a set of propensity-matched starts were also compared adjusting for time-varying covariates. The analysis was repeated including URI and bronchitis only and also for serious respiratory infections only. RESULTS: No evidence of differences was found in the incidence of any respiratory infection (URI, bronchitis, pneumonia) in patients receiving HCQ compared with other csDMARDs: HR=0.87 (0.70 to1.07) in adjusted analyses and HR=0.90 (0.70 to 1.17) in adjusted matched analysis. Similar results were found in the analysis of URI and bronchitis only and for serious respiratory infections only. CONCLUSIONS: In patients with RA, the risk for respiratory infections was similar among patients using HCQ as compared to other non-biologic DMARDs.
31498064 QT and QT dispersion intervals in long-standing and moderately active rheumatoid arthritis 2020 May OBJECTIVES: To define the prevalence of prolonged QT interval and QT dispersion (QTd) in rheumatoid arthritis (RA) patients and in a control population. METHODS: QT interval corrected by Bazett's formula (QTc) was calculated from standard 12-lead ECGs in 963 subjects free of previous cardiovascular events (646 RA patients and 317 controls strictly matched for age, sex and cardiovascular risk factors). RESULTS: RA patients (59.6±9.6 years, 68.1% females) had a long mean disease duration (10.6 years) and moderate disease activity (DAS28=3.68±1.23). QTc was 5 msec longer in RA patients than in controls (412±9 vs. 407±28 msec, p=0.013). However, the prevalence of QTc prolongation in RA patients and controls was not significantly different (5.3% vs. 6.3%, p=0.50). On the contrary, RA patients had a significantly greater QTd (42±26 vs. 35±18 msec, p<0.001) and a higher prevalence of increased QTd (33.3% vs. 18.3%, p<0.001) than controls. Furthermore, RA was independently associated to increased QTd [OR(95%CI)= 2.21(1.58-3.08), p=0.0001]. In the RA population, male gender and older age were independently associated with a higher prevalence of prolonged QTd. CONCLUSIONS: In this cohort of long-standing and moderately active RA patients, RA showed longer QTc but similar prevalence of prolonged QTc and an increased QTd with a 1.8-fold higher prevalence of increased QTd than the control population. Further studies in larger prospective cohorts are warranted to investigate whether QTd prolongation predicts sudden cardiac death and other adverse cardiovascular outcomes in RA.
32404343 Adalimumab dose tapering in patients with rheumatoid arthritis who are in long-standing cl 2020 Aug OBJECTIVE: To investigate the association between baseline disease activity and the occurrence of flares after adalimumab tapering or withdrawal in patients with rheumatoid arthritis (RA) in sustained remission. METHODS: The PREDICTRA phase IV, randomised, double-blind (DB) study (ImPact of Residual Inflammation Detected via Imaging TEchniques, Drug Levels, and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Patients) enrolled patients with RA receiving adalimumab 40 mg every other week who were in sustained remission ≥6 months. After a 4-week, open-label lead-in (OL-LI) period, patients were randomised 5:1 to DB adalimumab taper (every 3 weeks) or withdrawal (placebo) for 36 weeks. The primary endpoint was the association between DB baseline hand and wrist MRI-detected inflammation with flare occurrence. RESULTS: Of 146 patients treated during the OL-LI period, 122 were randomised to taper (n=102) or withdrawal (n=20) arms. Patients had a mean 12.9 years of active disease and had received adalimumab for a mean of 5.4 years (mean 2.2 years in sustained remission). Overall, 37 (36%) and 9 (45%) patients experienced a flare in the taper and withdrawal arms, respectively (time to flare, 18.0 and 13.3 weeks). None of the DB baseline disease characteristics or adalimumab concentration was associated with flare occurrence after adalimumab tapering. Approximately half of the patients who flared regained clinical remission after 16 weeks of open-label rescue adalimumab. The safety profile was consistent with previous studies. CONCLUSIONS: Approximately one-third of patients who tapered adalimumab versus half who withdrew adalimumab experienced a flare within 36 weeks. Time to flare was numerically longer in the taper versus withdrawal arm. Baseline MRI inflammation was not associated with flare occurrence. TRIAL REGISTRATION NUMBER: NCT02198651, EudraCT 2014-001114-26.
31823140 Risk of non-melanoma skin cancer for rheumatoid arthritis patients receiving TNF antagonis 2020 Mar OBJECTIVE: Tumor necrosis factor inhibitors (anti-TNF) have become the standard treatment for rheumatoid arthritis (RA). However, evidence is inconsistent as to whether RA patients with anti-TNF are associated with an increased risk of non-melanoma skin cancer (NMSC) compared with those without anti-TNF. We performed a systematic review and meta-analysis to evaluate the risk of NMSC in patients with anti-TNF drugs compared with those without anti-TNF. METHODS: We did a systematic literature search with PubMed, EMBASE, and the Cochrane Library from inception to April 1, 2019. Prospective observational studies were eligible for inclusion if they included any of the approved anti-TNF drugs and reported the risk estimates and 95% confidence interval (95% CI) of NMSC associated with anti-TNF in RA patients. Pooled relative risks (RRs) and 95% CIs were calculated using a fixed-effects model. To assess the heterogeneity and risk of publication bias, we respectively conducted the subgroup and sensitivity analysis, funnel plot, Begg's and Egger's test. RESULTS: The present meta-analysis included six studies with 123,031 patients. Compared with RA patients without anti-TNF, patients with anti-TNF drugs were associated with an increased risk of NMSC (RR 1.28, 95% CI 1.19 to 1.38; I(2) = 45.6%, P = 0.056), especially squamous cell skin cancer (SCC) (RR 1.30, 95% CI 1.09 to 1.54; I(2) = 0%, P = 0.854), but not basal cell skin cancer (RR 1.13, 95% CI 0.97 to 1.31; I(2) = 0%, P = 0.555). Sensitivity and subgroup analysis confirmed the robustness of the primacy results. There was no evidence of publication bias with Begg's and Egger's test or by inspection of the funnel plot. CONCLUSIONS: These results suggest that RA patients treated with anti-TNF are at an increased risk of NMSC, especially SCC. However, this association in RA urgently needs the more clinical studies and basic researches to further validate.Key Points• Rheumatoid arthritis patients treated with tumor necrosis factor inhibitors are associated with a higher risk of non-melanoma skin cancer compared to those patients treated without tumor necrosis factor inhibitors. Hence, tumor necrosis factor inhibitors may be avoided in rheumatoid arthritis patients who are at high risk of non-melanoma skin cancer.• Of note, rheumatoid arthritis patients who were treated for tumor necrosis factor inhibitors compared with patients who were not treated for tumor necrosis factor inhibitors were at significantly increased risk of squamous cell skin cancer, but were not at increased risk of basal cell skin cancer. Therefore, use of tumor necrosis factor inhibitors in rheumatoid arthritis patients should be paid attention to the occurrence of squamous cell skin cancer.
32039040 Molecular Characterization of Circulating Microbiome Signatures in Rheumatoid Arthritis. 2019 Rheumatoid Arthritis (RA) has been increasingly associated with perturbations to the microbial communities that reside in and on the body (the microbiome), in both human and animal studies. To date, such studies have mainly focused on the microbial communities that inhabit the gut and oral cavity. Mounting evidence suggests that microbial DNA can be detected in the blood circulation using a range of molecular methods. This DNA may represent an untapped pool of biomarkers that have the potential to report on changes to the microbiome of distant sites (e.g., example, the gut and oral cavity). To this end, through amplification and sequencing of the bacterial 16S rRNA variable region four, we evaluated the presence and identity of microbial DNA in blood samples obtained from RA patients (both prior to and 3 months following the instigation of treatment) in comparison to a small number of healthy control subjects and samples obtained from patients with ankylosing spondylitis (AS) and psoriatic arthritis (PA). Bacterial-derived DNA was identified in the majority of our patient samples. Taxonomic classification revealed that the microbiome community in RA was distinct from AS, PA, and the healthy state. Through analysis of paired patient samples obtained prior to and 3 months following treatment (V0 vs. V3), we found the microbiome to be modulated by treatment, and in many cases, this shift reduced the distance between these samples and the healthy control samples, suggesting a partial normalization following treatment in some patients. This effect was especially evident in seronegative arthritis patients. Herein, we provide further evidence for the existence of a blood microbiome in health and identify specific taxa modulated in disease and following treatment. These blood-derived signatures may have significant utility as disease biomarkers and suggest this area warrants further investigation.
33086968 A report of three cases which required tibialis anterior tendon resection to recover delay 2020 Jan Delayed wound healing is one of the severe complications after total ankle arthroplasty (TAA). In particular, once tibialis anterior (TA) tendon is exposed from tendon sheath of extensor retinaculum, wound healing will be critically intractable. We report three cases (mean age: 75.3 years old) of delayed wound healing after TAA cured by resection of TA tendon in patients with rheumatoid arthritis (RA). All three cases underwent TAA through an anterior approach, with careful suture of extensor retinaculum in wound closure. Ankle joint was fixed with splint and avoid weight bearing for three weeks after surgery. Delayed wound healing with TA tendon exposure was observed, and initially treated by debridement, basic fibroblast growth factor spray, and negative pressure wound therapy, which all failed to obtain wound healing. Finally, complete resection of TA tendon led to rapid wound healing. In all cases, ankle dorsal flexion was compensated by other extensors, with maintained range of motion and muscle strength (manual muscle testing 3 to 4) compared to pre-operation at 1 year after TAA operation. Resection of TA tendon may be considered as one of the salvage treatment options of severe delayed wound healing in TAA with anterior approach, especially in elderly patients.
32902083 Breathing Micelles for Combinatorial Treatment of Rheumatoid Arthritis. 2020 Dec 1 Breathing process involves inhalation and exhalation of different gases in animals. The gas exchange of the breathing process plays a critical role in maintaining the physiological functions of living organisms. Although artificial breathing materials exhibiting volume expansion and contraction upon alternate exposure to different gases have been well explored, those being able to realize the gas exchange remain elusive. Herein, we report breathing micelles (BM) capable of inhaling nitric oxide (NO) and exhaling carbon monoxide (CO), both of which are endogenous gaseous signaling molecules. We demonstrate that BM can simultaneously scavenge overproduced NO and attenuate proinflammatory cytokines in lipopolysaccharide (LPS)-challenged macrophage cells. In vivo studies revealed that BM outperformed conventional nonsteroidal anti-inflammatory drugs such as dexamethasone (Dexa) in treatment of rheumatoid arthritis (RA) in adjuvant-induced arthritis (AIA) rats, likely due to the combinatorial effect of NO depletion, CO-mediated deactivation of inducible NO synthase (iNOS) and activation of heme oxygenase-1 (HO-1). This work provides new insights into artificial BM for potential biomedical applications.
32862307 Development and initial validation of a questionnaire to assess facilitators and barriers 2020 Dec To develop and validate a self-administered questionnaire to identify in people with Inflammatory arthritis (IA) Facilitators And Barriers to Physical activity (PA): the IFAB questionnaire. The development of the questionnaire included a systematic review of barriers and facilitators to PA to identify key themes, face validity assessment by 11 experts, and cognitive debriefing with 14 patients. The psychometric properties of the questionnaire were assessed by convergent validity (Spearman correlation) against the modified Health Assessment Questionnaire (mHAQ), the Fear-Avoidance Beliefs Questionnaire subscale for PA and the Tampa Scale for Kinesiophobia, internal consistency (Cronbach α) in 63 IA patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA). Reliability and feasibility were assessed in 32 IA patients. The questionnaire comprises 10 items: 4 assessing either barriers or facilitators, 3 assessing barriers, and 3 assessing facilitators. The items are related to psychological status (N = 6), social support (N = 2), disease (N = 1), environmental factors (N = 1). The validation study included 63 patients: 26 RA, 24 axSpA, 13 PsA; with mean age 52.8 (standard deviation 16.5) years, mean disease duration 12.5 (12.3) years, and 53% of women. The questionnaire was correlated (rho = 0.24) with mHAQ. Internal consistency (Cronbach α 0.69) and reliability (interclass coefficient 0.79 [95% confidence interval 0.59; 0.88]) were satisfactory, as was feasibility (missing data 12%, mean completion time < 5 min). The questionnaire allows the assessment of barriers and facilitators to PA in patients with IA. This questionnaire may guide targeted interventions to increase levels of PA in these patients.
31818460 Combination of gp130-targeting and TNF-targeting small molecules in alleviating arthritis 2020 Feb 19 Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease that is characterized by T helper 17 (Th17) cell- and osteoclast-induced joint destruction and inflammation. In RA, several cytokines (interleukin (IL)-1, 6,17, and tumor necrosis factor (TNF)) are involved in almost all aspects of articular inflammation and destruction. This study aimed to evaluate the combinatorial effect of TNF and IL-6 inhibitors on the differentiation and activation of Th17 cells and osteoclasts in the context of RA, and to identify the RA-related mechanisms through IL-6 signaling. Tetrahydropapaverine (THP) showed direct binding to TNF in screening-ELISA, and SPR and TNF-neutralization assays. In a previous study, the therapeutic effect of gp130-targeting LMT-28 was confirmed in RA. Combinatorial treatment with LMT-28 and THP reduced the arthritis index and showed protective effects against bone and cartilage destruction in CIA mice. The secretion levels of TNF, IL-6, and IL-1β significantly decreased upon combinatorial treatment with LMT-28 and THP. Further, the LMT-28 and THP combination suppressed the differentiation and activation of Th17 cells in mouse splenocytes and human PBMCs. In human RA-FLS, the LMT-28 and THP combination inhibited cell proliferation and downregulated IL-6 and/or TNF-mediated signaling relative to that observed upon independent treatment with LMT-28 or THP. Furthermore, the combination of LMT-28 and THP significantly inhibited the differentiation of mouse bone marrow monocytes (BMMs) into osteoclasts. In conclusion, the LMT-28 and THP combination can attenuate RA through the inhibition of Th17 differentiation and osteoclastogenesis, and suppression of IL-6 or TNF-induced signaling pathways. This combinatorial therapy could be used as a new strategy for the treatment of RA.
32152704 Synovial fibroblast-derived exosomal microRNA-106b suppresses chondrocyte proliferation an 2020 Mar Fibroblast-derived exosomes have been reported to transfer microRNAs to recipient cells, where they regulate target gene expression, which is of interest for understanding the basic biology of inflammation, tissue homeostasis, and development of therapeutic approaches. Initial microarray-based analysis carried out in this study identified the rheumatoid arthritis (RA)-related differentially expressed gene pyruvate dehydrogenase kinase 4 (PDK4). Subsequently, the upstream regulatory microRNA-106b (miR-106b) of PDK4 was predicted with bioinformatic analyses. A collagen-induced arthritis (CIA)-induced mouse model was established, and exosomes were isolated from synovial fibroblasts (SFs) and transferred into chondrocytes to identify the role of exosomes in rheumatoid arthritis (RA). We found that PDK4 was poorly expressed in RA cartilage tissues and chondrocytes, while miR-106b was highly expressed in RA SFs and SF-derived exosomes. Notably, PDK4 was confirmed as a target gene of miR-106b. Over-expression of PDK4 promoted the proliferation and migration abilities of chondrocytes and inhibited their apoptosis as well as affected the receptor activator of nuclear factor kappa B ligand (RANKL)/RANK/osteoprotegerin (OPG) system. Meanwhile, miR-106b was delivered from SFs to chondrocytes through exosomes, which suppressed chondrocyte proliferation and migration and accelerated apoptosis as well as affected the RANKL/RANK/OPG system via down-regulation of PDK4. Furthermore, in vivo results validated that miR-106b inhibition could relieve CIA-induced RA. Taken together, SF-derived exosomal miR-106b stimulates RA initiation by targeting PDK4, indicating a physiologically validated potential approach for the prevention and treatment of RA. KEY MESSAGES: PDK4 is decreased in chondrocytes of RA, while miR-106b is increased in SFBs. PDK4 promotes proliferation and migration of chondrocytes. miR-106b could target 3'UTR of PDK4 gene. SFB-exosomal miR-106b inhibits proliferation and migration of chondrocytes. Inhibition of miR-106b attenuates RA progression in a CIA mouse model.
32105722 Dimeric artesunate phospholipid-conjugated liposomes as promising anti-inflammatory therap 2020 Apr 15 OBJECTIVE: The dimeric artesunate phospholipid conjugate (Di-ART-GPC) is a novel amphipathic artemisinin derivative, which can be assembled into liposomes. Di-ART-GPC liposomes were prepared and evaluated as potential anti-inflammatory agents for rheumatic arthritis (RA). METHODS: Di-ART-GPC was assembled into liposomes utilizing thin film dispersion-high pressure homogenization. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and electron cryo microscopy (cryo-EM) were employed to characterize the liposomal size and morphology. The in vitro cytotoxicity of the Di-ART-GPC liposomes was assessed using Cell Counting Kit-8 (CCK8). The anti-inflammatory effects were studied utilizing the inflammatory cell model. Finally, the in vivo efficacy of the Di-ART-GPC-conjugated liposomes was investigated using the arthritis rat model. RESULTS: The particle size of the Di-ART-GPC liposomes decreased to a narrow range of approximately 70 nm following high-pressure homogenization. The in vitro studies revealed low cytotoxicity and good anti-inflammatory effects of the Di-ART-GPC liposomes, which exhibited significantly higher inhibition of the cell secretion of pro-inflammatory cytokines than ART. The in vivo evaluation confirmed that treatment with Di-ART-GPC resulted in a decline in the ankle swelling rate and a low inflammatory response compared with the model control and ART. CONCLUSION: Di-ART-GPC liposomes demonstrate remarkable potential as novel ART-based anti-inflammatory agents for RA.
31845616 Pathological findings in central nervous system demyelination associated with infliximab. 2020 Aug BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) inhibitors, such as infliximab, are commonly used to treat rheumatoid arthritis (RA) and other immune-mediated disorders. OBJECTIVE: To determine whether infliximab-associated central nervous system (CNS) demyelination can be differentiated from multiple sclerosis (MS). METHODS: We present a case of pathologically proven CNS demyelination in a patient treated with infliximab and describe clinical-radiographic-neuropathological findings. Putative mechanisms of TNF-alpha inhibitor-associated CNS demyelination are described. RESULTS AND CONCLUSION: Infliximab treatment is associated with CNS inflammatory demyelinating activity, which is histopathologically indistinguishable from MS.
33054944 Programmed cell death protein 1 inhibitor-induced recalcitrant mixed small and medium vess 2020 Sep 15 Pembrolizumab, a programmed cell death protein 1 (PD1) inhibitor, has been known to be associated with several adverse reactions, including immune related adverse events. In less than one percent of patients, PD1 inhibitors have been linked to the development of connective tissue disease. Patients with previously known connective tissue disease are hypothesized to be at increased risk of flares in as many as 40% of cases. A 70-year-old man with a past medical history significant for rheumatoid arthritis in remission and stage IV lung adenocarcinoma presented to the dermatology clinic after one cycle of nivolumab and eight cycles of pembrolizumab exhibiting worsening, painful bilateral lower extremity ulcers for approximately one month. On the lower legs, three large black retiform eschars and bullous purpuric plaques were observed. Vasculitis is a rare complication of PD1 inhibitor therapy, with the majority of cases reported in literature either medium vessel or large vessel vasculitis. Only glucocorticoids have proven effective for PD1-induced vasculitis and these patients generally require multi-specialty management.
32480097 Validation of claims-based algorithms to identify interstitial lung disease in patients wi 2020 Aug OBJECTIVE: To develop and validate claims-based algorithms to identify interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) METHODS: Using Medicare claims data linked with the electronic medical records (2012-2014), we first selected RA patients based on ≥2 diagnostic codes for RA and ≥1 disease-modifying antirheumatic drugs.Then, to identify ILD in RA, we developed eight claims-based algorithms using a combination of ICD-9 diagnosis codes and procedure codes related to the diagnosis or management of ILD. We assessed the positive predictive value (PPV) for each of the eight algorithms relative to confirmed ILD cases using chest computerized tomography or lung biopsy as the gold standard. RESULTS: A total of 5,214 RA patients were included in the study, and the ILD cases identified by each algorithm ranged from 181 to 993. The PPV of the diagnosis code-based algorithms ranged from 43.4% (≥1 diagnosis code by any physician) to 52.0% (≥2 diagnosis codes by any physician). When the algorithms further required ≥1 procedure code (e.g., imaging, bronchoscopy), the PPV did not improve. However, the algorithms that required ILD diagnosis codes by specialists (i.e., pulmonologist or rheumatologist) had PPVs of 61.5% with ≥1 code; 72.4% with ≥2 codes. CONCLUSIONS: In a cohort of RA patients, our algorithm that required ≥2 ILD diagnosis codes by specialists demonstrated a PPV of 72.4% in ascertaining ILD. Our results support the utility of the claims-based algorithm to identify a population-based cohort of RA patients with ILD using large administrative claims data.
32496682 [Remarkable medical advances in rheumatology : may be…]. 2020 May The development of new drugs is a significant activity in a university hospital that favors access to therapeutic novelties to patients. Rheumatology, whose drug armamentarium was poor in the 1980s, has benefited from the huge progresses of immunology in the 1980-1990s, allowing a therapeutic revolution in whom the academic hospital of Liège (CHU Liège) has been strongly implicated. First protocols with anti-TNF-? monoclonal antibodies have been applied in 1997. Sixty-one protocols have been initiated in rheumatoid arthritis, 12 in ankylosing spondylitis, 10 in psoriatic arthritis, 9 in systemic erythematosus lupus, 3 in giant cell arteritis, 1 in polymyalgia rheumatica, 5 in osteoarthritis and 4 in osteoporosis. Potential and pitfalls will be discussed disease by disease and also by drug categories. The balance remains globally positive, but remission is far from be reached.
33217772 Tuberculosis comorbidity with rheumatoid arthritis: Gene signatures, associated biomarkers 2021 Jan Rheumatoid arthritis (RA) is known to be related to an elevated risk of infections because of its pathobiology and the use of immunosuppressive therapies. Reactivation of latent tuberculosis (TB) infection is a serious issue in patients with RA, especially after receiving anti-TNFs therapy. TNF blocking reinforces the TB granuloma formation and maintenance and the growth of Mycobacterium tuberculosis (Mtb). After intercurrent of TB infection, the standard recommendation is that the treatment with TNF inhibitors to be withheld despite its impressive effect on suppression of inflammation until the infection has resolved. Knowing pathways and mechanisms that are common between two diseases might help to find the mechanistic basis of this comorbidity, as well as provide us a new approach to apply them as therapeutic targets or diagnostic biomarkers. Also, screening for latent TB before initiation of an anti-TNF therapy can minimize complications. This review summarizes the shared gene signature between TB and RA and discusses the biomarkers for early detection of this infection, and screening procedures as well.
31883358 Resveratrol ameliorates rheumatoid arthritis via activation of SIRT1-Nrf2 signaling pathwa 2020 May The present study was designed to explore the biological role of resveratrol (RES) in rheumatoid arthritis (RA) and the underlying mechanism. The adjuvant-induced arthritic rats were administered RES on the 12th day after model establishment, and then arthritis assessment, oxidative stress measurement, histological examination, and immunohistochemical staining were performed. The primary rat fibroblast-like synoviocytes (FLS) were isolated and treated with RES in vitro and then cell proliferation and apoptosis assay were examined. Chromatin immunoprecipitation assay, luciferase reporter assay, intracellular reactive oxygen species (ROS) determination, western blot, and quantitative real time-polymerase chain reaction (qRT-PCR) were performed to investigate the mechanisms. RES administration decreased arthritis scores and serum levels of antioxidant enzymes, attenuated paw swelling, synovial hyperplasia, inflammatory cell infiltration, and cartilage degradation, as well as inhibited synoviocyte proliferation in synovial tissues. Further investigation indicated that RES inhibited ROS production and FLS proliferation through activating the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. NF-κB was confirmed to negatively regulate miR-29a-3p and miR-23a-3p expression by directly binding to its promoter. Mechanistic analyses further revealed that Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1), a negative regulator of Nrf2, was a downstream target of miR-29a-3p, while miR-23a-3p directly targeted cullin3 (cul3), a master regulator of ubiquitination and degradation of Nrf2. Together, the present study provided evidence that RES ameliorated RA through activation of Nrf2-ARE signaling pathway via SIRT1/NF-κB/miR-29a-3p/Keap1 and SIRT1/NF-κB/miR-23a-3p/cul3 signaling pathway.