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ID PMID Title PublicationDate abstract
30340074 Methotrexate (MTX)-associated malignant lymphoma of the bilateral breast: imaging features 2019 Jan Tumors originating from the nipple-areolar complex of the breast are rare. We herein report the case of a patient with metachronous bilateral areolar methotrexate (MTX)-associated lymphoma. The patient was a 67-year-old woman who presented with a rapidly enlarging tumor in the areolar region of her left breast. She had a long history of rheumatoid arthritis and had taken MTX for many years. On ultrasonography, the tumor showed well-demarcated margins and hyper-vascularity. On magnetic resonance imaging, the tumor showed a homogeneous low-to-moderate signal intensity that was similar to that of the nipple on both T1- and T2-weighted imaging; the diffusion was significantly reduced on diffusion-weighted images. The tumor showed a medium-plateau pattern on dynamic contrast-enhanced imaging. No necrotic change was observed. Based on the imaging findings, we considered the tumor to have originated from the areola. According to the internal homogeneity, the rapid growth and hyper-cellularity, the potential diagnoses included a small round cell tumor (including malignant lymphoma) and a mesenchymal neoplasm (especially leiomyoma or leiomyosarcoma, which frequently originate from the areolar region). An excisional biopsy of the tumor was performed. The pathological diagnosis was diffuse large, non GC B-cell lymphoma that we suspected was associated with MTX. The tumor shrank rapidly after the withdrawal of MTX. After three months, we detected a B-cell lymphoma of the same type originating in the contralateral areola. We compared the characteristics of the imaging findings of the MTX-associated lymphoma with the nipple-areolar or periareolar tumors and primary breast lymphoma.
30905706 Predicting Drug Binding to Human Serum Albumin and Alpha One Acid Glycoprotein in Diseased 2019 Aug Plasma protein binding, namely the fraction unbound (f(u)), can be an important determinant of the disposition and response of drugs. The primary objective of this study was to predict f(u) values of 183 drugs utilizing either a single binding protein model, where the predominant binding protein had been established, or a multiple binding protein model (MBPM), where the relative binding contribution of human serum albumin (HSA) or alpha 1 acid glycoprotein (AAG) is known. Mean protein concentrations, dependent on disease or age, were used to account for changes in f(u). A simple scaling approach for binding protein concentration was employed to account for quantitative changes in molar concentrations of either HSA or AAG in their respective conditions. The MBPM predictive model works best if the relative binding contribution of HSA and AAG is known, and a scaler for the change in protein concentration can be adjusted accordingly. The value of MBPM was most evident when considering reported changes in lidocaine binding because of increasing AAG concentration in response to trauma. The present approach enhances the ability to predict f(u) in diseased and age populations because of quantitative changes in major binding proteins.
30399509 Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and 2019 Jan OBJECTIVES: Human glutaminyl cyclases (QC and isoQC) play an important role in maintaining inflammatory conditions. Meanwhile a glutaminyl cyclase synthesized by Porphyromonas gingivalis (PgQC), a key pathogen in developing periodontitis and a potential link of periodontitis with rheumatoid arthritis (RA), was discovered. This study was aimed to determine the expression of QC, isoQC and PgQC in patients with chronic periodontitis (CP) and RA. DESIGN: Thirty volunteers were enrolled in a pilot study and divided into 3 groups (healthy, CP and RA individuals). Blood samples, biofilm and gingival crevicular fluid (GCF) were analysed for mRNA expression of QC, isoQC and P. gingivalis QC. Major bacteria being associated with periodontal disease were quantified in subgingival biofilm and protein levels for monocyte chemoattractant protein (MCP)-1, MCP-3 and interleukin (IL)-1β) were determined in the GCF. Expression of PgQC on the mRNA and protein levels was assessed in two P. gingivalis strains. RESULTS: PgQC is expressed in P. gingivalis strains and the protein seems to be located mainly in peri-plasmatic space. mRNA expression of QC was significantly increased in the peripheral blood from RA patients vs. healthy subjects and CP patients (p = 0.013 and p = 0.003, respectively). In GCF of RA patients, QC mRNA was detected more frequently than in healthy controls (p = 0.043). In these samples IL-1β levels were also elevated compared to GCF from periodontally healthy individuals (p = 0.003). PgQC was detected in eight out of the 13 P. gingivalis positive biofilm samples. CONCLUSION: Activity of QC may play a supportive role in maintaining chronic periodontal inflammation and destruction in RA. PgQC is expressed in vivo but further research is needed to evaluate biological importance of this enzyme and if it constitutes a potential target in periodontal antimicrobial therapy.
31837308 Leocarpinolide B attenuates LPS-induced inflammation on RAW264.7 macrophages by mediating 2020 Feb 5 Macrophages-mediated inflammation is involved in the regulation of rheumatoid arthritis (RA). Sigesbeckiae Herba (SH) has been traditionally used for rheumatism. However, the bioactive ingredients of SH are still unclear. Recently, we isolated a compound (Leocarpinolide B, LB) from SH and identified its potent anti-inflammatory and antioxidant effects on RAW264.7 macrophages for the first time. LB effectively inhibited excessive production of nitric oxide (NO), prostaglandin E2 (PGE(2)), cytokines (IL-6, TNF-α and MCP-1), and the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthases (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 cells. LB blocked the degradation of inhibitor of kappa B (IκBα) and translocation of nuclear factor kappa B (NF-κB) p65. Additionally, LB reduced the intracellular reactive oxygen species, and increased the expression of heme oxygenase-1 (HO-1) and the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence or absence of LPS. The results suggested that LB might be one of the bioactive components of SH, and be potential for the treatment of RA and valuable to be further investigated.
31277965 Extracellular traps and PAD4 released by macrophages induce citrullination and auto-antibo 2019 Dec The mechanisms underlying the transition of rheumatoid arthritis (RA) systemic autoimmunity to the joints remain largely unknown. Here, we demonstrate that macrophages in the secondary lymphoid organs (SLOs) and synovial ectopic lymphoid-like structures (ELSs) express peptidylarginine deiminase 4 (PAD4) in murine collagen induced arthritis (CIA) and synovial biopsies from RA patients. Moreover, peptidyl citrulline colocalized with macrophages in SLOs and ELSs, and depletion of macrophages in CIA decreased lymphoid tissue citrullination and serum anti-citrullinated protein/peptide antibody (ACPA) levels. Furthermore, PAD was released from activated murine and RA synovial tissue and fluid (SF) macrophages which functionally deiminated extracellular proteins/peptides in vitro. Additionally, activated murine and SF macrophages displayed macrophage extracellular trap formation (METosis) and release of intracellular citrullinated histones. Moreover, presentation of citrullinated proteins induced ACPA production in vitro. Thus, lymphoid tissue macrophages contribute to self-antigen citrullination and ACPA production, indicating that their selective targeting would potentially ameliorate citrullination-dependent autoimmune disorders.
30891933 Disease Burden in Osteoarthritis Is Similar to That of Rheumatoid Arthritis at Initial Rhe 2019 Aug OBJECTIVE: To analyze disease burden in osteoarthritis (OA) according to Multidimensional Health Assessment Questionnaire (MDHAQ)/Routine Assessment of Patient Index Data 3 (RAPID3) scores at the initial visit and the 6-month follow-up visit, compared with rheumatoid arthritis (RA) as a benchmark for high disease burden. METHODS: All patients with all diagnoses at the Rush University Medical Center Division of Rheumatology complete a paper MDHAQ at all visits, saved as a PDF in the electronic health record. MDHAQ 0-10 scores for physical function, pain, and patient global assessment (compiled into RAPID3 0-30 scores) and additional scales at the initial and 6-month follow-up visits, for new OA and RA patients seen from 2011 to 2017, were compared. OA and RA patients were classified as self-referred or physician-referred, and RA patients were classified as disease-modifying antirheumatic drug (DMARD)-naive or having prior-DMARD treatment. Patient groups were compared using t-tests and analysis of variance, adjusted for age, disease duration, body mass index (BMI), education, and ethnicity. RESULTS: Compared with RA patients, OA patients had higher age, BMI, and disease duration. At initial visit, the mean RAPID3 did not differ significantly in OA versus DMARD-naive RA patients, whether self- or physician-referred (range 14.8-16.4 [P = 0.38]), or in all OA patients versus DMARD-naive RA patients versus prior-DMARD RA patients (15.0, 15.7, and 15.8, respectively [P = 0.49]). After 6 months, RAPID3 was improved to 13.3, 10.3, and 10.8, respectively, which represented substantially greater improvement in RA patients than OA patients (P < 0.001). Similar results were seen for most self-reported measures and in adjusted analyses. CONCLUSION: MDHAQ/RAPID3 scores are similar in OA and RA patients at the initial visit, but higher in OA patients than in RA patients 6 months later, reflecting superior RA treatments. The same MDHAQ/RAPID3 allows comparisons of disease burdens in different diseases.
30620291 Incidence of first cardiovascular event in Spanish patients with inflammatory rheumatic di 2019 Sep OBJECTIVES: To determine the incidence and risk factors of first cardiovascular event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD). METHODS: Analysis of data after 2.5 years of follow-up from the prospective study CARMA project, that includes patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and matched individuals without CIRD from 67 hospitals in Spain. CVE cumulative incidence per 1000 patients was calculated after 2.5 years from the start of the project. Weibull proportional hazard model was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) of the risk factors. RESULTS: 2595 (89.1%) patients completed the 2.5 years of follow-up visit. Cumulative incidence of CVE in patients with CIRD was 15.30 cases per 1000 patients (95% CI: 12.93-17.67), being higher in the subgroup with AS; 22.03 (95% CI: 11.01-33.04). Patients with AS (HR: 4.11; 95% CI: 1.07-15.79), those with older age (HR: 1.09; 95% CI: 1.05-1.13), systolic hypertension (HR: 1.02; 95% CI: 1.00-1.04) and long duration of the disease (HR: 1.07; 95% CI: 1.03-1.12) were at higher risk of first CVE during the 2.5 years of follow-up. In contrast, female gender was a protective factor (HR: 0.43; 95% CI: 0.18-1.00). CONCLUSIONS: Among CIRD patients prospectively followed-up at rheumatology outpatient clinics, those with AS show higher risk of first CVE. Besides cardiovascular risk factors, such as hypertension, being a man and older as well as having a long disease duration increase the risk of CVE in patients with CIRD.
30982883 A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors 2019 Oct 1 OBJECTIVES: To evaluate the risk of serious infection (SI) and herpes zoster (HZ) in rheumatoid arthritis patients receiving JAK inhibitors. METHODS: We conducted a systematic literature review and meta-analysis of phase II and III randomized controlled trials of tofacitinib (5 mg bid), baricitinib (4 mg od) and upadacitinib (15 mg od). Patient-exposure years were calculated. A per-protocol analysis was applied, incorporating follow-up time from patients randomized to placebo who cross into the treatment arm. Pooled incidence rates per 100 person-years of SI and HZ were calculated. Incidence rate ratios (IRRs) of drug vs placebo were compared using a meta-synthesis approach. RESULTS: Twenty-one studies were included in the meta-analysis; 11 tofacitinib (5888 patients), six baricitinib (3520 patients) and four upadacitinib studies (1736 patients). For SI, the incidence rates were 1.97 (95% CI: 1.41, 2.68), 3.16 (95% CI: 2.07, 4.63) and 3.02 (95% CI: 0.98, 7.04), respectively. The IRRs comparing treatment arm to placebo were statistically non-significant: 1.22 (95% CI: 0.60, 2.45), 0.80 (95% CI: 0.46, 1.38) and 1.14 (95% CI: 0.24, 5.43), respectively. For HZ, the incidence rates were 2.51 (95% CI: 1.87, 3.30), 3.16 (95% CI: 2.07, 4.63) and 2.41 (95% CI: 0.66, 6.18), respectively. The IRR of HZ comparing baricitinib with placebo was 2.86 (95% CI: 1.26, 6.50). Non-significant IRRs were seen with tofacitinib and upadacitinib: 1.38 (95% CI: 0.66, 2.88) and 0.78 (95% CI: 0.19, 3.22), respectively. Indicator opportunistic infections excluding HZ were too rare to provide meaningful incidence rates. CONCLUSION: The absolute SI rates were low. However across the JAK inhibitors, the incidence of HZ is higher than expected for the population (3.23 per 100 patient-years). While the risk was numerically greatest with baricitinib, indirect comparisons between the drugs did not demonstrate any significant difference in risk. SYSTEMATIC REVIEW REGISTRATION NUMBER: Prospero 2017 CRD4201707879.
30616405 Etanercept biosimilar SB-4. 2019 Mar Biosimilars are highly similar molecules to other biological medicines that have already been authorized for use. Etanercept (ETN) was the first anti-tumor necrosis factor inhibitor (TNFi) approved by the Food and Drug Administration for the treatment of moderate to severe rheumatoid arthritis (RA) in November 1998 and in February 2000 by the European Medicines Agency. Twenty years later, the first ETN biosimilar has come of age. Areas covered: In this review we examined SB-4 as a biosimilar candidate to ETN, focusing on the available data. Current data indicate that SB-4 is a highly similar alternative to ETN in terms of safety, efficacy, tolerability, and immunogenicity. SB-4 has already been approved by health authorities in Europe, South Korea, Australia, and Canada, as a subcutaneous therapy option for the treatment of patients with RA but also for the full spectrum approved for its bio-originator ETN. Expert opinion: The current body of evidence suggests that all biologic activities have been demonstrated to be equivalent between SB-4 and the originator, including pharmacodynamic and pharmacokinetic activities. In some areas, and more specifically when it comes to immunogenicity, SB-4 showed lower incidents. Therefore, it is fully expected to have same efficacy and safety in all indications.
31152257 sICAM-1 as potential additional parameter in the discrimination of the Sjögren syndrome a 2019 Oct OBJECTIVE: Both Sjögren's syndrome (SS) and non-autoimmune sicca syndrome (nSS) can show symptoms of dry eyes and a dry mouth, and objective reductions in tear and saliva production. Dry eyes and dry mouth are frequent but they are distinct pathological entities that require diagnostic discrimination. METHODS: The aim of present study was to compare the serum levels of sICAM-1, TFF3, RANTES, adiponectin, and FGF in primary (pSS), secondary due to rheumatoid arthritis (sSS), non-autoimmune sicca syndrome (nSS), and healthy groups. The serum levels of selected molecules were determined by enzyme-linked immunosorbent assay (ELISA) in 29 patients with pSS, 30 with sSS, 17 with nSS, and 15 healthy subjects. RESULTS: sICAM-1 was significantly elevated in pSS and sSS patients compared with nSS group. Levels of FGF, TFF3, and RANTES were significantly increased in pSS, sSS, and nSS patients compared with healthy controls. No significant correlations were found between the levels of measured molecules and the clinical parameters. CONCLUSIONS: Our study showed that sICAM-1 might be useful as an additional parameter for differential diagnosis of SS and nSS, and TFF could be additional diagnostic marker for SS diagnosis. KEY POINTS: • sICAM-1 was significantly elevated in Sjögren syndrome patients compared with non-autoimmune sicca syndrome group. • TFF was significantly elevated in Sjögren syndrome patients compared with healthy controls. • They might be useful as additional parameters for differential diagnosis.
30097709 1,25-Dihydroxyvitamin D3 attenuates disease severity and induces synoviocyte apoptosis in 2019 May An aggressive proliferation of synoviocytes is the hallmark of rheumatoid arthritis (RA). Emerging evidence shows that inhibiting the NF-κB signaling pathway with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may be a therapeutic approach for controlling inflammatory diseases. In this study, we demonstrated the protective effects of three different 1,25(OH)2D3 concentration on adjuvant-induced arthritis (AA) rats through the NF-κB signaling pathway and their pro-apoptotic roles in cultured adjuvant-induced arthritis synoviocytes (AIASs). AA rats were prepared by injecting complete Freund's adjuvant and independently given daily intraperitoneal injection of 1,25(OH)2D3 at concentrations of 50, 100, and 300 ng/day/kg. Subsequently, AIASs were isolated from the inflamed joints of AA rats to test the effects of 1,25(OH)2D3 on AIASs in vitro. Intraperitoneal injection of 1,25-(OH)2D3 was found to induce a concentration- and time-dependent improvement in relieving the symptoms of AA. We found an increased paw withdrawal thermal latency (PWTL) in the affected paw of AA rats as the concentration of 1,25-(OH)2D3 increased. 1,25-(OH)2D3 treatment reduced levels of inflammatory factors in synovial tissues of AA rats. In the case of cultured AIASs, 1,25-(OH)2D3 was shown to inhibit cell proliferation and induce cell apoptosis in a concentration-dependent manner. Additionally, 1,25-(OH)2D3 inhibited the activation of the NF-κB signaling pathway. In conclusion, our study provides evidence emphasizing that 1,25(OH)2D3 has the potential to attenuate disease severity in RA potentially due to its contributory role in synoviocyte proliferation and apoptosis. The protective role of 1,25(OH)2D3 against RA depends on the NF-κB signaling pathway.
31119756 Knockdown of lncRNA NEAT1 inhibits Th17/CD4(+) T cell differentiation through reducing the 2019 Dec CD4+ T cells differentiated into Th17 cells are a main cause for occurrence and development of rheumatoid arthritis (RA). This study aims to define the role of long noncoding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) and its downstream molecule in Th17 cell differentiation. Determination of lncRNA NEAT1 expression in the peripheral blood mononuclear cells (PBMCs) of patients with RA and in Th17 cells induced differentiation in vitro used quantitative real-time polymerase chain reaction. Lentivirus-constructed short hairpin RNA interference for NEAT1 (Lenti-siRNA-NEAT1) was pretransfected into CD4+ T cells before inducing treatment of Th17 cell differentiation. NEAT1 targets STAT3 protein was proved by RNA pull down. Lenti-siRNA-NEAT1 was injected into the joint of the mice arthritis model to verify the function of NEAT1 knockdown. Our results showed that NEAT1 is significantly upregulated in the PBMCs of RA patients, as well as in Th17 cells in vitro induced from CD4+ T cells. The knockdown of NEAT1 restrains CD4+ T cells differentiate into Th17 cells. STAT3 protein, a critical molecule for Th17 cell differentiation, is a downstream molecule for NEAT and its cellular level can be positively targeted and regulated by NEAT via reducing the ubiquitination level. Moreover, the cotreatment of NEAT1 knockdown and STAT3 overexpression promotes Th17 cell differentiation compared with NEAT1 knockdown alone. Knockdown of Th17 by in vivo injection of lenti-siRNA-NEAT1 relieves arthritis degree in II type collagen induced mice arthritis model. These data concluded that NEAT1 is auxo-active molecule for CD4+ T cells differentiating into Th17 cells and knockdown of NEAT1 positively inhibits Th17/CD4+ T cell differentiation through reducing the STAT3 protein level.
30758239 miRNA-24 Gene Sequence, DHFR -829C-T Genotypes, and Methotrexate Response in Mexican Patie 2019 Mar AIM: The present study looked for variation in the miRNA-24 sequence, and evaluated the associations between the dihydrofolate reductase (DHFR) gene-829 C-T polymorphism and plasma DHFR concentrations with response to methotrexate (MTX) treatment in Mexican patients with rheumatoid arthritis (RA). METHODS: A total of 135 women with RA were classified as responders (disease activity score [DAS28] <3.2) or nonresponders to MTX (DAS28 > 3.2). We determined the genotype of the patients using the polymerase chain reaction-restriction fragment length polymorphism method. Plasma DHFR enzyme levels and mi-RNA24 sequences were assessed by enzyme-linked immunosorbent assay (ELISA) and Sanger sequencing, respectively. Allelic frequencies and the genotypic distribution of the polymorphism were analyzed by the chi-square test. RESULTS: The genotype frequencies of the DHFR -829C-T polymorphism among responders were 37.0% CC, 52.1% CT, and 10.9% TT and for nonresponders were 33.9% CC, 56.4% CT, and 9.7% TT. No significant differences in genotype frequencies were found between the groups (p = 0.88). The DHFR levels relative to genotype for responders were 6.8 ± 2.7, 6.1 ± 2.7, and 6.5 ± 1.5 ng/mL for CC, CT, and TT, respectively, and for nonresponders were 6.5 ± 2.0, 6.1 ± 3.1, and 7.4 ± 1.8 ng/mL for CC, CT, and TT, respectively. No significant differences were found between the two groups. Similarly, both groups showed no sequence variations in miRNA-24 gene. CONCLUSION: The -829C-T polymorphism of DHFR gene was not associated with response to MTX by RA patients, and no variations were found in the miRNA-24 sequence that might modify the response to treatment or DHFR enzyme levels in a Mexican population with RA.
30755793 Tumour necrosis factor signalling in health and disease. 2019 The master pro-inflammatory cytokine, tumour necrosis factor (TNF), has been shown to modulate multiple signalling pathways, with wide-ranging downstream effects. TNF plays a vital role in the typical immune response through the regulation of a number of pathways encompassing an immediate inflammatory reaction with significant innate immune involvement as well as cellular activation with subsequent proliferation and programmed cell death or necrosis. As might be expected with such a broad spectrum of cellular effects and complex signalling pathways, TNF has also been implicated in a number of disease states, such as rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. Since the time of its discovery over 40 years ago, TNF ligand and its receptors, TNF receptor (TNFR) 1 and 2, have been categorised into two complementary superfamilies, namely TNF (TNFSF) and TNFR (TNFRSF), and 19 ligands and 29 receptors have been identified to date. There have been significant advances in our understanding of TNF signalling pathways in the last decade, and this short review aims to elucidate some of the most recent advances involving TNF signalling in health and disease.
31052496 Curcumin in Autoimmune and Rheumatic Diseases. 2019 May 2 Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement in clinical or laboratory outcomes. Three trials were in ulcerative colitis, two of which yielded significant improvement in at least one clinical outcome. Additionally, two clinical trials on rheumatoid arthritis, one clinical trial on lupus nephritis, and two clinical trials on multiple sclerosis resulted in inconclusive results. Longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long term benefits of curcumin supplementation. Multiple mechanisms of action of curcumin on these diseases have been researched, including the modulation of the eicosanoid pathway towards a more anti-inflammatory pathway, and the modulation of serum lipid levels towards a favorable profile. Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal-to-no side effects, which can be added in conjunction to current standard of care.
31554457 Global public interest in systemic lupus erythematosus: an investigation based on internet 2019 Oct OBJECTIVE: This study aims at investigating the global public interest in seeking information about systemic lupus erythematosus (SLE) using Google Trends (GT). METHODS: An electronic search was performed using GT with the search term lupus as well as the option of disease from January 2004 to December 2018. Cosinor analysis was applied to detect the seasonality of SLE-related relative search volume (RSV). In addition, analysis on SLE-related topics including "hot topics" and "top rising topics" was also conducted. RESULTS: Overall, SLE-related RSV showed a decreasing trend from January 2004 to December 2013 and then demonstrated a slowly increasing trend from January 2014 to December 2018. Cosinor test showed no significant seasonal variation in SLE-related RSV (p > .025). RSV peaked in May and reached the trough in November. The top seven rising topics were Selena Gomez, Sjögren syndrome, autoimmunity, rheumatoid arthritis, rheumatology, antinuclear antibody and autoimmune disease. CONCLUSION: The results from GT analysis showed slowly increasing internet searches for SLE in recent years. This trend was followed by a peak of RSV in May and reached its lowest level in November. However, globally, the results did not reveal a significant seasonal variation in GT for SLE. Additionally, the top fast-growing topics regarding SLE may be valuable for doctors and nurses to provide timely education of the disease to patients, as well as promote the development of public health.
30763385 Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nat 2019 In recent years, low dose naltrexone (LDN) has been used as an off-label therapy for several chronic diseases. Results from small laboratory and clinical studies indicate some beneficial effects of LDN in autoimmune diseases, but clinical research on LDN in rheumatic disease is limited. Using a pharmacoepidemiological approach, we wanted to test the hypothesis that starting LDN leads to reduced dispensing of medicines used in the treatment of rheumatic disease. We performed a controlled before-after study based on the Norwegian Prescription Database (NorPD) to compare prescriptions to patients one year before and one year after starting LDN in 2013. The identified patients (n = 360) were stratified into three groups based on LDN exposure. Outcomes were differences in dispensing of medicines used in rheumatic disease. In persistent LDN users, there was a 13% relative reduction in cumulative defined daily doses (DDD) of all medicines examined corresponding to -73.3 DDD per patient (95% CI -120,2 to -26.4, p = 0.003), and 23% reduction of analgesics (-21.6 DDD (95% CI -35.5 to -7.6, p<0.009)). There was no significant DDD change in patients with lower LDN exposure. Persistent LDN users had significantly reduced DDDs of NSAID and opioids, and a lower proportion of users of DMARDs (-6.7 percentage points, 95% CI -12.3 to-1.0, p = 0.028), TNF-α antagonists and opioids. There was a decrease in the number of NSAID users among patients with the least LDN exposure. Important limitations are that prescription data are proxies for clinical effects and that a control group unexposed to LDN is lacking. The results support the hypothesis that persistent use of LDN reduces the need for medication used in the treatment of rheumatic and seropositive arthritis. Randomised clinical trials on LDN in rheumatic disease are warranted.
30409415 Musculoskeletal rheumatic complications of immune checkpoint inhibitor therapy: A single c 2019 Jun BACKGROUND: The use of immune checkpoint inhibition (ICI) has revolutionized cancer treatment. However, these medications are associated with significant and potentially debilitating immune-related adverse events (irAEs). While certain toxicities have been well studied, rheumatic complications have been less widely recognized and characterized. METHODS: We report our experience of patients who were evaluated by rheumatology after the development of a suspected rheumatic irAE following ICI treatment. Cases of rheumatic irAEs were included if active rheumatic signs or symptoms developed during or after ICI treatment and were confirmed by a treating rheumatologist. RESULTS: Twenty-nine patients were evaluated by rheumatology for suspected rheumatic irAEs. Eighteen patients had confirmed toxicity including inflammatory arthritis (n = 12) and PMR (n = 6). Twelve patients had de novo toxicity and six had a flare of a pre-existing rheumatic condition. The onset of de novo toxicity occurred late into treatment (median 38 weeks), while patients with pre-existing rheumatic disease flared soon after initiation of ICI treatment (median 4.6 weeks). Management often required systemic or intra-articular steroids, with initiation of disease modifying anti-rheumatic drug (DMARD) therapy in those unable to wean off steroids. CONCLUSION: De novo rheumatic irAEs are generally delayed in onset after ICI initiation, while flares of pre-existing rheumatic conditions occur shortly after ICI initiation. Effective management often requires systemic corticosteroids as well as DMARDs in a subset of patients. Future prospective studies are needed to accurately describe the incidence and spectrum of rheumatic irAEs and to identify the most effective management strategies.
31203226 Does Abatacept Increase Postoperative Adverse Events in Rheumatoid Arthritis Compared with 2020 Apr OBJECTIVE: To investigate whether abatacept (ABA) causes more adverse events (AE) than conventional synthetic disease-modifying antirheumatic drugs (csDMARD) after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: A retrospective multicenter nested case-control study was performed in 18 institutions. Patients receiving ABA (ABA group) were matched individually with patients receiving csDMARD and/or steroids (control group). Postoperative AE included surgical site infection, delayed wound healing, deep vein thrombosis or pulmonary embolism, flare, and death. The incidence rates of the AE in both groups were compared with the Mantel-Haenszel test. Risk factors for AE were analyzed by logistic regression model. RESULTS: A total of 3358 cases were collected. After inclusion and exclusion, 2651 patients were selected for matching, and 194 patients in 97 pairs were chosen for subsequent comparative analyses between the ABA and control groups. No between-group differences were detected in the incidence rates of each AE or in the incidence rates of total AE (control vs ABA: 15.5% vs 20.7% in total, 5.2% vs 3.1% in death). CONCLUSION: Compared with csDMARD and/or steroids without ABA, adding ABA to the treatment does not appear to increase the incidence rates of postoperative AE in patients with RA undergoing orthopedic surgery. Large cohort studies should be performed to add evidence for the perioperative safety profile of ABA.
31385283 Retrospective Claims Analysis Indirectly Comparing Medication Adherence and Persistence Be 2019 Sep INTRODUCTION: Patients' adherence to and persistence on treatment for inflammatory bowel disease (IBD) can vary, depending on type and distribution of disease and treatment modality. We aim to identify differences in adherence and persistence with treatments with different administration routes (intravenous vs oral) in IBD. METHODS: A retrospective cohort analysis of a claims database of adult patients diagnosed with IBD or rheumatoid arthritis (RA) who began treatment with vedolizumab, tofacitinib, or infliximab from January 2015 through December 2015. Adherence evaluated by proportion of days covered (PDC) and cumulative days with gaps at least 20% beyond expected interval (CG20) using multivariable generalized linear equation models. Persistence assessed as time to treatment discontinuation over 12 months of follow-up using Kaplan-Meier estimates and Cox proportional hazards models; proportion of persistent patients determined via multivariable logistic regression. Indirect comparisons across disease states adjusted using infliximab data. RESULTS: After indirect adjustment by disease, mean PDC difference was significantly higher (difference of 4.7%; P = 0.0376) and mean CG20 was lower (difference of 15 days; P = 0.0646) but not statistically significant in vedolizumab/IBD than tofacitinib/RA. CONCLUSION: We describe a novel adjustment method for interdisease treatment differences using infliximab treatment patterns to bridge differences between IBD and RA. After adjustment, adherence was higher with infusions than oral medications, which may affect outcomes. Indirect comparisons between vedolizumab and tofacitinib are not generalizable and should be confirmed in tofacitinib-treated IBD patients. FUNDING: Takeda Pharmaceuticals U.S.A., Inc.