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ID PMID Title PublicationDate abstract
32789817 Interleukin 6, interleukin 17, disease-related and contextual factor association with depr 2021 Mar OBJECTIVE: Depression is very prevalent in rheumatoid arthritis (RA) compared with the general population and may be associated with poor clinical outcomes. Identifying factors associated with depression could improve outcomes for this at risk group. However, few studies have comprehensively examined the association of contextual and disease-related factors as well as pro inflammatory cytokines interleukin 6 (IL-6) and interleukin 17 (IL-17) with depression in RA. Therefore, we aimed to identify the factors significantly associated with depression and severe depression in RA, thus providing a reference for applying clinical care interventions for patients with RA. METHODS: An observational cross-sectional study was conducted on 120 RA patients. Potential determinants included contextual and disease-related factors and laboratory variables. Enzyme-linked immunosorbent assay was used to measure serum IL-6 and IL-17 levels. Depression was assessed using the Arabic version of the Beck Depression Inventory-II questionnaire. RESULTS: A total of 120 patients were included, and up to 67.5% had some degree of depression with 60% having moderate to severe depression. The severity of disease activity of RA (DAS28-ESR (OR, 1.63; 95% CI, 0.899-3.755), HAQ scores (OR, 1.27; 95% CI, 0.702-2.933), and VAS scores for pain (OR, 2.2; 95% CI, 1.251-5.223)), besides elevated serum IL-6 (OR, 1.51; 95% CI, 0.832-3.475), IL-17 (OR, 1.28; 95% CI, 0.706-2.947), and CRP levels (OR, 1.20; 95% CI, 0.923-2.882) were significantly associated with depression and its severity in the multivariate analysis. CONCLUSION: Depression is frequent in RA and is strongly associated to elevated serum IL-6, IL-17, CRP levels, and disease activity-related factors. Key Points • RA patients are at increased risk of developing depression, particularly if their level of disease activity scores, serum IL-6, and IL-17 levels increases. • Patient characteristics associated with depression in RA include living without family, without employments, and with co-morbid hypertension, while RA disease factors are pain, functional disability, and high disease activity. • A multidisciplinary cooperative approach to RA patient care with regular assessments of these factors associated with depression should be incorporated into routine care programs to improve patients' self care capabilities and mitigate or prevent depression in these patients.
32351168 Predictors of fatigue and persistent fatigue in early rheumatoid arthritis: a longitudinal 2020 Jul OBJECTIVE: To determine, in a cohort of patients with early rheumatoid arthritis (RA), factors associated with fatigue at baseline, describe its evolution over 5 years of follow-up, and determine baseline predictors of persistent fatigue. METHOD: We selected patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA included in the ESPOIR cohort. Using bivariable and multivariable logistic regression models, we examined baseline variables associated with baseline fatigue (defined by visual analogue scale fatigue > 20) and baseline predictors of persistent fatigue (if the patient experienced fatigue at all visits during the 5 year follow-up period). RESULTS: We analysed 673 patients; 80.7% reported fatigue at baseline. At baseline, fatigue was associated with female gender, younger age, greater severity of morning stiffness, sleep problems, higher Health Assessment Questionnaire levels, presence of sicca symptoms, history of thyroid problems, and presence of psychological distress (depressive or anxiety symptoms). At 5 years of follow-up, the percentage of fatigued patients who reported fatigue at all time-points since baseline was 24.6% (referred to as 'persistent fatigue'). Independent baseline predictors were presence of sicca symptoms, greater severity of morning stiffness, and psychological distress. CONCLUSIONS: Fatigue is a frequent symptom in RA. The presence of sicca symptoms, greater severity of morning stiffness, and presence of psychological distress at baseline were associated with baseline fatigue and persistent fatigue at 5 years. We did not observe any association between baseline fatigue or persistent fatigue and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate.
31941804 Interleukin 17A and IL-17F Expression and Functional Responses in Rheumatoid Arthritis and 2020 Nov 1 OBJECTIVE: Targeting the interleukin 17 (IL-17) axis is efficacious in psoriasis and spondyloarthritis (SpA), but not in rheumatoid arthritis (RA). We investigated potential differences in tissue expression and function of IL-17A and IL-17F in these conditions. METHODS: mRNA expression of cytokines and their receptors was assessed by quantitative PCR in psoriasis skin samples, in SpA and RA synovial tissue (ST) samples and in fibroblast-like synoviocytes (FLS). Cytokines were measured in synovial fluid (SF) and FLS supernatants by ELISA. FLS were stimulated with IL-17A or IL-17F cytokines supplemented with tumor necrosis factor (TNF), or with pooled SF from patients with SpA or RA. RESULTS: Levels of IL-17A (P = 0.031) and IL-17F (P = 0.017) mRNA were lower in psoriatic arthritis ST compared to paired psoriasis skin samples. The level of IL-17A mRNA was 2.7-fold lower than that of IL-17F in skin (P = 0.0078), but 17.3-fold higher in ST (P < 0.0001). In SF, the level of IL-17A protein was 37.4-fold higher than that of IL-17F [median 292.4 (IQR 81.4-464.2) vs median 7.8 (IQR 7.7-8.7) pg/mL; P < 0.0001]. IL-17A and IL-17F mRNA and protein levels did not differ in SpA compared to RA synovitis samples, and neither were the IL-17 receptors IL-17RA and IL-17RC, or the TNF receptors TNFR1 and TNR2, differentially expressed between SpA and RA ST, nor between SpA and RA FLS. SpA and RA FLS produced similar amounts of IL-6 and IL-8 protein upon stimulation with IL-17A or IL-17F cytokines, supplemented with 1 ng/ml TNF. Pooled SpA or RA SF samples similarly enhanced the inflammatory response to IL-17A and IL-17F simulation in FLS. CONCLUSION: The IL-17A/IL-17F expression ratio is higher in SpA synovitis compared to psoriasis skin. Expression of IL-17A and IL-17F, and the functional response to these cytokines, appear to be similar in SpA and RA synovitis.
32557565 Rheumatoid arthritis synovial microenvironment induces metabolic and functional adaptation 2020 Nov Rheumatoid arthritis (RA) is a chronic autoimmune disease which causes degradation of cartilage and bone. It is well appreciated that the pathogenic hallmark of RA is the mass influx of inflammatory cells into the joint. However, the role that dendritic cells (DC) may play in this inflammatory milieu is still relatively unexplored. Moreover, the contribution this unique synovial microenvironment has on DC maturation is still unknown. Using monocyte-derived DC (MoDC), we established an in-vitro model to recapitulate the synovial microenvironment to explore DC maturation. MoDC treated with conditioned media from ex-vivo synovial tissue biopsy cultures [explant-conditioned media (ECM)] have increased expression of proinflammatory cytokines, chemokines and adhesion molecules. ECM DC have increased expression of CD83 and CC-chemokine receptor (CCR)7 and decreased expression of CCR5 and phagocytic capacity, suggestive of heightened DC maturation. ECM-induced maturation is concomitant with altered cellular bioenergetics, whereby increased expression of glycolytic genes and increased glucose uptake are observed in ECM DC. Collectively, this results in a metabolic shift in DC metabolism in favour of glycolysis. These adaptations are in-part mediated via signal transducer and activator of transcription-3 (STAT-3), as demonstrated by decreased expression of proinflammatory cytokines and glycolytic genes in ECM DC in response to STAT-3 inhibition. Finally, to translate these data to a more in-vivo clinically relevant setting, RNA-seq was performed on RA synovial fluid and peripheral blood. We identified enhanced expression of a number of glycolytic genes in synovial CD1c(+) DC compared to CD1c(+) DC in circulation. Collectively, our data suggest that the synovial microenvironment in RA contributes to DC maturation and metabolic reprogramming.
33053283 Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. 2020 Oct 15 BACKGROUND: Upadacitinib is an oral selective Janus kinase inhibitor to treat rheumatoid arthritis. The efficacy and safety of upadacitinib as compared with abatacept, a T-cell costimulation modulator, in patients with rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs (DMARDs) are unclear. METHODS: In this 24-week, phase 3, double-blind, controlled trial, we randomly assigned patients in a 1:1 ratio to receive oral upadacitinib (15 mg once daily) or intravenous abatacept, each in combination with stable synthetic DMARDs. The primary end point was the change from baseline in the composite Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP; range, 0 to 9.4, with higher scores indicating more disease activity) at week 12, assessed for noninferiority. Key secondary end points at week 12 were the superiority of upadacitinib over abatacept in the change from baseline in the DAS28-CRP and the percentage of patients having clinical remission according to a DAS28-CRP of less than 2.6. RESULTS: A total of 303 patients received upadacitinib, and 309 patients received abatacept. From baseline DAS28-CRP values of 5.70 in the upadacitinib group and 5.88 in the abatacept group, the mean change at week 12 was -2.52 and -2.00, respectively (difference, -0.52 points; 95% confidence interval [CI], -0.69 to -0.35; P<0.001 for noninferiority; P<0.001 for superiority). The percentage of patients having remission was 30.0% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P<0.001 for superiority). During the treatment period, one death, one nonfatal stroke, and two venous thromboembolic events occurred in the upadacitinib group, and more patients in the upadacitinib group than in the abatacept group had elevated hepatic aminotransferase levels. CONCLUSIONS: In patients with rheumatoid arthritis refractory to biologic DMARDs, upadacitinib was superior to abatacept in the change from baseline in the DAS28-CRP and the achievement of remission at week 12 but was associated with more serious adverse events. Longer and larger trials are required in order to determine the effect and safety of upadacitinib in patients with rheumatoid arthritis. (Funded by AbbVie; SELECT-CHOICE Clinicaltrials.gov number, NCT03086343.).
32646239 T-Cell Large Granular Lymphocyte Leukemia in a Patient With Rheumatoid Arthritis. 2020 Jan Large granular lymphocyte leukemia (LGL) is a clonal, lymphoproliferative disorder with an indolent disease course. T-cell LGL (T-LGL) is the most common type of LGL driven from T-cell lineage (85%). The coexistence of T-LGL with several types of autoimmune disorders, mostly rheumatoid arthritis (RA), has been reported. Felty's syndrome (FS) is defined by splenomegaly, low neutrophil count, and destructive arthritis and is usually seen in <1% of patients with RA. About 30% to 40% of patients with FS have been reported to have an expansion of large granulated lymphocytes in the circulation. FS and T-LGL are similar in terms of clinical manifestations, response to immunosuppressive therapy, their smoldering course, and immunogenetic findings, proposing FS and T-LGL with RA might be different aspects of a single disease spectrum. In this article, we present a case with long-standing RA who had never been on DMARD (Disease Modifying Anti-Rheumatic Drugs) treatment found to have constitutional symptoms, neutropenia, and splenomegaly, and the patient was diagnosed with T-LGL.
31410469 Experience with tofacitinib in Canada: patient characteristics and treatment patterns in r 2020 Mar 1 OBJECTIVES: To describe characteristics, treatment patterns and persistence in patients with RA treated with tofacitinib, an oral Janus kinase inhibitor, in Canadian clinical practice between 1 June 2014 and 31 May 2017. METHODS: Data were obtained from the tofacitinib eXel support programme. Baseline demographics and medication history were collected via patient report/special authorization forms; reasons for discontinuation were captured by patient report. Treatment persistence was estimated using Kaplan-Meier methods, with data censored at last follow-up. Cox regression was applied to analyse baseline characteristics associated with treatment discontinuation. RESULTS: The number of patients with RA enrolled from 2014 to 2017 was 4276; tofacitinib utilization increased during that period, as did the proportion of biologic (b) DMARD-naïve patients prescribed tofacitinib. Of patients who initiated tofacitinib, 1226/3678 (33.3%) discontinued, mostly from lack of efficacy (35.7%) and adverse events (26.9%). Persistence was 62.7% and 49.6% after 1 and 2 years of treatment, respectively. Prior bDMARD experience predicted increased tofacitinib discontinuation (vs bDMARD-naïve, P < 0.001). Increased retention was associated with older age (56-65 years and >65 years vs ⩽45 years; P < 0.05), and time since diagnosis of 15 to <20 years (vs <5 years; P < 0.01). In bDMARD-naïve, post-1 bDMARD, post-2 bDMARD and post-⩾3 bDMARD patients, median survival was >730, 613, 667 and 592 days, respectively. CONCLUSION: Since 2014, tofacitinib use in Canadian patients with RA increased, especially among bDMARD-naïve/post-1 bDMARD patients. Median drug survival was ∼2 years. Likelihood of persistence increased for bDMARD-naïve (vs bDMARD-experienced) patients and those aged ⩾56 (vs ⩽45) years.
31918275 Molecular mechanisms and clinical application of Iguratimod: A review. 2020 Feb Iguratimod (IGU) is a novel small-molecule anti-rheumatic drug with remarkable effectiveness and good safety for the treatment of active rheumatoid arthritis. Its mechanism of action is related to its ability to act simultaneously on T and B lymphocytes. IGU can effectively inhibit expression of various inflammatory factors, inhibit B cells from producing immunoglobulins and autoantibodies, downregulate T-cell-mediated cellular immunity, accelerate bone formation, and exert some activity against anti-pulmonary fibrosis. In recent years, IGU has been gradually applied to the treatment of a variety of rheumatic diseases, such as Sjögren's syndrome, ankylosing spondylitis and systemic lupus erythematosus. This article reviews the mechanism of action and clinical research status of IGU, and provides reference for future research on its mechanism of action and clinical application.
33034006 Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decision 2021 Jan INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation. METHODS: Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM(®) MarketScan(®) Commercial and Medicare Supplemental US insurance claims databases (March 2016-October 2018). Second, using data collected in the Corrona US RA Registry (February 2016-August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions. RESULTS: In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses. CONCLUSION: These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA. TRIAL REGISTRATION: Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.
32270333 TGF-β1 +869C/T polymorphism increases susceptibility to rheumatoid arthritis in North Ind 2020 Oct OBJECTIVES: Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease, characterized by chronic inflammation, hyperplasia (swelling), tenderness, erosion of cartilage and bones in synovial joints. Transforming growth factor-β1 (TGF-β1) is an important regulator of inflammation, and its polymorphism is implicated in several diseases. Therefore, the study was done to determine whether TGF-β1 C/T gene polymorphism was associated with RA in North Indian population. METHODS: Eighty-seven (male/female: 29/58) healthy controls and 76 (male/female: 17/59) RA patients were recruited for association study between TGF-β1 +869C/T polymorphism. TGF-β1 +869C/T polymorphism was genotyped by allele specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) to test susceptibility to clinical presentation of RA patients in North Indian population by comparing RA genotypes with control groups. RESULTS: The genotypic association studies and dominant, recessive, and allelic models revealed that TGF-β1 +869C/T gene polymorphism is involved in the onset of RA. TGF-β1 +869 T (either TT or CT) allele and TT v/s CC (OR = 36.18, 95% CI = 11.98-109.31, P = 0.001); TT + CT v/s CC (OR = 0.16, 95% CI = 0.08-0.33, P = 0.001); TT v/s CC + CT (OR = 0.04, 95% CI = 0.1-0.09, P = 0.001); and T v/s C (OR = 0.12, 95% CI = 0.07-0.2, P = 0.001) show significant association with RA as compared with CC genotype or C alleles (P = 0.001). The patient carrying T alleles showed significant associations with increased ESR, uric acid, CRP, DAS28-ESR, and number of tender joints as compared to other genotypes. In the presence of RF, DAS-28-ESR was high in CT genotype. ESR, CRP, and swollen joint count were highest in TT genotype of RF negative patients. CONCLUSIONS: TGF-β1 polymorphism is associated with disease activity of RA. Disease activity is strongly modulated in the presence of serum RF and TGF-β1 polymorphism. Key Points •TGF-β1 +869C/T polymorphism was found to be associated with RA in the patients. •The polymorphism showed significant association with all inflammatory parameters as ESR, CRP, and DAS-28 in RA subjects. •RF negative patients showed high ESR, CRP, and swollen joint count with TT genotype. •TGF-β1 polymorphism and serum RF are modulating disease activity in RA.
32710083 Mouse CD163 deficiency strongly enhances experimental collagen-induced arthritis. 2020 Jul 24 The scavenger receptor CD163 is highly expressed in macrophages in sites of chronic inflammation where it has a not yet defined role. Here we have investigated development of collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) in CD163-deficient C57BL/6 mice. Compared to wild-type mice, the CIA in CD163-deficient mice had a several-fold higher arthritis score with early onset, prolonged disease and strongly enhanced progression. Further, the serum anti-collagen antibody isotypes as well as the cytokine profiles and T cell markers in the inflamed joints revealed that CD163-deficient mice after 52 days had a predominant Th2 response in opposition to a predominant Th1 response in CD163+/+ mice. Less difference in disease severity between the CD163+/+ and CD163-/- mice was seen in the CAIA model that to a large extent induces arthritis independently of T-cell response and endogenous Th1/Th2 balance. In conclusion, the present set of data points on a novel strong anti-inflammatory role of CD163.
31612758 Feasibility of patient-oriented ultrasound joint selection: Cross-sectional observational 2020 Nov Objective: Ultrasonography (US) is a useful tool for evaluating the activity of rheumatoid arthritis (RA) patients. As the systemic evaluation of many joints is time-consuming, a method to evaluate this activity with a smaller number of joints is needed. The aim of this study was to clarify whether the number of joints assessed may be reduced using patient-oriented joint selection.Methods: A total of 492 RA patients were recruited at Kyoto University Hospital. Bilateral metacarpophalangeal (MCP), (proximal) interphalangeal (PIP/IP), and wrist joints were evaluated by US. Gray scale and power Doppler imaging findings were scored by a 0-3 semi-quantitative method. Clinical assessments were performed by physicians who were blind to US results, and a questionnaire on subjective symptoms was collected from each patient.Results: The correlation between the US score of all 22 joints (US22) and patient-oriented painful joints (PtUS) or physician-oriented tender and/or swollen joints were moderate (Spearman's ρ = 0.435) and weak (ρ = 0.383), respectively. These correlations were weaker than that between the total US score of 5 preselected joints (unilateral 2MCP, 3MCP, 2PIP, 3PIP, and the wrist) and US22 (ρ = 0.813). However, when focusing on patients whose painful joints were 5 and more, the correlation between PtUS and US22 was markedly stronger (ρ = 0.757).Conclusion: Patient-oriented joint selection reflected actual joint inflammation to some extent. However, excessive reductions in the number of joints assessed need to be avoided even if patients do not have arthralgia because of the potential for underestimations.
33050760 A pooled safety analysis of peficitinib (ASP015K) in Asian patients with rheumatoid arthri 2021 May OBJECTIVE: To evaluate the safety of peficitinib for the treatment of rheumatoid arthritis (RA) in Asian patients. METHODS: Safety data from one Phase 2b, two Phase 3, and one open-label long-term extension study [data cut-off 31 May 2018] were pooled into Phase 3 studies (peficitinib 100 and 150 mg/day, and placebo) and Phase 2/3 studies (all peficitinib-treated patients). Incidence rates per 100 patient-years (PY) of adverse events (AEs) of special interest were calculated. RESULTS: Overall, 1052 patients received peficitinib for 2336.3 PY of exposure (median 2.1 years); four deaths occurred, including one death after the studies. AE incidence was similar across peficitinib 100 and 150 mg/day groups (Phase 3 studies). Respective peficitinib and placebo incidence rates (95% confidence interval) per 100 PY were 2.9 (1.9, 4.6) and 0.0 for serious infections, 5.7 (4.2, 7.9) and 2.3 (0.6, 9.4) for herpes zoster-related disease, and 0.6 (0.2, 1.6) and 1.2 (0.2, 8.3) for malignancies (excluding non-melanoma skin cancer) (Phase 3 studies), and 0.1 (0.0, 0.3) for venous thromboembolism in all peficitinib-treated patients (Phase 2/3 studies). CONCLUSION: Peficitinib was well tolerated in Asian patients with RA over a median of 2 years, with no observed dose or temporal dependency for AEs with prolonged administration.
32124272 Patient Satisfaction with CIMZIA(®) (Certolizumab Pegol) AutoClicks(®) in the UK. 2020 Apr INTRODUCTION: The CIMZIA(®) AutoClicks(®) pre-filled pen (CZP PFP) was developed to overcome barriers to self-injection, by improving self-injection confidence, reducing fear associated with needle use, and supporting patients with impaired dexterity. The purpose of this research was to gather feedback on injection experience and the usefulness of training materials. METHODS: Eligible patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) were at least 18 years of age and initiated onto the CZP PFP. Routine self-injection training and support were provided by trained specialist nurses. Patient experience (pain and skin reactions, confidence, satisfaction, and ease of use) was evaluated at visits 1-3 using an amended version of the self-injection assessment questionnaire (SIAQ) v2.0. Nurse and patient feedback on the training materials, and nurse opinions on patient self-injection after self-injection at visit 1, were also collected. RESULTS: Of 355 patients invited to participate, 196 provided informed consent and 79 participated in all three visits. Patients generally found the CZP PFP easy to use, and self-confidence and satisfaction were high. From visit 1 to visit 3, there was a numerical trend towards improvement in all three aspects of patient experience, most notably in both confidence and satisfaction. After self-injection at visit 1, confidence around safe patient self-injection was higher among nurses than among patients. Meanwhile, "pain and skin reactions" remained low at all visits. Patients thought the training materials contained sufficient information and were easy to understand and useful. CONCLUSION: After training, patients generally found the device easy to use and showed high confidence and satisfaction with self-injection. Some patients may have been competent (based on nurse opinion), but initially lacked self-confidence. Increasing self-injection experience, together with patient training and continued support, may have facilitated high patient confidence and satisfaction, thereby potentially overcoming some of the barriers to self-injection.
32930551 Comparing patient OOP spending for specialty drugs in Medicare Part D and employer-sponsor 2020 Sep OBJECTIVES: Per capita spending on specialty drugs increased 55% between 2014 and 2018. Individuals aged 55 to 75 years using specialty drugs make the transition from employer-sponsored insurance (ESI) to Medicare Part D coverage. We compared out-of-pocket (OOP) spending across ESI, Medicare fee-for-service (FFS), and Medicare Advantage (MA) prescription drug plans to examine the impact of benefit design on OOP spending. STUDY DESIGN: Analyses consisted of Truven MarketScan and Medicare Part D prescription drug claims from 2013 to 2017 for individuals enrolled in ESI, FFS, and MA drug plans taking at least 1 drug among the top 4 specialty drug classes: rheumatoid arthritis (RA), multiple sclerosis (MS), cancer, and hepatitis C. METHODS: Multivariate regression analyses with fixed effects were used to assess whether there are differences in OOP spending by insurance type and the impact of benefit design differences. A secondary outcome was drug choice within a therapeutic class. RESULTS: There were small differences in drug choice between Medicare and ESI but significant differences in OOP spending. Monthly OOP spending for ESI relative to FFS was $108 less for RA drugs, $288 less for MS drugs, $504 less for cancer drugs, and $1437 less for hepatitis C drugs. Spending was slightly greater for beneficiaries in MA plans compared with FFS. Higher Medicare spending was driven by gaps in coverage in the Part D benefit phases because beneficiaries pay a percentage of list price. CONCLUSIONS: OOP spending was substantially higher for Medicare enrollees compared with ESI enrollees as a result of the Part D benefit structure.
33155486 Time Course of Quality of Life Improvement Between Resection Arthroplasty and Metatarsopha 2021 Feb BACKGROUND: Resection arthroplasty has long been a major treatment option for forefoot deformity caused by rheumatoid arthritis (RA). However, metatarsophalangeal (MTP) joint-preserving surgery is now surpassing classic resection arthroplasty. This study was performed to compare the postoperative results of these 2 operative methods. METHODS: Fifty-one toes of 40 patients with RA who underwent resection arthroplasty (resection group) or MTP joint-preserving arthroplasty (preservation group) from 2014 to 2017 for forefoot deformity were followed up for >1 year and were retrospectively analyzed. In the preservation group, open reduction of joint dislocation was performed if needed, and the deformity was corrected by metatarsal shortening osteotomy. The mean follow-up period was 21 months. The Japanese Society for Surgery of the Foot (JSSF) scales (objective outcome measures), the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) (subjective outcome measure), and radiographic indices were compared between the groups. The resection group and preservation group comprised 15 toes of 11 patients and 36 toes of 29 patients, respectively. RESULTS: There were no significant differences in the preoperative radiographic indices, JSSF scales, or SAFE-Q results between the 2 groups. The preservation group showed better JSSF scores at the last follow-up (median hallux scale, 89 vs 74; median lesser scale, 87 vs 79). In the preservation group, the SAFE-Q scores gradually improved with time until 12 months postoperatively. In the resection group, the scores decreased 3 months postoperatively and then improved and reached a plateau 6 months postoperatively. At 12 months postoperatively, there was no significant difference in the SAFE-Q scores between the 2 groups. CONCLUSIONS: MTP joint-preserving arthroplasty resulted in superior objective scores to resection arthroplasty in patients with RA forefoot deformity. Although the subjective scores did not differ between the groups at the last follow-up, the time course of postoperative quality of life improvement was different between the 2 surgeries. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
32342135 Anti-arthritic and anti- inflammatory effects of extract and fractions of Malva parviflora 2020 Jul Malva parviflora is used as food in the gastronomy of some regions of Mexico and, also, in Mexican traditional medicine for inflammation-related conditions like rheumatoid arthritis. The objective of this work was to evaluate its antiarthritic activity in a mice model. In ICR, female mice were tested the dichloromethane extract (MpD) and fractions MpF4 (extracted with a dichoromethane:methanol system) and MpFphy (a precipitate by acetone:methanol) by using the mono-arthritis with kaolin/carrageenan model. During the treatment, joint inflammation was measured daily, and hyperalgesia was measured using the hot plate test. The treatments diminished both joint inflammation and pain. At the end of the evaluation, the left joint and spleen were extracted for determination of pro- and anti-inflammatory cytokines. The results showed that the MpD, MpF4, and MpFphy treatments modulated the concentration of these proteins. Specifically, MpFphy at 1.0 mg/kg increased IL-4 and IL-10 and decreased IL-17, IL-1β, and TNF-α. GC-MS analysis showed that MpF4 contained a mixture of a total of nine compounds, three of them newly reported for the species. The studies confirmed the presence of five sterols in the MpFphy fraction, including stigmasterol and β-sitosterol. These results confirm the anti-rheumatoid and anti-inflammatory activities of a fraction rich in sterols from Malva parviflora. Graphical abstract.
30506552 Longitudinal Occurrence and Predictors of Patient-Provider Discordance Between Global Asse 2020 Jan OBJECTIVE: To identify longitudinal predictors of discordance between patients with rheumatoid arthritis (RA) and their health care providers, where patient global assessment of disease activity is substantially higher than provider global assessment. METHODS: This retrospective case-control study included 102 cases with positive discordance (i.e., ≥25 mm between patient and provider global assessments) and 102 controls without discordance who were matched for age, sex, RA duration, and Clinical Disease Activity Index (CDAI) score. Data were collected at the baseline visit (date of diagnosis or earliest available visit), the index visit (participation in a previous cross-sectional study), and at up to 11 additional visits before the index visit. Data included patient characteristics, disease activity measures, Disease Activity Score in 28 joints (3-variable) using the C-reactive protein level (DAS28-CRP), and medications. Data were analyzed by using linear and logistic regression models with smoothing splines for nonlinear trends. RESULTS: Overall, the mean age was 63 years, 75% of patients were female, and the mean RA duration was 10 years. Compared with controls, cases had higher rates of discordant visits during the 4 years before the index visit, and they had a higher CDAI score and DAS28-CRP earlier in the disease course. Cases more frequently had antinuclear antibodies, nonerosive disease, prior depression, or prior use of antidepressants or fibromyalgia medications. Disease-modifying medication use was not different between cases and controls. CONCLUSION: The findings inform new hypotheses about the relationships of disease activity and antinuclear antibodies to the later occurrence of positive discordance among patients with RA.
32206975 The predictive value of serum soluble ICAM-1 and CXCL13 in the therapeutic response to TNF 2020 Sep BACKGROUND: Tumor necrosis factor-α (TNFα) inhibitors (TNFi) have greatly improved the prognosis of RA and become the first therapeutic option for patients who failed the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) therapy, but not all these patients respond well to TNFi. So far, there has been no definite biomarker to predict the response to TNFi yet. METHODS: Sixty rheumatoid arthritis (RA) patients with disease duration more than 6 months and at least low disease activity defined by DAS28-CRP > 3.2 although after csDMARDs (including MTX and/or leflunomide) treatment for more than 3 months were included. They were further treated with TNFα receptor Fc fusion protein and MTX 10 mg per week for 12 weeks. Soluble ICAM-1 (sICAM-1) and CXCL13 concentrations in sera from 60 RA patients and 20 healthy controls were tested by ELISA right before and at the end of 12 weeks of TNFi therapy. The correlation between sICAM-1 and CXCL13 with disease activity and their predictive values for TNFi response were analyzed. RESULTS: The mean age of the 60 patients was 54.8 ± 11.6 years. Serum sICAM-1 and CXCL13 concentrations were higher in RA patients than heathy controls, higher in seropositive RA patients than in seronegative ones, and higher in RA patients with higher disease activity. Serum sICAM-1 and CXCL13 levels were decreased after TNFi therapy, especially in good responders. Baseline sICAM-1 concentration was independently associated with the EULAR response (p = 0.033, OR = 1.014, 95% CI = 1.003-1.026). The sICAM-1(high)/CXCL13(high) patients had the highest response rate, which was significantly higher than the sICAM-1(low)/CXCL13(low) group (OR = 8.143, 95% CI = 1.040-75.482, p = 0.045). CONCLUSION: sICAM-1 and CXCL13 are elevated in RA patients and correlated with disease activity. sICAM-1 is an independent predictor of TNFi response in csDMARDs refractory RA patients. Key Points • This study confirmed the predictive value of soluble ICAM-1 (sICAM-1) and CXCL13 on the response to TNFi in RA patient. • Baseline sICAM-1 concentration was independently associated with the EULAR response. • The sICAM-1(high)/CXCL13(high) patients had significantly higher response rate than the sICAM-1(low)/CXCL13(low) group.
32428513 Baseline Characteristics and Progression of a Spectrum of Interstitial Lung Abnormalities 2020 Oct BACKGROUND: Interstitial lung abnormalities (ILA) and interstitial lung disease (ILD) are seen in up to 60% of individuals with rheumatoid arthritis (RA), some of which will progress to have a significant impact on morbidity and mortality rates. Better characterization of progressive interstitial changes and identification of risk factors that are associated with progression may enable earlier intervention and improved outcomes. RESEARCH QUESTION: What are baseline characteristics associated with RA-ILD progression? STUDY DESIGN AND METHODS: We performed a retrospective study in which all clinically indicated CT chest scans in adult individuals with RA from 2014 to 2016 were evaluated for interstitial changes, and the data were further subdivided into ILA and ILD based on clinical record review. Progression was determined visually and subsequently semiquantified. RESULTS: Those individuals with a spectrum of interstitial changes (64 of 293) were older male smokers and less likely to be receiving biologics/small molecule disease-modifying antirheumatic drugs. Of 44% of the individuals with ILA, 46% had had chest CT scans performed for nonpulmonary indications. Of the 56 individuals with ILA/ILD with sequential CT scans, 38% had evidence of radiologic progression over 4.4 years; 29% of of individuals with ILA progressed. Risk factors for progressive ILA/ILD included a subpleural distribution and higher baseline involvement. INTERPRETATION: Of 293 individuals with RA with clinically indicated CT scans, interstitial changes were observed in 22%, one-half of whom had had a respiratory complaint at the time of imaging; radiologic progression was seen in 38%. Of individuals with progressive ILA, one-half had had baseline CT scans performed for nonpulmonary indications. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with progression. Prospective longitudinal studies of RA-ILA are necessary.