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Ceria-based nanotheranostic agent for rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease that affects 1-2% of the human population worldwide, and effective therapies with targeted delivery for local immune suppression have not been described. We address this problem by developing a novel theranostic nanoparticle for RA and assessed its therapeutic and targeting effects under image-guidance. Methods: Albumin-cerium oxide nanoparticles were synthesized by the biomineralization process and further conjugated with near-infrared, indocyanine green (ICG) dye. Enzymatic-like properties and reactive oxygen species (ROS) scavenging activities, as well as the ability to reprogram macrophages, were determined on a monocyte cell line in culture. The therapeutic effect and systemic targeting potential were evaluated in collagen-induced arthritis (CIA) mouse model using optical/optoacoustic tomographic imaging. Results: Small nanotheranostics with narrow size distribution and high colloidal stability were fabricated and displayed high ROS scavenging and enzymatic-like activity, as well as advanced efficacy in a converting pro-inflammatory macrophage phenotype into anti-inflammatory phenotype. When administrated into affected animals, these nanoparticles accumulated in inflamed joints and revealed a therapeutic effect similar to the gold-standard therapy for RA, methotrexate. Conclusions: The inflammation-targeting, inherent contrast and therapeutic activity of this new albumin-cerium oxide nanoparticle may make it a relevant agent for assessing severity in RA, and other inflammatory diseases, and controlling inflammation with image-guidance. The design of these nanotheranostics will enable potential clinical translation as systemic therapy for RA.

SUBMITTER: Kalashnikova I

PROVIDER: S-EPMC7667692 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Ceria-based nanotheranostic agent for rheumatoid arthritis.

Kalashnikova Irina I Chung Seock-Jin SJ Nafiujjaman Md M Hill Meghan L ML Siziba Mzingaye E ME Contag Christopher H CH Kim Taeho T

Theranostics 20201025 26

Rheumatoid arthritis (RA) is an autoimmune disease that affects 1-2% of the human population worldwide, and effective therapies with targeted delivery for local immune suppression have not been described. We address this problem by developing a novel theranostic nanoparticle for RA and assessed its therapeutic and targeting effects under image-guidance. <b>Methods:</b> Albumin-cerium oxide nanoparticles were synthesized by the biomineralization process and further conjugated with near-infrared, ...[more]

PMID: 33204316

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Project description:BACKGROUND: The role of biologic therapies in the treatment of rheumatoid arthritis has expanded, but dosing patterns in the first versus subsequent lines of therapy have not been thoroughly explored. METHODS: In order to describe patterns of biologic agent utilization among patients with rheumatoid arthritis, health care claims data on use of abatacept, rituximab, or the anti-tumor necrosis factor (TNF) agents etanercept, adalimumab, and infliximab in first- or subsequent-line settings were used to form patient cohorts. Variables included: starting dose (first administration or fill), maintenance dose (third administration or fill), average dose, dose escalation, inter-infusion interval, and discontinuation (gap in therapy > 60 days or switch). Time to discontinuation was assessed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Over 1 year, average (SD) doses of first-line etanercept (N = 1593; 45.4 [8.8] mg/week), adalimumab (N = 1040; 40.7 [10.4] mg/2 weeks), and abatacept (N = 360; 715.4 [214.5] mg/4 weeks) were similar to the starting and maintenance doses; the average infliximab dose (N = 538; 441.0 [209.2] mg/8 weeks) was greater than the starting and maintenance doses. Trends in the subsequent-line anti-TNF cohorts were similar. The percentages with a dose escalation or discontinuation were greater in the subsequent-line anti-TNF cohorts. The proportion with a dose escalation was greatest for the infliximab cohorts (61.2% first-line and 80.2% subsequent-line). The average period between abatacept infusions was 4.8 [1.4] weeks (4-week approved schedule); and 6.8 [2.6] months between rituximab courses (currently approved schedule is 6 months). Time to discontinuation was significantly shorter for subsequent-line than first-line anti-TNF therapy (median 9.7 vs. 12.5 mo; p < 0.001). The hazard ratio for discontinuing subsequent-line versus first-line anti-TNF therapy was 1.177 (p < 0.001). CONCLUSIONS: Subsequent-line anti-TNF therapy cohorts had higher rates of discontinuation, dose escalation, and shorter time to discontinuation than first-line anti-TNF cohorts.

Project description:IntroductionUnderstanding the durability of response to treatment and factors associated with failure to maintain response in a real-world setting can inform treatment decisions for patients with rheumatoid arthritis (RA). The aim of this study was to analyze durability of response to tocilizumab (TCZ) and factors associated with durability among US patients with RA in routine clinical practice.MethodsTCZ initiators in the Corrona RA Registry were included. Durability of response was defined as maintaining continuous TCZ treatment and either an improvement of at least minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score or low disease activity (LDA). Secondary analyses included patients treated with intravenous (IV) TCZ and excluded those who discontinued TCZ without reporting reasons for discontinuation. Durability was calculated with Kaplan-Meier survival analysis. Cox proportional hazards modeling identified factors associated with durability.ResultsAmong 1789 TCZ initiators, 466, 272, and 162 were persistent (with or without durable response) with follow-up visits at 1, 2, and 3 years, respectively. Median MCID durability of response in CDAI was > 50% after 36 months overall, 26 months for TCZ-IV, and > 50% after 36 months for those with known reasons for discontinuation; longer durability was associated with increased duration of RA and higher baseline CDAI score and shorter durability with history of malignancy and history of diabetes. Median LDA durability of response was 13.0 months overall, for TCZ-IV, and for those with known reasons for discontinuation; shorter durability was associated with history of malignancy, history of diabetes, and higher baseline CDAI score.ConclusionsMedian durability of response to TCZ in RA was > 3 years when defined as maintenance of MCID in CDAI score and > 1 year with the more stringent criteria of maintenance of LDA.Trial registrationClinicalTrials.gov identifier, NCT01402661.

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Ceria-based nanotheranostic agent for rheumatoid arthritis.

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Ceria-based nanotheranostic agent for rheumatoid arthritis.

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