Efficacy and Safety of Etanercept in Elderly Patients with Rheumatoid Arthritis: A Post-Hoc Analysis of Randomized Controlled Trials.

BACKGROUND: Elderly individuals are disproportionately affected by rheumatoid arthritis (RA), but few studies have addressed the efficacy and safety of treatments in this population. OBJECTIVE: Our objective was to assess the efficacy and safety of etanercept in elderly patients (aged ≥ 65 years) with RA. METHODS: The efficacy analysis was a post hoc analysis of data from the open-label period of three phase IV clinical trials of etanercept for RA. Least squares (LS) change from baseline (cfb) in 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and modified Total Sharp Scores (mTSS) were analyzed by age (< 65 vs. ≥ 65 years) for each study. The safety analyses were of data pooled from the double-blind, placebo-controlled periods of 19 phase I-IV randomized studies of etanercept in patients with RA. The percentage occurrence of adverse events (AEs) in placebo- and etanercept-treated patients was analyzed by age (< 65 vs. ≥ 65 years). RESULTS: There were no significant differences in LS mean cfb in DAS28 or mTSS between the two age groups. LS mean cfb in HAQ-DI scores was consistently lower in elderly than in non-elderly patients, although significant differences were not observed in all trials. Overall, AE occurrence was higher in elderly than non-elderly patients, regardless of treatment. In etanercept-treated patients, there were small yet statistically significant increases in the occurrence of congestive heart failure, serious infections, and non-melanoma skin cancers in elderly versus non-elderly patients. For most AEs, occurrence did not significantly differ between elderly and non-elderly patients. CONCLUSION: Overall, there were no substantial differences in the efficacy or safety of etanercept between elderly and non-elderly patients with RA.

Real-world utilization of methotrexate or prednisone co-therapy with etanercept among Canadian patients with rheumatoid arthritis: a retrospective cohort study.

Objective: To evaluate whether initiation of etanercept therapy among patients with rheumatoid arthritis (RA) impacts use of co-therapy with methotrexate or prednisone, and to describe etanercept dosing dynamics compared to product monograph in the Canadian real-world setting. Methods: A retrospective cohort study was conducted using claims-level data from IQVIA Private Drug Plan database, Ontario Public Drug Plan database and Régie de l'assurance maladie du Québec database. Bio-naïve RA patients initiating etanercept between July 2014 and June 2015 were identified and their claims for methotrexate or prednisone were analyzed. Utilization of methotrexate or prednisone was calculated as average weekly dose in milligrams, and compared in the 6 months pre-initiation versus 12 months post-initiation of etanercept. Weekly etanercept dosing of each patient was calculated and analyzed to determine whether patients had at least 20% higher or lower average dose than monograph recommended dose (50 mg/week), and were then flagged as above-monograph or below-monograph, respectively. Results: A total of 2876 patients with RA (66% female, 76% aged 18-65) were included; 62% (n = 1,140) used methotrexate and 27% used prednisone (n = 498) both pre- and post-initiation of etanercept. In methotrexate patients, the average weekly dose dispensed was 25.4 mg in the 6 months pre-etanercept, and 25.0 mg in the 12 months post-etanercept initiation (p = .5282). In prednisone patients, the average weekly dose dispensed reduced from 122.6 mg pre-etanercept to 107.1 mg post-etanercept initiation (p = .2173). Among patients who were already on methotrexate or prednisone, after initiating on etanercept 16% (n = 213) and 34% (n = 254) of patients stopped methotrexate and prednisone, respectively. When compared to the recommended dose, 12% (n = 168) of patients were below-monograph and 7.1% of patients were above-monograph during their first year of etanercept therapy. Average etanercept dosing was consistently lower than product monograph during the follow-up year. Conclusions: Patients had a modest but not statistically significant decrease in prescribed doses of co-therapy with methotrexate and prednisone when etanercept was added to patients' therapy. In addition, 12-14% of patients stopped their co-therapy with methotrexate or prednisone. Further study is needed to understand the impact on patient outcomes and safety.

Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review.

OBJECTIVE: Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. METHODS: Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab, etanercept, and infliximab. RESULTS: Of 83 publications identified, 16 publications were included for analysis (RA: originators, n = 5; biosimilars, n = 6; PsO: originators, n = 2; biosimilars, n = 3). American College of Rheumatology 20% response rates were higher among patients with RA receiving originator biologics and biosimilars in biosimilar trials than among patients receiving the originator biologics in pivotal trials. In etanercept studies in PsO, a difference was observed in Psoriasis Area and Severity Index 75% response rates between biosimilar and pivotal trials. Insufficient efficacy data were available from adalimumab and infliximab biosimilar studies in PsO to determine any differences in treatment responses between pivotal and biosimilar studies. CONCLUSIONS: Observed differences in treatment response rates between pivotal originator trials and trials of originator biologics and their respective biosimilars may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis.

Improving inflammatory arthritis management through tighter monitoring of patients and the use of innovative electronic tools.

Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists.