Objective. To investigate the validity, reproducibility, and responsiveness of a simplified power Doppler ultrasound (PDUS) assessment of joint inflammation compared with a comprehensive 44-joint PDUS assessment in patients with rheumatoid arthritis (RA) who started therapy with a biologic agent. Methods. A total of 160 patients with active RA who started a biologic agent were prospectively recruited in 18 Spanish centers. The patients underwent clinical and laboratory assessment and blinded PDUS examination at baseline and 6 months. A PDUS examination of 128 synovial sites in 44 joints was performed. US synovitis and PD signal were semiquantitatively graded from 1 to 3 in all synovial sites. US count and index for synovitis and PD signal were obtained. PDUS intraobserver and interobserver reliability were evaluated. A process of data reduction based on the frequency of involvement of synovial sites by both synovitis and PD signal was conducted. Construct and discriminant validity of a simplified PDUS assessment was investigated. Results. A PDUS simplified assessment including 24 synovial sites from 12 joints detected 100% of patients with synovitis and 91% of patients with PD signal. There was a highly significant correlation between the 44-joint count and index for synovitis and PD signal and the 12-joint count and index for synovitis and PD signal at baseline and 6 months (r ‫؍‬ 0.84 -0.90, P < 0.0005). The smallest detectable difference was lower than the mean change in simplified PDUS variables. Conclusion. A 12-joint PDUS assessment of RA joint inflammation may be a valid, feasible method for multicenter monitoring of therapeutic response to biologic agents.

This observational, longitudinal retrospective, noncomparative study was designed to assess the persistence and effectiveness of golimumab as a second anti-tumor necrosis factor (TNF) drug in patients with spondyloarthritis requiring discontinuation from a first anti-TNF drug. Data were collected retrospectively for all patients with axial spondyloarthritis or psoriatic arthritis from 20 rheumatology clinics in Spain who started golimumab as a second anti-TNF drug between January 2013 and December 2015. Golimumab persistence was assessed with Kaplan-Meier survival analysis, and associated factors were assessed with Cox regression analysis. 210 patients started golimumab as a second anti-TNF drug: 131 with axial spondyloarthritis and 79 with psoriatic arthritis. In axial spondyloarthritis patients, the mean (standard deviation) Bath Ankylosing Spondylitis Disease Activity Index score at baseline was 5.5 (2.1), decreasing to 3.9 (2.0) at month 3 and 3.5 (2.0) at year 1, and remaining stable thereafter. In psoriatic arthritis patients, mean (standard deviation) baseline Disease Activity Score was 4.0 (1.3), reducing to 2.5 (1.2) at month 3 and to 2.2 (1.3) at year 1. Corresponding improvements were recorded from baseline in C-reactive protein levels and erythrocyte sedimentation rates. The probability of persistence of treatment with golimumab was 80% at year 1, 70% at year 2 and 65% at years 3 and year 4, and was similar in those who had stopped the first anti-TNF due to loss of efficacy or other reasons. Cox regression analysis showed that the probability of survival with golimumab was higher in patients with higher erythrocyte sedimentation rate, in patients with axial spondyloarthritis than with psoriatic arthritis, and in those who had discontinued adalimumab as first anti-TNF. Seventy-two patients (34.3%) discontinued golimumab during follow-up, 50 of them due to lack of efficacy. In patients with spondyloarthritis requiring discontinuation from a first anti-TNF drug, treatment with golimumab was effective and showed a high probability of persistence up to 4 years of treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic DMARDs poses a significant economic burden. The Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) trial was a head-to-head, randomized study comparing abatacept in serum anti-citrullinated protein antibody (ACPA)-positive patients, with increasing efficacy across ACPA quartile levels. The aim of this study was to evaluate the cost per response accrued using abatacept versus adalimumab in ACPA-positive and ACPA-negative patients with RA from the health care perspective in Germany, Italy, Spain, the US and Canada. A cost-consequence analysis (CCA) was designed to compare the monthly costs per responding patient/patient in remission. Efficacy, safety and resource use inputs were based on the AMPLE trial. A one-way deterministic sensitivity analysis (OWSA) was also performed to assess the impact of model inputs on the results for total incremental costs. Cost per response in ACPA-positive patients favoured abatacept compared with adalimumab (ACR20, ACR90 and HAQ-DI). Subgroup analysis favoured abatacept with increasing stringency of response criteria and serum ACPA levels. Cost per remission (DAS28-CRP) favoured abatacept in ACPA-negative patients, while cost per CDAI and SDAI favoured abatacept in ACPA-positive patients. Abatacept was consistently favoured in ACPA-Q4 patients across all outcomes and countries. Cost savings were greater with abatacept when more stringent response criteria were applied and also with increasing ACPA levels, which could lead to a lower overall health care budget impact with abatacept compared with adalimumab.

Background Effective treatment of rheumatoid arthritis (RA) with biologic DMARDs poses a significant economic burden. The AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE RA subjects with background methotrexate) trial was a head-to-head, randomized study comparing abatacept with adalimumab. A post hoc analysis showed improved efficacy for abatacept in patients with versus without seropositive, erosive early RA. Objective The aim of the current study was to evaluate the cost per response (ACR20/50/70/90 and HAQ-DI) and patient in remission (DAS28-CRP, CDAI, and SDAI) for abatacept relative to adalimumab, in patients with seropositive, erosive early RA in the US, Germany, Spain, and Canada. Methods A previously published model was used to compare abatacept and adalimumab in a cohort of 1000 patients over 2 years. Clinical inputs were updated based on two subpopulations from the AMPLE trial. Cohort 1 included patients with early RA (disease duration ≤ 6 months), RF and/or ACPA seropositivity, and > 1 radiographic erosion. Cohort 2 included patients with RA in whom at least one of these criteria was absent. Results For cohort 1, all incremental costs per additional health gain (patient response or patient in remission) favoured abatacept in all countries, except for DAS28-CRP remission in Canada. Cost savings versus adalimumab were greater when more stringent response criteria were applied and also in cohort 1 patient (versus cohort 2 patients). Conclusion The cost per responder and patient in remission favoured abatacept in patients with seropositive, erosive early RA across all the countries. In this patient population, the use of abatacept instead of adalimumab can lead to lower costs in the US, Germany, Spain, and Canada.

Background:The HLA class II Shared Epitope (SE) is a known Rheumatoid Arthritis (RA) risk allele linked to autoantibody production and disease progression. The recent Early AMPLE study suggests an enhanced treatment benefit of abatacept (ABA) over adalimumab (ADA) in SE positive patients with early seropositive RA.1Economic implications beyond the trial follow-up duration are unknown.Objectives:To estimate the cost-effectiveness of ABA vs ADA in biologic-naive RA patients seropositive for anti-citrullinated protein antibody and rheumatoid factor based on the Early AMPLE study.Methods:We developed a microsimulation model to estimate clinical response, medical cost, quality of life and survival from a Spanish payer perspective. The model captures the patient’s disease and treatment journey using response outcomes and the Health Assessment Questionnaire (HAQ) score. Patients who fail to respond switch to the next treatment line. Six treatment lines are included to capture a lifetime horizon. Responding patients (ACR50 and EULAR response) achieve an improvement in their HAQ score. Patient mortality was modelled as a function of HAQ. For both the overall Early AMPLE population and SE+ patients, incremental monthly cost per response over 2 years and incremental cost per QALY over a lifetime were estimated. Costs were based on local tariffs in Spain.Results:Baseline characteristics for the Early AMPLE (n=80) and the SE+ (n=61) patients were well balanced between the treatment groups.2Compared to ADA, the ABA cohort had a lower cost per response and the difference was more pronounced in the SE+ population, compared to the entire Early AMPLE population for both the response criteria (Table 1). Compared with ADA, the ABA cohort showed greater quality adjusted life years (QALYs) gains, and a modest increase in cost due to a prolonged time on treatment (Table 2). The incremental cost per QALY over a lifetime fell below commonly used thresholds in Spain (25-60 thousand Euros per QALY).3Table 1.Cost per response resultsFull Early AMPLEACR50EULARABAADAABAADACost per response (€) – 2 years25,86040,65426,99340,643Incremental monthly cost per response (€)-616-569SE positiveACR 50EULARABAADAABAADACost per response (€) – 2 years24,27240,24925,33741,425Incremental monthly cost per response (€)-666-670All incremental results are for ABA – ADATable 2.Cost-effectiveness results (discounted)Full Early AMPLEACR50EULARABAADAABAADALYs*30.1430.0630.1130.03QALYs8.327.817.577.12Time on treatment (years)4.172.035.143.06Costs (€)75,54768,15785,12280,933Incremental LYs*0.080.08Incremental QALYs0.520.45Incremental Costs (€)7,3904,189Incremental cost per QALY (€)14,3089,275SE positiveACR50EULARABAADAABAADALYs*30.3830.2230.1630.09QALYs8.207.597.406.90Time on treatment (years)4.482.025.383.02Costs (€)78,11368,65187,58681,321Incremental LYs*0.150.06Incremental QALYs0.610.50Incremental Costs (€)9,4626,265Incremental cost per QALY (€)15,41012,503*LY results are presented undiscounted. All incremental results are for ABA – ADAConclusion:Compared with ADA, ABA is a cost-effective alternative and is associated with a lower 2 years cost per response for both populations. The economic benefit and quality of life gain is greater in a SE+ patient population.References:[1]Rigby W, et al. EULAR Annual Meeting, June 2019; Poster LB0008[2]Buckner J, et al. ACR/ARP Annual Meeting, Nov 2019; Poster 1424[3]Sacristán JA, et al.Gaceta Sanitaria2019Disclosure of Interests:José M. Rodríguez-Heredia: None declared, Lisanne Verburg-Baltussen Consultant of: Consultant for Bristol-Myers Squibb, Paid instructor for: Training sessions for Pharmaceutical companies, Dhanda Devender Shareholder of: BMS, Employee of: BMS, Nicholas Durno Consultant of: Consultant for Bristol-Myers Squibb, Paid instructor for: Training sessions for Pharmaceutical companies, Carlos Sanchez Shareholder of: Shareholder of Bristol-Myers Squibb, Employee of: Bristol Myers-Squibb, Neelanjana Ray Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Maarten Treur Consultant of: Consultant for Bristol-Myers Squibb, Paid instructor for: Training sessions for Pharmaceutical companies, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb