BACKGROUND: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. METHODS: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. RESULTS: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. CONCLUSION: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

• Klíčová slova
• Arthritis, Rheumatoid, Biological Therapy, Epidemiology, Therapeutics, Tumor Necrosis Factor Inhibitors,
• MeSH
• abatacept terapeutické užití   MeSH
• antirevmatika * terapeutické užití   MeSH
• inhibitory Janus kinas * terapeutické užití   MeSH
• inhibitory TNF MeSH
• interleukin-6 MeSH
• lidé MeSH
• revmatoidní artritida * chemicky indukované   farmakoterapie   MeSH
• TNF-alfa MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• abatacept MeSH
• antirevmatika * MeSH
• inhibitory Janus kinas * MeSH
• inhibitory TNF MeSH
• interleukin-6 MeSH
• TNF-alfa MeSH

Some evidences suggest that obesity impairs the effectiveness of TNF inhibitors. We examined the impact of body mass index (BMI) on the clinical effectiveness of abatacept in rheumatoid arthritis (RA) patients. This is a pooled analysis of 10 prospective cohorts of RA patients. All patients with available BMI were included in this study. The primary endpoint was drug retention of abatacept in the different BMI categories. Multivariable Cox regression was used to estimate hazard ratios (HRs) for drug discontinuation. A secondary endpoint was EULAR/LUNDEX response rates at 6/12 months. Of the 2015 RA patients initiating therapy with IV abatacept, 380 (18.9%) were classified as obese. Obese patients had more functional disability, and were less often RF positive. The median abatacept retention time was 1.91 years for obese RA patients compared to 2.12 years for non-obese patients (p = 0.15). The risk of abatacept discontinuation was not significantly different for overweight (HR 1.03 (95% CI 0.89-1.19)), or for obese (HR 1.08 (95% CI 0.89-1.30)) compared to normal-weight patients. Rheumatoid factor positivity reduced the risk of abatacept discontinuation (HR 0.83 (95% CI 0.72-0.95)), while previous biologic therapy was positively associated with drug interruption (HRs increasing from 1.68 to 2.16 with the line of treatments). Obese and non-obese patients attained similar rates of EULAR/LUNDEX clinical response at 6/12 months. Drug retention and clinical response rates to abatacept do not seem to be decreased by obesity in RA patients.

• Klíčová slova
• Abatacept, Body mass index, Drug survival, Rheumatoid arthritis,
• MeSH
• abatacept aplikace a dávkování   škodlivé účinky   MeSH
• antirevmatika aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• index tělesné hmotnosti * MeSH
• indukce remise MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• registrace MeSH
• revmatoidní artritida farmakoterapie   MeSH
• revmatoidní faktor krev   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• abatacept MeSH
• antirevmatika MeSH
• revmatoidní faktor MeSH

BACKGROUND: Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). METHODS: Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes. FINDINGS: We identified three types of treatment response trajectories: 'gradual responders' (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; 'rapid responders' (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; 'inadequate responders' (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (p=0.03), and EULAR good or moderate responses at 1year was much higher among 'rapid responders' (p<0.001). INTERPRETATION: Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.

• Klíčová slova
• Abatacept, DAS28, Disease activity, Drug retention, Longitudinal data, Response rate, Rheumatoid arthritis,
• MeSH
• antirevmatika terapeutické užití   MeSH
• biologické faktory terapeutické užití   MeSH
• biologické markery MeSH
• komorbidita MeSH
• lidé MeSH
• následné studie MeSH
• progrese nemoci MeSH
• revmatoidní artritida diagnóza   farmakoterapie   MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• antirevmatika MeSH
• biologické faktory MeSH
• biologické markery MeSH

BACKGROUND: The emergence of new therapies for the treatment of rheumatoid arthritis (RA), the paucity of head-to-head studies, and the heterogeneous nature of responses to current biologics highlight the need for the identification of prognostic factors for treatment response and retention in clinical practice. Prognostic factors for patient retention have not been explored thoroughly despite data for abatacept and other biologics being available from national registries. Real-world data from the ACTION study may supplement the findings of randomized controlled trials and show how abatacept is used in clinical practice. The aim of this interim analysis was to identify prognostic factors for abatacept retention in patients with RA who received at least one prior biologic agent. METHODS: A large, international, non-interventional cohort of patients with moderate-to-severe RA who initiated intravenous abatacept in Canada and Europe (May 2008-January 2011) enrolled in the ACTION study. Potential prognostic factors for retention in this interim analysis (data cut-off February 2012; including patients from Canada, Germany, Greece, and Italy) were baseline demographics and disease characteristics, medical history, and previous and concomitant medication. Clinically relevant variables with p ≤ 0.20 in univariate analysis and no collinearity were entered into a Cox proportional hazards regression model, adjusted for clustered data. Variables with p ≤ 0.10 were retained in the final model (backward selection). RESULTS: The multivariate model included 834 patients. Anti-cyclic citrullinated peptide (CCP) antibody positivity (hazard ratio [95% confidence interval]: 0.55 [0.40, 0.75], p < 0.001), failure of <2 prior anti-tumor necrosis factors (TNFs) (0.71 [0.56, 0.90], p = 0.005 versus ≥2 prior anti-TNFs), and cardiovascular comorbidity at abatacept initiation (0.48 [0.28, 0.83], p = 0.009) were associated with lower risk of abatacept discontinuation. Patients in Greece and Italy were less likely to discontinue abatacept than patients in Germany and Canada (Greece: 0.30 [0.16, 0.58]; Italy: 0.50 [0.33, 0.76]; Canada: 1.04 [0.78, 1.40], p < 0.001 versus Germany). CONCLUSIONS: Real-world prognostic factors for abatacept retention include anti-CCP positivity and fewer prior anti-TNF failures. Differences in retention rates between countries may reflect differences in healthcare systems. The finding that abatacept has potential advantages in patients with cardiovascular comorbidities needs to be confirmed in further research.

• MeSH
• abatacept aplikace a dávkování   MeSH
• adherence k farmakoterapii * MeSH
• antirevmatika aplikace a dávkování   MeSH
• biologické přípravky aplikace a dávkování   MeSH
• internacionalita * MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prognóza MeSH
• prospektivní studie MeSH
• revmatoidní artritida diagnóza   farmakoterapie   epidemiologie   MeSH
• senioři MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Itálie epidemiologie   MeSH
• Kanada epidemiologie   MeSH
• Německo epidemiologie   MeSH
• Řecko epidemiologie   MeSH
• Názvy látek
• abatacept MeSH
• antirevmatika MeSH
• biologické přípravky MeSH
• TNF-alfa MeSH