E. Alemao

Cardiovascular Outcomes Associated with Lowering Low-density Lipoprotein Cholesterol in Rheumatoid Arthritis and Matched Nonrheumatoid Arthritis

Objective. To examine the associations between lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular (CV) outcomes among patients with rheumatoid arthritis (RA) and patients without it. Methods. Adult patients with RA and 2 age- and sex-matched control cohorts [RA plus general controls (RA/GN), RA plus osteoarthritis (OA) controls (RA/OA)] were identified between January 1, 2007, and December 31, 2011. Patients with a diagnosis of hyperlipidemia who initiated statin therapy without prior CV events were included. Multivariable Cox proportional hazard analyses were used. Results. The study identified 1522 patients with RA with 6511 general controls (RA/GN cohort); and 1746 patients with RA with 2554 OA controls (RA/OA cohort). During followup, mean (SD) LDL-C (mg/dl) was 96.8 (32.7) for RA, 100.1 (35.1) for general controls, and 99.1 (34.3) for OA. The relationship between lowering LDL-C and CV outcomes was similar for both RA and non-RA controls (p for interaction = 0.852 in RA/GN cohort, and p = 0.610 in RA/OA cohort). After adjusting for baseline CV risk factors, lowering LDL-C was associated with a 29%–50% lower risk of CV events (HR [95% CI] = 0.71 [0.57–0.89] in RA/GN, 0.50 [0.43–0.58] in RA/OA). Subgroup analyses showed that lowering LDL-C was associated with a similar degree of reduction of CV events in RA and non-RA controls (HR of 0.67–0.68 for RA, 0.72 for general controls, 0.76 for OA controls). Conclusion. Lowering LDL-C levels was associated with reduced CV events. The relationship between lowering LDL-C and CV outcomes in RA was similar to the relationship found in matched general and OA controls.

Traditional Cardiovascular Disease Risk Factor Management in Rheumatoid Arthritis Compared to Matched Nonrheumatoid Arthritis in a US Managed Care Setting.

To compare traditional cardiovascular (CV) risk factor management among patients with rheumatoid arthritis (RA) to that of matched non‐RA controls within a large US managed care setting.

Effects of Achieving Target Measures in RA on Functional Status, Quality of Life and Resource Utilization: Analysis of Clinical Practice Data

To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study.

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data.

To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study.

Cardiovascular risk factor management in patients with RA compared to matched non-RA patients

Objective. RA is associated with a 50–60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. Methods. A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. Results. Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. Conclusion. There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management.

Comparison of cardiovascular risk algorithms in patients with vs without rheumatoid arthritis and the role of C-reactive protein in predicting cardiovascular outcomes in rheumatoid arthritis

Objectives The aims were to compare the performance of cardiovascular risk calculators, Framingham Risk Score (FRS) and QRISK2, in RA and matched non-RA patients and to evaluate whether their performance could be enhanced by the addition of CRP. Methods We conducted a retrospective analysis, using a clinical practice data set linked to Hospital Episode Statistics (HES) data from the UK. Patients presenting with at least one RA diagnosis code and no prior cardiovascular events were matched to non-RA patients using disease risk scores. The overall performance of the FRS and QRISK2 was compared between cohorts, and assessed with and without CRP in the RA cohort using C-Index, Akaike Information Criterion (AIC) and the net reclassification index (NRI). Results Four thousand seven hundred and eighty RA patients met the inclusion criteria and were followed for a mean of 3.8 years. The C-Index for the FRS in the non-RA and RA cohort was 0.783 and 0.754 (P < 0.001) and that of the QRISK2 was 0.770 and 0.744 (P < 0.001), respectively. Log[CRP] was positively associated with cardiovascular events, but improvements in the FRS and QRISK2 C-Indices as a result of inclusion of CRP were small, from 0.764 to 0.767 (P = 0.026) for FRS and from 0.764 to 0.765 (P = 0.250) for QRISK2. The NRI was 3.2% (95% CI: -2.8, 5.7%) for FRS and -2.0% (95% CI: -5.8, 4.5%) for QRISK2. Conclusion The C-Index for the FRS and QRISK2 was significantly better in the non-RA compared with RA patients. The addition of CRP in both equations was not associated with a significant improvement in reclassification based on NRI.

FRI0205 Relationship between Anti-Citrullinated Protein Antibody Status and Response To Abatacept or Anti-Tumour Necrosis Factor Therapy in Patients with Rheumatoid Arthritis: A US National Observational Study

Background Anti-citrullinated protein antibodies (ACPA) are associated with more severe, erosive rheumatoid arthritis (RA), but the extent to which ACPA status predicts response to therapy is not known.1,2 Objectives To evaluate in a real-world, observational RA cohort whether baseline ACPA status is associated with response to biologics among patients with RA. Methods Using the Corrona RA registry, we identified patients with RA who initiated abatacept (ABA) or a tumour necrosis factor-alpha inhibitor (TNFi) between June 2002 and January 2015, had a follow-up visit 6 months (±3 months) after initiation and anti-cyclic citrullinated peptide (anti-CCP [a surrogate of ACPA]) measured at or prior to initiation. Anti-CCP positivity was defined as anti-CCP ≥20 U/mL. The primary outcome was mean change from baseline in Clinical Disease Activity Index (CDAI) at 6 months. Secondary outcomes at 6 months included: 1) achievement of low disease activity (LDA; CDAI ≤10) among those with moderate or high disease activity who initiated treatment; 2) achievement of remission (CDAI ≤2.8) in those with low, moderate or high disease activity who initiated treatment; 3) Minimally Important Clinical Difference (MCID) in CDAI; and 4) modified ACR20/50/70. Unadjusted and adjusted linear and logistic analyses were performed based on anti-CCP status (positive [+] vs negative [–]). Results 566 patients initiated ABA: 204 (36.0%) were anti-CCP– and 362 (64.0%) anti-CCP+. There were no differences by CCP status for age (mean 57–58 years), disease duration (median 7 years) or prior biologic use (0, 1 or ≥2 prior); however, median baseline CDAI was greater in anti-CCP– vs anti-CCP+ patients (21 vs 19, p=0.035). 1715 patients initiated a TNFi: 602 (35.1%) were anti-CCP– and 1113 (64.9%) anti-CCP+. There were no differences by CCP status for age (mean 55–56 years), prior biologic use or median baseline CDAI; however, median disease duration was greater in anti-CCP+ vs anti-CCP– patients (4 vs 3 years, p=0.021). In adjusted analyses, anti-CCP+ ABA initiators had a mean (SE) change in CDAI of –8.5 (0.6) vs –4.1 (0.8) for anti-CCP– (p<0.001); in TNFi initiators, this was –7.4 (0.3) vs –6.4 (0.4) (p=0.071). In the multivariate model for secondary outcomes, the magnitude of response was greater in anti-CCP+ vs anti-CCP– ABA initiators. Outcomes did not differ by anti-CCP status in TNFi initiators (Figure). Conclusions In a clinical practice setting, anti-CCP positivity was associated with a differential treatment response to abatacept, but not TNFis. These real-world data suggest that anti-CCP+ patients with RA show incremental improvements in response while receiving abatacept therapy compared with anti-CCP– patients. References Lv Q, et al. PLoS One 2014;9:e89442. Sokolove J, et al. Ann Rheum Dis 2015; doi:10.1136/annrheumdis-2015-207942. Disclosure of Interest L. R. Harrold Grant/research support from: Pfizer, H. J. Litman Employee of: Corrona, S. E. Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Kelly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, W. Hua Employee of: Corrona, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Rebello Employee of: Corrona, J. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Bristol-Myers Squibb, Genentech, Lilly, Novartis, Pfizer, Employee of: Corrona, Speakers bureau: Genentech (non-branded talks only)

FRI0059 Routine Assessment of Patient Index Data 3 (RAPID3) – Defined Remission is as Stringent as ACR/Eular Boolean-Defined Remission in a Clinical Trial of Patients with Early Rheumatoid Arthritis Treated with Abatacept

Background Routine Assessment of Patient Index Data 3 (RAPID3) comprises the three patient-reported ACR RA Core Data Set measures: function (HAQ-DI), pain and patient global estimate of status (10-cm visual analogue scale). These can be scored in <10 seconds, making it suitable for use in routine clinical practice where it provides quantitative data to supplement qualitative assessments. Significant correlations between RAPID3 scores and DAS28 (CRP) and CDAI have been previously reported.1,2 Objectives To examine whether RAPID3-defined remission performs similarly to definitions of remission by DAS28 (CRP), CDAI, SDAI or Boolean criteria in patients with early RA. Methods We performed post hoc analyses on data from the AVERT study, described previously.3 RAPID3 scores were calculated at baseline and 3-monthly intervals thereafter, up to 12 months. Definitions of remission were RAPID3 ≤1 (scale of 1–10); DAS28 (CRP) <2.6; CDAI ≤2.8; SDAI ≤3.3; and Boolean: TJC28 ≤1, SJC28 ≤1, patient global assessment of disease activity (0–10 cm) ≤1 and high-sensitivity CRP ≤1 mg/dL. Proportions of patients in RAPID3, DAS28 (CRP), CDAI, SDAI and ACR/EULAR Boolean remission at each time point were calculated. Proportions at 3, 6, 9 and 12 months were compared using cross-tabulation analysis. Agreement between RAPID3 disease activity states and those of other measures were assessed using kappa and weighted kappa statistics. Results Among the total AVERT population, the respective percentages of patients in remission according to each measure at Months 3, 6 and 9 were: RAPID3, 12.3%, 17.4%, 21.9%; Boolean, 8.5%, 12.5%, 21.1%; SDAI, 10.8%, 21.4%, 27.4%; CDAI, 10.0%, 20.8%, 27.1%; and DAS28 (CRP), 25.1%, 35.0%, 42.7%. Similar trends held at Month 12: 29.3%, 28.8%, 32.2%, 33.6%, 50.1%, respectively. When weighted kappa correlations were calculated for RAPID3 versus other remission criteria, RAPID3 remission showed good correlation with Boolean remission, and kappa correlations with SDAI and CDAI remission were higher than those with DAS28 (CRP) (Table). These trends were similar for each treatment arm. Conclusions RAPID3-defined remission may be as stringent as ACR/EULAR Boolean-defined remission and agrees well with SDAI and CDAI remission criteria. RAPID3 may be used in clinical trials in addition to routine clinical care in early RA, and its ease of use may be an advantage over other indices. Disclosure of Interest Y. Yazici Shareholder of: Samumed, Grant/research support from: Bristol-Myers Squibb, Genentech, Consultant for: AbbVie, Bristol-Myers Squibb, Genentech, UCB, Employee of: Samumed, K. K. Gandhi Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, D. E. Furst Grant/research support from: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, National Institutes of Health, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Janssen, Gilead, GlaxoSmithKline, National Institutes of Health, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: (CME only) AbbVie, Actelion, UCB

Effect of Anticitrullinated Protein Antibody Status on Response to Abatacept or Antitumor Necrosis Factor-alpha Therapy in Patients with Rheumatoid Arthritis: A US National Observational Study

Objective. Assess whether baseline anticyclic citrullinated peptide antibodies (anti-CCP) status is associated with treatment response in patients with rheumatoid arthritis (RA) initiating abatacept (ABA) or a tumor necrosis factor-α inhibitor (TNFi). Methods. Using the Corrona RA registry, patients were identified who initiated ABA or a TNFi (June 2004–January 2015), had a followup visit 6 months (± 3 mos) after initiation, and anti-CCP measured at or prior to initiation. Primary outcome was mean change in Clinical Disease Activity Index (CDAI) from initiation to 6 months. Treatment response was evaluated based on a typical patient profile (female, aged 57 yrs, body mass index of 30 kg/m2, baseline CDAI of 20, 1 prior biologic, and no comorbidities other than RA). Secondary outcomes included remission and low disease activity. Results. There were 566 ABA initiators [anti-CCP+ (≥ 20 units/ml): n = 362; anti-CCP− (< 20 units/ml): n = 204] and 1715 TNFi initiators (anti-CCP+: n = 1113; anti-CCP−: n = 602). Differences between treatment groups included baseline disease duration, CDAI, and prior biologic use. At 6 months, anti-CCP+ ABA initiators were associated with significantly greater CDAI response versus anti-CCP− ABA initiators; no significant difference was observed for TNFi initiators. When considering a typical RA patient profile, CDAI response was greater in anti-CCP+ versus anti-CCP− ABA initiators; anti-CCP+ versus anti-CCP− TNFi initiators were similar. Secondary outcome responses were also greater in anti-CCP+ versus anti-CCP− ABA initiators; TNFi initiators did not differ by anti-CCP status. Conclusion. In a US-based clinical practice setting, anti-CCP status was associated with a differential treatment response to ABA, but not TNFi.

Cost-Effectiveness Analysis of Abatacept Compared with Adalimumab on Background Methotrexate in Biologic-Naive Adult Patients with Rheumatoid Arthritis and Poor Prognosis

OBJECTIVES To assess cost effectiveness of abatacept versus adalimumab, each administered with methotrexate, in treating patients with rheumatoid arthritis (RA) stratified according to baseline anticitrullinated protein antibody (ACPA) levels (marker of poor prognosis in RA). METHODS A payer-perspective cost-effectiveness model simulated disease progression in patients with RA who had previously failed conventional disease-modifying antirheumatic drugs and were starting biologic therapy. Patients commenced treatment with abatacept or adalimumab plus methotrexate and were evaluated after 6 months. Therapy continuation was based on the European League Against Rheumatism treatment response; disease progression was based on the Health Assessment Questionnaire Disability Index score. These score changes were used to estimate health state utilities and direct medical costs. Quality-adjusted life-years (QALYs) and incremental cost per QALY gained were calculated by baseline ACPA groups (Q1, 28-234 AU/ml; Q2, 235-609 AU/ml; Q3, 613-1045 AU/ml; and Q4, 1060-4894 AU/ml). Scenario analysis and one-way and probabilistic sensitivity analyses were used to evaluate robustness of model assumptions. RESULTS Abatacept resulted in QALY gain versus adalimumab in ACPA Q1, Q3, and Q4; between-treatment difference (difference: Q1, -0.115 Q2, -0.009 Q3, 0.045; and Q4, 0.279). Total lifetime discounted cost was higher for abatacept versus adalimumab in most quartiles (Q2, £77,612 vs. £77,546; Q3, £74,441 vs. £73,263; and Q4, £78,428 vs. £76,696) because of longer time on treatment. Incremental cost per QALY for abatacept (vs. adalimumab) was the lowest in the high ACPA titer group (Q4, £6200/QALY), followed by the next lowest titer group (Q3, £26,272/QALY). CONCLUSIONS Abatacept is a cost effective alternative to adalimumab in patients with RA with high ACPA levels.