A.J. Lehman

Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies

Objective To determine the magnitude of the risk of incident cardiovascular disease (CVD; fatal and non-fatal), including acute myocardial infarction (MI), cerebrovascular accidents (CVA) and congestive heart failure (CHF), in patients with rheumatoid arthritis (RA) compared to the general population through a meta-analysis of controlled observational studies. Methods The authors searched the Medline, Embase, LILACS and Cochrane databases from their inception to June 2011. Observational studies meeting the following criteria were included: (1) prespecified RA criteria; (2) predefined CVD criteria for incident CVD (MI, CVA or CHF); (3) a comparison group; and (4) RR estimates, 95% CI or data for calculating them. The authors calculated the pooled RR using the random-effects model and tested for heterogeneity using the bootstrap version of the Q statistic. Results Fourteen studies comprising 41 490 patients met the inclusion criteria. Overall, there was a 48% increased risk of incident CVD in patients with RA (pooled RR 1.48 (95% CI 1.36 to 1.62)). The risks of MI and CVA were increased by 68% (pooled RR 1.68 (95% CI 1.40 to 2.03)) and 41% (pooled RR 1.41 (95% CI 1.14 to 1.74)). The risk of CHF was assessed in only one study (RR 1.87 (95% CI 1.47 to 2.39)). Significant heterogeneity existed in all main analyses. Subgroup analyses showed that inception cohort studies were the only group that did not show a significantly increased risk of CVD (pooled RR 1.12 (95% CI 0.97 to 1.65)). Conclusions Published data indicate that the risk of incident CVD is increased by 48% in patients with RA compared to the general population. Sample and cohort type influenced the estimates of RR.

Spouse depression and disease course among persons with rheumatoid arthritis.

OBJECTIVE To examine the role of spouse mood in the disability and disease course of persons with rheumatoid arthritis (PWRA). METHODS A total of 133 married PWRA completed questionnaires, including the Rheumatoid Arthritis Disease Activity Index and the Disabilities of the Arm, Shoulder, and Hand, assessing PWRA arthritis disease activity and disability, respectively, at 2 time points 1 year apart. In addition, both PWRA and their spouses completed the Center for Epidemiologic Studies Depression Scale, a standardized community measure of depression at both time points. RESULTS Multiple regression analysis revealed spouse depressive symptoms at initial assessment to be predictive of followup PWRA disability and disease activity, even after controlling for initial levels of PWRA depression, disability, disease activity, age, number of years married, education, disease duration, and employment. Specifically, higher levels of spouse depression predicted worse disease course over a 1-year period for PWRA, as indicated by higher reports of subsequent PWRA disability and disease activity. CONCLUSION Our findings highlight the key role played by the spouse in PWRA disease course, and point to the importance of including the spouse in clinical interventions. Implications for theory, research, and treatment are discussed with a focus on examining pathways through which spouse depressive symptoms may affect PWRA disease course and disability.

Do spouses know how much fatigue, pain, and physical limitation their partners with rheumatoid arthritis experience? Implications for social support†

To determine whether perceptions of clinical manifestations (fatigue, pain, and physical limitation) of rheumatoid arthritis (RA) differ between spouses and their partners with RA, and to determine whether the differences are associated with the perception of beneficial and problematic spousal social support.

Use of corticosteroids in patients with rheumatoid arthritis treated with infliximab: treatment implications based on a real-world Canadian population.

Objective To describe the rate of concomitant oral corticosteroid use at antitumour necrosis factor (TNF) initiation and at disease remission, and to assess its effect on incidence of infection and sustainability of remission among patients with rheumatoid arthritis (RA) treated with infliximab in Canadian routine care. Methods Biological naïve patients with RA followed in the Biologic Treatment Registry Across Canada (BioTRAC) were included. The time-dependent association between corticosteroid dose (no use, ≤5 mg/day, >5 mg/day) and the incidence of first infection, while considering possible confounders, remission sustainability and the incidence of subsequent infections were assessed with Cox regression. Results 838 patients were included; mean (SD) baseline age and disease duration were 55.6 (13.5) and 10.5 (9.8) years, respectively. After a mean (SD) of 51.3 (43.6) months, the total incidence of adverse events (AEs) and infections were 110.2 and 19.6 per 100 person-years (PY), respectively. In multivariate analysis, the HR (95% CI) for acquiring an infection was 2.48 (1.24 to 4.98) with >5 mg/day of corticosteroids versus no corticosteroids. Similarly, ≤5 mg/day of corticosteroids was associated with increased hazard for infection (2.12 (0.97 to 4.66)). Despite DAS28 (disease activity score 28) or Clinical Disease Activity Index (CDAI) remission, corticosteroids were continued in 16.4% and 16.7% of cases, respectively. Continued corticosteroid treatment was not associated with sustainability of remission (HRDAS28 (95% CI) 1.40 (0.95 to 2.06); HRCDAI 1.19 (0.75 to 1.88)), however, it had a significant impact on development of infection (HRDAS28 (95% CI) 1.78 (1.00 to 3.19); HRCDAI 2.38 (1.14 to 4.99)). Conclusions Oral corticosteroid treatment was associated with increased risk of development of infection without impacting sustainability of remission. These results support the notion that corticosteroids should be used concomitantly with anti-TNF for the shortest period possible to achieve remission, and then tapered. Trial registration number NCT00741793.

Depressive Symptoms and Rheumatoid Arthritis: Spouse Empathic Responding as a Buffer

To examine the effects of depressive symptoms and spouse empathic responding on patient disability and marital quality over time and to identify factors that contribute to patients perceiving their spouses as responding empathically to their rheumatoid arthritis (RA).

Effectiveness and Safety of Infliximab in Rheumatoid Arthritis: Analysis From a Canadian Multicenter Prospective Observational Registry

To describe the profile of rheumatoid arthritis (RA) patients treated with infliximab in Canadian routine care and to assess the real‐world effectiveness and safety of infliximab.

Real-world validation of the minimal disease activity index in psoriatic arthritis: an analysis from a prospective, observational, biological treatment registry

Objective To describe the minimal disease activity (MDA) rate over time in patients with psoriatic arthritis (PsA) receiving antitumour necrosis factor agents, evaluate prognostic factors of MDA achievement and identify the most common unmet criteria among MDA achievers. Design Biologic Treatment Registry Across Canada (BioTRAC): ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis, ankylosing spondylitis or PsA with infliximab (IFX), golimumab (GLM) or ustekinumab. Setting 46 primary-care Canadian rheumatology practices. Participants 223 patients with PsA receiving IFX (enrolled since 2005) and GLM (enrolled since 2010) with available MDA information at baseline, 6 months and/or 12 months. Primary and secondary outcome measures MDA was defined as ≥5 of the following criteria: 28-item tender joint count (TJC28) ≤1, 28-item swollen joint count (SJC28) ≤1, Psoriasis Area and Severity Index (PASI) ≤1 or body surface area≤3, Pain Visual Analogue Scale (VAS) ≤15 mm, patient’s global assessment (PtGA) (VAS) ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, tender entheseal points ≤1. Independent prognostic factors of MDA achievement were assessed with multivariate logistic regression. Results MDA was achieved by 11.7% of patients at baseline, 43.5% at 6 months, 44.8% at 12 months and 48.8% at either 6 or 12 months. Among MDA achievers at 6 months, 75.7% had sustained MDA at 12 months. Lower baseline HAQ (OR=0.210; 95% CI: 0.099 to 0.447) and lower TJC28 (OR=0.880; 95% CI: 0.804 to 0.964), were significant prognostic factors of MDA achievement over 12 months of treatment. The most commonly unmet MDA criteria among MDA achievers was patient reported pain (25%), PtGA (15%) and PASI (12%). Conclusions Almost 50% of patients treated with IFX or GLM in routine clinical care achieved MDA within the first year of treatment. Lower baseline HAQ and lower TJC28, were identified as significant prognostic factors of MDA achievement. The most commonly unmet criteria in patients who achieved MDA were pain, PtGA and PASI. Trial registration number BioTRAC (NCT00741793).

Biologic Treatment Registry Across Canada (BioTRAC): a multicentre, prospective, observational study of patients treated with infliximab for ankylosing spondylitis.

Objectives To describe the profile of patients with ankylosing spondylitis (AS) treated with infliximab in Canadian routine care and to assess the effectiveness and safety of infliximab in real world. Setting 46 primary care rheumatology practices across Canada. Participants 303 biological-naïve patients with AS or patients previously treated with a biological for <6 months and who were eligible for infliximab treatment as per routine care within the Biologic Treatment Registry Across Canada (BioTRAC). Intervention Not applicable (non-interventional study). Primary and secondary outcomes Effectiveness was assessed with changes in disease parameters (AS Disease Activity Score (ASDAS), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Health Assessment Questionnaire Disease Index (HAQ-DI), physician global assessment of disease activity (MDGA), patient global disease activity (PtGA), back pain, C-reactive protein, erythrocyte sedimentation rate (ESR), morning stiffness). Safety was assessed with the incidence of adverse events (AEs). Results Of the 303 patients included, 44.6% were enrolled in 2005–2007 and 55.4% in 2008–2013. Patients enrolled in 2005–2007 had significantly higher MDGA and ESR at baseline while all other disease parameters examined were numerically higher with the exception of PtGA. Treatment with infliximab significantly (p<0.001) improved all disease parameters over time in both groups. At 6 months, 56% and 31% of patients achieved clinically important (change≥1.1) and major (change≥2.0) improvement in ASDAS, respectively; at 48 months, these proportions increased to 75% and 50%, respectively. Among patients unemployed due to disability at baseline, 12.1% returned to work (mean Kaplan-Meier (KM)-based time=38.8 months). The estimated retention rate at 12 and 24 months was 78.3% and 60.1%, respectively. The profile and incidence of AEs were comparable to data previously reported for tumour necrosis factor-α inhibitors. Conclusions Characteristics of patients with AS at infliximab initiation changed over time towards lower disease activity and shorter disease duration. Infliximab treatment significantly reduced disease activity independent of treatment initiation year, although patients enrolled in recent years achieved lower disease activity over 48 months. Trial registration number NCT00741793.

AB0684 Gender Specific Differences in Ankylosing Spondylitis at Treatment Initiation in Patients Treated with Infliximab or Golimumab

Background The prevalence of ankylosing spondylitis (AS) is 2–3 times higher in men compared to women. Recent studies have suggested that clinical differences exist between both genders with women experiencing a higher burden of disease. Objectives This analysis examined gender-specific differences with respect to patient and disease parameters at initiation of infliximab (IFX) or golimumab (GLM) for the treatment of AS in a Canadian routine clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis with IFX or GLM. Patients with AS treated with IFX who were enrolled since 2002 or with GLM enrolled since 2010 were included in this analysis. Between group differences were assessed with the Fishers Exact test or the independent samples t-test, while linear regression was used to assess the independent association of gender with HAQ-DI, ASDAS, BASDAI, and BASFI improvements at 12 months. Results A total of 539 AS patients were included in this analysis; 188 (34.9%) patients were treated with GLM and 351 (65.1%) with IFX. The majority of patients were male (61.8%). Mean age and disease duration were comparable between genders for both GLM and IFX, (Table 1). Overall, disease parameters (ESR, PtGA, MDGA, HAQ-DI, ASDAS, and BASFI) were similar for GLM with the exception of BASDAI where higher disease severity was observed among females. Among patients treated with IFX, between gender differences were observed for CRP with significantly lower levels in female patients; however BASDAI and HAQ-DI where significantly higher in females compared to males. Other parameters (ESR, PtGA, MDGA, ASDAS, and BASFI) were similar for IFX between genders. Regression analysis showed that, upon adjusting for baseline levels, female gender (ΔBASDAI=0.603; P=0.035) was associated with increased BASDAI at 12 months of treatment as compare to males. HAQ-DI, ASDAS, and BASFI, on the other hand, at 12 months were comparable between genders.Table 1. Patient characteristics at baseline by gender AS-GLM, mean (SD) Male (n=115) Female (n=73) P-value Age, years 46.3 (15.2) 44.4 (11.8) 0.498 Disease duration, yrs 5.2 (10.0) 6.0 (10.6) 0.704 CRP, mg/L 12.6 (15.2) 17.5 (50.5) 0.389 BASDAI 5.6 (2.3) 6.5 (1.7) 0.007 AS-IFX, mean (SD) Male (n=218) Female (n=133) P-value Age, years 45.1 (12.0) 47.0 (10.8) 0.163 Disease duration, years 9.6 (10.3) 8.8 (9.6) 0.505 CRP, mg/L 19.2 (26.9) 12.5 (17.6) 0.012 HAQ-DI 1.11 (0.58) 1.27 (0.63) 0.019 BASDAI 6.0 (2.1) 6.6 (2.1) 0.013 Conclusions Overall, at anti-TNF initiation, female AS patients experience greater disease activity relative to men at initiation of biologic therapy. Whether this represents a gender bias in prescribing, or a gender based difference in the acceptance of biologic treatment or disease assessment, requires additional research. Disclosure of Interest M. Starr: None declared, M. Zummer: None declared, D. Choquette: None declared, B. Haraoui: None declared, P. Rahman: None declared, M. Sheriff: None declared, E. Rampakakis Employee of: JSS Medical Research Inc;, E. Psaradellis Employee of: JSS Medical Research Inc;, B. Osborne Employee of: Janssen, A. Lehman Employee of: Janssen, K. Maslova Employee of: Janssen, F. Nantel Employee of: Janssen, C. Tkaczyk Employee of: Janssen

FRI0473 What Proportion of Patients with PSA Fail To Achieve Mda Based on Patient Reported Outcomes? An Analysis from A Prospective, Observational Registry

Background Recent treat-to-target guidelines in PsA recommend that minimal disease activity (MDA) is achieved as early as possible. Patient reported outcomes (PROs) have been criticized for not accurately assessing PsA disease activity as they may reflect aspects not directly related to PsA such as fibromyalgia, depression or other comorbidities. Objectives The aim of this analysis was to assess the proportion of patients failing to achieve MDA based on PROs in a real-world, routine clinical care setting in Canada. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis, ankylosing spondylitis, or PsA with infliximab (IFX) or golimumab (GLM). Eligible participants for this analysis included those with PsA treated with IFX who were enrolled since 2005 or with GLM enrolled since 2010 and with available MDA information at baseline, 6 months, and/or 12 months. MDA was defined as the fulfillment of ≥5 of the following criteria: TJC28≤1, SJC28≤1, PASI≤1, pain (VAS)≤15 mm, PtGA (VAS)≤20 mm, HAQ≤0.5, tender entheseal points ≤1. Near MDA was defined as fulfillment of 4 criteria. Results A total of 196 PsA patients (51.4% male) were included with a mean (SD) age of 49.8 (11.1) years and disease duration since diagnosis of 5.4 (6.3) years. The majority (62.2%) received concomitant DMARD therapy. The proportion of patients with MDA at baseline, 6 months and 12 months was 11.7%, 43.5%, and 44.8%, respectively. Overall, achievement of each individual MDA criterion was: TJC28: 43.0% of cases; SJC28: 51.3%; PASI 68.7%; pain: 27.7%; PtGA: 34.9%; HAQ: 36.8%; entheseal points: 79.4%. Among the 309 instances of non-MDA, 51 (16.5%) were near MDA cases. The most common reason for non-MDA in near MDA cases was patient-reported pain (82.4%) followed by PtGA (68.6%), and HAQ-DI (60.8%). Assuming that these criteria were met (i.e., not included in the MDA formula), the total number of MDA instances would increase from 29.6% to 36.7% (HAQ), 37.6% (PtGA), and to 39.2% (pain). Conclusions The results of the current analysis have shown that, similar to prior analyses in RA, the most common limiting factors in achieving MDA in PsA are PROs, including PtGA, pain, and HAQ-DI, accounting for as many as 82.4% of near MDA cases. Further analyses are required to identify the determinants of the differences in PROs and clinical outcomes. Disclosure of Interest P. Rahman: None declared, A. Avina-Zubieta: None declared, R. Arendse: None declared, W. Bensen: None declared, P. Baer: None declared, J. Kelsall: None declared, M. Starr: None declared, J. Stewart: None declared, D. Sholter: None declared, M. Zummer: None declared, L. Picard: None declared, E. Rampakakis: None declared, E. Psaradellis: None declared, K. Masolova Employee of: Janssen, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, C. Tkaczyk Employee of: Janssen, B. Osborne Employee of: Janssen