F. Nantel

Incidence and Management of Infusion Reactions to Infliximab in a Prospective Real-world Community Registry

Objective. Infliximab (IFX) is a therapeutic monoclonal antibody targeting tumor necrosis factor-α indicated in the treatment of chronic inflammatory diseases. IFX is administered by intravenous infusion and may be associated with different types of infusion reactions. Methods. RemiTRAC Infusion (NCT00723905) is a Canadian observational registry in which patients receiving IFX are followed prospectively to document premedication use, adverse events, infusion reactions, and the management of infusion reactions. The primary endpoint was to assess factors associated with infusion reactions. Results. There were 1632 patients enrolled and 24,852 infusions recorded. Most patients (63.1%) were treated for rheumatologic conditions such as rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. Of the 1632 patients, 201 (12.3%) reported at least 1 infusion reaction. Three hundred twenty-two infusions were associated with an infusion reaction (1.3%), and most were mild to moderate in severity (95%). The most common infusion reactions were pruritus (19.9%), flushing (9.9%), or dyspnea (6.2%). Multivariate analysis showed that antihistamines premedication, number of previous infusion reactions, and female sex were significantly associated with an increased incidence of infusion reactions (p < 0.0011). The use of any concomitant immunosuppressant or corticosteroids did not influence the incidence of infusion reactions. Antihistamine premedication was associated with an increased incidence of infusion reactions (OR 1.58, p = 0.0007). Conclusion. This registry shows that in community-based infusion clinics, infusion reactions to IFX are uncommon and mild to moderate in nature. Antihistamines, intravenous steroids, and acetaminophen are widely used as preventative premedication, although this study showed an absence of benefit with their use.

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.

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).

Adherence and dosing interval of subcutaneous antitumour necrosis factor biologics among patients with inflammatory arthritis: analysis from a Canadian administrative database

Objectives Subcutaneous tumour necrosis factor alpha TNFαinhibitors (SC-TNFis) such as golimumab (GLM), adalimumab (ADA), etanercept (ETA) and certolizumab pegol (CZP) have been used for many years for the treatment of inflammatory arthritis. Non-adherence to therapy is an important modifiable factor that may compromise patient outcomes. The aim of this analysis was to compare adherence and dosing interval of SC-TNFis in the treatment of people with inflammatory arthritis. Design We used the IMS Brogan database combining both Canadian private and public drug plan databases of Ontario and Quebec. Target drugs included SC-TNFis for inflammatory arthritis. The index period was from 1 January 2010 to 30 June 2012 and patients were followed for 24 months through 30 June 2014. Inclusion criteria were adult patients newly prescribed a SC-TNFis with at least three prescriptions and retained on therapy at 24 months. Dosing regimens as per the product monographs were used to compare actual versus expected drug utilisation. The mean possession ratio was used as a marker for adherence. Patients who scored >80% were considered adherent. The average days between units was estimated by taking the total days on therapy and divided by the number of units the patient received. Results 4035 patients were included: 683 (16.9%), 1400 (34.7%), 1765 (43.7%) and 187 (4.6%) were treated with GLM, ADA, ETA and CZP, respectively. The proportion of adherent patients in the GLM cohort (n=595/683, 87%, p<0.0001) was greater compared with ADA (n=1044/1400, 75%), ETA (n=1285/1765, 73%) and CZP-treated patients (132/187, 71%). In addition, the number of patients receiving biological drug at a shorter dosing interval was similar between cohorts, and was 5%, 6%, 12% and 4% in GLM (≤26 days), ADA (≤12 days), ETA (≤6 days) and CZP-treated patients (≤12 days), respectively. Conclusions In this real-life administrative database, GLM had better adherence compared with other SC-TNFis.

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

AB0661 Predictors of Response in Patients with Ankylosing Spondylitis Treated with Infliximab or Golimumab in A Real-World Setting

Background Recent studies have suggested that early and aggressive treatment of spondyloarthritis, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), may be associated with favorable patient outcomes, reducing synovial inflammation, delaying joint damage, and maintaining functional status. Objectives The objective of this analysis was to determine the predictive factors of ASDAS remission in AS patients treated with infliximab (IFX) or golimumab (GLM) in a Canadian routine clinical care setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis (RA), ankylosing spondylitis, or psoriatic arthritis with IFX or GLM. Eligible patients for this analysis included AS patients treated with IFX or GLM between 2005 and 2015. Variables associated with ASDAS remission (<1.3) were examined using univariate analysis and those showing a statistical trend (P<0.150) were considered in multivariate logistic regression analysis to identify independent predictors. Results A total of 582 patients were included in the analysis with a mean (SD) age of 45.8 (12.2) years and a disease duration of 8.3 (10.2) years. The majority of patients were male (57.2%). Upon 12 months of treatment statistically significant and clinically meaningful improvements were observed in ASDAS (3.6 vs. 2.3; P<0.001), BASDAI (6.2 vs. 3.8; P<0.001), BASFI (5.6 vs. 3.9; P<0.001), morning stiffness (74.2 vs. 42.8; P<0.001), and HAQ-DI (1.12 vs. 0.77; P<0.001). The proportion of patients who achieved ASDAS remission was 22.3% and 22.2% at 6 and 12 months, respectively. Sustained remission was achieved by 16.0%. In univariate analysis, male gender (male vs. female: 25.2% vs. 14.1%; P=0.073), previous use of a biologic (experienced vs. naive: 37.5% vs. 20.9%; P=0.129), lower ESR (P=0.096), lower BASFI (P=0.003), lower BASDAI (P=0.002), lower morning stiffness (P=0.120) and lower HAQ-DI (P=0.001) showed a statistical trend in their association with ASDAS remission at 12 months of treatment. Age, disease duration, CRP, psoriasis, peripheral arthritis, inflammatory bowel disease, uveitis, HLA-B27 and presence of enthesitis did not have an impact of ASDAS remission. Multivariate logistic regression analysis showed that, upon adjusting for covariates, non-exposure to a previous biologic (OR=3.40; P=0.078) approached statistical significance and lower HAQ-DI (OR=0.36; P=0.004) was a significant independent predictor of ASDAS remission. Conclusions Twelve-month treatment with IFX or GLM in a real-world setting was associated with significant improvements in disease parameters. Prior exposure to a biologic and lower HAQ-DI were identified as independent predictors of ASDAS remission upon adjusting for potential confounders. Disclosure of Interest L. Bessette: None declared, S. Kapur: None declared, M. Zummer: None declared, M. Starr: None declared, D. Choquette: None declared, M. Sheriff: None declared, W. Olszynski: None declared, E. Rampakakis Employee of: JSS Medical Research Inc;, E. Psaradellis Employee of: JSS Medical Research Inc;, B. Osborne Employee of: Janssen, K. Maslova Employee of: Janssen, F. Nantel Employee of: Janssen, A. Lehman Employee of: Janssen, C. Tkaczyk Employee of: Janssen

SAT0394 Impact of Disease Duration on Patient Reported and Clinical Outcomes in Patients with Ankylosing Spondylitis Treated with Anti-TNF: An Analysis from A Prospective, Observational Registry

Background Previous studies have shown that treatment outcomes are affected by disease-related aspects and patient-related factors. Objectives The aim of this analysis was to compare ankylosing spondylitis (AS) patient profiles in terms of patient characteristics and disease parameters based on disease duration and to investigate the impact of disease duration on patient reported and clinical outcomes in patients treated with anti-TNF. Methods BioTRAC is an ongoing, prospective registry of pts initiating treatment for rheumatoid arthritis, AS, or psoriatic arthritis with infliximab (IFX) or golimumab (GLM). Eligible people for this analysis included AS patients treated with IFX and enrolled since 2005 or with GLM and enrolled since 2010. Patients were classified in three subgroups (≤1 yr, 2–10 yrs, >10 yrs) based on the tertile distribution of the time elapsed since their diagnosis. The impact of disease duration on outcomes upon adjusting for potential confounders was assessed with generalized linear models and logistic regression. Results A total of 580 AS patients were included in this analysis with a mean age of 45.8 yrs and disease duration of 8.3 yrs. The majority were male and 92.6% were biologic naïve. At baseline, mean BASFI was 5.6, BASDAI was 6.2, and ASDAS was 3.6. With the exception of age which was significantly higher among pts with longer disease duration (P<0.001) no significant between-group differences were observed in baseline demographics and disease parameters. Upon 6 mos of treatment, clinically meaningful and statistically significant improvements were observed in BASFI, BASDAI and ASDAS which were further enhanced at 12 mos. Upon adjusting for baseline age and respective parameter levels, pts diagnosed within ≤1 yr experienced significantly lower improvements in BASFI (P=0.030), BASDAI (P<0.001), and ASDAS (P=0.030) at 12 mos as compared to pts with disease duration >10 ys. For ASDAS, concomitant DMARD use was also identified as a significant predictor of improved outcome (P=0.042). Gender and prior biologic experience did not have a significant impact on outcomes. Inactive or moderate disease activity, based on ASDAS, was achieved by 47.2% of pts while clinically important and major improvements were observed for 54.9% and 32.7% of pts, respectively. Similarly to the absolute improvements, pts diagnosed within ≤1 yr were significantly less likely to achieve these endpoints. Conclusions The results of this real-world analysis have identified prior disease duration at anti-TNF initiation as a significant independent predictor of treatment outcome. Concomitant use of a DMARD was associated with significantly higher improvement in ASDAS. These results suggest that pts with early disease may be harder to treat and highlight the need for more aggressive treat-to-target approaches in this patient subgroup. Disclosure of Interest M. Starr: None declared, M. Zummer: None declared, D. Choquette: None declared, B. Haraoui: None declared, D. Sholter: None declared, R. Arendse: None declared, I. Fortin: None declared, L. Bessette: None declared, P. Rahman: None declared, E. Rampakakis Employee of: JSS Medical Research Inc;, E. Psaradellis Employee of: JSS Medical Research Inc;, A. Lehman Employee of: Janssen, K. Maslova Employee of: Janssen, B. Osborne Employee of: Janssen, F. Nantel Employee of: Janssen, C. Tkaczyk Employee of: Janssen