D. Sholter

Relative urgency for referral from primary care to rheumatologists: The Priority Referral Score

Timely access to rheumatology consultation is fundamental to appropriate and effective management of patients with musculoskeletal and autoimmune diseases. Yet, for a variety of reasons, limited and delayed access is commonplace. Moreover, information exchange for referral is often inadequate or poorly communicated. The objective of this work was to improve referral from primary care to rheumatology by formulating and testing a clinically coherent, reliable, and non–diagnosis‐dependent Priority Referral Score (PRS).

Time to Disease-modifying Antirheumatic Drug Treatment in Rheumatoid Arthritis and Its Predictors: A National, Multicenter, Retrospective Cohort

Objective. To determine the proportion of patients with rheumatoid arthritis (RA) under rheumatologic care treated with disease-modifying antirheumatic drugs (DMARD) within 6 months from symptom onset and the components of time to treatment and its predictors. Methods. A historical inception cohort of 339 patients with RA randomly selected from 18 rheumatology practices was audited. The proportion that initiated DMARD treatment within 6 months from symptom onset was estimated using Kaplan-Meier analysis. Time to each component of the care pathway was estimated. Multivariable modeling was used to determine predictors of early treatment using 12 preselected variables available in the clinical charts. Bootstrapping was used to validate the model. Results. Within 6 months from symptom onset, 41% (95% CI 36%−46%) of patients were treated with DMARD. The median time to treatment was 8.4 (interquartile range 3.8−24) months. Events preceding rheumatology referral accounted for 78.1% of the time to treatment. The most prominent predictor of increased time to treatment was a concomitant musculoskeletal condition, such as osteoarthritis or fibromyalgia. The significance of other variables was less consistent across the models investigated. Included variables accounted for 0.69 ± 0.03 of the variability in the model. Conclusion. Fewer than 50% of patients with RA are treated with DMARD within 6 months from symptom onset. Time to referral to rheumatology represents the greatest component delay to treatment. Concomitant musculoskeletal condition was the most prominent predictor of delayed initiation of DMARD. Implications of these and other findings warrant further investigation.

Early Management of Newly Diagnosed Rheumatoid Arthritis by Canadian Rheumatologists: A National, Multicenter, Retrospective Cohort

Objective. To describe early rheumatologic management for newly diagnosed rheumatoid arthritis (RA) in Canada. Methods. A retrospective cohort of 339 randomly selected patients with RA diagnosed from 2001–2003 from 18 rheumatology practices was audited between 2005–2007. Results. The most frequent initial disease-modifying antirheumatic drugs (DMARD) included hydroxychloroquine (55.5%) and methotrexate (40.1%). Initial therapy with multiple DMARD (15.6%) or single DMARD and corticosteroid combinations (30.7%) was infrequent. Formal assessment measures were noted infrequently, including the Health Assessment Questionnaire (34.6%) and Disease Activity Score for 28 joints (8.9%). Conclusion. Initial pharmacotherapy is consistent with guidelines from the period. The infrequent reporting of multiple DMARD combinations and formal assessment measures has implications for current clinical management and warrants contemporary reassessment.

Successful Switch of Patients with Rheumatoid Arthritis Developing Anti-tumor Necrosis Factor (anti-TNF)-induced Lupus to Another Anti-TNF Agent

Patient 1. A 43-year-old woman with a 15-year history of seropositive rheumatoid arthritis (RA) achieved remission when treated with adalimum ab 50 mg biweekly 8 years ago. Adalimumab was increased to 50 mg week ly when she developed an arthritis flare. Her arthritis worsened and she developed severe pleuritis but no other lupus features. Laboratory investi gations revealed anti-dsDNA antibodies that were not present in her preadalimumab antibody profile and persistence of anti-SSA antibodies that were present prior to adalimumab. A diagnosis of adalimumab-induced lupus was made and adalimumab was discontinued. Her symptoms resolved while taking prednisone 60 mg daily. One month later, she was asympto matic on a tapering course of prednisone. Her antibody profile at that time remained positive for anti-SSA antibodies but was negative for anti-dsDNA antibodies. She had a flare of RA off prednisone; therefore, she was treated with etanercept 25 mg twice weekly. The disease went into remission and has remained so for the past 4 years. Her antibody profile remains positive for anti-SSA antibodies and negative for anti-dsDNA antibodies. Patient 2. A 58-year-old woman with a 20-year history of seropositive RA was treated with infliximab 3 mg/kg in addition to leflunomide 20 mg/day. Ten weeks after starting infliximab she developed oral ulcers and increased joint symptoms with, active synovitis on examination. Laboratory investi gations revealed anti-dsDNA antibodies that were not present in her preinfliximab antibody profile. Her extractable nuclear antigen (ENA) profile was negative. She was diagnosed with infliximab-induced lupus and the infliximab was discontinued. She was maintained on leflunomide 20 mg/day. Her joint symptoms improved and oral ulcers resolved 2 months later. A repeat antibody profile showed that her ENA remained negative and her anti-dsDNA antibodies were negative. Her disease remained under control for 3 years taking leflunomide. She subsequently developed a dis ease flare and etanercept 25 mg twice weekly was added, with resolution of her synovitis. Two and a half years later she remains asymptomatic and her ENA and anti-dsDNA antibody profiles are negative. Treatment of patients with active RA who have had anti-TNF-induced lupus with a second TNF inhibitor should be monitored closely. Anti -TNF -induced lupus may be a class effect, as it has been reported to occur with all forms of this therapy. It is recognized that antinuclear anti bodies occur in association with anti-TNF therapies but anti-TNF-induced lupus is uncommon. In one study of RA patients treated with one of 3 anti -TNF therapies, infliximab, etanercept, and adalimumab were all shown to cause the development of anti-nucleosome antibodies, antibodies that have a role in the diagnosis and followup of patients with systemic lupus erythematosus 3 . However, the investigators comment that the devel opment of anti-TNF-induced lupus is uncommon with these agents. In another study over 50% of infliximab-treated patients and 10% of etaner cept-treated patients developed anti-dsDNA antibodies, suggesting differ ences in immunogenicity between the drugs 4. This observation is of inter est in view of the data reported in another study of anti-TNF-induced lupus that shows infliximab is associated with anti-TNF-induced lupus more fre quently than etanercept or adalimumab 5 . Anti-TNF-induced lupus differs from the classic drug-induced lupus in that it is characterized by a greater frequency of skin involvement, the pres ence of anti-dsDNA antibodies, and the lack of anti-histone antibodies.

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.

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

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

FRI0467 Predictors of Early Minimal Disease Activity in PSA Patients Treated with Anti-TNF in A Real-World Registry

Background Early achievement of minimal disease activity (MDA) is recommended as a valid treat-to-target approach in psoriatic arthritis (PsA). Objectives The purpose of the current analysis was to evaluate predictors of MDA achievement in PsA patients treated with anti-TNF agents in Canadian routine clinical care. 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 people for this analysis included PsA patients 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)≤15mm, PtGA (VAS)≤20mm, HAQ ≤0.5, tender entheseal points ≤1. Independent predictors of MDA achievement were assessed with logistic regression. Results A total of 196 patients (51.4% male and 87.2% bionaive) were included with a mean (SD) age and disease duration of 49.8 (11.1) and 5.4 (6.3) years, respectively. The proportion of patients with MDA was 11.7% at baseline, 43.5% at 6 months, 44.8% at 12 months, and 49.1% at either 6 or 12 months. Among patients with MDA at 6 months, 75.7% had sustained MDA at 12 months. Patients achieving MDA during follow-up had significantly lower disease activity at baseline; mean (SD) disease parameters were: SJC28: 3.24 (3.58) vs. 5.47 (4.31), P<0.001; TJC28: 3.75 (4.00) vs. 8.66 (6.53), P<0.001; pain: 35.39 (25.11) vs. 55.70 (22.93), P<0.001; PtGA: 38.51 (25.00) vs. 56.15 (25.13), P<0.001; HAQ-DI: 0.71 (0.61) vs. 1.33 (0.57), P<0.001; MDGA: 4.25 (2.38) vs. 5.84 (2.07), P<0.001); enthesitis count: 2.62 (1.60) vs. 4.97 (3.48), P=0.008. Multivariate logistic regression analysis showed that lower baseline HAQ (OR=0.243; P<0.001), lower TJC28 (OR=0.889; P=0.008), and lower enthesitis count (OR=0.817; P=0.817) were significant predictors of MDA achievement over 12 months of treatment. Conclusions The results of the current analysis have shown that 50% of patients treated with IFX or GLM in routine clinical care achieve MDA within the first year of treatment. Lower baseline HAQ, lower TJC28, and lower enthesitis count were identified as significant predictors of MDA achievement. Disclosure of Interest M. Zummer: None declared, P. Rahman: None declared, M. Starr: None declared, J. Kelsall: None declared, A. Avina-Zubieta: None declared, P. Baer: None declared, D. Sholter: None declared, M. Teo: 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

THU0196 Is the Basdai Score Driven by Pain in Ankylosing Spondylitis Patients Treated with Anti-TNF?

Background The present standard for measuring disease activity in Ankylosing Spondylitis (AS) is the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) which focuses on five major symptoms including fatigue, axial pain, peripheral pain, enthesitis and morning stiffness (severity and duration). Objectives Given that the BASDAI instrument contains two pain questions, the objective was to assess whether pain symptoms are the main drivers of BASDAI scores among AS patients treated with anti-TNFs in routine clinical practice. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with infliximab (IFX) or golimumab (GLM). Patients with AS treated with IFX or GLM and enrolled between 2005 and 2014 were included in this analysis. A modified weighted BASDAI score (m-BASDAI) was calculated excluding the axial (Q2) and peripheral (Q3) pain questions of the BASDAI. The correlation of BASDAI, each of its components, and the modified BASDAI (m-BASDAI) was assessed with the Pearson correlation coefficient. BASDAI low disease activity (LDA) and m-BASDAI LDA were defined as a score ≤3. The association between the number of administered analgesics (0, 1, >1) and BASDAI/m-BASDAI was assessed with one-way ANOVA. Results A total of 413 AS patients with 1,709 assessments were included in this analysis. Correlation analysis showed a strong correlation between the full BASDAI and m-BASDAI scores (r=0.98, P<0.001). With respect to the individual BASDAI questions, a strong positive linear correlation was observed between all questions and the BASDAI score as well as the m-BASDAI score. As expected, a lower correlation was observed between Q2 and Q3 with the m-BASDAI relative to BASDAI. Axial pain was most strongly correlated with the severity of morning stiffness, whereas the highest correlation of peripheral pain was observed with localized tenderness. The cross-tabulation of BASDAI LDA and m-BASDAI LDA showed a strong measure of agreement (kappa=0.871, P<0.001). Omission of the pain questions from BASDAI resulted in a comparable proportion of LDA cases (41.7% vs. 40.9%) when using the same LDA definition. Increased use of analgesics (0 vs. 1 vs. >1) over 2 years of follow-up was associated with significantly (P<0.05) higher mean scores in BASDAI, m-BASDAI, and each of the BASDAI components. No significant association was observed between increased use of analgesics and treatment retention. Conclusions Higher levels of AS pain are significantly associated with a higher BASDAI score and increased use of analgesic medications among patients treated with anti-TNFs. In addition to pain, fatigue, tenderness, and morning stiffness are likewise important contributing components in the BASDAI score and the disease burden of AS. Disclosure of Interest P. Rahman Consultant for: Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer, Roche, A. Jovaisas: None declared, W. Bensen Consultant for: Janssen, W. Olszynski: None declared, A. Jaroszynska: None declared, P. Baer Consultant for: AbbVie, Amgen,BMS, Janssen, Pfizer, Roche, M. Sheriff: None declared, D. Sholter: None declared, E. Psaradellis Employee of: JSS Medical Research, J. Sampalis Shareholder of: JSS Medical Research, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen, A. Lehman Employee of: Janssen, C. Tkaczyk Employee of: Janssen, M. Shawi Employee of: Janssen

FRI0036 What is the Level of Agreement Between Disease Activity Indices and Response Criteria Among Rheumatoid Arthritis Patients Treated with TNF Inhibitors

Background Several standardized response criteria and disease activity indices are used to assess treatment efficacy in rheumatoid arthritis (RA). These measures comprise different types and number of variables resulting in different weighting of individual variables within each of them. Objectives The aim of this analysis was to compare the performance of ACR, SDAI major and minor, and HAQ response criteria and to determine their level of agreement with the DAS28, SDAI, and CDAI definitions of low disease activity (LDA) and remission in RA patients treated with infliximab (IFX) or golimumab (GLM) in a real-world, Canadian, clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with IFX or GLM. The analysis was based on RA patients treated with IFX between 2002-2014 or GLM between 2010-2014. Response was assessed with ACR20, ACR50, ACR70, HAQ improvement of 0.22 and 0.5, SDAI major (≥22) and minor improvement (≥10). Disease state was assessed with DAS28, SDAI, and CDAI definitions of LDA (<3.2, ≤11, ≤10, respectively) and remission (<2.6, ≤3.3, ≤2.8, respectively). The level of agreement was assessed with the proportion of concordant pairs over the total number of cases in each cross-tabulation and the Kappa statistic. Results A total of 830 RA patients with 4,100 available observations were included. The criteria for each definition of response/disease state were met for the following proportion of cases: ACR20 (66.4%), ACR50 (44.5%), ACR70 (26.4%), ΔHAQ≥0.22 (65.5%), ΔHAQ≥0.5 (53.4%), SDAI major improvement (55.8%), SDAI minor improvement (80.8%), DAS28 remission (29.4%), CDAI remission (20.4%), SDAI remission (21.8%), CDAI LDA (57.5%), SDAI LDA (58.1%), and DAS28-ESR LDA (46.0%). Statistically significant (Kappa P<0.001) associations were observed for all combinations of variables examined. Overall, the ACR response criteria performed better than the HAQ and SDAI response criteria in their agreement with LDA and remission. In general, higher levels of response in all three measures (ACR20 vs. ACR50 vs. ACR70; ΔHAQ≥0.22 vs. ΔHAQ≥0.5; SDAI minor vs. major) showed better agreement with LDA and remission. The highest level of agreement between response criteria and disease state was observed between the strictest definitions, namely between ACR70 and CDAI/SDAI remission; whereas, SDAI minor improvement showed the lowest level of agreement with remission, irrespective of definition. Conclusions This analysis showed that significant variation exists in the agreement between the various efficacy outcome measures. Thus, the choice of outcome measure used to make treatment decisions could have a significant impact on patient management. Disclosure of Interest E. Keystone Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, P. Baer Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, A. Avina-Zubieta: None declared, A. Jaroszynska: None declared, J. Rodrigues: None declared, R. Arendse Consultant for: Janssen, D. Sholter: None declared, M. Starr Consultant for: Janssen, A. Masetto: None declared, J. Sampalis Shareholder of: JSS Medical Research, Employee of: JSS Medical Research, E. Rampakakis Employee of: JSS Medical Research, C. Tkaczyk Employee of: Janssen, M. Shawi Employee of: Janssen, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen