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ObjectiveAxial spondyloarthritis (axSpA) is a chronic, immune-mediated, inflammatory condition consisting of 2 clinical subsets: nonradiographic axSpA and ankylosing spondylitis, the latter having an estimated prevalence of 0.2% to 1% in Canada. Secukinumab (SEC) received Health Canada approval in 2016 for the treatment of adults with axSpA who have responded inadequately to conventional treatment, and has demonstrated efficacy and safety through extensive clinical trials. However, there is limited evidence on its real-world use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC in the Canadian axSpA population.MethodsThis was an observational cohort study of Canadian patients with axSpA aged 18 to 65 years within the CanSpA network who had received treatment with SEC. Patients were indexed on the first date of SEC initiation. Retention and clinical effectiveness were assessed at 12 months postindex. Clinical effectiveness was measured as the proportion in remission and change in disease activity using multiple clinical indices.ResultsA total of 146 patients were included. Overall retention was estimated at 62.9%. Low disease activity (ie, Bath Ankylosing Spondylitis Disease Activity Index < 4) was achieved in 29.2% of patients, and 2% had achieved remission based on the Ankylosing Spondylitis Disease Activity Score. Bath Ankylosing Spondylitis Metrology Index scores improved by more than 60% from baseline to 12 months.ConclusionThe results of this real-world study of Canadian patients with axSpA, one of the first of its kind, support the effectiveness of SEC for treatment of axSpA. The CanSpA network presents an opportunity to continue building and improving the real-world evidence base for treatment of Canadian patients with spondyloarthritis.

ObjectivePsoriatic arthritis (PsA) is an immune-mediated disease characterized by pain, stiffness, and swelling of peripheral joints, with an estimated prevalence in Canada of 0.45%. Treatment aims to minimize disease activity, reduce progression of damage, and improve quality of life. Secukinumab (SEC) is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy and safety for PsA in clinical trials; however, there is limited real-world evidence on its use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC among Canadian patients with PsA.MethodsThis was an observational cohort study of Canadian patients with PsA, 18 to 65 years of age, who attended a clinic of the CanSpA network and received treatment with SEC. Patients were indexed on the date they first initiated SEC. Retention was assessed at 12 months postindex. Clinical effectiveness was measured as the proportion of patients in remission and change in disease activity from baseline to 12 months using several clinical indices.ResultsIn total, 213 patients were included. Overall retention was estimated at 73.6% at 12 months (81.8% for bDMARD- or targeted synthetic DMARD-naïve patients). Out of 110 patients, 17 (15.5%) were in remission based on the Disease Activity Index in Psoriatic Arthritis in 28 joints, and 10 out of 70 patients (14.3%) were in remission based on the Psoriatic Arthritis Disease Activity Score at 12 months. The Psoriasis Area and Severity Index improved by 65.8%; the tender joint count in 68 joints and the swollen joint count in 66 joints improved by 65.5% and 73.7%, respectively.ConclusionThis is the first nationwide study that we know of to describe real-world use of SEC in Canada for PsA, and the results support its effectiveness in a Canadian real-world setting. The CanSpA network represents a unique opportunity to build and improve the real-world evidence base for SpA treatment in Canada.

Psoriatic arthritis (PsA) is an immune-mediated disease characterized by pain, stiffness, and swelling of peripheral joints, with an estimated prevalence in Canada of 0.45%. Treatment aims to minimize disease activity, reduce progression of damage, and improve quality of life. Secukinumab is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy and safety for PsA in clinical trials, however there is limited real-world evidence on its use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe realworld retention and effectiveness of secukinumab among Canadian patients with PsA.Observational cohort study of Canadian PsA patients 18-65 years who attended a clinic of the CanSpA network and received treatment with secukinumab. Patients were indexed on the date they first initiated secukinumab. Retention was assessed at 12-months post-index. Clinical effectiveness was measured as proportion in remission and change in disease activity from baseline to 12-months using several clinical indices.213 patients were included. Overall retention was estimated at 73.6% at 12-months (81.8% for bt/sDMARD-naive patients). 17/110 (15.5%) patients were in DAPSA28-based remission, and 10/70 (14.3%) were in PASDAS-based remission at 12-months. PASI improved by 65.8%; TJC68 and SJC66 improved by 65.5% and 73.7%, respectively.This is the first nationwide study to describe real-world use of secukinumab in Canada for PsA, and supports its effectiveness in a Canadian real-world setting. The CanSpA network represents a unique opportunity to build and improve the real-world evidence base for SpA treatment in Canada.

ObjectiveTo compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts.MethodsThe 4 longitudinal cohorts included the following: the Canadian Early Arthritis Cohort (CATCH; n = 2878), Ontario Best Practices Research Initiative (OBRI; n = 3734), RHUMADATA (Quebec, n = 2890), and the Rheum4U Precision Health Registry (Calgary, Alberta, n = 709). Data were from cohort inception (range 1998–2016) to 2020. Clinical characteristics and drug treatments were summarized descriptively.ResultsIn total, 10,211 patients with RA were included. The percentage of patients who entered the cohort with early RA (2 yrs of disease at enrollment) ranged from 29% (Rheum4U) to 100% (CATCH). Mean age (55 yrs), sex (74% female), and seropositivity (69%) were similar between cohorts. At the time of initial disease-modifying antirheumatic drug (DMARD) use, median Disease Activity Score in 28 joints (DAS28) varied, ranging from 2.99 (Rheum4U) to 5.19 (CATCH), but were more similar at the time of the first DMARD switch (range 3.57–5.03), first biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) use (range 4.01–4.67), and second bDMARD or tsDMARD (range 3.71–4.39). The initial DMARD was most commonly methotrexate, either in monotherapy (32%, range 18–40%) or dual therapy (34%, range 29–42%). The first DMARD switch was to another DMARD monotherapy in 20% (range 10–32%), dual therapy in 49% (range 39–56%), and bDMARD or tsDMARD in 24% (range 15–28%). The first bDMARD was an anti–tumor necrosis factor in 79% (range 78–82%).ConclusionCanadian RA cohorts demonstrate some heterogeneity in treatment, which could reflect differences in inclusion criteria, calendar year, or regional differences. This project is a first step toward conducting harmonized analyses across Canadian RA cohorts.

ObjectivesThe expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi.MethodsThis is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders.Results365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies.ConclusionsAfter failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.

The Canadian Tofacitinib for Rheumatoid Arthritis Observational (CANTORAL) is the first Canadian prospective, observational study assessing tofacitinib. The objective was to assess effectiveness and safety for moderate to severe rheumatoid arthritis (RA). Coprimary and secondary outcomes are reported from an interim analysis.Patients initiating tofacitinib from October 2017 to July 2020 were enrolled from 45 Canadian sites. Coprimary outcomes (month 6) included the Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA) and remission. Secondary outcomes (to month 18) included the CDAI and the 4-variable Disease Activity Score in 28 joints (DAS28) using the erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) level to define LDA and remission; the proportions of patients achieving mild pain (visual analog scale20 mm), and moderate (≥30%) and substantial (≥50%) pain improvements; and the proportions of patients achieving a Health Assessment Questionnaire disability index (HAQ DI) score greater or equal to normative values (≤0.25) and a HAQ DI score greater or equal to minimum clinically important difference (MCID) (≥0.22). Safety was assessed to month 36.Of 504 patients initiating tofacitinib, 44.4% received concomitant methotrexate. At month 6, 52.9% and 15.4% of patients were in CDAI-defined LDA and remission, respectively; a similar proportion of patients achieved outcomes by month 3 (first post-baseline assessment). By month 3, 27.2% and 41.7% of patients, respectively, were in DAS28-ESR-defined LDA and DAS28-CRP3.2; 14.7% and 25.8% achieved DAS28-ESR remission and DAS28-CRP2.6. By month 3, mild pain and moderate and substantial pain improvements occurred in 29.6%, 55.6%, and 42.9% of patients, respectively; 19.9% and 53.7% of patients achieved a HAQ DI score greater than or equal to normative values and a HAQ DI score greater than or equal to MCID, respectively. Outcomes were generally maintained to month 18. Incidence rates (events per 100 patient-years) for treatment-emergent adverse events (AEs), serious AEs, and discontinuations due to AEs were 126.8, 11.9, and 14.5, respectively, and AEs of special interest were infrequent.Tofacitinib was associated with early and sustained improvement in RA signs and symptoms in real-world patients. Effectiveness and safety were consistent with the established tofacitinib clinical profile.

ObjectivesThe similarity in retention of tumour necrosis factor inhibitors (TNFi) and tofacitinib (TOFA) was previously reported separately by the Ontario Best Practices Research Initiative and the Quebec cohort Rhumadata. However, because of small sample sizes in each registry, we aimed to confirm the findings by repeating the analysis of discontinuation of TNFi compared with TOFA, using pooled data from both these registries.DesignRetrospective cohort study.SettingPooled data from two rheumatoid arthritis (RA) registries in Canada.ParticipantsPatients with RA starting TOFA or TNFi between June 2014 and December 2019 were included. A total of 1318 patients were included TNFi (n=825) or TOFA (n=493).Outcome measuresTime to discontinuation was assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Propensity score (PS) stratification (deciles) and PS weighting were used to estimate treatment effects.ResultsThe mean disease duration in the TNFi group was shorter (8.9 years vs 13 years, pDiscontinuation was reported in 309 (37.5%) and 181 (36.7%) TNFi and TOFA patients, respectively. After covariate adjustment using PS, there was no statistically significant difference between the two groups in discontinuation due to any reason HR=0.96 (95% CI 0.78 to 1.19, p=0.74)) as well as discontinuation due to ineffectiveness only HR=1.08 (95% CI 0.81 to 1.43, p=0.61)).TNFi users were less likely to discontinue due to adverse events (AEs) (adjusted HRs: 0.46, 95% CI 0.29 to 0.74; p=0.001). Results remained consistent for firstline users.ConclusionsIn this pooled real-world data study, the discontinuation rates overall were similar. However, discontinuation due to AEs was higher in TOFA compared with TNFi users.

Background:Industry, regulators, and the rheumatology community have recognized the need for observational studies to monitor the safety of new antirheumatic agents. Registries provide a unique opportunity to understand the safety of newer therapies, but pharmacovigilance studies require large number of patients to evaluate rare drug-related adverse-events (AEs). Because JAK-inhibitors (JAKi) have only recently been approved for the treatment of rheumatoid arthritis, it makes sense to combine data from several registries in order to obtain a sufficiently large sample size to promote earlier detection of adverse events.Objectives:The purpose of this analysis was to evaluate how AEs are assessed in the various registries in preparation for a collaborative pharmacovigilance analysis, and present preliminary results.Methods:The “JAK-pot” collaboration includes 19 RA registries. The principal investigators of the participating registries were sent a structured questionnaire on AE assessment and 18 (94%) provided complete responses on the AE assessment procedures of their registries. We present simple descriptive statistics of the AE assessment procedures employed by the participating registries.Results:The 19 registries represent 7186 patients initiating a JAKi (Table 1), who are on average 57 years old, with a mean disease duration 11 years, seropositive (83%), female (82%) and with moderate disease activity at treatment initiation.Table 1.Country, registryN° of patients on JAKi includedAustria, BIOREG87Belgium, TARDIS2113Canada, RHUMADATA363Czech Republic, ATTRA197Denmark, DANBIO506Finland, ROB-FIN229Germany, RABBIT620Italy, GISEA244Israel, I-RECORD96Netherlands, METEOR4Norway, NOR-DMARD97Portugal, REUMA.PT44Romania, RRBR252Russia, ARBITER428Slovenia, biorx.si141Spain, BIOBADASER139Switzerland, SCQM738Turkey, TURKBIO404UK, BSRBR484After ineffectiveness, AEs was the second most common reason for JAKi discontinuation (25.5%), with large differences between registries (Figure 1).Of the participating registries, 2 registries do not collect AEs, while 16 (89%) assess incident AEs, by means of a pre-specified extraction form (3 registries), by free text (5 registries), by a combination of both (6 registries) and/or the use of linkage to external electronic records (3registries). AEs are coded using a predefined coding system by 11 registries (MeDRA (8), other (3)), but nearly all are recording the severity of the AE (15, 94%), AE related-death (15, 94%), or AE-related hospitalisation (15, 94%). AEs of special interest, such as serious infections (15, 94%), thromboembolic events (15, 94%), or shingles (9, 56%), are recorded by most registries. Incident AEs are linked by the treating physician to specific therapies in 11 registries (69%), while the other 5 registries extrapolate potential causal associations based on therapy start and stop dates. A pre-specified adjudication process for AEs is made only by 5 registries (31%).Conclusion:Substantial heterogeneity exists among registries regarding AE assessment within the JAK-pot collaboration. These differences must be taken into account when analysing the safety of JAKi across different countries in collaborative studies. For comparative analyses, stratified analyses by country are required to account for differential AE assessment and varying degrees of potential under-reporting.Disclosure of Interests:Kim Lauper: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette: None declared, Catalin Codreanu: None declared, Diederik De Cock: None declared, Lene Dreyer: None declared, Ori Elkayam: None declared, Kimme Hyrich: None declared, Florenzo Iannone: None declared, Nevsun Inanc: None declared, Eirik kristianslund: None declared, Tore K. Kvien: None declared, Burkhard Leeb: None declared, Galina Lukina: None declared, Dan Nordström: None declared, Karel Pavelka: None declared, Manuel Pombo-Suarez: None declared, Ziga Rotar: None declared, Maria Jose Santos: None declared, Anja Strangfeld: None declared, Delphine Courvoisier: None declared, Axel Finckh Speakers bureau: Eli-Lilly, Pfizer, Consultant of: Eli-Lilly, Pfizer, Grant/research support from: BMS, Pfizer.

Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment as the first or an alternative option to biologic disease- modifying antirheumatic drugs (bDMARDs), including tumor necrosis factor inhibitors (TNFi). The similarity in retention of TNFi and TOFA was previously reported separately by the Ontario Best Practices Research Initiative (OBRI) and the Quebec cohort RHUMADATA®.Objectives:To increase the study power, we propose to evaluate the discontinuation rate (due to any reason) of TNFi compared to TOFA, using pooled data from both these registries.Methods:RA patients enrolled in the OBRI and RHUMADATA initiating their TOFA or TNFi between 1st June 2014 (TOFA approval date in Canada) and 31st Dec 2019 were included. Time to discontinuation was assessed using adjusted Kaplan-Meier (KM) survival and Cox regression models. To deal with confounding by indication, we estimated propensity scores for covariates with a standard difference greater than 0.1. Models were then adjusted using stratification and inverse probability of treatment weight (IPTW) methods. Multiple imputation (Imputation by Chained Equation method, N=20) was used to deal with missing data for covariates at treatment initiation.Results:A total of 1318 patients initiated TNFi (n=825) or TOFA (n=493) with mean (SD) disease duration of 8.9 (9.3) and 13.0 (10.1) years, respectively. In the TNFi group, 78.8% were female and mean age (SD) at treatment initiation was 57.6 (12.6) years. In the TOFA group, 84.6% were female and mean (SD) age at treatment initiation was 59.5 (11.5) years. The TNFi group was less likely to have prior biologic use (33.9%) than the TOFA group (66.9%). At treatment initiation, the mean (SD) CDAI was significantly (pOver a mean follow-up of 23.2 months, discontinuation was reported in 309 (37.5%) and 182 (36.9%) of all TNFi and TOFA patients, respectively. After adjusting for propensity score deciles across 20 imputed datasets, there was no significant difference in discontinuation between treatment groups (adjusted HRs: 0.96, 95% CI: 0.78-1.18; p=0.69). The results were similar for two propensity adjustment methods. Figure 1 shows IPTW adjusted KM survival curves comparing discontinuation rates in patients treated with TNFi and TOFA.Figure 1.Note: Propensity Score Weighted (IPTW) Survival Curves was performed using one imputed datasetConclusion:In this pooled real -world data study, we found that TNFi and TOFA retention is similar in patients with RA. In the next step we will analysis the data for specific reasons of dicontinutaion. We will also repeat analysis comparing discontinuation in the first users versus those after one or more biologic failure.Disclosure of Interests:Mohammad Movahedi: None declared, Denis Choquette Grant/research support from: Rhumadata® is supported by unrestricted grants from Abbvie Canada, Amgen Canada, Eli Lilly Canada, Novartis Canada, Pfizer Canada, Sandoz Canada and Sanofi Canada., Louis Coupal: None declared, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm. Speaker Honoraria Agreements: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis. Consulting Agreements/Advisory Board Membership: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Claire Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Aurora, Bristol-Meyers Squibb, Celgene, Hospira, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Roche, Sanofi, & UCB.Dr. Bombardier held a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic DMARDs poses a significant economic burden. The Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) trial was a head-to-head, randomized study comparing abatacept in serum anti-citrullinated protein antibody (ACPA)-positive patients, with increasing efficacy across ACPA quartile levels. The aim of this study was to evaluate the cost per response accrued using abatacept versus adalimumab in ACPA-positive and ACPA-negative patients with RA from the health care perspective in Germany, Italy, Spain, the US and Canada. A cost-consequence analysis (CCA) was designed to compare the monthly costs per responding patient/patient in remission. Efficacy, safety and resource use inputs were based on the AMPLE trial. A one-way deterministic sensitivity analysis (OWSA) was also performed to assess the impact of model inputs on the results for total incremental costs. Cost per response in ACPA-positive patients favoured abatacept compared with adalimumab (ACR20, ACR90 and HAQ-DI). Subgroup analysis favoured abatacept with increasing stringency of response criteria and serum ACPA levels. Cost per remission (DAS28-CRP) favoured abatacept in ACPA-negative patients, while cost per CDAI and SDAI favoured abatacept in ACPA-positive patients. Abatacept was consistently favoured in ACPA-Q4 patients across all outcomes and countries. Cost savings were greater with abatacept when more stringent response criteria were applied and also with increasing ACPA levels, which could lead to a lower overall health care budget impact with abatacept compared with adalimumab.

Introduction Brenzys was developed as an etanercept biosimilar of Enbrel. The aim of this study was to assess preference and perceived ease of use for the new Brenzys autoinjector compared to the currently available marketed Enbrel MYCLIC autoinjector (Australia) and Enbrel SureClick autoinjector (Canada) for the treatment of rheumatoid arthritis (RA). Because RA affects manual dexterity, ease of use of an autoinjector is a particularly important consideration in developing effective self-delivery of long-term courses of therapy. Methods Patients (N = 191) reporting a diagnosis of RA and nurses and rheumatologists (N = 90) with experience managing RA were shown how to use Brenzys and Enbrel autoinjectors (in counterbalanced order between participants), then they used each autoinjector by injecting into a pad simulating skin, and completed a questionnaire. Study sessions took place in Australia and Canada. Results A binomial test showed that significantly more patients indicated that the Brenzys autoinjector was easier to use than the Enbrel autoinjector (79% reporting Brenzys easier to use; p

Background:In many countries, JAK-inhibitors (JAKi) have only recently been approved as treatment for patients with rheumatoid arthritis (RA).Objectives:To evaluate the effectiveness of JAKi compared to bDMARDs in RA patients in the real-world population in an international collaboration of registers (the “JAK-pot” collaboration).Methods:Patients initiating either JAKi, TNFi, IL-6i or abatacept (ABA) during a time period when JAKi were available in each country (19 registers, Table) were included. We compared the effectiveness of JAKi and bDMARDs in terms of retention using crude and adjusted survival analysis. Missing covariates were imputed using multiple imputation.Results:Among 25521 included patients, 6063 initiated a JAKi, 13879 a TNFi, 2348 ABA, and 3231 an IL-6i. Patients were on average 55 years old, with a mean disease duration 10 years, mostly seropositive (67%), female (77%) and with moderate disease activity at treatment initiation. The main reason of stopping treatment was ineffectiveness (49%), followed by adverse events (21%). Patients on JAKi were treated more often as monotherapy, had higher CRP and disease activity at baseline and had experienced more previous ts/bDMARDs. Crude median retention was 1.4 (95% CI 1.2-1.5) years for JAKi, 1.6 (1.6-1.7) for TNFi, 1.5 (1.3-1.7) for IL6i and 1.1 (1.0-1.3) for ABA. After adjustment, the hazard ratio (HR) for discontinuation tended to be lower for JAKi (HR 0.86 (0.65-1.13)) compared to TNFi, but comparable for ABA (1.02 (0.94-1.10)) and IL6i (0.99 (0.88-1.10)) (Figure 1). HRs differed notably between countries (Figure 2).Table 1.RegistersCountry, registerNJAKi, n (%)Austria, BIOREG*Belgium, TARDIS62882113 (33.6)Canada, RHUMADATA528114 (21.6)Czech Republic, ATTRA374253 (67.6)Denmark, DANBIO4721506 (10.7)Finland, ROB-FIN807234 (29.0)Germany, RABBIT*Italy, GISEA757250 (33.0)Israel, I-RECORD40094 (23.5)Netherlands, METEOR16424 (0.2)Norway, NOR-DMARD50799 (19.5)Portugal, REUMA.PT79744 (5.5)Romania, RRBR593328 (55.3)Russia, ARBITER526483 (91.8)Slovenia, BIORX.SI583146 (25.0)Spain, BIOBADASER781139 (17.8)Switzerland, SCQM2956796 (26.9)Turkey, TURKBIO2150397 (18.5)UK, BSRBR111163 (5.7)*Registers planning to participate in future studies but not included yetConclusion:The adjusted overall drug retention of JAKi tended to be higher than for TNFi, with large variation between countries. Other measures of effectiveness, such as the evaluation of CDAI remission and low disease activity are planned to shape a more comprehensive picture of JAKi effectiveness in the real world.Disclosure of Interests:Kim Lauper: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Diederik De Cock: None declared, Lene Dreyer: None declared, Ori Elkayam Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Novartis, Jansen, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Nevsun Inanc: None declared, Eirik kristianslund: None declared, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Burkhard Leeb Grant/research support from: chairman of BioReg, Consultant of: AbbVie, Pfizer, Roche, Lilly, Grünenthal, Gebro,, Paid instructor for: Lilly, Biogen, Speakers bureau: Biogen, Lilly, Pfizer, Grünenthal, Astropharma,, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Manuel Pombo-Suarez Consultant of: Janssen, Lilly, MSD and Sanofi., Speakers bureau: Janssen, Lilly, MSD and Sanofi., Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Maria Jose Santos Speakers bureau: Novartis and Pfizer, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Delphine Courvoisier: None declared, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific

Background Long-term clinical registries are essential tools to evaluate new therapies in a patient population that differs from those in randomized clinical trials. The objectives are to describe the profile of rheumatoid arthritis (RA) patients treated with anti-TNF agents in Canadian routine care. Methods RA patients eligible for treatment with Infliximab (IFX), golimumab (GLM) or intravenous golimumab (GLM-IV) as per their respective Canadian product monographs were enrolled into the BioTRAC registry between 2002 and 2017. Study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in disease activity. Safety was evaluated by the incidence of adverse events (AEs) and drug survival. Results Of the 890 IFX-, 530 GLM- and 157 GLM-IV-treated patients, the proportion of females ranged from 77.0–86.6%, the mean ages from 55.8–57.7 and the mean disease duration from 6.5–8.6 years. A significant decrease in baseline disease duration and disease activity parameters (DAS, TJC, SJC, HAQ, AM stiffness, MDGA, PtGA, CRP, ESR) was observed over time. Treatment with IFX, GLM- and GLM-IV significantly improved all disease parameters over time. The incidence of AEs was 105, 113 and 82.6 /100 PYs and the incidence of SAEs was 11.7, 11.2 and 4.68 /100 PYs for IFX, GLM- and GLM-IV-treated patients, respectively. Conclusion Differences in baseline characteristics between patients treated with an anti-TNFs over time shows the evolution of treatment modalities over time. All treatments significantly reduced disease activity and improved functionality in a similar fashion. The incidence of adverse events was consistent with the safety profiles of IFX and GLM. Trial registration ClinicalTrials.gov Identifier: NCT00741793 (Retrospectively registered on August 26, 2008).

To compare direct costs and treatment utility associated with the second-line therapy with rituximab and tumour necrosis factor inhibitors (TNFis) (adalimumab, etanercept, and infliximab) in patients with Rheumatoid Arthritis (RA) using data from a prospective registry. Health Assessment Questionnaire Disability Index (HAQ-DI) scores and RA-related healthcare resource utilization data (biologic agents and visits to rheumatologists) were extracted from a registry (Quebec, Canada) for patients with RA (n = 129) who had to discontinue a first-line TNFi and were treated with rituximab, adalimumab, etanercept, or infliximab as the second-line therapy between January 2007 and May 2016. A decision analytic model followed patients for 1 and 6 years. Treatment utility was measured as quality-adjusted life-years (QALYs) gained, which were calculated from HAQ-DI scores observed over the follow-up time. Quebec 2020 unit costs (Canadian Dollars, $) were used to value healthcare resource consumption. A probabilistic sensitivity analysis was performed with 10,000 Monte Carlo simulations to assess uncertainty around point-estimates of cost-utility. Over 1-year, rituximab and etanercept resulted in the effectiveness of 0.80 QALYs gained at the cost of $14,291and $18,880, respectively, and were dominant (i.e., associated with lower costs and more QALYs gained) compared to adalimumab (0.79 QALYs, $18,825) and infliximab (0.76 QALYs, $20,158). Over 6-years, rituximab (4.42 QALYs, $82,402) was dominant compared to adalimumab (4.30 QALYs, $101,420), etanercept (4.02 QALYs, $99,191), and infliximab (3.71 QALYs, $100,396). In the probabilistic analysis, rituximab was dominant over adalimumab, etanercept, and infliximab with the probability of 0.51, 0.62, and 0.65, respectively. Real-world data revealed differences between alternative biologic agents used as the second-line therapy in terms of both treatment costs for the healthcare system and utility of treatment for patients. Therefore, new guidelines on the order of selecting and switching biologic agents should be explored.

Background Tofacitinib (TOFA), a targeted synthetic DMARD, has been approved for the treatment of rheumatoid arthritis (RA) in Canada since April 2014. This oral agent preferentially inhibits signalling by cytokine receptors associated with JAK1 and JAK3 subunits. It is now indicated for the treatment of psoriatic arthritis (PsA) and ulcerative colitis (UC) since October 2018. Clinical experience with this molecule has been increasing, and questions relating to its efficacy and long-term safety are of interest. Data collection through RHUMADATA®, a Quebec based clinical database and registry, allows comparison of various advanced treatment options including TOFA and non-TNFi biologic agents (i.e., agents with other modes of action - OMA) such as fusion proteins (abatacept), and IL-6 (sarilumab, tocilizumab) and CD20 inhibitors (rituximab). Objectives This analysis compares TOFA and OMAs used with and without methotrexate (MTX). Methods Data collected since January 1, 2014 (since TOFA became available in Canada) at the Institut de Recherche en Rhumatologie de Montreal (IRRM) and the Centre de l’Osteoporose et de Rhumatologie de Quebec (CORQ) was extracted from the Rhumadata® on January 7, 2019. The selected patients had initiated therapy with either TOFA or OMA (either without or in combination with MTX). The collected data include baseline characteristics (socio-demographic variables, concomitant and past medication, comorbidities and the Charlson comorbidity index (CCI)), variables measured over time (laboratory test results, patient and physician-reported outcomes, and disease activity measures such as CDAI and DAS28(4)-ESR) and persistence data (treatment duration, reason for cessation). The groups were compared to identify potential confounder, and persistence data were analyzed using Kaplan-Meier and proportional hazard methods. Results A total of 483 patients were initiated on TOFA (n=162) or an OMA (n=321) since January 1, 2014. Of those, 57% (n=92) and 59% (n=191) were treated with MTX in the TOFA and OMA group respectively. These represent the first treatment following csDMARD inadequate response for 33%(TOFA) and 29%(OMA) of these patients. These patients had a mean disease duration of 12.1 (standard deviation=11.0) and 11.1 (10.3) years. In the TOFA group, 84% were women, 15% were smokers, and the mean age at treatment initiation was 57.7 (11.5). In the OMA group, 75% were women, 18% were smokers, and the mean age at treatment initiation was 57.3 (12.0) years. Patient global, pain and fatigue assessments, made on a visual analogue scale ranging from 1 to 10, were 5.6 (2.5), 5.9 (2.7) and 5.7 (2.9) in the TOFA group and 5.7 (2.5), 6.1 (2.7) and 6.0 (2.8) in the OMA group. Disease activity was assessed as moderate or high/severe in 85.9% and 88.3% of patients (DAS28(4)-ESR criteria). Among the 56 (35%) TOFA and 149 (46%) OMA patients ceasing therapy, reasons for cessation were “inefficacy” (TOFA: 64% vs OMA: 59%) and “adverse events” (TOFA: 16% vs TNFi: 17%). Patients remaining on TOFA and OMA therapy at last follow-up had an average treatment duration of 1.7 (1.1) and 2.6 (1.4) years. No difference in retention was observed between TOFA and OMA treated patients (log-rank p=0.6138). Patients treated with an OMA+/-MTX had similar retention (log-rank p=0.2640) as did patients treated with TOFA+/-MTX (log-rank p=0.9553). These results remain unchanged when we adjust for age at treatment initiation, gender, disease duration, and comorbidities (CCI) using Cox models. Conclusion OMA and TOFA have similar retention as do subjects treated with OMA or TOFA with or without MTX. Disclosure of Interests Denis Choquette Grant/research support from: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Celgene, Eli Lilly, Novartis, Pfizer Inc, Loic Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant for: AbbVie, Amgen, Novartis, Pfizer, Speakers bureau: Amgen, Pfizer, Paul Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Consultant for: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Speakers bureau: Pfizer, Frederic Massicotte Consultant for: AbbVie, Pfizer, Janssen, Eli Lilly, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: Shareholder in ArthroLab Inc., Grant/research support from: Study funded by TRB Chemedica SA, Consultant for: TRB Chemedica SA, Jean-Pierre Raynauld Consultant for: ArthroLab Inc., Marie-Anais Remillard Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Edith Villeneuve Consultant for: AbbVie, UCB, Celgene, Roche, Pfizer, Amgen, BMS, Sanofi-Genzyme, Paid instructor for: AbbVie, Speakers bureau: AbbVie, Pfizer, BMS, Roche, Louis Coupal: None declared

Background Long-term registries are essential to evaluate new therapies in a patient population that differs from clinical trials and usually varies over time. Objectives To describe the profile of rheumatoid arthritis (RA) patients treated with infliximab (IFX), golimumab subcutaneous (GLM) or intravenous (GLM-IV) in Canadian routine care, along with its effectiveness and safety. Methods 1577 RA patients treated with IFX, GLM or GLM-IV were enrolled into the Biologic Treatment Registry Across Canada (BioTRAC) between 2006-2015, 2010-2017 and 2014-2017, respectively. Study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed with changes in TJC28, SJC28, MDGA, PtGA, pain, HAQ, and acute phase reactants. Safety was evaluated with the incidence of adverse events (AEs) and drug survival. Results Of the 890 IFX-, 530 GLM- and 157 GLM-IV-treated patients, the proportion of females were 75.7%- 77.1%, the mean age were 55.8-57.7 and the mean disease duration were 6.5-8.6 years. Most patients were bio-naive (> 80%). A significant decrease in disease duration and disease activity scores (DAS, TJC, SJC, HAQ, AM stiffness, MDGA, PtGA, CRP, ESR) were observed in the IFX cohort over time (p Treatment with IFX, GLM and GLM-IV significantly improved all disease parameters over time (P AEs were reported for 61.5%, 67.4% and 59.2% (105, 113 and 82.6 events/100 PYs) and SAEs for 21.2%, 15.5% and 3.8% (11.7, 34.4 and 9.0 events/100 PYs) covering 2714, 1077 and 257 years of exposure for IFX, GLM and GLM-IV-treated patients, respectively. The most frequently occurring AEs were arthralgia and upper respiratory tract infection (>5%). Eighteen, 7 and 1 deaths occurred among IFX-, GLM- and GLM-IV-treated patients, respectively. The proportion of patients who discontinued treatment were 74.0% over a mean 3.0 years of exposure to IFX-, 52.8% over 2.0 years of exposure to GLM and 45.2% over 1.6 year of exposure to GLM-IV. Conclusion In this real-world study of Canadian patients with RA, differences in baseline characteristics between patients treated with an anti-TNF over time and between agents shows potential selection biases when selecting a given therapy and may impact the proportion of patients achieving a target-specific outcome. Treatment significantly reduced disease activity and improved functionality in a similar fashion and were also safe and well tolerated. Disclosure of Interests: Proton Rahman: None declared, Philip Baer Grant/research support from: Janssen sponsored study, Consultant for: Eli Lilly, Pfizer, Abbvie, Amgen, Merck, Novartis, Sanofi Genzyme, Paladin, Janssen, Johnson & Johnson, Speakers bureau: Eli Lilly, Pfizer, Abbvie, Amgen, Janssen, Denis Choquette Grant/research support from: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Rafat Faraawi: None declared, Louis Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Celgene, Lilly, Novartis, Speakers bureau: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Milton Baker Grant/research support from: Janssen Sponsored Study, Raman Rai Consultant for: Janssen, Amgen, BMS, Roche, Abbvie, Pfizer, Merck, Novartis, Speakers bureau: Janssen, Amgen, Roche, BMS, Abbvie, John Kelsall Grant/research support from: Janssen Sponsored Study, Larissa Lisnevskaia Grant/research support from: Janssen Sponsored Study, Jodie Reis Grant/research support from: Janssen Sponsored Study, Keltie Anderson Grant/research support from: Janssen Sponsored Study, Wojciech Olszynski Grant/research support from: Janssen sponsored study, Emmanouil Rampakakis : None declared, Odalis Asin MIilan Employee of: Employee of Janssen, Allen Lehman Employee of: Employee of Janssen, Meagan Rachich Shareholder of: Janssen, Employee of: Employee of Janssen, Francois Nantel Shareholder of: Janssen, Employee of: Employee of Janssen

Background: Anemia is a common feature of RA. Prior to the appearance of biologic treatments, improvement of hemoglobin (Hb) levels was unusual and inconsistent. With better control of the inflammatory process with cytokine inhibitors, it has been shown that Hb levels can improve substantially. Recently in the development of IL-6 receptor antagonists (sarilumab (SARI) and tocilizumab (TOCI)) data have shown improvement in Hb levels related to the down-regulation of hepcidin. No direct comparison of Hb levels between TNF and IL-6 inhibition has been explored in observational data (1). Objectives: This analysis compares the impact of TNF and IL-6 inhibitors on Hb levels over time. Methods: Data collected since January 1, 2015 (when TOCI and SARI were available in Canada) at the Institut de Recherche en Rhumatologie de Montreal (IRRM) and the Centre de l’Osteoporose et de Rhumatologie de Quebec (CORQ) was extracted from the Rhumadata® clinical database and registry on January 7, 2019. Selected patients were those initiated on an IL-6 antagonist or a TNFi (adalimumab, certolizumab, etanercept, golimumab or infliximab) and had been treated for at least one year. Furthermore, patients were cancer free and had no diagnosis of Crohn’s disease or ulcerative colitis and had creatinine (Cr) and ALT levels within the normal sex-specific range. IL-6 patients were matched (ratio 1:2) to TNFi patients based on age at treatment initiation, gender and baseline Hb. The collected data include baseline characteristics (socio-demographic variables, concomitant and past medication, comorbidities and the Charlson comorbidity index (CCI)), variables measured over time (Hb and other laboratory test results, patient and physician-reported outcomes, and disease activity measures such as CDAI and DAS28(4)-ESR. The groups were compared to identify potential confounder. Results: A total of 145 patients initiating an IL-6 antagonist since January 1, 2015 were matched with 286 patients prescribed a TNF inhibitor during the same time-period. Most patients were women (86%), the mean age at treatment initiation was 54.1 (standard deviation=11.7) years, and 16% were smokers. Baseline patient global, pain and fatigue assessments, made on a visual analogue scale ranging from 1 to 10, were 5.4 (2.5), 6.1 (2.5) and 5.5 (3.0) in the IL6 group and 5.1 (2.7), 5.5 (3.0) and 5.0 (3.2) in the TNFi group. Baseline disease activity was assessed as moderate or high/severe in 85.5% (IL6) and 85.9% (TNFi) of patients (DAS28(4)-ESR criteria). At treatment initiation, mean Hb level was 126.6 (12.4) g/L, and Cr and ALT levels were 66.2 (11.5) umol/L and 18.7 (6.5) U/L in the IL6 group and 67.0 (12.0) umol/L and 19.3 (6.8) U/L in the TNFi group. At three months, Hb had increased by 5.4 (10.2) g/L in the IL6 group and by 1.8 (13.9) g/L in the TNFi group (p-value=0.024). These respective changes at 12 months were 8.7 (11.4) g/L and 5.4 (9.2) g/L (p-value=0.042). Conclusion: This analysis confirms that IL-6 inhibition provides a numerically and statistically superior increase in Hb over TNFi. Reference: [1] Song, et al. Arthritis Research & Therapy 2013, 15:R141 Disclosure of Interests: Denis Choquette Grant/research support from: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Celgene, Eli Lilly, Novartis, Pfizer Inc, Loic Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant for: AbbVie, Amgen, Novartis, Pfizer, Speakers bureau: Amgen, Pfizer, Paul Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Consultant for: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Speakers bureau: Pfizer, Frederic Massicotte Consultant for: AbbVie, Pfizer, Janssen, Eli Lilly, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: Shareholder in ArthroLab Inc., Grant/research support from: Study funded by TRB Chemedica SA, Consultant for: TRB Chemedica SA, Jean-Pierre Raynauld Consultant for: ArthroLab Inc., Marie-Anais Remillard Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Edith Villeneuve Consultant for: AbbVie, UCB, Celgene, Roche, Pfizer, Amgen, BMS, Sanofi-Genzyme, Paid instructor for: AbbVie, Speakers bureau: AbbVie, Pfizer, BMS, Roche, Louis Coupal: None declared

Background Tofacitinib (TOFA), a targeted synthetic DMARD, has been approved for the treatment of rheumatoid arthritis (RA) in Canada since April 2014. This oral agent preferentially inhibits signalling by cytokine receptors associated with JAK1 and JAK3 subunits. It is also indicated for the treatment of PsA and UC since October 2018. Clinical experience with this molecule has been increasing, and questions relating to its efficacy and long-term safety are of interest. Data collection through RHUMADATA®, a Quebec based clinical database and registry, allows comparison of newer options with more traditional agents such as tumor necrosis factor inhibitors (TNFi). Objectives The current analysis compares TOFA to TNFi used with and without methotrexate (MTX) among patients with RA. Methods Data collected since January 1, 2014 (when TOFA became available in Canada) at the Institut de Recherche en Rhumatologie de Montreal (IRRM) and the Centre de l’Osteoporose et de Rhumatologie de Quebec (CORQ) was extracted from Rhumadata® on January 7, 2019. Patients initiated on TOFA or a TNFi (adalimumab, certolizumab, etanercept, golimumab, infliximab) without or with MTX were selected. Data include baseline characteristics (socio-demographic variables, concomitant and past medication, comorbidities and the Charlson comorbidity index (CCI)), variables measured over time (lab results, patient and physician-reported outcomes, and disease activity measures) and persistence data (treatment duration, reason for cessation). The groups were compared to identify potential confounder, and persistence data were analyzed using Kaplan-Meier and Cox methods. Results A total of 480 patients were prescribed TOFA (n=162) or a TNFi (n=318) since January 1, 2014. Of those, 57% (n=92) and 70% (n=224) were treated with MTX in the TOFA and TNFi group respectively and mean disease duration was 12.1 (standard deviation=11.0) and 7.2 (8.1) years. TOFA and TNFi represent the first treatment following csDMARD-IR for 33%(TOFA) and 62%(TNFi). In the TOFA group, 84% were women, 15% were smokers and the mean age at treatment initiation was 57.7 (11.5) years. In the TNFi group, 77% were women, 12% were smokers and the mean age at treatment initiation was 54.2 (13.7) years. At treatment initiation, patient global, pain and fatigue assessments, made on a visual analogue scale ranging from 1 to 10, were 5.6 (2.5), 5.9 (2.7) and 5.7 (2.9) in the TOFA group and 5.0 (2.9), 5.5 (3.0) and 5.1 (3.1) in the TNFi group. Baseline disease activity was assessed as moderate or high/severe in 85.9% and 76.7% of TOFA (?) patients (DAS28(4)-ESR criteria). Among the 56 (35%) TOFA and 146 (46%) TNFi patients ceasing therapy, reasons for cessation were “inefficacy” (TOFA: 64% vs TNFi: 56%) and “adverse events” (TOFA: 16% vs TNFi: 11%). Patients remaining on TOFA and TNFi therapy at last follow-up had an average treatment duration of 1.7 (1.1) and 2.7 (1.5) years and no difference in retention was observed between TOFA and TNFi treated patients (log-rank p=0.41). Patients treated with a TNFi in combination with MTX had better treatment retention than those treated without MTX (log-rank p=0.04) while patients treated with TOFA+/-MTX had similar retention (log-rank p=0.96). These results remain unchanged when adjusted for gender, age at treatment initiation, disease duration, and comorbidities. Conclusion In our real-world data registry, treatment with TNFi and TOFA yielded similar retention over time. Subjects treated with TNFi and MTX remained on treatment longer than those treated without MTX while subjects treated with tofacitinib with or without MTX had similar retention. Disclosure of Interests Denis Choquette Grant/research support from: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Celgene, Eli Lilly, Novartis, Pfizer Inc, Loic Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant for: AbbVie, Amgen, Novartis, Pfizer, Speakers bureau: Amgen, Pfizer, Paul Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Consultant for: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Speakers bureau: Pfizer, Frederic Massicotte Consultant for: AbbVie, Pfizer, Janssen, Eli Lilly, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: Shareholder in ArthroLab Inc., Grant/research support from: Study funded by TRB Chemedica SA, Consultant for: TRB Chemedica SA, Jean-Pierre Raynauld Consultant for: ArthroLab Inc., Marie-Anais Remillard Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Edith Villeneuve Consultant for: AbbVie, UCB, Celgene, Roche, Pfizer, Amgen, BMS, Sanofi-Genzyme, Paid instructor for: AbbVie, Speakers bureau: AbbVie, Pfizer, BMS, Roche, Louis Coupal: None declared

Background Secukinumab (SECU) is a human IgG1κ monoclonal antibody that binds to the protein interleukin-17A approved for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis (PsA). Recently presented data suggest that combination with methotrexate (MTX) in patients with PsA may not be as necessary as in rheumatoid arthritis as it improves neither efficacity nor sustainability (1,2,3,4). Objectives This analysis describes the use of SECU with or without MTX. Methods The data of patients with psoriatic arthritis seen since January 1, 2015 (date at which SECU appeared in the Canadian market) at the Institut de Recherche en Rhumatologie de Montreal (IRRM) and the Centre de l’Osteoporose et de Rhumatologie de Quebec (CORQ) was extracted from the Rhumadata® clinical database and registry on January 7, 2019. Selected patients initiated SECU either without (MTX-) or with MTX (MTX+). The collected data include baseline characteristics (socio-demographic variables, concomitant and past medication, comorbidities and the Charlson comorbidity index (CCI)), variables measured over time (laboratory test results, patient and physician-reported outcomes, and disease activity measures such as minimal disease activity (MDA), CDAI and DAS28(4)-ESR) and persistence data (treatment duration, reason for cessation). The groups were compared to identify potential confounder, and persistence data were analyzed using Kaplan-Meier and proportional hazard methods. Results A total of 96 patients were prescribed SECU since January 1, 2015. Of those, 49% (n=47) treated with MTX. No significant differences in baseline (at treatment initiation) were observed between the MTX+ and MTX- groups. Average age at treatment initiation was 52.4 (standard deviation=11.3) and 53.7 (13.4) in the MTX+ and MTX- groups respectively. Women represent 45% and 55% of these groups, and the average body mass index was 29.9 (6.2) and 28.1 (6.0) kg/m2. Patient global, pain and fatigue assessments, made on a visual analogue scale ranging from 1 to 10, were 4.9 (2.6), 5.3 (2.9) and 4.3 (2.9) in the MTX+ group and 6.3 (2.2), 6.9 (2.1) and 6.5 (2.9) in the MTX- group. Among the 38 (40%) patients ceasing therapy, the principal reason for cessation was “inefficacy” (MTX+: 15/17 (88%) vs MTX-: 15/21 (71%)). Patients remaining on treatment at last follow-up had an average treatment duration of 1.7 (0.8) and 1.5 (0.7) years. The improvement in CDAI, HAQ and the percentage of patients reaching MDA are similar for both groups. No difference in retention was observed between the MTX+ and MTX- groups (log-rank p=0.4867). These results remain unchanged when we adjust for age at treatment initiation, gender, disease duration, and comorbidities (Charlson comorbidity index). Conclusion Combining MTX to SECU does not improve its sustainability over time. Efficacy was also the same for both cohorts. References [1] Mease PJ, et al. Arthritis Rheumatol. 2018; 70 (suppl 10). Abstract L11 [2] Benryane O, et al. Arthritis Rheumatol. 2018; 70 (suppl 10). Abstracts 693 and 694 [3] Benryane O, et al. CRA-2019, Montreal, Canada. Disclosure of interests Denis Choquette Grant/research support from: abbvie, amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Consultant for: abbvie, amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: abbvie, amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Louis Bessette Grant/research support from: abbVie, amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer inc, Roche, Sanofi, UCB, Consultant for: abbVie, Celgene, Eli Lilly, Novartis, Pfizer inc, Loic Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant for: abbVie, amgen, Novartis, Pfizer, Speakers bureau: amgen, Pfizer, Paul Haraoui Grant/research support from: abbvie, amgen, Pfizer, UCB, Consultant for: abbvie, amgen, Lilly, Pfizer, Sandoz, UCB, Speakers bureau: Pfizer, Frederic Massicotte Consultant for: abbVie, Pfizer, Janssen, Eli Lilly, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: Shareholder in arthroLab inc., Grant/research support from: Study funded by TRB Chemedica SA, Consultant for: TRB Chemedica SA, Jean-Pierre Raynauld Consultant for: arthroLab inc., Marie-Anais Remillard Consultant for: abbvie, amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: abbvie, amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: abbvie, amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Edith Villeneuve Consultant for: abbVie, UCB, Celgene, Roche, Pfizer, amgen, BMS, Sanofi-Genzyme, Paid instructor for: abbVie, Speakers bureau: abbVie, Pfizer, BMS, Roche, Louis Coupal: None declared

Background: Recent approvals for novel agents such as the small molecule Janus kinase inhibitors (JAKi), combined with the advent of biosimilars has widened the gamut of available therapeutic options in the treatment of rheumatoid arthritis (RA). This combined with the introduction of mandatory non- medical switches to biosimilars in some jurisdictions by both public and private payors has led to a significant increase in the volume of therapeutic changes for patients. Pharmacists are well positioned to ensure effective and safe transitions, however there is a significant unmet need for objective and subjective clinical guidance around therapy as well disease state monitoring in RA that facilitates best practices throughout the patient journey. Objective: In this paper we aim to create a consensus derived monitoring algorithm for pharmacists to facilitate best practices throughout therapeutic transitions from originator biologic to other originator biologics, biosimilars, and Janus kinase inhibitors in RA. Methods: The Nominal Group Technique (NGT) was used to understand if consensus could be found among the participants. Clinically relevant questions were developed to capture solutions to the identified unmet need. The faculty considered the questions as individuals, and privately generated answers/ideas. After discussion and consideration, the participants ranked the ideas and established a consensus. Results: Based on the outcome of the consensus discussions, an algorithm was created to help guide pharmacists through therapeutic transitions in RA. The tool covers important topics such as pre-transition considerations, avoiding the nocebo effect for biosimilars, specific considerations for each drug or class, monitoring efficacy, and when to refer. Conclusions: New classes of anti-rheumatic drugs including JAKi, along with the introduction of biosimilars are presenting more opportunity for therapeutic changes and monitoring in patients with RA. We hope our evidence-based consensus derived guidance tool will assist frontline pharmacists in supporting their patients to a successful therapeutic transition in RA.

Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment and is prescribed alone or with methotrexate (MTX). We previously reported the similarity in retention between TOFA monotherapy and TOFA with MTX using data from two different registries separately; the Ontario Best Practices Research Initiative (OBRI) and the Quebec registry RHUMADATA.Objectives:To increase the study power, we propose to evaluate the discontinuation rate (due to any reason) of TOFA with and without MTX, using pooled data from these two registries.Methods:RA patients enrolled in the OBRI and RHUMADATA initiating their TOFA between 1st June 2014 (TOFA approval date in Canada) and 31st Dec 2019 were included. Concurrent MTX use was defined as MTX use for more than 75% of the time while using TOFA. Multiple imputation (Imputation Chained Equation method, N=20) was used to deal with missing data for covariates at treatment initiation.Time to discontinuation was assessed using Cox regression models. To deal with confounding by indication, we estimated propensity scores for selected covariates with an absolute standard difference greater than 0.1. We then adjusted Cox regression models for propensity quantile to compare the discontinuation of TOFA with MTX versus TOFA without MTX.Results:A total of 493 patients were included. Of those, 244 (49.5%) and 249 (51.5%) were treated with MTX and without MTX, respectively. Compared to TOFA monotherapy, the TOFA with MTX group had a significantly lower mean HAQ-DI, fatigue score, and the number of prior biologic use at the time of TOFA initiation. A lower proportion of positive ACPA (59% vs. 66%), prevalence of hypertension (31% vs 37%), and concomitant use of Leflunomide (11% vs. 23%) were also observed for patients using TOFA with MTX.Over a mean follow-up of 19.0 months, discontinuation was reported in 182 (36.9%) of all TOFA patients. After adjusting for propensity score quantile across 20 imputed datasets, there was no significant difference in discontinuation between treatment groups (adjusted HRs: 1.12, 95% CI: 0.83-1.51; p=0.49).Conclusion:In this pooled real-world data study, we found that in patients with RA, the retention of TOFA is similar if it is used as monotherapy or in combination with MTX.Disclosure of Interests:Movahedi: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by unrestricted grants from Abbvie Canada, Amgen Canada, Eli Lilly Canada, Novartis Canada, Pfizer Canada, Sandoz Canada and Sanofi Canada., Louis Coupal: None declared, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm. Speaker Honoraria Agreements: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis. Consulting Agreements/Advisory Board Membership: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Claire Bombardier Grant/research support from: OBRI was funded by peer reviewed grants from CIHR (Canadian Institute for Health Research), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from: Abbvie, Amgen, Aurora, Bristol-Meyers Squibb, Celgene, Hospira, Janssen, Lilly, Medexus, Merck, Novartis, Pfizer, Roche, Sanofi, & UCB.Acknowledgment: :Dr. Bombardier held a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care and a Pfizer Research Chair in Rheumatology

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.

Background:Biosimilar etanercept (ETA-B) was recently introduced in Canada but real-world data descriptions of drug persistence (and comparisons with the originator product, ETA-O) are still scarce.Objectives:To describe and compare persistence of ETA-B and ETA-O in RA.Methods:We used data from four ongoing, prospective cohorts in Canada: the Canadian Early Arthritis Cohort (CATCH), the Rheumatoid Arthritis Pharmacovigilance Program and Outcomes Research in Therapeutics (RAPPORT), the Early Undifferentiated Polyarthritis (EUPA) cohort, and the RHUMADATA® registry. We studied biologic-naïve and biologic-experienced RA adults initiating ETA-B or ETA-O between Jan. 2015 and Oct. 2019. Switchers from ETA-O to ETA-B (or vice-versa) were included. We assessed persistence of therapy in the first 12 or 24 months, measured as time from therapy initiation (time zero) to discontinuation. Individuals switching between products could contribute further person-time to the new exposure category. Multivariable Cox regression models were performed with each cohort dataset separately, following a common protocol. Model variables included age, sex, comorbidity, past biologic use, and disease duration. After testing for between-study heterogeneity (Higgin’s I2), cohort-estimated hazard ratios (HR) were pooled using random effects meta-analysis.Results:We identified 262 episodes of etanercept use (118 ETA-B and 144 ETA-O) from 250 RA patients. Sex, age, and other baseline characteristics across the four cohorts are shown in Table 1. Across cohorts, there was considerable variation in RA duration at the time of initiating ETA-B or ETA-O. In the pooled analysis, the HR for discontinuation at 24 months comparing ETA-B to ETA-O was 0.51 (95% confidence interval, CI: 0.26-0.98). The pooled analysis for therapy discontinuation at 12 months adjusted HR in this analysis was 0.82 (95% CI: 0.42-1.60).Table 1.Characteristics of studied patients according to their treatment episodes, biosimilar etanercept (ETA-B) or bio-originator etanercept (ETA-O).CharacteristicEUPARAPPORTRHUMADATACATCHETA-BETA-OETA-BETA-OETA-BETA-OETA-BETA-ON=19N=27N=32N=30N=39N=52N=28N=35Female sex, (%)12 (63)18 (67)20 (63)22 (73)28 (72)38 (73)20 (71)27 (77)Mean age in years1, SD59 (13)59 (16)51 (15)54 (15)59 (15)54 (15)55 (12)51 (13)Current smoker, (%)3 (17)5 (21)9 (32)5 (19)8 (21)9 (17)5 (18)8 (23)Cardiovascular disease, (%)0 (0)0 (0)1 (3.1)1 (3.3)8 (21)2 (4)NANADiabetes, (%)0 (0)0 (0)4 (13)1 (3)2 (5)3 (6)NANAHypertension, (%)NANA5 (16)4 (13)14 (36)22 (42)NANARA duration in years1, SD2 (3)7 (13)8 (6)12 (15)12 (12)9 (9)4 (4)3 (3)DAS-2812 (NA)4 (2.8)6 (1)6 (1)4 (2)4 (1)4.0 (2)4 (2)SDAI113 (14)44 (5)NANA21 (15)23 (8)23 (14)25 (16)Past oral steroids, N(%)Past biologic, N(%)15 (79)17 (63)6 (19)4 (13)29 (74)31 (60)9 (32)13 (37)Past non-biologic DMARD,8 (42)6 (22)2 (6)0 (0)21 (54)20 (38)19 (68)21 (60)N(%)19 (100)27 (100)30 (94)26 (87)39 (100)52(100)25 (89)33 (94)1At time zero or at the closest date before time zero. SD=standard deviationConclusion:Despite wide confidence intervals, the 24-month data suggested potential better persistence with ETA-B versus ETA-O, with a similar trend at 12 months. Some of the observed associations may be related to residual confounding (e.g. disease activity, time-dependent effects of concomitant medications) and/or survivorship bias (in patients transitioning from ETA-O to ETA-B).Disclosure of Interests:Cristiano S Moura: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Coupal: None declared, Orit Schieir: None declared, Marie-France Valois: None declared, Vivian Bykerk: None declared, Gilles Boire Grant/research support from: Merck Canada (Registry of biologices, Improvement of comorbidity surveillance)Amgen Canada (CATCH, clinical nurse)Abbvie (CATCH, clinical nurse)Pfizer (CATCH, Registry of biologics, Clinical nurse)Hoffman-LaRoche (CATCH)UCB Canada (CATCH, Clinical nurse)BMS (CATCH, Clinical nurse, Observational Study Protocol IM101664. SEROPOSITIVITY IN A LARGE CANADIAN OBSERVATIONAL COHORT)Janssen (CATCH)Celgene (Clinical nurse)Eli Lilly (Registry of biologics, Clinical nurse), Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, Speakers bureau: Merck, BMS, Pfizer, Walter P Maksymowych Grant/research support from: Received research and/or educational grants from Abbvie, Novartis, Pfizer, UCB, Consultant of: WPM is Chief Medical Officer of CARE Arthritis Limited, has received consultant/participated in advisory boards for Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Received speaker fees from Abbvie, Janssen, Novartis, Pfizer, UCB., Sasha Bernatsky: None declared

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.References:[1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012.[2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9].Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4.Disclosure of Interests:Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme,UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared

Background Treatment persistence is an important consideration when selecting a therapy for chronic conditions such as rheumatoid arthritis (RA). We assessed the long-term persistence of abatacept or a tumor necrosis factor inhibitor (TNFi) following (1) inadequate response to a conventional synthetic disease-modifying antirheumatic drug (first-line biologic agent) and (2) inadequate response to a first biologic DMARD (second-line biologic agent). Methods Data were extracted from the Rhumadata® registry for patients with RA prescribed either abatacept or a TNFi (adalimumab, certolizumab, etanercept, golimumab, or infliximab) who met the study selection criteria. The primary outcome was persistence to abatacept and TNFi treatment, as first- or second-line biologics. Secondary outcomes included the proportion of patients discontinuing therapy, reasons for discontinuation, and predictors of discontinuation. Persistence was defined as the time from initiation to discontinuation of biologic therapy. Baseline characteristics were compared using descriptive statistics; cumulative persistence rates were estimated using Kaplan-Meier methods, compared using the log-rank test. Multivariate Cox proportional hazard models were used to compare the persistence between treatments, controlling for baseline covariates. Results Overall, 705 patients met the selection criteria for first-line biologic agent initiation (abatacept, n = 92; TNFi, n = 613) and 317 patients met the criteria for second-line biologic agent initiation (abatacept, n = 105; TNFi, n = 212). There were no clinically significant differences in baseline characteristics between the treatments with either first- or second-line biologics. Persistence was similar between the first-line biologic treatments (p = 0.7406) but significantly higher for abatacept compared with TNFi as a second-line biologic (p = 0.0001). Mean (SD) times on first-line biologic abatacept and TNFi use were 4.53 (0.41) and 5.35 (0.20) years, and 4.80 (0.45) and 2.82 (0.24) years, respectively, as second-line biologic agents. The proportion of patients discontinuing abatacept and TNFi in first-line was 51.1% vs. 59.5% (p = 0.1404), respectively. In second-line, it was 57.1% vs. 74.1% (p = 0.0031). The main reasons for stopping both treatments were inefficacy and adverse events. Conclusions Abatacept and TNFi use demonstrated similar persistence rates at 9 years as a first-line biologic agent. As a second-line biologic agent, abatacept had better persistence rates over a TNFi.

Background Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are used as diagnostic tools, but may also be used as prognostic factors, as these biomarkers have been associated with better clinical responses to some biologic agents in rheumatoid arthritis (RA). Objectives To compare the impact of seropositivity on drug discontinuation and effectiveness for abatacept (ABA) and TNF inhibitors (TNFi) in patients (pts) with RA. Methods Pooled analysis of 13 observational RA registries from countries (FR, IT, CZ, DK, NO, PT, RO, ES, SE, CH, NL, JP, CA) where both ABA and TNFi were available concomitantly. Inclusion criteria were RA diagnosis, treatment with ABA or TNFi, and available RF or ACPA status. Main exposure was seropositivity: positive if RF or ACPA were positive, negative if both were negative, and missing if one was missing and the other was negative. Primary endpoint was drug discontinuation, analysed using Cox models, including treatment, seropositivity, and their interaction, adjusting for patient-, treatment-, and disease-characteristics, using strata terms for country and calendar year. We first tested for effect modification by country by additionally including an interaction term between treatment, seropositivity and country. Since we found no effect modification, we took out the interaction term. Effectiveness was analysed using DAS28 remission and low disease activity (LDA) at 1 year, corrected for attrition using Lundex1. Results Using data from 39 266 treatment-courses, in crude analyses, seronegativity was associated with higher drug discontinuation for pts on ABA but not on TNFi (p interaction The proportion of pts reaching DAS28 remission or LDA at 1 year was significantly higher for seropositive vs seronegative pts on ABA (difference in proportion: remission: 5.0%; LDA: 9.7%), but similar for seropositive vs seronegative pts on TNFi (difference in proportion: remission: −2.7%; LDA: −2.3%). Conclusions Data from this large pooled registry suggests that seropositivity in RA pts is associated with increased drug retention and effectiveness for ABA but not for TNFi. Reference [1] Kristensen, et al. AR(54):600–6. Acknowledgements Unrestricted research grant from BMS Disclosure of Interest D. Courvoisier Consultant for: BMS, D. Mongin: None declared, M. Hetland Consultant for: Abbvie, Biogen, BMS, CellTrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB, K. Pavelka Grant/research support from: Ministry of Health, Czech Republic 023728, Consultant for: AbbVie, Roche, MSD, BMS, Amgen, Egis, Medac, UCB, Pfizer, Biogen, C. Turesson Grant/research support from: Abbvie, Bristol Myers-Squibb, Roche. Consultant for: MSD, Bristol Myers-Squibb, Roche, Paid instructor for: Abbvie, Bristol-Myers Squibb, Janssen, MSD, Pfizer, Roche, UCB, S. A. Bergstra: None declared, T. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Epirus, Hospira, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, UCB, M. J. Santos: None declared, V. Hernandez: None declared, F. Iannone Consultant for: BMS, J.-E. Gottenberg Consultant for: BMS, X. Mariette Consultant for: BMS, S. Kubo Speakers bureau: BMS, Pfizer, Takeda, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, Daiichi-Sankyo, Pfizer, Eisai, Ono, Consultant for: Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, BMS, Chugai, YL Biologics, Eli Lilly, Sanofi, Janssen, UCB, D. Choquette: None declared, R. Ionescu: None declared, A. Finckh Grant/research support from: BMS, Consultant for: BMS, AbbVie, AB2BIO, MSD, Pfizer, Roche, UCB

Background The Biologic Trial Registry Across Canada (BioTRAC) was a multi-centre, prospective, longitudinal, observational program that gathered and analysed data on inflammatory arthritis patients treated with infliximab (IFX), golimumab and ustekinumab. Patients specifically treated with IFX were recruited from July 2002 to June 2015 and followed up to June 2017. Objectives The objective of this abstract is to document the final consolidated safety data from the BioTRAC IFX cohort. Methods Treatment was prescribed by the physician per actual clinical practice or standard of care for rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA); there was no randomised assignments to treatment. There were no restrictions on the use of concomitant medications. At enrolment (baseline) and approximately every 6 months thereafter, information was collected to assess safety, clinical outcomes, quality of life, comorbidities, pharmaco-economics and treatment regimens. Results A total of 1390 patients were enrolled and used for this analysis. The proportion of patients by indication was 59.2% for RA (n=890), 25.9% for AS (n=389) and 7.4% for PsA (n=111). The mean (SD) exposure was 3.10 (3.26) years for a sum of 4290.25 patient-years. Treatment with IFX was generally safe, with AEs and SAEs being reported for 64.3% and 19.5% of patients, respectively. The incidence rate of AEs and SAEs was 116.0 and 11.2 events per 100 pt-years, respectively. More specifically, 338 SAEs were reported by 189 (21.2%) RA patients [SAEs/100 pt-yrs: 11.7], 130 SAEs were reported by 60 (15.4%) AS patients [SAEs/100 pt-yrs: 10.5] and 28 SAEs were reported by 22 (19.8%) PsA patients [SAEs/100 pt-yrs: 8.82]. The most commonly reported AE identified was arthralgia, viral upper respiratory tract infection, upper respiratory tract infection and nausea. For SAEs, the most commonly reported SOC (≥3% of patients) was “Infections and infestations” [5.3% (n=73); 2.16 SAEs/100 pt-yrs] and “Neoplasms benign, malignant and unspecified” [3.5% (n=49); 1.24 SAEs/100 pt-yrs] which occurred at similar rates to the general RA patient population1 and included two lymphomas [0.1%; 0.05/100 pt-yrs]. Across 3 closely monitored categories of AEs, a total of 302 closely monitored AEs were reported by 293 (21.1%) patients, including cancer (3.7%), lack of efficacy (17.1%) and tuberculosis (0.2%). A total of 21 deaths were reported during the study in 18 RA, 1 AS and 2 PsA patients. Cause of death included MACE (x5), lung cancer (x2), pulmonary fibrosis (x2), pneumonia (x2), respiratory failure, bronchitis, intestinal cancer, throat cancer, intestinal gangrene, disseminated TB, septic shock, procedural complication and drowning. The cause of death was not known for one patient. Conclusions The results of this longitudinal observational study showed that treatment with IFX was well tolerated in people living with AS, PsA and RA over a 15 year period in a real-world setting. Reference [1] Askling, et al. Arthritis & Rheum2009;60:3180–9. Disclosure of Interest D. Choquette Grant/research support from: Janssen Inc., P. Rahman Grant/research support from: Janssen Inc., Consultant for: Janssen Inc., Speakers bureau: Janssen Inc., A. Chow: None declared, R. Faraawi Consultant for: Janssen Inc., Speakers bureau: Janssen Inc., W. Olszynski Consultant for: Janssen Inc., E. Rampakakis: None declared, O. Asin-Milan Employee of: Janssen Inc., B. Osborne Employee of: Janssen Inc., A. Lehman Employee of: Janssen Inc., F. Nantel Shareholder of: Johnson and Johnson, Employee of: Janssen Inc.

Objective.To develop a Canadian Rheumatoid Arthritis Core Clinical Dataset (CAN-RACCD) to standardize documentation encouraging high-quality care.Methods.A set of candidate elements was drafted through meetings with 27 rheumatologists, researchers, and patients, and supplemented with focused literature reviews. A 3-round online-modified Delphi consensus process was held with rheumatologists (n = 26), allied health professionals (n = 7), and patients (n = 4); for the remainder there was no demographic information. Participants rated both the importance and feasibility of documenting candidate elements on a Likert scale of 1–9, contributed to an online moderated discussion, and re-rated the elements for inclusion in the CAN-RACCD. Elements were included in the final set if importance and feasibility ratings had a median score of ≥ 6.5 and there was no disagreement among participants.Results.Fifty-five individual elements in 10 subgroups were proposed to the Delphi participants: measures of RA disease activity; dates to calculate waiting times, disease duration, and disease-modifying antirheumatic drug start; comorbidities; smoking status; patient-reported pain and fatigue; physical function; laboratory and radiographic investigations; medications; clinical characteristics; and vaccines. All groups were included in the final set, with the exception of vaccination status. Additionally, 3 individual elements from the smoking subgroup were eliminated with a recommendation to record smoking status as never/ever/current, and 2 elements relating to coping and effect of fatigue were eliminated due to low feasibility and importance ratings.Conclusion.The CAN-RACCD stands as a national recommendation on which data elements should be routinely collected in clinical practice to monitor and support high-quality RA care.

Background In the absence of biomarkers predicting response to a specific therapy, the choice of second biologic is based mostly on habit and availability of an alternative agent. Traditionally, a second anti-TNF was the preferred option, but recent registry data point to better responses and retention if a drug with a different mode of action is prescribed. Objectives Assess the long-term retention of abatacept (ABA) and TNFi following first biologic (b)DMARD inadequate response in RHUMADATA® registry patients (pts) with RA. Methods Data from RHUMADATA® pts with RA prescribed either ABA or TNFi as the second bDMARD after 1 January 2006 were analysed. Pts were followed until treatment discontinuation or 9 January 2017 cut-off. Pt characteristics were compared using descriptive statistics, bDMARD discontinuation rates using Kaplan-Meier methods, and proportional hazard models were used to identify predictors of treatment discontinuation. Results Data for 92 and 194 pts prescribed ABA or a TNFi, respectively, as second-line treatment were extracted. No clinically significant differences in baseline characteristics were noted between treatment groups. Most pts were women (76.2%), average age (SD) was 45.1 (13.3) years at diagnosis and disease duration 10.8 (9.0) years. Most pts were stopping an anti-TNF agent: 97% of those who were switched to ABA and 83% of those who were prescribed a second anti-TNF. Overall, 77.6% of pts stopped their first bDMARD after >6 months of treatment (secondary failure). Significant differences in retention between ABA and TNFi groups (log-rank p=0.0002) were observed (Table, Figure). Results remained unchanged for pts treated with TNFi only in first line, and primary/secondary failure of the first bDMARD did not affect sustainability of the second agent. Lack of efficacy (57.7%) and AEs (16.5%) were the most commonly cited reasons for treatment discontinuation. Conclusions Abatacept has better sustainability over a second line TNFi in RA patients having failed one prior bDMARD. Disclosure of Interest D. Choquette Consultant for: BMS, Speakers bureau: BMS, L. Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Celgene, Lilly, Novartis, E. Alemao Shareholder of: BMS, Employee of: BMS, B. Haraoui Grant/research support from: BMS, Janssen, Roche, Consultant for: Abbvie, Amgen, BMS, Celgene, Janssen, Merck, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Pfizer, UCB, F. Massicotte: None declared, M. Mtibaa Shareholder of: BMS, Employee of: BMS, E. Muratti Employee of: BMS, J.-P. Pelletier: None declared, R. Postema Shareholder of: BMS, Employee of: BMS, J.-P. Raynauld Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Sanofi, Novartis, UCB, M.-A. Remillard: None declared, D. Sauvageau: None declared, A. Turcotte Consultant for: Amgen, Abbvie, BMS, Celegene, Janssen, Roche, Pfizer, Lilly, Novartis, Merck, Sanofi, UCB, Speakers bureau: Amgen, Abbvie, BMS, Celegene, Janssen, Roche, Pfizer, Lilly, Novartis, Merck, Έ. Villeneuve Speakers bureau: Abbvie, Roche, BMS Consultant - Celgene, Cimzia, Pfizer, L. Coupal: None declared

Background Sustainability of treatment is important to consider when selecting a therapy for chronic conditions such as RA. Sustainability is a useful clinical marker for both long-term efficacy and safety. A recently published randomized controlled trial has demonstrated similar efficacy and safety profiles between abatacept (ABA) and adalimumab over 2 years. 1,2 Objectives To assess the long-term sustainability of ABA and anti-TNFs following treatment failure with a conventional synthetic DMARD (csDMARD) in comparable cohorts of patients (pts) with RA. Methods Data from pts with RA seen at two tertiary centres and prescribed either ABA or a TNF inhibitor (adalimumab, certolizumab, etanercept, golimumab or infliximab) as their first biologic (b)DMARD after 1 January 2006 were extracted from the RHUMADATA® registry. The choice of therapy was a joint decision between the pt and the treating physician. Pts were followed until either they discontinued treatment, were lost to follow-up or the cut-off date of 9 January 2017. Pt baseline characteristics were compared using descriptive statistics and the cumulative incidence of biologic agent discontinuation using Kaplan-Meier methods. Overall differences in the discontinuation rates of biologic agents were tested using the log-rank test. Results Overall, 641 pts met study criteria; 82 pts received ABA and 559 TNF inhibitors (adalimumab=136, certolizumab=52, etanercept=226, golimumab=88 and infliximab=57) as first-line treatment following inadequate response to csDMARDs. No clinically significant differences in baseline characteristics were noted between treatment groups. Most pts were diagnosed after January 2000 (72.5%) and were women (77.5%). Average age at diagnosis was 47.1 (SD=13.4) years, with a mean disease duration of 7.2 (7.8) years, and a mean CDAI of 43.1 (32.5) at baseline. No significant differences in retention rates were observed in the ABA and anti-TNF groups (Table, Figure). On average, pts treated with anti-TNFs and ABA maintained their treatment for 1.59 (1.91) and 1.90 (2.08) years, respectively. Lack of efficacy (47.6%) and adverse effects (22.0%) were the most commonly cited reasons for treatment discontinuation. Conclusions Abatacept and TNF inhibitors demonstrate similar sustainability at 8-year, supporting studies 1,2 that demonstrate that abatacept used after csDMARDs inadequate response is as safe and effective as a TNF targeting agents in the long term. References Schiff M, et al. Ann Rheum Dis 2014;73:86–94. Schiff M, et al. Ann Rheum Dis 2008;67:1096–1103. Disclosure of Interest D. Choquette Consultant for: BMS, Speakers bureau: BMS, L. Bessette Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Consultant for: BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Celgene, Lilly, Novartis, E. Alemao Shareholder of: BMS, Employee of: BMS, B. Haraoui Grant/research support from: BMS, Janssen, Roche, Consultant for: Abbvie, Amgen, BMS, Celgene, Janssen, Merck, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Pfizer, UCB, F. Massicotte: None declared, M. Mtibaa Shareholder of: BMS, Employee of: BMS, E. Muratti Employee of: BMS, J.-P. Pelletier: None declared, R. Postema Shareholder of: BMS, Employee of: BMS, J.-P. Raynauld Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Sanofi, Novartis, UCB, M.-A. Remillard: None declared, D. Sauvageau: None declared, A. Turcotte Consultant for: Amgen, Abbvie, BMS, Celegene, Janssen, Roche, Pfizer, Lilly, Novartis, Merck, Sanofi, UCB, Speakers bureau: Amgen, Abbvie, BMS, Celegene, Janssen, Roche, Pfizer, Lilly, Novartis, Merck, Έ. Villeneuve Consultant for: Celgene, Cimzia, Pfizer, Speakers bureau: Abbvie, Roche, BMS, L. Coupal: None declared

Objective 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. Methods Biologics-naive RA patients from the Biologic Treatment Registry Across Canada were stratified based on their enrollment year. Effectiveness was assessed with the changes in clinical/laboratory parameters and patient-reported outcomes and the achievement of minimal disease activity and remission. Safety was assessed with the incidence of treatment-emergent adverse events (AEs). Results Among 628 patients, 45.9%, 34.6%, and 19.6% were enrolled between 2002–2005, 2005–2008, and 2008–2011, respectively. Patients recruited in more recent years had significantly lower Disease Activity Score with a 28-joint count using the C-reactive protein level (DAS28-CRP), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), swollen joint count in 28 joints, tender joint count in 28 joints, physician's global assessment of disease activity, patient's global assessment of disease activity, Health Assessment Questionnaire disability index, pain, erythrocyte sedimentation rate, and CRP level (P < 0.01 for all). Patient management also changed with a trend to initiate infliximab after failure of fewer disease-modifying antirheumatic drugs (DMARDs). Six-month treatment with infliximab resulted in statistically significant and clinically important improvements in all disease parameters examined, which were sustained over 36 months. The cumulative probability of achieving remission by 36 months, as defined by the DAS28, SDAI, and CDAI, was 56.2 (95% confidence interval [95% CI] 47.8–64.8), 31.0 (95% CI 23.8–39.8), and 36.2 (95% CI 28.5–45.3), respectively, which was significantly greater in patients with lower baseline disease activity. The profile and incidence of AEs were comparable to data previously reported for tumor necrosis factor α inhibitors. Conclusion RA patient characteristics at infliximab initiation changed over time toward lower disease activity. Furthermore, a trend to treat patients with fewer DMARDs before initiation of infliximab was observed. However, treatment with infliximab was effective in significantly reducing disease activity independent of the treatment initiation year.

Objective To predict, using clinical and qMRI data, the incidence of total knee replacement (TKR) during the long-term follow-up of knee osteoarthritis (OA) patients who formerly received chondroitin sulfate (CS) or placebo treatment. Design A post hoc intention-to-treat analysis to evaluate the incidence of TKR was done on knee OA patients who had participated in a 12-month trial evaluating the impact of CS (800 mg/d) versus placebo for 6 months, followed by a 6-month open-phase in which all patients received CS. Additionally, the clinical and qMRI predictors of TKR were determined. Results Thirteen TKRs were performed in the population after a 4-year follow-up. More TKRs were performed in the placebo group than in the CS group (69% vs. 31%, P = 0.150, logistic regression). The statistically significant predictors of TKRs were, at baseline, higher WOMAC pain and function scores, presence of bone marrow lesions (BMLs), and higher C-reactive protein levels. Loss of medial cartilage volume and increase in WOMAC pain and function at one-year were also predictors of TKR. Multivariate analyses revealed that baseline presence of BML and higher WOMAC pain score were independent predictors. Time to occurrence of the TKR also favored the CS group versus placebo (log-rank, P = 0.094). Conclusion Symptoms such as knee pain and function, presence of BML, and cartilage volume loss predict the long-term occurrence of a “hard” outcome such as TKR.

Every pound of aluminum or aluminum alloys cast and sold is certified to meet The Aluminum Association Inc. registered limits or other specified composition limits. Certification of aluminum and aluminum alloys to specified composition limits is typically done using Spark-Atomic Emission Spectrometry (Spark-AES) following the procedures in ASTM International (ASTM) E716 Standard Practices for Sampling and Sample Preparation of Aluminum and Aluminum Alloys for Determination of Chemical Composition by Spectrochemical Analysis and ASTM E1251 Standard Test Method for Analysis of Aluminum and Aluminum Alloys by Spark–AES. Spark-AES laboratories at major aluminum production facilities normally have excellent analytical practices and follow strict quality control protocols to provide the best results possible. However, every measurement has an associated uncertainty and the measurement of composition using Spark-AES is no exception to the rule. This paper provides a brief discussion of: 1. The uncertainty inherent in the elemental analysis of aluminum and aluminum alloys by Spark-AES. 2. The benefits of using guard bands to set internal operating limits, which are offset from specified composition limits. 3. A model of the risk for sale of out-of-specification product based on the analysis uncertainty relative to the specified composition limits. 4. The main sources of uncertainty of Spark-AES and their potential causes.

Objective To identify predictive factors for total knee replacement (TKR) using data from MRI of knee osteoarthritis patients in a phase III multicentre diseasemodifying osteoarthritis drug (DMOAD) study. Methods Knee osteoarthritis patients from a 2-year clinical trial evaluating licofelone versus naproxen were investigated for the incidence of TKR of the study knee. Patients (n=161) who completed the study according to protocol were selected. Incidence of TKR was assessed blindly to the treatment following telephone interviews (n=123). Results 18 TKR (14.6%) were performed in 4–7 years following enrolment in the original study. More TKR were performed within the naproxen than the licofelone group (61% vs 39%, p=0.232). Baseline score of bone marrow lesions (BML) in the medial compartment (p=0.0001), medial joint space width (JSW) as assessed by standardised radiographs (p=0.0008), presence of severe medial meniscal tear (p=0.004), medial meniscal extrusion (p=0.013), and C-reactive protein level (p=0.049) were strong predictors of TKR. Changes at the end of the study also yielded strong predictors: change in cartilage volume of the medial compartment (p=0.005) and of the global knee (p=0.034), reduction in the JSW of greater than 7% (p=0.009), and WOMAC pain (p=0.009) and function (p=0.023) scores. Multivariate analysis showed that baseline severe medial meniscal tear (p=0.023) and presence of medial BML (p=0.025) were the strongest independent long-term predictors of TKR. Conclusion This study shows that in the context of osteoarthritis trials, clinical data and structural changes identifi ed by MRI allow prediction of a ‘hard’ outcome such as TKR. The fi ndings support the usefulness and predictive value of MRI in defi ning study outcome in DMOAD trials.

Objectives The aim of the study was to evaluate by quantitative magnetic resonance imaging the effect of celecoxib 200 mg daily on cartilage volume loss over 12 months in knee osteoarthritis. Methods The primary outcome of this study was to evaluate cartilage volume loss in the medial compartment of the knee (femoral condyle and tibial plateau) assessed by quantitative magnetic resonance imaging on subjects receiving continuous treatment with celecoxib 200 mg daily for 12 months compared with a modelized historical control cohort, as expressed by the percentage loss from baseline. Safety of the medication was also assessed. Comparison of the observed volume loss to the expected loss was evaluated by a multivariate linear regression model based on a historical cohort. Results For the primary outcome, the 95% confidence intervals for the mean observed celecoxib cohort joint medial compartment cartilage volume loss (6.81% [6.01; 7.60]) and mean predicted loss (modelized historical cohort) (5.65% [5.10; 6.19]) overlap, indicating no significant difference and hence no effect of celecoxib on the medial compartment cartilage volume loss. Similar findings were demonstrated for the lateral compartment cartilage loss. The safety data reported several minor adverse events similar to those typically seen in a 1-year clinical trial. Conclusions Although celecoxib was demonstrated to be safe for knee osteoarthritis at a 200 mg daily dose, it did not provide a protective effect on knee cartilage loss. Cohort modelization is an efficient and unbiased way to provide a comparator group for the assessment of novel treatments when classic head-to-head randomized controlled trials are not feasible.

ObjectivesTo explore the impact of disease-modifying osteoarthritis drug (DMOAD) treatment on biomarker levels and their correlation with cartilage volume loss and disease symptoms in a 2-year phase III clinical trial in patients with knee OA.Methods161 patients with knee OA (according-to-protocol population) were selected from a 2-year DMOAD trial studying the effect of licofelone (200 mg twice daily) versus naproxen (500 mg twice daily). Clinical evaluation of patients was carried out using the Western Ontario and McMaster Universities (WOMAC) questionnaire. Biomarker measurements of matrix metalloproteinase (MMP)-1, MMP-3, interleukin (IL)-6, C reactive protein (CRP), cartilage oligomeric matrix protein (COMP) and type I collagen C-terminal telopeptide (CTX-I) in serum, type II collagen C-terminal telopeptide (CTX-II) in urine, and knee MRI were performed at baseline and 2 years.ResultsOver time an increase occurred in all biomarker levels with the exception of IL-6, CRP and CTX-II which decreased. The increase in MMP-1 and MMP-3 was significantly less (p=0.05; pConclusionHigher baseline values of IL-6, CRP and COMP are predictive of greater risk of cartilage loss in OA. However, over time a reduction in MMP-1 and MMP-3 levels correlated best with reduction in cartilage volume loss and the effect of drug treatment. Baseline CRP was found to be a good predictor of the symptomatic response to treatment.

Objective To compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging (MRI) in patients with active ankylosing spondylitis (AS). Methods This was a randomized, multicenter, double-blind, placebo-controlled study. Patients (n = 82) received 40 mg adalimumab or placebo every other week during an initial 24-week double-blind period. MRIs of both the spine and SI joints were obtained at baseline, week 12, and week 52. Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. Results The spine SPARCC score in placebo-treated patients increased by a mean of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab-treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of 12.7% from baseline in placebo-treated patients and by 52.9% in adalimumab-treated patients (P = 0.017). The response in adalimumab-treated patients was maintained at week 52. Placebo-treated patients were switched to open-label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52. Similar large reductions in the spine and SI joint SPARCC scores were noted, even in patients who failed to meet the ASsessment in Ankylosing Spondylitis (International Working Group) criteria (nonresponders) at 12 weeks. In adalimumab-treated patients, a reduced C-reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score (P = 0.018). Conclusion Adalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment, and these improvements were maintained for up to 52 weeks.

Objective We previously reported that patients with systemic lupus erythematosus (SLE) in the US incurred ∼19% and 12% higher direct medical costs than patients in Canada and the UK, respectively, without experiencing superior outcomes expressed as disease damage or quality of life. In the present study, we compared cumulative indirect costs over 4 years in these patients. Methods A total of 715 patients with SLE (269 US, 231 Canada, 215 UK) were surveyed semiannually for 4 years on employment status and time lost from labor and nonlabor market activities. Cross-country comparisons of indirect costs were performed. Results In the US, Canada, and the UK, mean 4-year cumulative indirect costs (95% confidence interval [95% CI]) due to diminished labor market activity were $56,745 ($49,919, $63,571), $38,642 ($32,785, $44,500), and $42,213 ($35,859, $48,567), respectively, and cumulative indirect costs due to diminished nonlabor market activity were $5,249 ($2,766, $7,732), $5,455 ($3,290, $7,620), and $8,572 ($5,626, $11,518), respectively. Regression results showed that cumulative indirect costs (95% CI) due to diminished labor market activity in the US were $6,750 ($580, $12,910) greater than in Canada and $10,430 ($4,050, $16,800) greater than in the UK. Indirect costs due to diminished nonlabor market activity in the US were $280 (−$2,950, $3,520) less than in Canada and $2,010 (−$1,490, $5,510) less than in the UK, both results insignificant due to wide CIs. Conclusion Despite American patients incurring greater direct medical costs than Canadian and British patients, they do not experience superior health outcomes in terms of less productivity loss in either labor market or nonlabor market activities.

Objectives: To study the association between two common polymorphisms in the peroxisome proliferator-activated receptor γ ( PPARγ ) gene and susceptibility to, and severity of, osteoarthritis in a French-Canadian population. Methods: Genomic DNA was obtained from 172 patients with osteoarthritis and 210 ethnically matched healthy controls. Genotyping for the polymorphisms in the PPARγ gene (Pro12Ala and C1431T) was carried out using polymerase chain reaction–restriction fragment length polymorphism. The standard Kellgren–Lawrence grading score and the French version of the Western Ontario and McMaster Universities Osteoarthritis Index were used to assess the radiological and functional severity of the disease. Estimated haplotypes were generated using the expectation maximisation algorithm. Genotype and allele frequencies were analysed using the χ 2 test. Results: Genotype and allele frequencies for either polymorphism in the PPARγ gene did not differ significantly between patients with osteoarthritis and controls. Moreover, no significant differences were observed after stratification of patients according to age at disease onset, radiological or functional severity. Similarly, haplotype analysis of both polymorphisms in the PPARγ gene showed no association of any haplotype with susceptibility to, or severity of, osteoarthritis. Conclusion: These findings suggest that the examined polymorphisms in the PPARγ gene do not contribute to susceptibility to, or severity of, osteoarthritis in the French-Canadian population.

Purpose We examined whether a continuing medical education intervention increased general practitioners' ability to select the proper pharmacological treatment for patients with osteoarthritis. Subjects and methods Eight towns in Quebec, Canada were randomly allocated to one of four intervention options, workshop and decision tree, workshop, decision tree, or no intervention. All general practitioners practicing in each town were eligible to participate. We evaluated all dispensed prescriptions for either a cyclooxygenase (COX)-2 inhibitor, nonselective nonsteroidal anti-inflammatory drug or acetaminophen written by eligible general practitioners between May 2000 and June 2001 to elderly patients suffering from osteoarthritis. We used a multi-level Bayesian hierarchical model to assess the impact of the interventions on prescription adequacy. Results We analyzed 5318 dispensed prescriptions written by 249 general practitioners in the five-month preintervention period and 4610 dispensed prescriptions written by the same physicians in the five-month postintervention period. A score of zero or one was given to every prescription, with one indicating prescription adequacy according to guidelines provided during the interventions. Bayesian hierarchical models showed some improvement in scores in the post- versus preintervention periods in all four groups. The probability of an improvement in the towns allocated the workshop and decision tree over the control was 94%, compared with 74% in the workshop group and 55% in the decision tree group. Conclusion An interactive approach offered by peers and complemented by easy to use guidelines may enhance the general practitioner's ability to manage osteoarthritis patients.

Objective. We have shown that SLE patients in Canada and the UK incurred 20% and 13% lower health costs than those in the US, respectively, but did not experience worse outcomes as expressed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. We now compare change in quality of life in these patients. Patients and methods. Seven hundred and fifteen SLE patients (Canada 231, US 269, UK 215) completed the SF-36 annually over four years. The annual change in the SF-36 Physical and Mental Component Summary (PCS and MCS) scores over the course of the study were summarized by estimating a linear trend for each individual patient using hierarchical modelling. Cross-country comparison of the slopes in the PCS and MCS scores was then performed using simultaneous regressions. Results. The estimated mean annual changes (95% credible interval [CrI]) in the PCS scores in Canada, the US, and the UK were 0.18 (� 0.07, 0.43), � 0.05 (� 0.27, 0.17), and 0.03 (� 0.20, 0.27), respectively; the mean annual changes in the MCS scores were 0.15 (� 0.04, 0.34), 0.23 (0.09, 0.37), and 0.08 (� 0.10, 0.27), respectively. Regression results showed that the mean annual changes in PCS and MCS scores did not substantially differ across countries. Conclusion. Quality of life remained stable across countries. Despite Canadian and British patients incurring lower health costs, on average, patients experienced similar changes in physical and mental well-being.

CURATA is a multifaceted continuing medical education (CME) intervention, developed with input from 12 healthcare organizations to address the gap between current and recommended osteoarthritis (OA) treatment of general practitioners in Québec, Canada. Focusing on appropriate prescription of non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 selective inhibitors (coxibs), the intervention comprised small-group, case-based workshops modelled after the Script Concordance test, and a decision tool reflecting current evidence-based clinical practice guidelines. A self-reported questionnaire measured knowledge of recommended OA treatment on an eight-point scale. Participants (n = 381) showed a mean 10.1% improvement in questionnaire score immediately following the workshop (15.2% improvement relative to mean pre-workshop score). Knowledge was maintained for three months post-workshop.

Objective To evaluate the change in osteoarthritic (OA) knee cartilage volume over a two-year period with the use of magnetic resonance imaging (MRI) and to correlate the MRI changes with radiologic changes. Methods Thirty-two patients with symptomatic knee OA underwent MRI of the knee at baseline and at 6, 12, 18, and 24 months. Loss of cartilage volumes were computed and contrasted with changes in clinical variables for OA and with standardized semiflexed knee radiographs at baseline at 1 and 2 years. Results Progression of cartilage loss at all followup points was statistically significant (P 15% of global cartilage loss; n = 11) over the 2 years of study. At baseline, there was a greater proportion of women (P = 0.001), a lower range of motion (P = 0.01), a greater circumference and higher level of pain (P = 0.05) and stiffness in the study knee, and a higher body mass index in the fast progressor group compared with the slow progressor group. No statistical correlation between loss of cartilage volume and radiographic changes was seen. Conclusion Quantitative MRI can measure the progression of knee OA precisely and can help to identify patients with rapidly progressing disease. These findings indicate that MRI could be helpful in assessing the effects of treatment with structure-modifying agents in OA.

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.

mg/day diacerein (50 mg twice daily) was significantly superior (P < 0.05) to placebo using the primary criterion (visual analog scale [VAS] assessment of pain on movement). Significant improvement (P < 0.05) was also observed for the secondary criteria, which included the Western Ontario and McMaster Universities OA Index (WOMAC), the WOMAC subscores, and the VAS assessment of handicap. In patients treated with diacerein dosages of 50 mg/day and 150 mg/day, favorable but not significant results were observed for the primary criterion. The best daily dosage of diacerein, calculated from the effect on the VAS assessment of pain on movement, was 90.1 mg. In the per-protocol population, the analysis of the primary criterion showed significant dose-dependent differences (P < 0.05) between each of the 3 diacerein dosages and the placebo. No differences were observed among the 3 diacerein groups. A significantly higher incidence (P < 0.05) of adverse events (AEs), as well as a higher rate of dropoout due to AEs, was observed in patients treated with 150 mg/day diacerein versus those treated with placebo, 50 mg/day diacerein, or 100 mg/day diacerein. Mild-to-moderate transient changes in bowel habits were the most frequent AEs, increasing with the dosage. Conclusion. Diacerein, a drug for the treatment of OA, was shown to be an effective treatment for symptoms in patients with knee OA. Taking into account both efficacy and safety, the optimal daily dosage of diacerein for patients with knee OA is 100 mg/day (50 mg twice daily).

Objective As part of an ongoing study of health resource utilization and diminished productivity in patients with systemic lupus erythematosus (SLE), the use of alternative medical therapies was assessed. Methods A cohort of 707 patients with SLE from 3 countries completed questionnaires on demographics, social support, health status (using the Short Form 36 health survey), satisfaction with health care, health resource utilization (conventional resources and alternative therapies), and time losses in labor market and non–labor market activities. Annual direct and indirect costs (1997 Canadian dollars) were calculated and compared for users and nonusers of alternative medical therapies. Results Among the 707 patients, 352 (49.8%) were found to use alternative therapies and at similar rates across Canada, the United States, and the United Kingdom. Users were younger and better educated than nonusers, exhibited poorer levels of self-rated health status and satisfaction with medical care, and had minimal to no objective evidence of worse disease (according to the revised Systemic Lupus Activity Measure instrument). The mean of log direct medical costs for conventional resources was higher for users of select alternative therapies compared with nonusers. In a logistic regression, neither the number of alternative therapies used nor the individual therapy increased the probability of incurring indirect costs. Conclusion The use of alternative medical therapies is common in patients with SLE. Users of many alternative medical therapies accrue greater conventional medical costs compared with nonusers. The use of alternative medical therapy may be a marker for care-seeking behavior associated with higher consumption of conventional medical resources in the absence of demonstrable additional morbidity and should be considered in future cost analyses of patients with SLE.

Objective To identify determinants of mental and physical health as a function of disease state in patients with systemic lupus erythematosus (SLE). Methods A sample of 129 SLE patients (mean age 42.01 years; SD 11.09) was recruited from 9 immunology/rheumatology clinics across Canada. Patients completed questionnaires assessing psychological distress, social support, coping, stress, and health-related quality of life. Physicians rated disease activity (using the revised Systemic Lupus Activity Measure; SLAM-R) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). Mental and physical health composite scores were derived from the Medical Outcomes Study Short Form 36. Patients were subdivided into more active (SLAM-R ≥ 10; n = 38) or less active disease states (n = 91). Results Better mental health was predicted by more education and less emotion-oriented coping in the patients in a more active disease state (P = 0.0001; R2 = 0.46). Better mental health was predicted by less stress, less emotion-oriented coping, and more task-oriented coping in patients during a less active disease state (P = 0.0001; R2 = 0.45). Better physical health was predicted by more emotion-oriented coping in patients in a more active disease state (P = 0.04; R2 = 0.11). Better physical health was predicted by less stress and younger age in patients during a less active disease state (P = 0.0001; R2 = 0.20). Conclusion The positive association between emotion-oriented coping and better physical health in patients during a more active disease state suggests that this style of coping may be more adaptive in situations that are considered uncontrollable (e.g., SLE flare). Predictors of mental health were similar to those found in the literature, especially for SLE patients in a less active disease state.

A biosimilar is intended to be highly similar to a reference biologic such that any differences in quality attributes (i.e., molecular characteristics) do not affect safety or efficacy. Achieving this benchmark for biologics, especially large glycoproteins such as monoclonal antibodies, is challenging given their complex structure and manufacturing. Regulatory guidance on biosimilars issued by the U.S. Food and Drug Administration, Health Canada and European Medicines Agency indicates that, in addition to a demonstration of a high degree of similarity in quality attributes, a reduced number of nonclinical and clinical comparative studies can be sufficient for approval. Following a tiered approach, clinical studies are required to address concerns about possible clinically significant differences that remain after laboratory and nonclinical evaluations. Consequently, a critical question arises: can clinical studies that satisfy concerns regarding safety and efficacy in one condition support “indication extrapolation” to other conditions? This question will be addressed by reviewing the case of a biosimilar to infliximab that was approved recently in South Korea, Europe, and Canada for multiple indications through extrapolation. The principles discussed should also apply to biosimilars of other monoclonal antibodies that are approved to treat multiple distinct conditions.