OBJECTIVE:To characterize the long-term incidence of infection in patients with rheumatoid arthritis (RA) treated with subcutaneous golimumab (GOL) in Canadian routine care, assess the effect of infections on GOL retention, and explore factors associated with infection incidence.METHODS:Patients with RA enrolled in the Biologic Treatment Registry Across Canada (BioTRAC) initiating GOL treatment were included. The incidence density rates (IDRs) of total infection (TI), serious infection (SI), and nonserious infection (NSI) were calculated for the overall follow-up (90 months) and by 6-month intervals. Determinants of infection over time or within the first 6 months were explored using generalized estimating equation models and logistic regression, respectively.RESULTS:Five hundred thirty patients were included; mean baseline age was 57.7 years and RA duration was 8.0 years. Over an average follow-up of 27.0 months, the IDR for TIs was 35.1 events per 100 person-years (PYs), the majority occurring during the first 6 months; IDRs for NSIs and SIs were 32.9 and 2.2 events per 100 PYs, respectively. No predictors were identified for infection incidence within 6 months. Comorbid pulmonary disease was associated with significantly higher odds of TIs and NSIs over time, whereas higher age and high corticosteroid (CS) dose (> 5 mg/day) predicted higher odds of SIs. Incidence of SIs, but not NSIs, was associated with significantly higher odds of GOL discontinuation.CONCLUSION:Long-term GOL treatment was associated with relatively low infection rates, most being nonserious and occurring during the first 6 months. Pulmonary disease, higher age, and high CS dose were identified as significant predictors of infections. SIs, but not NSIs, predicted higher odds of GOL discontinuation. (ClinicalTrials.gov: NCT00741793).

ObjectivesTo (i) determine whether sustained disease activity states, as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), impact function, and (ii) evaluate characteristics predicting sustained low functional impairment in a prospective axial spondyloarthritis (axSpA) cohort.MethodsBiologic Treatment Registry Across Canada (BioTRAC) was a multi-center, prospective registry that collected real-world data on axSpA patients receiving infliximab or golimumab between 2006 and 2017. Generalized estimating equations (GEE) were used to test baseline characteristics, treatment, and duration (at 6 and 12 months vs. only at 6 or 12 months vs. neither) of low BASDAI (< 3), ASDAS-inactive disease (ID)(< 1.3), and ASDAS-low disease activity (LDA) in predicting sustained low Bath Ankylosing Spondylitis Functional Index (BASFI)(< 3) between 12 and 18 months. The adjusted impact of achieving low disease state at 6 and/or 12 months on BASFI at 18 months was analyzed by generalized linear models.ResultsEight hundred ten patients were enrolled. 33.7%, 13.4%, and 24.7% achieved sustained low BASDAI, ASDAS-ID, and ASDAS-LDA, respectively. In univariable GEE of baseline variables, age and baseline BASDAI, BASFI, and ASDAS significantly predicted sustained low BASFI. In multivariable GEE, sustained low BASDAI (p < 0.001), low BASDAI only at 6 or 12 months (p = 0.001), and baseline BASFI (p < 0.001) were the only predictors of sustained low BASFI. Sustained ASDAS-ID (p = 0.040) and ASDAS-LDA (p < 0.001) were also predictors when forced into the model. Similar results were obtained when evaluating the BASFI score at 18 months.ConclusionSustained BASDAI < 3 may be a valid and feasible target for a treat-to-target strategy in axSpA having function as treatment goal.

BackgroundAlthough biologic use in rheumatoid arthritis (RA) has a well-characterized infections risk factor, most studies evaluating this association were conducted on first-generation anti-tumor necrosis factor (TNFi) agents or in early years post-drug development (early 2000).ObjectivesTo (i) characterize the long-term incidence of infection in a real-world cohort of RA patients treated with subcutaneous golimumab (GLM) in Canadian routine care; (ii) assess the impact of infections on GLM retention, and (iii) explore factors associated with the risk of infection.MethodsBioTRAC registry was a prospective, multicenter study that collected real-world clinical, laboratory, safety and patient-reported data from TNFi naïve patients or treated with biologics for a period of <6 months before enrolment. This post-hoc analysis included patients with RA who initiated GLM treatment. The incidence density rates (IDR) of total serious (SI) and non-serious (NSI) infections were calculated for the overall follow-up (90 months) period as well as by 6-month interval. Time to first infection and time to treatment discontinuation were assessed with the Kaplan-Meier estimator of the survival function. Determinants of infection over time or within the first 6 months were explored using generalized estimating equation models and logistic regression, respectively.Results530 patients were included with a mean (SD) age of 57.7 (13.0) years and disease duration of 8.0 (8.3) years. Of these, 404 (76.2%) were females, 74 (14.0%) were treated with ≤15mg/week MTX, 280 (52.8%) with >15mg/week MTX, while 173 (32.6%) were not on MTX. In terms of corticosteroids (CS), 72 (13.6%) were treated with ≤5mg/day, 63 (11.9%) with >5mg/day, and 391 (73.8%) were not on CS. Diabetes (4.5%), pulmonary disease (8.9%), and renal disease (18.5%) were present.Over a mean follow-up duration of 27.0 months, the IDR for total infections, NSI, and SI was 35.10 events/100 PYs, 32.90 events/100 PYs, and 2.23 events/100 PYs. Median estimated time to first infection was 52.9 months (SI: 84.9 months; NSI: 55.1 months) (Table 1). The incidence of total infections was 44.0, 37.3, 35.1, 29.4, 31.1, 35.7, 19.3 and 7.4 events/100 PYs at 0-6 months, 6-12 months, 12-24 months, 24-36 months, 36-48 months, 48-60 months, 60-72 months, 72-84 months, respectively and no infections between 84-90 months. In terms of determinants, no significant associations were identified for the incidence of infections within the first 6 months. However, presence of pulmonary disease was identified as a significant determinant of total infections (OR [95%CI]: 2.19 [1.36-3.52]) and NSI (2.22 [1.35-3.66]) over time, while higher age (1.08 [1.00-1.26]) and high (≥5 mg/day) CS dose (7.25 [1.12-46.80]) were associated with significantly higher odds of SI. Incidence of SI (6.48 [1.16-36.13]), but not NSI, was associated with significantly higher odds of GLM discontinuation; additional predictors of discontinuation were increased baseline CDAI (1.06 [1.04-1.08]) and use of concomitant MTX at low dose (0.52 [0.30-0.91]) or high dose (0.71 [0.49-1.04]).Table 1.Incidence Density Rate (IDR) by Infection Type.Infection TypeIDR (Events/100 PYs)Median Time to 1st Infection (months)Total Infections35.152.9Non-serious Infections32.984.9Serious Infections2.255.1ConclusionThe infection rates reported with GLM in this cohort are low compared to the rates reported in earlier registry studies with TNFi. Changes in the characteristics of patients starting TNFi (lower disease activity, shorter disease duration, less exposure to CS) in recent years may explain the decreased risk of infection. Compared to the available literature, treatment with GLM was associated with relatively low infection rate. Most infections occurred during the first 6 months of treatment and decreased thereafter. Presence of pulmonary disease, higher age, and higher CS dose were identified as significant predictors of infections. SIs, but not NSIs, were associated with significantly higher odds of treatment discontinuation-TNFi.Disclosure of InterestsLouis Bessette Speakers bureau: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilead, Sandoz, Fresenius Kabi, Teva, Consultant of: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilead, Sandoz, Fresenius Kabi, Teva, Grant/research support from: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilead, Sandoz, Fresenius Kabi, Teva, Proton Rahman Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, John Kelsall: None declared, Jane Purvis: None declared, Emmanouil Rampakakis Consultant of: Janssen, Allen Lehman Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Meagan Rachich Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Francois Nantel Shareholder of: Johnson & Johnson, Employee of: Retiree from Janssen Pharmaceutical Companies of Johnson & Johnson, Marilise Marrache Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Odalis Asin Milan Shareholder of: Johnson & Johnson, Employee of: Employees of Janssen Pharmaceutical Companies of Johnson & Johnson

This retrospective, observational study aimed to analyze and assess adherence, persistence, dosing, and use of concomitant medications of seven self-administered target drugs (abatacept, golimumab, secukinumab, tocilizumab, ustekinumab, apremilast, and tofacitinib) that are currently available in Canada for the treatment of inflammatory arthritis (IA). We used IQVIA’s longitudinal claims databases, which include private drug plans and public plans. Patients with IA identified using a proprietary indication algorithm who initiated treatment with any of the target drugs between January 2015 and February 2019 were selected and followed for 12 months. Golimumab and apremilast had the highest proportion of patients (~ 75%) who were bio-naïve and secukinumab had the fewest bio-naïve patients (~ 43%). The oral therapies, apremilast and tofacitinib, had the lowest percentage of adherent patients (73% and 71%) followed by abatacept (83%), while the remaining drugs had adherence around 90%. Secukinumab and tofacitinib had the highest 12-month persistence rate (63% and 61%), while abatacept and apremilast had the lowest persistence rate (52% and 47%). Oral corticosteroid (OCS) use was not significantly associated with adherence. Tocilizumab, secukinumab, and ustekinumab had the highest proportion of patients (> 20%) with dose escalation at 3–4 months from index. OCS and conventional disease-modifying antirheumatic drugs (cDMARD) use decreased in post-index period across all target drugs. This study identified substantial differences in patient baseline characteristics. Patients on injectable biologics were more likely to be adherent compared with those on oral drugs, possibly owing to longer dosing intervals. Other outcomes at 12 months appeared similar as evidenced by tapering of concomitant medications, although differences in persistence and dose escalation were noted.