AB0357 INCIDENCE AND DETERMINANTS OF INFECTION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH GOLIMUMAB IN REAL-WORLD PRACTICE

Abstract

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