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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.

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).

ObjectiveTo describe the rate of concomitant oral corticosteroid use at antitumour necrosis factor (TNF) initiation and at disease remission, and to assess its effect on incidence of infection and sustainability of remission among patients with rheumatoid arthritis (RA) treated with infliximab in Canadian routine care.MethodsBiological naïve patients with RA followed in the Biologic Treatment Registry Across Canada (BioTRAC) were included. The time-dependent association between corticosteroid dose (no use, ≤5 mg/day, >5 mg/day) and the incidence of first infection, while considering possible confounders, remission sustainability and the incidence of subsequent infections were assessed with Cox regression.Results838 patients were included; mean (SD) baseline age and disease duration were 55.6 (13.5) and 10.5 (9.8) years, respectively. After a mean (SD) of 51.3 (43.6) months, the total incidence of adverse events (AEs) and infections were 110.2 and 19.6 per 100 person-years (PY), respectively. In multivariate analysis, the HR (95% CI) for acquiring an infection was 2.48 (1.24 to 4.98) with >5 mg/day of corticosteroids versus no corticosteroids. Similarly, ≤5 mg/day of corticosteroids was associated with increased hazard for infection (2.12 (0.97 to 4.66)). Despite DAS28 (disease activity score 28) or Clinical Disease Activity Index (CDAI) remission, corticosteroids were continued in 16.4% and 16.7% of cases, respectively. Continued corticosteroid treatment was not associated with sustainability of remission (HRDAS28 (95% CI) 1.40 (0.95 to 2.06); HRCDAI 1.19 (0.75 to 1.88)), however, it had a significant impact on development of infection (HRDAS28 (95% CI) 1.78 (1.00 to 3.19); HRCDAI 2.38 (1.14 to 4.99)).ConclusionsOral corticosteroid treatment was associated with increased risk of development of infection without impacting sustainability of remission. These results support the notion that corticosteroids should be used concomitantly with anti-TNF for the shortest period possible to achieve remission, and then tapered.Trial registration numberNCT00741793.

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Background Infliximab (IFX) is a therapeutic monoclonal antibody targeting TNFa indicated in the treatment of a number of chronic inflammatory diseases. IFX is administered by intravenous infusion and may be associated with infusion reactions (IRs). RemiTRAC Infusion was a prospective observational registry conducted in 12 Canadian sites from 2005-2012. Objectives The primary objective of this registry was to describe the types and frequency of IRs to IFX and access factors potentially associated with their incidence. Methods An IR was defined as any AE occurring during the infusion or within 1 hour post-infusion. The primary endpoint was to access factors potentially associated with the incidence of infusion reactions using multilevel logistic regression analysis. Another major secondary endpoint was to assess the effect of pre-infusion medications and concomitant medications on infusion reactions by propensity score adjusted analysis using a Multilevel logistic regression model with the following variables as predictors: Patient age, weight and gender; prior enrolment use of IFX, any prior biologic use; indication; season and year of infusion; patient eligibility; dose; time since the last infusion and number of previous IRs. Results 1632 patients were enrolled and 24,852 infusions were recorded. The majority (63%) of patients in this cohort are treated with IFX for rheumatologic conditions such as RA (40%), AS (18%) and PsA (6%). 201/1632 (12.3%) patients reported at least one IR. Of 24,852 infusions, 322 resulted in an IR (1.3%) and most IRs were mild to moderate in severity (95%). The most common IR was pruritus, occurring in 19.9% of infusion reactions. Flushing (9.9%) and dyspnoea (6.2%) are the only other infusion AEs occurring in ≥5% of IRs. Four serious IRs (fever, itching/flushing, chest pain, chest pain/flushing) and no serious anaphylactic reactions occurred. Multivariate analysis showed that the use of antihistamines as pre-treatment (2.49% vs 1.32%; p<0.0001), number of previous IRs (O.R. 2.04; p<0.001), female gender (2.21% vs 1.49%; p<0.0011), and corticosteroids before enrolment (p=0.0003) were significantly associated with an increase incidence of IRs. There was a negative association with the year of administration (O.R. 0.68; p<0.0001) which could reflect the improved experience of sites over time. Propensity score adjusted analysis showed that the use of any concomitant immunosuppressant or corticosteroids did not influence the incidence of IRs. Anti-histamines (O.R. 1.58; p=0.0007) and steroids (O.R. 1.50; p=0.0057) were associated with an increased incidence of IRs and only the use of acetaminophen monotherapy was associated with a significant reduction in the incidence of IRs (O.R. 0.61; p=0.0426). Conclusions This registry shows that in community-based infusion clinics, IR to IFX are uncommon and largely mild to moderate in nature. Anti-histamines, intravenous steroids and acetaminophen have been widely used as preventative medication but data shown in this registry demonstrate ...

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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-SC- 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-SC 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-SC 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.