One-year risk of serious infection in patients treated with certolizumab pegol as compared with other TNF inhibitors in a real-world setting: data from a national U.S. rheumatoid arthritis registry

Srihari Jaganathan,Joel M. Kremer,Jeffrey Stark,Heather J. Litman,Bernice Gershenson,Kimberly J. Dandreo,Mohamed Yassine,Katherine C. Saunders,Jeffrey D. Greenberg,Robert Low,Robert Suruki,Leslie R. Harrold

doi:10.1186/s13075-017-1496-5

Abstract

BackgroundRegistry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias. Comparing safety outcomes without accounting for channeling bias can lead to inaccurate comparisons between TNFi prescribed at different stages of the disease. In the present study, we examined the incidence of serious infection and other adverse events during certolizumab pegol (CZP) use vs other TNFi in a U.S. RA cohort before and after using a methodological approach to minimize channeling bias.MethodsPatients with RA enrolled in the Corrona registry, aged ≥ 18 years, initiating CZP or other TNFi (etanercept, adalimumab, golimumab, or infliximab) after May 1, 2009 (n = 6215 initiations), were followed for ≤ 12 months. A propensity score (PS) model was used to control for baseline characteristics associated with the probability of receiving CZP vs other TNFi. Incidence rate ratios (IRRs) of serious infectious events (SIEs), malignancies, and cardiovascular events (CVEs) in the CZP group vs other TNFi group were calculated with 95% CIs, before and after PS matching.ResultsPatients were more likely to initiate CZP later in the course of therapy than those initiating other TNFi. CZP initiators (n = 975) were older and had longer disease duration, more active disease, and greater disability than other TNFi initiators (n = 5240). After PS matching, there were no clinically important differences between CZP (n = 952) and other TNFi (n = 952). Before PS matching, CZP was associated with a greater incidence of SIEs (IRR 1.53 [95% CI 1.13, 2.05]). The risk of SIEs was not different between groups after PS matching (IRR 1.26 [95% CI 0.84, 1.90]). The 95% CI of the IRRs for malignancies or CVEs included unity, regardless of PS matching, suggesting no difference in risk between CZP and other TNFi.ConclusionsAfter using PS matching to minimize channeling bias and compare patients with a similar likelihood of receiving CZP or other TNFi, the 1-year risk of SIEs, malignancies, and CVEs was not distinguishable between the two groups.

Highlights

Registry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias
Among all initiators, on average, patients initiating certolizumab pegol (CZP) were older, had longer disease duration, had more active disease based on the Clinical Disease Activity Index (CDAI), and had more functional impairment based on the modified Health Assessment Questionnaire than patients in the other TNFi group (p ≤ 0.01) (Table 2)
Body mass index (BMI), age at RA onset, and the prevalence of comorbidities were balanced between groups (Table 2), as were rheumatoid factor positivity, anticitrullinated protein antibody positivity, smoking status, and blood pressure

Summary

Introduction

Registry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias. Comparing safety outcomes without accounting for channeling bias can lead to inaccurate comparisons between TNFi prescribed at different stages of the disease. We examined the incidence of serious infection and other adverse events during certolizumab pegol (CZP) use vs other TNFi in a U.S RA cohort before and after using a methodological approach to minimize channeling bias. Tumor necrosis factor inhibitors (TNFi), often the first class of biologic therapy prescribed to patients with RA, have been demonstrated to reduce disease activity and improve clinical, radiographic, and functional outcomes [6]. Effective control of disease activity with TNFi has been linked with a reduced risk of cardiovascular disease [7, 8]. The impact of TNFi on the incidence of cancer is unclear [11, 22,23,24,25]

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Results

Discussion

Conclusion