The online version of this article (doi:10.1186/s13075-017-1496-5) contains supplementary material, which is available to authorized users.
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. 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.
Patients 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.
Patients 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.
After 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.
Additional file 1: Modified Charlson comorbidity index. Table S1. Other AEs of interest. (PDF 246 kb)13075_2017_1496_MOESM1_ESM.pdf
Barnabe C, Martin BJ, Ghali WA. Systematic review and meta-analysis: anti-tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011;63(4):522–9. CrossRef
Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford). 2013;52(1):53–61. CrossRef
Galloway JB, Hyrich KL, Mercer LK, et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology (Oxford). 2011;50(1):124–31. CrossRef
Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2016;5:CD012183.
Burmester GR, Panaccione R, Gordon KB, et al. Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis. 2013;72(4):517–24. CrossRefPubMed
FDA. Cimzia (certolizumab pegol) Prescribing Information; last updated April 2016. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125160s241lbl.pdf. Last accessed: September 2016.
Kremer JM. The CORRONA database. Clin Exp Rheumatol. 2005;23(5 Suppl 39):S172–7. PubMed
Curtis JR, Patkar NM, Jain A, et al. Validity of physician-reported hospitalized infections in a US arthritis registry. Rheumatology (Oxford). 2009;48(10):1269–72. CrossRef
Emery P, Gallo G, Boyd H, et al. Association between disease activity and risk of serious infections in subjects with rheumatoid arthritis treated with etanercept or disease-modifying anti-rheumatic drugs. Clin Exp Rheumatol. 2014;32(5):653–60. PubMed
Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2:CD008794.
Silva-Fernández L, Lunt M, Kearsley-Fleet L, et al. The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis. Rheumatology (Oxford). 2016;55(11):2033–9. CrossRef
Morgan CL, Emery P, Porter D, et al. Treatment of rheumatoid arthritis with etanercept with reference to disease-modifying anti-rheumatic drugs: long-term safety and survival using prospective, observational data. Rheumatology (Oxford). 2014;53(1):186–94. CrossRef
Mercer LK, Green AC, Galloway JB, et al. The influence of anti-TNF therapy upon incidence of keratinocyte skin cancer in patients with rheumatoid arthritis: longitudinal results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2012;71(6):869–74. CrossRefPubMedPubMedCentral
Turesson C. Comorbidity in rheumatoid arthritis. Swiss Med Wkly. 2016;146:w14290. PubMed
Curtis JR, Chen L, Bharat A, et al. Linkage of a de-identified United States rheumatoid arthritis registry with administrative data to facilitate comparative effectiveness research. Arthritis Care Res (Hoboken). 2014;66(12):1790–8. CrossRef
- 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
Leslie R. Harrold
Heather J. Litman
Katherine C. Saunders
Kimberly J. Dandreo
Jeffrey D. Greenberg
Joel M. Kremer
- BioMed Central
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