Real-life drug survival of tumour necrosis factor-α antagonists in inflammatory arthritis

Hamilton, Stefan (2014) Real-life drug survival of tumour necrosis factor-α antagonists in inflammatory arthritis. Masters thesis, Memorial University of Newfoundland.

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Abstract

Introduction: Inflammatory arthritis is a spectrum of diseases arising from immune dysregulation in the body causing pain, stiffness, swelling, and tenderness in the joints. In severe cases, it can lead to permanent joint damage and even total joint destruction. Due to incomplete understanding of its pathogenesis, management has classically been directed at relieving symptoms in the short term, with little to no treatment capable of stemming the long-term progression of joint damage. Recently, tumor necrosis factor-α (TNF-α) antagonists (or simply, “anti-TNFs”) have revolutionized inflammatory arthritis treatment because of their ability to act on the molecules driving joint inflammation. As a result, most inflammatory arthritis patients treated with these agents have significant reductions in disease activity. Although randomized controlled trials (RCTs) have been instrumental in demonstrating this effect, observational studies on the effectiveness and sustainability of anti-TNFs have been lacking. Such studies add value by ascertaining the long-term effects of an intervention in a highly generalizable population; in short, they are better at revealing real-life conditions. Objectives: The two main objectives of this study were to compare the efficacy of a first course of anti-TNF therapy in three common forms of inflammatory arthritis [rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS)], and to compare the first-course efficacy of three widely used anti-TNFs (infliximab, etanercept, and adalimumab) within each of RA, PsA, and AS. Secondary objectives were to compare the efficacy of first and second courses of anti-TNF therapy in inflammatory arthritis patients overall, and to compare the efficacy of a second course of anti-TNF therapy by indication (RA, PsA, and AS) and by anti-TNF type (infliximab, etanercept, and adalimumab). Methods: This study used a retrospective cohort study design. Efficacy was measured in all cases using the proven surrogate outcome of drug survival. Crude anti-TNF survival was compared using Kaplan-Meier curves with log rank testing, and anti-TNF survival adjusted for several potential confounders was compared using Cox regression with hazard ratios (HRs) for treatment termination. First and second course anti-TNF survival was compared using a paired samples t-test. Results: 332 patients were eligible for the first-course analysis (114 RA patients, 58 PsA patients, and 160 AS patients). Crude first-course anti-TNF survival was significantly greater in AS patients compared to RA (p = 0.028) or PsA (p = 0.045) patients. However, no significant differences were found between RA, PsA, and AS in the adjusted Cox regression. Both crude and adjusted first-course drug survival was greater in RA patients taking adalimumab vs. etanercept {p = 0.010 and HR = 0.34 [95% confidence interval (CI) 0.14-0.80]}. Male AS patients had superior first-course anti-TNF survival than did female AS patients [HR = 0.51 (95% CI 0.27-0.95)]. 98 patients were eligible for the second-course analysis. There was no significant difference in drug survival between first and second courses of anti-TNF therapy (p = 0.443). Both crude and adjusted second-course drug survival was greater in PsA patients than in RA patients [p = 0.029 and HR = 0.42 (95% CI 0.19-0.93)]. Conclusions: This study helps to validate two key findings observed in previous studies. These are the superior first-course anti-TNF survival in AS vs. PsA and RA patients and the superior first-course anti-TNF survival in male vs. female AS patients. However, it produced few significant findings which is most likely attributable to inadequate sample sizes. The greatest value of this study is in the novel questions it asked, such that the trends and findings identified here might be useful for generating hypotheses for future, sufficiently powered studies.

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