Retrospective Analysis to Describe Associations Between Tumor Necrosis Factor Alpha Inhibitors and COPD-Related Hospitalizations

Background: Limited information exists on the impact of tumor necrosis factor inhibition on COPD exacerbations. This retrospective study characterized this impact among COPD patients with underlying autoimmune conditions, exposed to tumor necrosis factor inhibitors (TNFi) and/or non-biologic disease-modifying antirheumatic drugs (DMARDs).Patients and methods: Adult COPD patients with ≥1 diagnosis for rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) before or within 6 months following the index COPD diagnosis were identified from the Truven Health MarketScan® databases. Patients were required to have a second claim for RA, PsO, PsA, AS, or DMARD use (biologic or non-biologic) prior to or up to 6 months following the index date. Incidence of COPD-related hospitalizations and emergency room (ER) visits was evaluated in relation to treatment with TNFi and/or DMARDs and other potential risk factors.Results: The study cohort included 40,687 patients (untreated, 37.7%; non-biologic DMARD, 35.4%; TNFi + non-biologic DMARD, 18%; TNFi, 8.8%). The proportion of patients with a COPD-related hospitalization and the incidence of COPD-related hospitalization (per 100 person-years) were lowest in the TNFi cohort (8.6%; 3.54, 95% confidence interval [CI]: 3.16–3.95) and the TNFi + non-biologic DMARD cohort (8.4%; 2.85, 95% CI: 2.63–3.08). In multivariate models, treatment with TNFi + non-biologic DMARD reduced the risk of COPD-related hospitalization or ER visits by 32% relative to non-biologic DMARDs (hazard ratio: 0.68; 95% CI: 0.61–0.75).Conclusion: In real-world settings, TNFi monotherapy confers similar risk for COPD-related hospitalization or ER visits as a non-biologic DMARD. Decreased risk was found among those treated with both TNFi and a non-biologic DMARD

Characteristics of Included Models.

<p>AF = atrial fibrillation; ASA = aspirin; CI = contraindication; ECH = extracranial hemorrhage; F = foundation; G = government; GI = gastrointestinal; ICH = intracranial hemorrhage; INR = international normalized ratio; MI = myocardial infarction; NA = not applicable; NR = not reported; NHS = National Health Service; P = pharmaceutical company; RE-LY = Randomized Evaluation of Long-Term Anticoagulation Therapy; ROCKET-AF = Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation; QHES = Quality of Health Economic Studies; TIA = transient ischemic attack; TTR = time in therapeutic range; UK = United Kingdom; US = United States; VKA = vitamin k antagonist.</p>a<p>Sequential dabigatran = 150 mg BID in those <80 years of age and 110 mg BID in those >80 years of age.</p

Proportion of Reported Incremental Cost-Effectiveness Ratios Below Reported Willingness-to-Pay Threshold.

<p>*Includes results of dabigatran compared to “real-world prescribing”, “trial-like” warfarin control and genotype-guided warfarin †Includes results of dabigatran compared to “trial-like” warfarin control and genotype-guided warfarin.</p

Results of Included Models.

<p>AF = atrial fibrillation; ASA = aspirin; CAD = Canadian dollar; CI = contraindication; ECH = extracranial hemorrhage; EUR = Euro; GI = gastrointestinal; GBP = Great Britain Pound; HR = hazard ratio; ICH = intracranial hemorrhage; INR = international normalized ratio; MCS = Monte Carlo Simulation; MI = myocardial infarction; NR = not reported; QALY = quality adjusted life year; RE-LY = Randomized Evaluation of Long-Term Anticoagulation Therapy; ROCKET-AF = Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation; RR = relative risk; TIA = transient ischemic attack; TTR = time in therapeutic range; USD = United States dollar; VKA = vitamin k antagonist; WTP = willingness to pay.</p>a<p>Based on a Letter to the Editor update related to overestimation of cost to dabigatran. Cost of dabigatran 150 mg twice daily reduced from $13.00/day to$8.00.</p

Characteristics of Underlying Trials.

<p>BID – twice daily; DB = double blind; ITT = Intention to Treat; MI = Myocardial Infarction; N = Population of Study; OL = Open Label; R = Randomized Trial; TTR = Time in Therapeutic Range.</p>a<p>Double-blinding was used in RE-LY, but only for the dabigatran arms. Since the corresponding Markov model compared the cost-effectiveness of dabigatran (both doses) to warfarin, we report this trial as “open-label” above;</p>b<p>Difference between rate of major or clinically relevant nonmajor bleeds and major bleeds.</p>c<p>Difference between reported any bleed and reported major bleed rates;</p>‡<p>Stroke or systemic embolism;</p