(P-636) Risk of Acute Respiratory Failure Among Non-elderly Patients with Solid Tumors Receiving Pegfilgrastim and Concomitant Opioids: A Nested Case-control Study

Background: Pegfilgrastim is prescribed to reduce the risk of febrile neutropenia in 71% of US patients with solid tumor cancers before chemotherapy. About half of these patients will experience pegfilgrastim-induced bone pain (PIBP); 24% severe enough to warrant opioid medication. Because pegfilgrastim can increase the risk of acute respiratory failure (ARF), it is important to assess whether its concurrent prescription with opioids increases that risk.

Objectives: To examine the association between concomitant opioid treatment and risk of ARF.

Methods: Using a 10% random sample of IQVIA PharMetrics® Plus from 2006 to 2015, we conducted a case-control study nested within a cohort of patients with solid tumor cancers ≤65 years, receiving their first pegfilgrastim cycle. ARF cases were defined using a composite measure that included ICD-9/CPT/HCPCS codes for acute respiratory distress syndrome, acute lung injury, endotracheal intubation, oxygenation, or mechanical ventilation). Cases were matched to controls (age, sex) by incidence-density sampling in ratio 1:≤20. We defined concomitant opioid use as any overlap between opioid treatment days’ supply and the 12-day bioavailability of a pegfilgrastim bolus, if overlap occurred less than 14 days before ARF event. Using conditional logistic regression adjusted for age group, sex, mean number of pegfilgrastim-containing chemotherapy cycles, taxane chemotherapy and metastatic cancer status, we estimated adjusted odds ratios (aORs) with 95% confidence intervals (CI).

Results: We identified 4,064 pegfilgrastim initiators of whom 135 ARF cases were matched to 458 controls. Concomitant opioids were prescribed in 23% of cases compared to 12% of controls. Cases had a higher prevalence of mental disorder (30% vs 20%) and CNS tumors (16% vs 9%) but lower average pegfilgrastim-containing cycles (mean, CI: 2.9, 2.7-3.1 vs 4.4, 4.4-4.5). The odds of ARF were two times higher among concomitant opioid users (aOR 2.18 CI 1.16-4.08) when compared to no opioid use.

Conclusions: Our findings suggest increased risk of ARF associated with concomitant pegfilgrastim and opioid treatment. Further studies are needed to confirm this relationship, and to explore the safety and effectiveness of non-opioid treatments for managing severe PIBP especially among patients with CNS tumors or comorbid mental disorders.