Switching to low-dose oral prolonged-release oxycodone/naloxone from WHO-Step I drugs in elderly patients with chronic pain at high risk of early opioid discontinuation

Abstract

Purpose: Chronic pain has a high prevalence in the aging population. Strong opioids also should be considered in older people for the treatment of moderate to severe pain or for pain that impairs functioning and the quality of life. This study aimed to assess the efficacy and safety of the direct switch to low-dose strong opioids (World Health Organization-Step III drugs) in elderly, opioid-naive patients.

Patients and methods: This was a single-center, retrospective, observational study in opioid-naive patients aged ≥75 years, with moderate to severe chronic pain (>6-month duration) and constipation, who initiated treatment with prolonged-release oxycodone/naloxone (OXN-PR). Patients were re-evaluated after 15, 30, and 60 days (T60, final observation). Response to treatment was defined as an improvement in pain of ≥30% after 30 days of therapy without worsening of constipation.

Results: One-hundred and eighty-six patients (mean ± SD age 80.7±4.7 years; 64.5% women) with severe chronic pain (mean average pain intensity 7.1±1.0 on the 11-point numerical rating scale) and constipation (mean Bowel Function Index 64.1±24.4; 89.2% of patients on laxatives) were initiated treatment with OXN-PR (mean daily dose 11.3±3.5 mg). OXN-PR reduced pain intensity rapidly and was well tolerated; 63.4% of patients responded to treatment with OXN-PR. At T60 (mean daily OXN-PR dose, 21.5±9.7 mg), the pain intensity was reduced by 66.7%. In addition, bowel function improved (mean decrease of Bowel Function Index from baseline to T60, -28.2, P<0.0001) and the use of laxatives decreased. Already after 15 days and throughout treatment, ~70% of patients perceived their status as much/extremely improved. Only 1.6% of patients discontinued treatment due to adverse events.

Conclusion: Low-dose OXN-PR in elderly patients naive to opioids proved to be an effective option for the treatment of moderate to severe chronic pain. Large-scale trials are needed to improve clinical guidance in the assessment and treatment of pain in older people.

Keywords: chronic pain; elderly; naloxone; opioid; oxycodone.

Figure 1

Changes in average pain severity score measured on an 11-point NRS during the 60-day treatment with OXN-PR. Notes: *P=0.02 T60 vs T30 result; **P<0.0001 T30 vs T15 result. Abbreviations: NRS, numerical rating scale; OXN-PR, prolonged-release oxycodone/naloxone; T0, baseline; T15, day 15; T30, day 30; T60, day 60.

Figure 2

Waterfall image of individual changes in pain severity after 30 days of treatment with OXN-PR. Notes: Decreases in pain severity from baseline ≥30% indicate analgesic efficacy (below the dashed line). A 30%–49% (dash-dot line), 50%–69%, and 70%–100% (below the dotted line) decrease in pain severity was reported by 18%, 41%, and 32% patients, respectively. Only 9% patients reported lack of analgesic efficacy or worsened pain after OXN-PR. Abbreviation: OXN-PR, prolonged-release oxycodone/naloxone.

Figure 3

Changes in bowel function according to the Bowel Function Index during the 60-day treatment with OXN-PR. Note: **P<0.0001 T30 vs T15 result. Abbreviations: OXN-PR, prolonged-release oxycodone/naloxone; T0, baseline; T15, day 15; T30, day 30; T60, day.

Figure 4

Changes in (A) average pain severity score measured on an 11-point NRS and (B) bowel function in the age subgroups 75–85 years (n=148) and >85 years (n=38). Notes: **P<0.0001 T30 vs T15 result. No differences between subgroups at all time points. Abbreviations: NRS, numerical rating scale; T0, baseline; T15, day 15; T30, day 30; T60, day 60.

Figure 5

PGIC scale analysis after 15 days (T15), 30 days (T30), and 60 days (T60) with OXN-PR. Note: “Extremely worsened” of the PGIC scale is not shown, as no patient reported extreme worsening. Abbreviations: PGIC, Patient Global Impression of Change; OXN-PR, prolonged-release oxycodone/naloxone.