Effectiveness, Safety, and Tolerability of Nabiximols Oromucosal Spray vs Typical Oral Long-Acting Opioid Analgesics in Patients with Severe Neuropathic Back Pain: Analysis of 6-Month Real-World Data from the German Pain e-Registry

Abstract

Objective: To compare the effectiveness, safety, and tolerability of add-on nabiximols (NBX) oromucosal spray vs typical oral long-acting opioid (LAO) analgesics in patients with severe (± chronic) peripheral neuropathic back pain poorly responsive to other treatments.

Methods: Retrospective analysis of anonymized, propensity score-matched data from the German Pain e-Registry of adult outpatients who initiated NBX or LAO between March 2017 and March 2020.

Results: Data were analyzed from propensity score-matched patients treated with NBX (n = 655) or LAO (n = 655): mean age ≈51 years; 57% female; mean pain duration ≈2.6 years; chronic pain 61%; severe dysfunctional pain 93%. At 6 months, NBX was noninferior to LAO for overall symptom relief, based on the least-squares mean difference between cohorts in change from baseline in patient-reported, pain-related aggregated nine-item scale scores (-27.84%; 95% confidence interval [CI] -29.71 to -25.96; P < 0.001) and individual pain-related scale scores. Subsequent prespecified superiority analysis of the primary endpoint showed that NBX was superior to LAO: all secondary endpoints measuring symptoms of pain and physical function improved significantly with NBX and LAO, with between-group differences favoring NBX (all P < 0.001). Fewer patients treated with NBX than LAO experienced treatment-related adverse events (25.5% vs 76.0%; P < 0.001) or discontinued treatment because of treatment-related adverse events (7.9% vs 29.3%; P < 0.001).

Conclusion: Within study limitations (e.g., observational design, all potential biases), add-on NBX was superior to and better tolerated than add-on treatment with typical oral LAO analgesics in patients with neuropathic back pain inadequately controlled by recommended/established systemic therapies.

Keywords: Long-Acting Opioid Analgesics; Low Back Pain; Nabiximols; Neuropathic Pain; Oromucosal Spray; Real-World Data.

Figure 1.

Mean relative (percent vs baseline) improvement in the ASR-9 score over time in patients treated with NBX (n = 655) or oral LAO analgesics (n = 655). *P < 0.001 vs oral LAO.

Figure 2.

Relative improvement (%) from baseline in individual components of the ASR-9 in patients treated with NBX (n = 655) or oral LAO analgesics (n = 655). Box plots show median (middle horizontal line in the box), 25% and 75% quartiles (bottom and top lines of the box), and whiskers corresponding to the 2.5–97.5% quartiles. Blue upper boxes: relative improvement with NBX. White upper boxes: relative improvement with LAO. DASS= Depression, Anxiety, and Stress Scale; MFHW= Marburg Questionnaire on Habitual Well-Being; mPDI= modified pain disability index; PDQ7 = painDETECT Questionnaire; SF-12 MCS= 12-item Short-Form Health Survey Mental Component Summary; SF-12 PCS= 12-item Short-Form Health Survey Physical Component Summary.

Figure 3.

Effect sizes (Cohen’s d; 95% CIs) for individual components of the ASR-9 and composite ASR-9 score. Cohen’s d effect size legend: <0.2, insignificant; 0.2–0.5, small; 0.5–0.8, medium; >0.8, large. DASS= Depression, Anxiety, and Stress Scale; MFHW= Marburg Questionnaire on Habitual Well-Being; mPDI= modified pain disability index; PDQ7 = painDETECT Questionnaire; SF-12 MCS= 12-item Short-Form Health Survey Mental Component Summary; SF-12 PCS= 12-item Short-Form Health Survey Physical Component Summary.

Figure 4.

TRAE-related discontinuation profiles (rate ± 95% CI) for NBX and oral LAO analgesics during the 24-week evaluation period.