Study register · detailReal-World-Register (Propensity-Score-Matched) · Neuropathic Pain · 2022
Comparison of the Effectiveness and Tolerability of Nabiximols (THC:CBD) Oromucosal Spray versus Oral Dronabinol (THC) as Add-on Treatment for Severe Neuropathic Pain in Real-World Clinical Practice: Retrospective Analysis of the German Pain e-Registry.
Ueberall et al.·Journal of Pain ResearchImpact 2.3
Nabiximols was significantly superior to dronabinol with regard to aggregated symptom reduction and tolerability in severe neuropathic pain disease.
Summary
German Pain e-Registry: n=674 patients with severe neuropathy (337 nabiximols vs. 337 dronabinol, propensity-matched); ASR-9 total score improvement 55.4% (NBX) vs. 40.5% (DRO), difference 14.0 (95% CI 12.6–15.4, p<0.001); ADR rate 21.1% vs. 35% (p<0.001); more NBX patients discontinued concomitant opioid medication (p<0.001) — NBX both non-inferior and superior to DRO.
P
PopulationAdult outpatients with severe neuropathic pain disease, insufficient response to established therapies, propensity-score-matched sample: n=337 (NBX) vs. n=337 (DRO)
I
InterventionNabiximols (THC:CBD) oromucosal spray (mean THC dose 16,6 mg/day) as add-on over 24 weeks
C
ControlOral dronabinol (synthetic THC, mean dose 17,2 mg/day) as add-on
O
OutcomeMedian improvement in ASR-9 composite score: 55,4% (NBX) vs. 40,5% (DRO); LS-mean difference 14,0 (95% CI 12,6–15,4; p<0,001); TRAE incidence: 21,1% vs. 35% (p<0,001); TRAE-related discontinuations: 5,9% vs. 14,8% (p<0,001)
Confidence in the evidence
Very lowLowModerateHigh
Low
The second of four GRADE levels, the effect estimate is of limited reliability.
Quality profile
Sample size★★★★★
Blinding—
Effect sizeClear benefit
Citations / year★★★★★
Authors
Ueberall MA, Essner U, Vila Silván C, Mueller-Schwefe GHH.
<h4>Purpose</h4>To compare the effectiveness and tolerability of add-on treatment with nabiximols (NBX: delta-9-tetrahydrocannabinol: cannabidiol) oromucosal spray or oral dronabinol (DRO: synthetic tetrahydrocannabinol) in patients with severe neuropathic pain poorly responsive to established treatments.<h4>Methods</h4>An analysis was conducted of anonymized, propensity score-matched real-world data from the German Pain e-Registry, using a sequential non-inferiority superiority approach, for adult outpatients with neuropathic pain who had initiated treatment with NBX or DRO between 10 March 2017 and 31 December 2019. The primary effectiveness variable was percent change from baseline in a 9-factor aggregated symptom relief (ASR-9) score, a composite index of nine distinct pain- and health-related parameters assessed using validated patient-reported instruments. Safety was assessed by the incidence of physician-confirmed treatment-related adverse events (TRAEs), and TRAEs leading to discontinuation.<h4>Results</h4>Propensity score-matched data were analyzed for 337 patients treated with NBX and 337 patients treated with DRO. Mean (standard deviation) THC dose over the 24-week evaluation period was 16.6 (6.5) mg for NBX and 17.2 (7.6) mg for DRO (p<0.001). Median (standard error) improvement relative to baseline in the ASR-9 composite score was 55.4% (0.5) for NBX and 40.5% (0.5) for DRO (least squares mean difference, 14.0 (0.7), 95% confidence interval 12.6-15.4; p<0.001), and incidences of TRAEs (21.1 vs 35%) and TRAE-related discontinuations (5.9 vs 14.8%) were significantly lower with NBX than DRO (p<0.001 for both), collectively indicating pre-specified non-inferiority and superiority of NBX. More NBX- than DRO-treated patients discontinued non-cannabinoid background pain medications and rescue analgesics, especially opioid analgesics (p<0.001 for both).<h4>Conclusion</h4>Add-on treatment with cannabinoids is effective for treatment of severe neuropathic pain with inadequate response to established treatments. In daily practice, NBX had superior effectiveness and tolerability compared to DRO. The results emphasize the importance of combining CBD with THC in this patient population.