Safety and effectiveness of cannabinoids to Danish patients with treatment refractory chronic pain—A retrospective observational real‐world study

Abstract

Background: Cannabinoids are considered a therapeutic option to patients suffering from treatment refractory chronic pain (TRCP) insufficiently relieved by conventional analgesics or experiencing intolerable adverse events (AEs) from those. This study aimed to explore safety and effectiveness of oral cannabinoids among patients with TRCP.Methods: A retrospective study was conducted among Danish patients with TRCP being prescribed oral cannabinoids. Data on AEs and changes in pain intensity by numeric rating scale (NRS) before and after initiation of oral cannabinoid therapy were analysed.Results: Among 826 eligible patients ≥18 years old, 529 (64%) were included for data analysis at first follow-up (F/U1) (median 56 days from baseline) and 214 (26%) for second follow-up (F/U2) (median 126 days from F/U1). Mean age was 60 ± 15.9 years and 70% were females. AEs were in general reported mild to moderate by 42% of patients at F/U1 and 34% at F/U2. AEs were mainly related to gastrointestinal (F/U1: 17% and F/U2: 13%) and nervous system disorders (F/U1: 14% and F/U2: 11%). Reduction in NRS was significantly different at both follow-up consultations compared with baseline (<0.0001). Clinically relevant pain reduction (NRS ≥30%) was reported by 17% at F/U1 and 10% of patients at F/U2 in intentionto-treat analysis whereas the figures were 32% and 45% respectively, in per-protocol analysis. Conclusion:Oral cannabinoid therapy seems to be safe and mildly effective in patients with TRCP. Randomized controlled trials with focus on comparable pain characteristics in diagnostical homogenous patient subgroups are needed for further improvement of evidence level for relief of chronic pain using oral cannabinoids. Significance:The findings in this retrospective study conducted in a real-world clinical setting suggest a favourable safety profile of cannabinoids. Moreover, onesixth (intention-to-treat) and one-third (per-protocol) of patients with chronic pain This accompanies the following article: Eisenberg E. Is there an added value in more real-world cannabinoids studies?

Is there an added value in more real‐world cannabinoids studies?

“…The percentage of patients achieving 30% pain relief in the Horsted et al (2022) study, which ranges between 32%-45% in the PP analysis and 10-17% in the ITT, seems congruent with previous reports. For example, Bialas et al (2022) reported of 38.3% of patients achieving the 30% target in all six included studies, and 20.5% after removing four studies for which an imputation method was used to calculate responder rates.…”

“…The same is probably true for the improvement in secondary outcomes such as sleep and quality‐of‐life, and for the rates and types of reported adverse events. Hence, the authors concluded that ‘oral cannabinoid therapy seems to be safe and mildly effective in patients with chronic pain’ (Horsted et al, 2022 ) may strengthen what is already known, but is marginal in terms of added value. An additional major drawback of this and most other real‐world observational studies is their low patient retention rate (26% in the second follow‐up in this study), which creates a significant bias and makes the results difficult to interpret.…”

“…This journal recently published a paper by Horsted et al ( 2022 ) entitled ‘Safety and Efficacy of Cannabinoids to Danish Patients with Treatment Refractory Chronic Pain—A Retrospective Observational Real‐world Study’. Eight hundred and twenty‐six patients with ‘refractory’ chronic pain, were prescribed oral cannabinoids consisting of either delta‐9‐tetrahydrocannabinol 14 (THC), cannabidiol (CBD) or their combination.…”

“…In summary, the growing use of medicinal cannabinoids and the failure of RCTs to provide clear evidence for their efficacy and safety in patients with chronic pain justify the use of additional study designs such as Horsted et al ( 2022 ) real‐world observational study. In line with previous real‐world studies, this study's results suggest a reasonable safety profile and modest effectiveness.…”

Methodology considerations for ‘Safety and effectiveness of cannabinoids to Danish patients with treatment‐refractory chronic pain’ by Horsted et al.

“…The recently published exploratory, non‐controlled, study by Horsted et al (2023) reports on the potential safety and pain‐relieving effects of cannabinoids (THC, CBD), or mixed in a non‐randomized order. The authors conclude that ‘oral cannabinoid therapy in general appears to be safe and effective for relief of chronic pain in some patients, including a subset of patients with cancer‐related pain (9%), not responding adequately to conventional treatment regimens or experiencing intolerable adverse events’.…”