Pablo Katz

Sublingual, transdermal and intravenous patient-controlled analgesia for acute post-operative pain: systematic literature review and mixed treatment comparison

Abstract Objective: To conduct a systematic literature review (SLR) and quantitative analysis to assess the comparative efficacy and safety of the sufentanil sublingual tablet system (SSTS) against other available patient controlled analgesia (PCA) options for post-operative analgesia. Methods: An SLR was conducted for studies published between 2004 and 2016. Due to study heterogeneity, subgroup analyses were conducted controlling for differences in imputation methods for missing values, baseline pain severity, and type of surgery. Where sufficient data was available, a mixed treatment comparison (MTC) was performed. Results: The MTC and subgroup analyses used 13 studies. In direct meta-analysis, there was a statistically significant difference in favor of SSTS compared with intravenous (IV) PCA (morphine) at 24 hours for the patient global assessment (PGA) scores of “good” or “excellent”. For the Pain Intensity Score, there were numerical but not statistically significant differences in favor of the SSTS versus IV PCA (morphine) and the patient controlled transdermal system (PCTS) (fentanyl) in the MTC at 6 hours (standardized mean difference −0.27 [credible interval −2.78, 2.09] and −0.36 [−3.89, 3.03], respectively). The onset of pain relief was earlier with the SSTS versus IV PCA (morphine) as shown by the Pain Intensity Difference. Likewise, the onset was earlier compared with PCTS (fentanyl) where data was available. There was a significant difference in favor of SSTS compared with IV PCA (morphine) and with PCTS (fentanyl) for any adverse event, and numerical improvements for withdrawals due to adverse events. Conclusions: This meta-analysis shows that SSTS is an option for non-invasive management of moderate-to-severe post-operative pain which can be more effective, faster in onset and better tolerated than IV PCA (morphine) and PCTS (fentanyl).

Indirect treatment comparison of two non-invasive patient-controlled analgesia treatments for acute post-operative pain management.

Abstract Objectives: To evaluate the relative clinical efficacy, safety, and tolerability associated with two non-invasive patient-controlled analgesia (PCA) treatments, sufentanil sublingual tablet system (SSTS) and fentanyl iontophoretic patient-controlled transdermal system (PCTS). These two treatments have recently been approved in the EU for the management of acute moderate-to-severe post-operative pain in adult patients. Methods: As no head-to-head trials comparing SSTS and PCTS currently exist, indirect treatment comparison (ITC) analyses were conducted to evaluate SSTS or PCTS versus intravenous (IV) morphine PCA. Results: Five studies, four assessing PCTS and one assessing SSTS, were included in this analysis. SSTS had statistical or numerical advantages over PCTS for both patient global assessment (PGA) and healthcare professional global assessment (HPGA) outcomes at all time points investigated. SSTS was also associated with greater patient ease of use (weighted mean difference [WMD]: 0.13; 95% confidence interval [CI]: −0.02–0.28) and a higher patient satisfaction score (WMD: 0.31; 95% CI: 0.05–0.57; p = .019) compared with PCTS. In terms of tolerability, all-cause withdrawals from treatment were reported to be less likely with SSTS (risk ratio: 0.65; 95% CI: 0.42–1.02). No significant differences were observed between SSTS and PCTS in terms of safety and adverse events. Conclusions: In the absence of direct head-to-head data, the combination of promising phase III trial results compared to IV morphine PCA, a SLR comparison against other opioid treatments, and the results of this exploratory analysis present a strong rationale in support of SSTS as a key option for management of post-operative pain.

Characteristics, resource utilization and safety profile of patients prescribed with neuropathic pain treatments: a real-world evidence study on general practices in Europe – the role of the lidocaine 5% medicated plaster

Abstract Objectives: To identify characteristics, resource utilization, and safety profile of patients prescribed with lidocaine 5% medicated plaster, pregabalin, gabapentin, amitriptyline and duloxetine when experiencing pain in the real-world setting of general practitioners (GPs) in Europe. Methods: Retrospective analysis on real world data from IMS Health Longitudinal Patient Database. Patients with at least one prescription of the drugs of interest during 2014 were selected and those with a non-neuropathic pain-related diagnosis were excluded. Patients’ demographic and clinical characteristics, resource utilization data and adverse drug reactions (ADRs) as described in the leaflet were extracted. The association between treatments and ADR occurrence was evaluated applying multivariate logistic models. Results: A total of 70,515 patients were selected from Italy, Germany, the UK, Spain and Belgium. Lidocaine 5% medicated plaster patients were the oldest in Italy, the UK and Spain and the most health impaired in Italy, Spain and Belgium. No relevant differences in the number of co-prescriptions, specialist visits, examinations and hospitalizations were found. Significantly less lidocaine 5% plasters patients experienced ADRs, with odds ratios in favor of lidocaine 5% medicated plasters ranging from 3.41 (p = .036) to 52.33 (p < .001). Conclusions: Evidence from daily clinical practice in GP settings agrees with the findings from more controlled clinical-trial settings, with lidocaine 5% medicated plaster patients showing a better safety profile, but also a comparable level of resource utilization. A possible re-evaluation of the scientific value coming from this retrospective study in building up a diagnostic as well as a therapeutic algorithm is suggested.