A Novel Algorithm to Identify Predictors of Treatment Response: Tapentadol Monotherapy or Tapentadol/Pregabalin Combination Therapy in Chronic Low Back Pain?

Abstract

Purpose: High dose monotherapies or drug combinations are used to achieve sufficient analgesia for the treatment of severe chronic low back pain, before invasive therapy options are considered. In order to demonstrate an alternative for an empirical treatment approach, the authors' primary aim was to present an algorithm for the objective identification of treatment predictors. Additionally, the study identified baseline-characteristics in chronic low back pain patients prior to tapentadol PR treatment, as well as scrutinized those patients, either benefitting from a medium/high dose tapentadol PR monotherapy or a combination therapy (medium dose tapentadol PR + pregabalin).Patients and Methods: The statistical approach included data of a previously published randomized, double blind, phase 3b study which compared the effectiveness and safety of tapentadol PR vs. a combination of tapentadol PR and pregabalin. In total, 46 clinical parameters were included in the statistical prediction models which were applied separately either to 50 patients who already responded well during the titration period (i.e., medium dose tapentadol PR) or to 261 patients with in the comparative treatment period [i.e., monotherapy (high dose tapentadol PR) or combination therapy (medium dose tapentadol PR/pregabalin)].Results: The first statistical model identified three co-variables (NRS-3, PDQ, SQ) with predictive effects on patients responding well (“optimal responders”) to a medium dose tapentadol PR titration. Those patients presented low baseline pain intensity scores, good sleep quality and high painDETECT scores. The second statistical model identified eight co-variables (PDQ, numbness, SF-12 MCS, SF-12 PCS, VAS, HADS-A, HADS-D, SQ) with predictive effects on patients responding to high dose tapentadol PR monotherapy vs. a combination therapy (tapentadol PR + pregabalin). The high dose tapentadol PR responders indicated high painDETECT scores, little numbness and a good mental health status. Whereas, the combination therapy (tapentadol PR + pregabalin) responders were characterized by severe sleep disturbances and little anxiety.Conclusion: The statistical analysis characterized chronic low back pain patients and identified factors contributing to a treatment response. Thus, this retrospective statistical algorithm represents an elegant method, which may contribute to future strategies toward a more individualized and improved mechanism based pain therapy.

Modulation of sensitization processes in the management of pain and the importance of descending pathways: a role for tapentadol?

“…With regards to the combination of tapentadol with other analgesics, the paper by Otto et al on low back pain [72] and that by Lockwood and Dickenson on osteoarthritis [44], both published in 2019, demonstrated the useful combination of tapentadol and pregabalin.…”

“…glutamate release). A recent study conducted in LBP patients suggests that the combination therapy (tapentadol PR + pregabalin) exerts its best clinical efficacy in subjects characterized by severe sleep disturbances and little anxiety [72]. Moreover, a study by D'Amato et al showed the efficacy of the combination of tapentadol and ketoprofen after hip arthroplasty [73].…”

Cannabis oil extracts for chronic pain: what else can be learned from another structured prospective cohort?

“…Retrospective subgrouping of patients (ie, “responders” vs “nonresponders”) has been suggested as an elegant statistical method for identifying factors contributing to a treatment response. 25 Accordingly, we retrospectively classified our patients into “responders” and “nonresponders” but unfortunately failed to identify neither objective nor patient-reported baseline characteristics that may predict treatment success (except for catastrophizing). This somewhat contradicts the finding of another cannabis cohort, which was able to point predictors for good response (≥30% decrease in average pain intensity) including normal to long sleep duration, lower BMI, lower depression scores, and a diagnosis other than neuropathic pain.…”

Bedside testing for precision pain medicine

“…Post hoc prediction models of treatment efficacy were performed incorporating different outcome parameters. A retrospective analysis of a study comparing the efficacy of tapentadol versus tapentadol plus pregabalin in chronic low back pain identified predictive parameter combinations for response to median doses of tapentadol [41]: low baseline pain intensity, good sleep quality and high PD-score.…”