1. 2021;24;E75-E85Long-Term Effectiveness and Tolerability of Pain Treatment with Tapentadol Prolonged Release
   Observational Study
   Cesar Margarit Ferri, MD, Luis Miguel Torres Morera, MD, Daniel Samper Bernal, MD, Rafael Galvez Mateos, MD, and Ana Esquivias Escobar, PharmD.

BACKGROUND: The central analgesic tapentadol prolonged release (PR) has proven effective and generally well tolerated in a broad range of chronic pain conditions. Long-term data of its use are still scarce.

OBJECTIVES: To evaluate long-term effectiveness, tolerability, and safety of tapentadol PR in patients with severe chronic osteoarthritis (OA) knee pain or low back pain (LBP) who responded to tapentadol in 1 of 4 preceding 12-week phase 3b clinical trials.

STUDY DESIGN: Open-label, uncontrolled, observational extension study of up to 72 weeks.

SETTING: Fourteen centers in Spain. Protocol approval by the reference ethics committee for all the participating centers.

METHODS: Eligible patients started the extension trial on the tapentadol PR dosage optimized for them in the preceding trial; dose adjustments were permitted throughout the extension. Treatment effectiveness outcomes included changes in pain intensity, sleep, state of health, quality of life, patient and clinician global impression of change, and patients’ satisfaction with treatment. Patients with OA knee pain also answered the Western Ontario and McMaster Universities OA index, and patients with LBP with a possible neuropathic pain component completed neuropathic pain-related questionnaires.

RESULTS: Eighty-three patients were enrolled: 40 with OA knee pain, 43 with LBP. The full analysis set consisted of 81 patients. Mean pain intensity remained relatively stable over the 72-week extension period with mean increases from baseline of 0.44 (95% confidence interval [CI], -0.1,1.0; Numeric Rating Scale) for all patients, 0.2 (95% CI, -0.5, 0.9) for patients with OA, and 0.68 (95% CI, -0.2, 1.6) for patients with LBP. State of health and quality of life baseline ratings were maintained; overall impression of change was “improved.” Most patients (88.9%) reported at least good treatment satisfaction at the end of treatment. Mean daily tapentadol PR doses slightly increased from 313.3 ± 139.5 mg at baseline to 315.7 ± 140.1 mg at end of study. Uptitration was required for 8.4% of the patients, 4.8% had a dose reduction during the trial. Adverse events considered probably/likely or certainly related to tapentadol PR treatment by the investigator were documented for 18.1% of all patients, most commonly constipation (7.2%). Seven patients (8.4%) experienced adverse events leading to premature discontinuation.

LIMITATIONS: An open-label design, stable concomitant analgesics (World Health Organization step I), and dose adjustments were allowed during the study. All patients had benefitted from tapentadol PR in preceding trials.

CONCLUSIONS: Sustained pain relief and quality of life for up to 72 treatment weeks under relatively stable dosing, as well as the good safety profile, indicate the usefulness of tapentadol PR for patients who suffer from severe chronic OA knee pain and LBP with limited risk for tolerance development.

KEY WORDS: Tapentadol prolonged release, extension study, long-term, chronic pain, osteoarthritis, low back pain, efficacy, safety