POS0279 WEARABLE TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION DEMONSTRATED BETTER EFFICACY AND SAFETY THAN WEAK OPIOIDS IN THE TREATMENT OF MODERATE TO SEVERE, CHRONIC NOCICEPTIVE PAIN IN KNEE OSTEOARTHRITIS. A RANDOMIZED, CONTROLLED, NON-INFERIORITY TRIAL

Abstract

Background:In knee osteoarthritis (KOA) recommendations, the first pharmacological analgesic line is paracetamol. However, its low efficacy, frequently leads to the use of weak opioids (WO) despite their poor tolerance, especially in elderly patients.Objectives:The primary objective was to compare analgesic efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) to those of WO in the treatment of moderate to severe, nociceptive, chronic pain in KOA patients.Methods:ArthroTENS study was a phase 3, non-inferiority, multicentric, prospective, randomized, single-blinded for primary efficacy outcome, controlled, in 2-parallel groups, clinical study comparing W-TENS versus WO on two periods: a 3-month controlled period and an additional, optional, non-controlled, 3-month follow-up for patients in W-TENS group.Eligible participants were KOA patients, ≥55 years old, at Kellgren-Lawrence radiographic grade ≥2, with moderate to severe nociceptive chronic (≥3 months) mean 8-day pain ≥4 on a 11-point numerical rating scale, and in treatment failure with non-opioid analgesics, including NSAIDs. Patients with neuropathic pain were excluded.Co-primary endpoints were, for efficacy, mean pain intensity (PI), assessed at M3 and, for safety, the number of adverse events (AE) during the 3-month follow-up period.In W-TENS group, an advanced, mobile app enabled, wearable TENS was used. High (100 Hz) and low (2 Hz) frequency stimulations were delivered via electrodes with standardized positioning (Figure 1).Figure 1.Electrode’s positioningIn WO group, investigators chose, for each patient, the best suitable WO and its daily dose, and could switch to another WO, and/or adapt its daily dose if necessary.A non-inferiority analysis was performed on the primary efficacy endpoint using a pre-defined non-inferiority margin (0.825 point) on PI, below the minimal clinically significant improvement.Results:Demographic and baseline characteristics were balanced across both groups.110 patients (55/group) were randomized and 48/55 (87.3%) and 44/55 (80.0%) patients completed the 3-month follow-up in W-TENS and WO groups, respectively. WO’s prescriptions were balanced between codeine, opium-powder, tramadol and WO-paracetamol combinations.Non-inferiority of W-TENS was demonstrated in the PP and ITT populations (Table 1). Since the 95% confidence interval (CI) of the between-treatments difference was below 0 in the ITT population, a planned superiority analysis was performed showing that W-TENS was significantly superior to WO at M3 (p=0.0124) on PI. Additionally, the number of AEs was significantly lower (p<0.001) in W-TENS (n=7) group than in WO (n=36) group. In WO group, AEs were systemic AEs usually reported with WO while AEs in W-TENS group were local, related to the technique used, such as local cutaneous reaction (erythema).Table 1.Non-inferiority analyses on pain intensity at M3. ITT and PP populations. Least squares means for each study group and study group difference estimate and corresponding 95% CIGroup PopulationWithin-group changeBetween-group differenceW-TENSWOW-TENS - WOITT Population (n)5555Non inferiorityMean (SD)3.83 (0.28)<0.0014.74 (0.28)<0.001-0.92 (0.40)Non inferiority‡ demonstrated95% CI[3.27, 4.40][4.18, 5.30][-1.71, -0.12]PP Population (n)5247Mean (SD)3.87 (0.30)<0.0014.66 (0.32)<0.001-0.79 (0.44)Non inferiority‡ demonstrated95% CI[3.28, 4.46][4.03, 5.28][-1.65, 0.08]‡ Noninferiority was demonstrated when 95% CI < 0.825Thirty-nine (70.9%) patients wished to extend W-TENS treatment for 3 additional months. Only one patient discontinued this additional period and results obtained at M3 remained stable at M6.Conclusion:In this study, W-TENS was more effective and better tolerated than WO in the treatment of nociceptive KOA chronic pain and should represent an interesting non-pharmacological alternative to WO.Acknowledgements:We gratefully thank P. Fardellone (Amiens), E. Coudeyre (Clermont-Ferrand), Y. Donazzolo (Gieres), A. Amouzougan (Saint-Etienne), L. Grange (Grenoble), T. Conrozier (Belfort), E. Senbel (Marseille), J.P. Sanchez (Billere), R. Forestier (Aix-les-Bains), H. Bard (Paris) and E. Gibert (Ivry-sur-Seine) for their active contribution throughout arthroTENS studyDisclosure of Interests:Emmanuel Maheu Speakers bureau: TRB chemedica, Consultant of: SUBLIMED, Moirans, FRANCE; Sandrine Soriot-Thomas Speakers bureau: Grunenthal, Consultant of: SUBLIMED, Moirans, FRANCE;GrunenthalKyowa Kirin pharma, Grant/research support from: GrunenthalSanofiTevaMylanTherable, Eric Noel Consultant of: SUBLIMED, Moirans, FRANCE; Eric Lespessailles Consultant of: SUBLIMED, Moirans, FRANCE; Bernard Cortet Consultant of: SUBLIMED, Moirans, FRANCE;