title: Neuropathic pain phenotyping as a predictor of treatment response in painful diabetic neuropathy: data from the randomized, double-blind, COMBO-DN study.
abstract: Sensory profiles are heterogeneous in neuropathic pain disorders, and subgroups of patients respond differently to treatment. To further explore this, patients in the COMBO-DN study were prospectively assessed by the Neuropathic Pain Symptom Inventory (NPSI) at baseline, after initial 8-week therapy with either duloxetine or pregabalin, and after subsequent 8-week combination/high-dose therapy. Exploratory post hoc cluster analyses were performed to identify and characterize potential subgroups through their scores in the NPSI items. In patients not responding to initial 60 mg/d duloxetine, adding 300 mg/d pregabalin for combination treatment was particularly effective regarding the dimensions pressing pain and evoked pain, whereas maximizing the duloxetine dose to 120 mg/d appeared more beneficial regarding paresthesia/dysesthesia. In contrast, adding 60 mg/d duloxetine to 300 mg/d pregabalin in case of nonresponse to initial pregabalin led to numerically higher decreases in all NPSI dimensions/items compared to maximizing the pregabalin dose to 600 mg/d. Cluster analysis revealed 3 patient clusters (defined by baseline scores for the 10 NPSI sensory items) with different pain profiles, not only in terms of overall pain severity, but also across NPSI items. Mean Brief Pain Inventory average pain improved in all clusters during combination/high-dose therapy. However, in patients with severe pain, the treatment effect showed a trend in favor of high-dose monotherapy, whereas combination therapy appeared to be more beneficial in patients with moderate and mild pain (not significant). These complementary exploratory analyses further endorse the idea that sensory phenotyping might lead to a more stratified treatment and potentially to personalized pain therapy.
authors.affiliation: INSERM U987 Centre d'Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, Boulogne Billancourt, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Bouhassira
authors.affiliation: Regional Medical Affairs, Lilly Deutschland GmbH, Bad Homburg, Germany. Electronic address: wilhelm_stefan@lilly.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilhelm
authors.affiliation: Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schacht
authors.affiliation: INSERM U-987 Centre de la Douleur, Hôpital Hotel Dieu, Université Paris Descartes, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Perrot
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Kosek
authors.affiliation: Sapienza University, Department of Neurology & Psychiatry, Roma, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cruccu
authors.affiliation: Zentrum für Anästhesiologie, Intensivmedizin, Schmerztherapie & Palliativmedizin, Benedictus Krankenhaus, Tutzing, und Klinik für Anästhesiologie, Technische Universität München, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Freynhagen
authors.affiliation: Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: Solomon
authors.initials: S
authors.lastname: Tesfaye
authors.affiliation: Departamento de Neurología, Clínica Creu Blanca, Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lledó
authors.affiliation: Section of Rheumatology, Institute of Infection & Immunity, Cardiff University, Cardiff, UK.
authors.forename: Ernest
authors.initials: E
authors.lastname: Choy
authors.affiliation: Pain Medicine Center, Department of Neurology, Hospital San Raffaele, Milano, Italy and Pain Pathophysiology and Therapy, University of Southern Switzerland, Manno, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchettini
authors.affiliation: Department of Neuroscience, CIBER of Mental Health, CIBERSAM, University of Cádiz, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Micó
authors.affiliation: Spital Linth, Rheumatologie, Uznach, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Spaeth
authors.affiliation: Lilly Research Laboratories, Indianapolis, IN, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Skljarevski
authors.affiliation: Neurologische Klinik und Poliklinik, Technische Universität, München, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tölle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000150:complications / Q000175:diagnosis*; D000069583:Pregabalin / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D000068736:Duloxetine Hydrochloride
keywords: Diabetic neuropathy; Duloxetine; Neuropathic Pain Symptom Inventory; Pregabalin; Sensory symptoms; Stratified treatment