Long-Term Effectiveness and Tolerability of Pain Treatment with Tapentadol Prolonged Release

Objetivos: Evaluar la eficacia, tolerabilidad y seguridad a largo plazo de tapentadol PR en pacientes con dolor crónico grave de rodilla por osteoartritis (OA) o dolor lumbar (DL) que respondieron a tapentadol en 1 de los 4 ensayos clínicos precedentes de fase 3b de 12 semanas de duración. Diseño del estudio: Estudio observacional de extensión, abierto y no controlado, de hasta 72 semanas de duración. Entorno: Catorce centros en España. Aprobación del protocolo por el comité ético de referencia de todos los centros participantes. Métodos: Los pacientes elegibles comenzaron el ensayo de extensión con la dosis de tapentadol PR optimizada para ellos en el ensayo precedente; se permitieron ajustes de dosis a lo largo de la extensión. Los resultados de la eficacia del tratamiento incluyeron cambios en la intensidad del dolor, el sueño, el estado de salud, la calidad de vida, la impresión global del cambio por parte del paciente y del médico, y la satisfacción de los pacientes con el tratamiento. Los pacientes con dolor de rodilla por OA también respondieron al índice de OA de las Universidades Western Ontario y McMaster, y los pacientes con dolor lumbar con un posible componente de dolor neuropático completaron cuestionarios relacionados con el dolor neuropático. Resultados: Se incluyeron 83 pacientes: 40 con dolor de rodilla por OA y 43 con dolor lumbar. El conjunto de análisis completo estaba formado por 81 pacientes. La intensidad media del dolor se mantuvo relativamente estable durante el periodo de extensión de 72 semanas, con un aumento medio desde el inicio de 0,44 (intervalo de confianza [IC] del 95%, -0,1,1; escala de valoración numérica) para todos los pacientes, 0,2 (IC del 95%, -0,5, 0,9) para los pacientes con OA y 0,68 (IC del 95%, -0,2, 1,6) para los pacientes con dolor lumbar. Se mantuvieron las calificaciones basales del estado de salud y la calidad de vida; la impresión general de cambio fue "mejoró". La mayoría de los pacientes (88,9%) manifestaron al menos una buena satisfacción con el tratamiento al final del mismo. La dosis media diaria de tapentadol PR aumentó ligeramente de 313,3 ± 139,5 mg al inicio a 315,7 ± 140,1 mg al final del estudio. El 8,4% de los pacientes necesitó un aumento de dosis y el 4,8% sufrió una reducción de dosis durante el ensayo. En el 18,1% de los pacientes se documentaron acontecimientos adversos que el investigador consideró probable o ciertamente relacionados con el tratamiento con tapentadol PR, siendo el más frecuente el estreñimiento (7,2%). Siete pacientes (8,4%) experimentaron acontecimientos adversos que condujeron a la interrupción prematura. Limitaciones: Se permitió un diseño abierto, analgésicos concomitantes estables (escalón I de la Organización Mundial de la Salud) y ajustes de dosis durante el estudio. Todos los pacientes se habían beneficiado de tapentadol PR en ensayos anteriores. Conclusiones: El alivio sostenido del dolor y la calidad de vida durante un máximo de 72 semanas de tratamiento con una dosificación relativamente estable, así como el buen perfil de seguridad de tapentadol PR, han demostrado ser eficaces en el alivio del dolor y la calidad de vida.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.Laboratorio Grunentha

High-frequency spinal cord stimulation as rescue therapy for chronic pain patients with failure of conventional spinal cord stimulation

El objetivo de este estudio es evaluar la eficacia de los dispositivos de alta frecuencia (HF10) de 10 kHz como tratamiento en pacientes con fracaso de la terapia convencional de estimulación medular (EME) para el dolor crónico sin necesidad de cambiar el hardware medular. Métodos. En este estudio prospectivo del mundo real, se incluyeron pacientes con dolor neuropático tratados con EME tónica convencional en los que la terapia había fracasado, ya fuera durante la fase de prueba o tras un periodo óptimo. Resultados. Once de los 18 (61%) pacientes incluidos en el estudio fueron rescatados con éxito con HF10-SCS. De ellos, 5 de 12 (45%) estaban en fase de prueba y 6 de 6 (100%) tenían implantes que funcionaban previamente. Se obtuvo una mejora significativa del dolor lumbar y de las extremidades (p = 0,003 y p = 0,0001, respectivamente). El éxito del tratamiento se asoció significativamente con el sexo (p = 0,037), el peso (p = 0,014), el índice de masa corporal (IMC) (p = 0,007) y el tiempo de rescate (p = 0,015). Una prueba de regresión lineal confirmó una asociación significativa entre el fracaso del tratamiento y el IMC y el sexo (p = 0,004). Conclusiones. Nuestros resultados sugieren que el rescate analgésico con SCS-HF10 es una opción terapéutica eficaz para los pacientes que no responden a la SCS convencional, aunque la obesidad podría ser un factor limitante del éxito del tratamiento. No obstante, se necesitan estudios más exhaustivos para corroborar nuestros hallazgos.This study aims to evaluate the efficacy of 10-kHz high-frequency (HF10) devices as a rescue treatment in patients with failure of conventional spinal cord stimulation (SCS) therapy for chronic pain without the need to change the spinal hardware. Methods. In this real-world prospective study, patients with neuropathic pain treated with conventional tonic SCS in whom the therapy had failed, either during the trial phase or after a period of optimal. Results. Eleven of the 18 (61%) patients included in the study were successfully rescued with HF10-SCS. Of them, 5 out of 12 (45%) were in the trial phase and 6 out of 6 (100%) had previously functioning implants. A significant improvement in low-back and limb pain was obtained (p = .003 and p = .0001, respectively). Treatment success was significantly associated with gender (p = .037), weight (p = .014), body mass index (BMI) (p = .007) and time of rescue (p = .015). A linear regression test confirmed a significant association between treatment failure and BMI and gender (p = .004). Conclusions.Our results suggest that analgesic rescue with HF10-SCS is an effective therapeutic option for nonresponders to conventional SCS, although obesity might be a limiting factor for treatment success. Nevertheless, more comprehensive studies are needed to corroborate our findings

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Capsaicin 8% Patch Repeat Treatment in Nondiabetic Peripheral Neuropathic Pain A 52-Week, Open-Label, Single-Arm, Safety Study

Objetivos: Investigar la seguridad y tolerabilidad a largo plazo del tratamiento repetido con parches de capsaicina al 8% en pacientes no diabéticos con dolor neuropático periférico (DN). Métodos: Estudio prospectivo, abierto y observacional en pacientes con neuralgia postherpética, lesión nerviosa postraumática o posquirúrgica, polineuropatía sensorial distal asociada al VIH u otro NP periférico, y puntuación media diaria de dolor ≥4, recibieron ≤6 tratamientos con parches de capsaicina al 8% durante 52 semanas según a la necesidad clínica (retratamiento a intervalos de 9-12 semanas). Las pruebas sensoriales y la eficacia analgésica se evaluaron mediante "pruebas de cabecera" y el Inventario Breve del Dolor. Resultados: En total, 306 pacientes recibieron tratamiento. 252 (82,4%) y 207 (67,6%) pacientes notificaron efectos adversos emergentes del tratamiento (AETT) y AETT relacionados con el fármaco. El EAE relacionado con el fármaco más frecuente fue el dolor en el lugar de aplicación (n=112, 36,6%); no se notificó ningún EAE grave relacionado con el fármaco. Los análisis de cambio de categoría sensorial desde el inicio hasta el final del estudio en pacientes que acudieron al menos a dos visitas sensoriales (n=278 para todas las pruebas excepto la de calor, n=277) hallaron deterioro/pérdida sensorial en al menos una modalidad en el 50,4% (n=112, 36,6%), en al menos una modalidad en el 50,4% (n=140); el deterioro/pérdida en una, dos, tres, cuatro o cinco modalidades se produjo en el 26,6% (n=74), 14,0% (n=39), 5,8% (n=16), 2,5% (n=7) y 1,4% (n=4). La hiperestesia o alodinia en el 1,1-3,6% (según la modalidad). Entre el 25,2% y el 32,0% de los pacientes informaron de mejoría en una modalidad sensorial mediante EoS. El dolor diario medio fue de 6,6 y 4,7 al inicio del estudio y en el mes 12. Conclusiones: En general, el tratamiento repetido con parches de capsaicina al 8% durante 52 semanas fue bien tolerado, con alteración variable de la función sensorial y mínima probabilidad de pérdida sensorial completa.Objectives: To investigate long-term safety and tolerability of capsaicin 8% patch repeat treatment in non-diabetic patients with peripheral neuropathic pain (NP). Methods: Prospective, open-label, observational study in patients with post-herpetic neuralgia, posttraumatic or post-surgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral NP, and average daily pain score ≥4, received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9–12 week intervals). Sensory testing and analgesic effectiveness were assessed using „bedside tests‟ and Brief Pain Inventory (question 5). Results: Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAE) and drugrelated TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least two sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least one modality in 50.4% (n=140); deterioration/loss in one, two, three, four or five modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7) and 1.4% (n=4). Newly emergent hyperaesthesia or allodynia was apparent in 1.1–3.6% (depending on modality) by EoS. Between 25.2 and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and Month 12. Conclusions: Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.Laboratorio Grunentha

Off-label pharmacological treatment for neuropathic pain: A Delphi study by the Spanish Pain Society Neuropathic Pain Task Force

Objetivos: El uso de farmacoterapias farmacoterapias para el dolor neuropático (DN) está en relación con las numerosas necesidades no satisfechas de los pacientes. Sin embargo, las guías clínicas no lo abordan, y las pruebas disponibles son escasas y fragmentadas. Hemos organizado un consenso formal de expertos para abordar este controvertido tema y ofrecer algunas sobre su uso adecuado. Métodos: Se realizó una encuesta encuesta Delphi estándar de dos rondas en la que participaron especialistas con experiencia en la investigación y el tratamiento del DN de 40 preguntas ad hoc preparado por los autores. El consenso sobre cada afirmación se definió como la aprobación o el rechazo de al menos el 80% de las afirmaciones tras la segunda ronda. Resultados: Cuarenta y tres y treinta y siete panelistas participaron en la primera y ronda, respectivamente. Se alcanzó un consenso en 34 de las 40 declaraciones. Las alternativas aprobadas en para pacientes que no responden incluyen antiepilépticos no antiepilépticos (oxcarbazepina y eslicarbazepina), venlafaxina, lidocaína intravenosa (cuando las dosis dosis pueden optimizarse), y algunos cannabinoides vaporizados (bajo vigilancia adecuada). Además, lacosamida, dosis bajas de naltrexona, propofol o ketamina podrían resultar beneficiosas si se someten a más investigaciones. Se rechazaron otras opciones, y hubo controversia sobre la utilidad de los preparados tópicos. Discusión: Para los pacientes que no responden a los tratamientos NP estándar, algunas otras opciones farmacológicas viables antes de pasar a otros estadios terapéuticos estadios terapéuticos. Esto puede ayudar a los pacientes que son reacios o tienen alguna contraindicación para las terapias intervencionistas.Objectives: The use of off-label pharmacotherapies for neuropathic pain (NP) is growing relating to the many unmet needs of patients. However, clinical guidelines fail to address it, and the available evidence is sparse and fragmented. We arranged a formal expert consensus to address this controversial issue and provide some guidance on judicious use. Methods: A two-round standard Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 40-item questionnaire prepared by the authors. Consensus on each statement was defined as at least either 80% endorsement or rejection after the second round. Results: Forty-three and thirty-seven panelists participated in the first and second round, respectively. Consensus was reached in 34 out of 40 statements. Endorsed alternatives for unresponsive patients include non-gabapentinoid antiepileptics (oxcarbazepine and eslicarbazepine), venlafaxine, intravenous lidocaine (when doses can be optimized), and some vaporized cannabinoids (under appropriate surveillance). In addition, lacosamide, low-dose naltrexone, propofol, or ketamine could prove beneficial if subjected to more research. Other options were rejected, and there was controversy about the usefulness of topical preparations. Discussion: For patients who do not respond to standard NP treatments, some other viable pharmacological options can be attempted before advancing to other therapeutic stages. This may help patients who are reluctant to or have some contraindication for interventional therapiesSociedad Española del Dolo

Effectiveness of Pregabalin as Monotherapy or Combination Therapy for Neuropathic Pain in Patients Unresponsive to Previous Treatments in a Spanish Primary Care Setting

Journal Article; Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.BACKGROUND AND OBJECTIVE Patients from a previous study of neuropathic pain (NP) in the Spanish primary care setting still had symptoms despite treatment. Subsequently, patients were treated as prescribed by their physician and followed up for 3 months. Since pregabalin has been shown to be effective in NP, including refractory cases, the objective of this study was to assess the effectiveness of pregabalin therapy in patients with NP refractory to previous treatments. METHODS This was a post hoc analysis of pregabalin-naïve NP patients treated with pregabalin in a 3-month follow-up observational multicenter study to assess symptoms and satisfaction with treatment. Patients were evaluated with the Douleur Neuropathique en 4 questions (DN4), the Brief Pain Inventory (BPI) and the Treatment Satisfaction for Medication Questionnaire (SATMED-Q) overall satisfaction domain. RESULTS 1,670 patients (mean age 58 years, 59 % women), previously untreated or treated with ≥1 drug other than pregabalin, were treated with pregabalin (37 % on monotherapy). At 3 months, pain intensity and its interference with activities decreased by half (p < 0.0001), while the number of days with no or mild pain increased by a mean of 4.5 days (p < 0.0001). Treatment satisfaction increased twofold (p < 0.0001). Patients with a shorter history of pain and those with neuralgia and peripheral nerve compression syndrome (PCS) as etiologies had the highest proportion on monotherapy and showed the greatest improvements in pain-related parameters in their respective group categories. CONCLUSION Treatment with pregabalin (as monotherapy or combination therapy) provides benefits in pain and treatment satisfaction in patients with NP, including refractory cases. Shorter disease progression and neuralgia and PCS etiologies are favorable factors for pregabalin treatment response.This study was sponsored by Pfizer SLU, Madrid, Spain.Ye

Analgesic efficacy of tramadol/dexketoprofen vs Ibuprofen after impacted lower third molar extraction: a randomized controlled clinical trial

Objective Impacted third molar extraction is associated with acute moderate-to-severe pain for up to 48 hours post-surgery. This trial was designed to compare the analgesic effectiveness, swelling, and adverse events after impacted third molar surgery following multimodal therapy with 75 mg tramadol hydrochloride plus 25 mg dexketoprofen or monotherapy with 400 mg ibuprofen. Methods Seventy-two patients were randomly assigned to receiving ibuprofen (n = 36) or tramadol-dexketoprofen (n = 36). Postoperative pain intensity and swelling were measured using a visual analog scale (VAS); pain relief experienced was reported using a 4-point verbal rating scale; the rescue medication requirement, adverse effects, and global impression of the medication were recorded. Results No statistically significant between-group difference in pain intensity was observed at any time point; however, pain relief was significantly higher in the tramadol-dexketoprofen treated-group at 6 and 36 hours. Self-reported verbal rating scale assessments showed significantly lower swelling in the tramadoldexketoprofen group at 24 hours post-surgery but not at 48 or 72 hours, and VAS- swelling scores showed no significant between-group difference. The frequency of postoperative nausea and dizziness was significantly higher in the tramadoldexketoprofen group. Conclusions Multimodal therapy proved more effective to manage moderate-severe pain after impacted third molar surgery in comparison to monotherapy. However, the improvement in relief must be balanced against the increased risk of adverse effects when considering this multimodal approach