Skip to main content
SpringerLink
Log in

Early Add-on Lacosamide in a Real-Life Setting: Results of the REALLY Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and objectives

Many patients with epilepsy are treated with antiepileptic drug (AED) polytherapy. Several factors influence the choice of early add-on therapy, and deciding on the most appropriate drug can be difficult. This study aimed to assess the efficacy and tolerability of lacosamide as early add-on therapy in patients with partial-onset seizures.

Methods

REALLY (REtrospective study of lAcosamide as earLy add-on aLong one Year) was a multicenter, retrospective, 1-year, real-life study. Patients included were aged older than 16 years, had partial-onset seizures, and were treated with lacosamide as add-on therapy after one or two prior AEDs. Data were collected retrospectively from clinical records. The primary study objective was to assess the efficacy of lacosamide over 12 months (seizure-free and responder rates), and the secondary objective was to assess the tolerability of lacosamide at 3, 6, and 12 months [adverse events (AEs) and discontinuation].

Results

One hundred and ninety-nine patients were enrolled in the study; 89 patients (44.7 %) had tried one AED and 110 patients (55.3 %) had tried two AEDs before lacosamide. At 12 months, the proportion of patients who were seizure free was 44.9 %, and 76 % of patients were responders. The seizure-free rate at 12 months for patients who had previously received one or two AEDs was 58 and 34.3 %, and the responder rate at 12 months was 83.0 and 70.4 %, respectively. The AE rate was 21.5 % at 3 months, 27.1 % at 6 months, and 31.2 % at 12 months, with 7.0 % of patients discontinuing treatment because of an AE. The most common AE reported was dizziness (11.6 %). Cryptogenic epilepsy, a higher number of prior AEDs, and the use of a sodium channel blocker at onset were associated with a worse outcome. The number of concomitant AEDs decreased over 1 year (Z = 5.89; p < 0.001). Twenty-two patients were converted to lacosamide monotherapy with at least one evaluation ≥6 months from the beginning of monotherapy conversion.

Conclusions

Lacosamide was effective and well tolerated as early add-on treatment in patients who had received one or two previous AEDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Steinhoff BJ, Maren Staack A, Wisniewski I. Seizure control with antiepileptic drug therapy in 517 consecutive adult outpatients at the Kork Epilepsy Centre. Epileptic Disord. 2012;14(4):379–87. doi:10.1684/epd.2012.0544.

    PubMed  Google Scholar 

  2. Ben-Menachem E. Medical management of refractory epilepsy: practical treatment with novel antiepileptic drugs. Epilepsia. 2014;55(Suppl 1):3–8. doi:10.1111/epi.12494.

    Article  CAS  PubMed  Google Scholar 

  3. Mercadé-Cerdá JM, Sancho-Rieger J, Mauri-Llerda JÁ, López-Gonzalez FJ, Salas-Puig J. Guía oficial de práctica clínica en epilepsia. Guías diagnósticas y terapéuticas de la Sociedad Española de Neurología. 2012. http://www.epilepsiasen.net/system/files/GUIA%20OFICIAL%20SEN%20EPILEPSIA.pdf. Accessed May 14, 2014.

  4. Cretin B, Hirsch E. Adjunctive antiepileptic drugs in adult epilepsy: how the first add-on could be the last. Expert Opin Pharmacother. 2010;11(7):1053–67. doi:10.1517/14656561003709755.

    Article  CAS  PubMed  Google Scholar 

  5. St Louis EK. Truly “rational” polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects. Curr Neuropharmacol. 2009;7(2):96–105. doi:10.2174/157015909788848929.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs): part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clin Pharmacokinet. 2013;52(11):927–66. doi:10.1007/s40262-013-0087-0.

    Article  CAS  PubMed  Google Scholar 

  7. Ryvlin P, Montavont A, Nighoghossian N. Optimizing therapy of seizures in stroke patients. Neurology. 2006;67(12 Suppl 4):S3–9.

    Article  PubMed  Google Scholar 

  8. Vecht CJ, Wagner GL, Wilms EB. Interactions between antiepileptic and chemotherapeutic drugs. Lancet Neurol. 2003;2(7):404–9.

    Article  CAS  PubMed  Google Scholar 

  9. Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007;48(7):1308–17. doi:10.1111/j.1528-1167.2007.01188.x.

    Article  CAS  PubMed  Google Scholar 

  10. Chung S, Sperling MR, Biton V, Krauss G, Hebert D, Rudd GD, et al. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010;51(6):958–67. doi:10.1111/j.1528-1167.2009.02496.x.

    Article  CAS  PubMed  Google Scholar 

  11. Halasz P, Kalviainen R, Mazurkiewicz-Beldzinska M, Rosenow F, Doty P, Hebert D, et al. Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia. 2009;50(3):443–53. doi:10.1111/j.1528-1167.2008.01951.x.

    Article  CAS  PubMed  Google Scholar 

  12. Thomas D, Scharfenecker U, Schiltmeyer B, Koch B, Rudd D, Cawello W, et al. Lacosamide has low potential for drug–drug interaction (abstract p. 562). Epilepsia. 2006;47(Suppl 3):1–272.

    Article  Google Scholar 

  13. Cawello W, Rosenkranz B, Schmid B, Wierich W. Pharmacodynamic and pharmacokinetic evaluation of coadministration of lacosamide and an oral contraceptive (levonorgestrel plus ethinylestradiol) in healthy female volunteers. Epilepsia. 2013;54(3):530–6. doi:10.1111/epi.12085.

    Article  CAS  PubMed  Google Scholar 

  14. European Medicines Agency. Vimpat (lacosamide). Summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000863/WC500050338.pdf. Accessed April 16, 2014.

  15. Stockis A, van Lier JJ, Cawello W, Kumke T, Eckhardt K. Lack of effect of lacosamide on the pharmacokinetic and pharmacodynamic profiles of warfarin. Epilepsia. 2013;54(7):1161–6. doi:10.1111/epi.12192.

    Article  CAS  PubMed  Google Scholar 

  16. Flores L, Kemp S, Colbeck K, Moran N, Quirk J, Ramkolea P, et al. Clinical experience with oral lacosamide as adjunctive therapy in adult patients with uncontrolled epilepsy: a multicentre study in epilepsy clinics in the United Kingdom (UK). Seizure. 2012;21(7):512–7. doi:10.1016/j.seizure.2012.05.005.

    Article  PubMed  Google Scholar 

  17. Garcia-Morales I, Delgado RT, Falip M, Campos D, Garcia ME, Gil-Nagel A. Early clinical experience with lacosamide as adjunctive therapy in patients with refractory focal epilepsy and nocturnal seizures. Seizure. 2011;20(10):801–4. doi:10.1016/j.seizure.2011.08.005.

    Article  PubMed  Google Scholar 

  18. Harden CL, Cohn A, Lowe M, Serrano E. Initial post marketing experience with lacosamide in adult patients with epilepsy. Epilepsy Res. 2012;98(2–3):260–3. doi:10.1016/j.eplepsyres.2011.09.010.

    Article  PubMed  Google Scholar 

  19. Novy J, Bartolini E, Bell GS, Duncan JS, Sander JW. Long-term retention of lacosamide in a large cohort of people with medically refractory epilepsy: a single centre evaluation. Epilepsy Res. 2013;106(1–2):250–6. doi:10.1016/j.eplepsyres.2013.05.002.

    Article  CAS  PubMed  Google Scholar 

  20. Maschio M, Dinapoli L, Mingoia M, Sperati F, Pace A, Pompili A, et al. Lacosamide as add-on in brain tumor-related epilepsy: preliminary report on efficacy and tolerability. J Neurol. 2011;258(11):2100–4. doi:10.1007/s00415-011-6132-8.

    Article  CAS  PubMed  Google Scholar 

  21. Stephen LJ, Kelly K, Parker P, Brodie MJ. Adjunctive lacosamide in clinical practice: sodium blockade with a difference? Epilepsy Behav. 2011;22(3):499–504. doi:10.1016/j.yebeh.2011.07.035.

    Article  PubMed  Google Scholar 

  22. Villanueva V, Lopez FJ, Serratosa JM, Gonzalez-Giraldez B, Campos D, Molins A, et al. Control of seizures in different stages of partial epilepsy: LACO-EXP, a Spanish retrospective study of lacosamide. Epilepsy Behav. 2013;29(2):349–56. doi:10.1016/j.yebeh.2013.07.024.

    Article  PubMed  Google Scholar 

  23. Villanueva V, Lopez-Gomariz E, Lopez-Trigo J, Palau J, Garcia M, Villarroya T, et al. Rational polytherapy with lacosamide in clinical practice: results of a Spanish cohort analysis RELACOVA. Epilepsy Behav. 2012;23(3):298–304. doi:10.1016/j.yebeh.2011.11.026.

    Article  PubMed  Google Scholar 

  24. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51(4):676–85. doi:10.1111/j.1528-1167.2010.02522.x.

  25. Noack-Rink M, Mayer T, Arnold SS, Runge U. Lacosamide added to an existing monotherapy in epilepsy patients with partial onset seizures: outcome of 2nd interim analysis of the VITOBA study (poster 1.218). American Epilepsy Society 67th Annual Meeting; December 6–12, 2013; Washington, DC

  26. Stephen LJ, Kelly K, Wilson EA, Parker P, Brodie MJ. A prospective audit of adjunctive zonisamide in an everyday clinical setting. Epilepsy Behav. 2010;17(4):455–60. doi:10.1016/j.yebeh.2010.01.016.

    Article  PubMed  Google Scholar 

  27. Knoester PD, Keyser A, Renier WO, Egberts AC, Hekster YA, Deckers CL. Effectiveness of lamotrigine in clinical practice: results of a retrospective population-based study. Epilepsy Res. 2005;65(1–2):93–100. doi:10.1016/j.eplepsyres.2005.05.005.

    Article  CAS  PubMed  Google Scholar 

  28. Werhahn KJ, Klimpe S, Balkaya S, Trinka E, Kramer G. The safety and efficacy of add-on levetiracetam in elderly patients with focal epilepsy: a one-year observational study. Seizure. 2011;20(4):305–11. doi:10.1016/j.seizure.2010.12.015.

    Article  PubMed  Google Scholar 

  29. Schiller Y, Najjar Y. Quantifying the response to antiepileptic drugs: effect of past treatment history. Neurology. 2008;70(1):54–65. doi:10.1212/01.wnl.0000286959.22040.6e.

    Article  PubMed  Google Scholar 

  30. Brodie MJ, Barry SJ, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548–54. doi:10.1212/WNL.0b013e3182563b19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Noack-Rink M, Mayer T, Arnold SS, Kumke T, Runge U. Lacosamide as add-on to monotherapy in patients with partial-onset seizures: interim results of the post-marketing VITOBA study (Vimpat added to one baseline AED) [poster p. 639]. Epilepsia. 2012;53(Suppl 5):185.

    Google Scholar 

  32. Sake JK, Hebert D, Isojarvi J, Doty P, De Backer M, Davies K, et al. A pooled analysis of lacosamide clinical trial data grouped by mechanism of action of concomitant antiepileptic drugs. CNS Drugs. 2010;24(12):1055–68. doi:10.2165/11587550-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  33. Stephen LJ, Kelly K, Parker P, Brodie MJ. Adjunctive lacosamide: 5 years’ clinical experience. Epilepsy Res. 2014;108(8):1385–91. doi:10.1016/j.eplepsyres.2014.06.018.

    Article  CAS  PubMed  Google Scholar 

  34. Wechsler RT, Li G, French J, O’Brien TJ, D’Cruz O, Williams P et al. Conversion to lacosamide monotherapy in the treatment of focal epilepsy: results from a historical-controlled, multicenter, double-blind study. Epilepsia. 2014. doi:10.1111/epi.12681.

Download references

Acknowledgments

The authors would like to thank Sheridan Henness, PhD, and Simone Boniface, of Springer Healthcare Communications, for medical writing assistance. The authors also thank Patricia Santagueda for conducting the statistical analyses. This assistance was funded by UCB.

Financial disclosures/conflicts of interest

Medical writing assistance and statistical work were funded by an unrestricted grant provided by UCB. UCB was not involved in the study design, the collection, analysis, and interpretation of the data gathered, and the writing of the study report.

Dr. Villanueva has participated in advisory boards and pharmaceutical industry-sponsored symposia for Eisai Inc., UCB, Merck Sharp & Dohme, Bial, Pfizer, and GlaxoSmithKline (GSK). Dr. Garces has participated in pharmaceutical industry-sponsored symposia for Eisai Inc. and UCB. Dr. Serratosa has received honoraria from UCB, Eisai Inc., Bial, Merck Sharp & Dohme, and Johnson and Johnson for participation in advisory boards or pharmaceutical industry-sponsored symposia. Dr. González-Giraldez has participated in pharmaceutical industry-sponsored symposia for Eisai Inc. and UCB. Dr. Parra has received honoraria from UCB, Eisai Inc., Bial, and GSK for participation in advisory boards or pharmaceutical industry-sponsored symposia. Dr. Rodríguez-Uranga has participated in pharmaceutical industry-sponsored symposia for Eisai Inc., UCB, BIAL, and GSK. Dr. Toledo has received honoraria for activities organized by Eisai Inc., UCB, Bial, and GSK. Dr. López-Gonzalez has participated in advisory boards and pharmaceutical industry-sponsored symposia for Eisai Inc., UCB, Bial, and GSK. Dr. Molins has participated in advisory boards and pharmaceutical industry-sponsored symposia for Eisai Inc., UCB, Bial, Pfizer, and GSK. Dr. Campos has participated in advisory boards and pharmaceutical industry-sponsored symposia for Eisai Inc., UCB, Bial, and GSK. Dr. Mauri has received honoraria from UCB, Bial, Eisai Inc., GSK, and Pfizer. Dr. Serrano-Castro has received honoraria from UCB, Eisai Inc., Bial, GSK, Novartis, and Merck Sharp & Dohme for participation in advisory boards or pharmaceutical industry-sponsored symposia. Dr. Bonet has received honoraria from UCB, Bial, and Eisai Inc. Dr. López-Gomáriz, Dr. Bermejo, Dr. Giner, Dr. Castillo, Dr. Muñoz, Dr. del Villar, and Dr. Saiz-Díaz have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Hospital Universitario y Politécnico La Fe, Bulevard Sur, s/n, Carretera de Malilla, 46026, Valencia, Spain

    Vicente Villanueva & Mercedes Garcés

  2. Hospital Lluis Alcanyis, Valencia, Spain

    Elena López-Gomáriz

  3. Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

    José María Serratosa & Beatriz González-Giráldez

  4. Hospital San Rafael, Madrid, Spain

    Jaime Parra

  5. Hospital Quirón, Sevilla, Spain

    Juan Rodríguez-Uranga

  6. Hospital Universitario Vall d´Hebron, Barcelona, Spain

    Manuel Toledo

  7. Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain

    Francisco Javier López González

  8. Hospital Universitario Puerta de Hierro, Madrid, Spain

    Pedro Bermejo

  9. Hospital Universitario Dr. Peset, Valencia, Spain

    Pau Giner

  10. Consorcio Hospital General Universitario de Valencia, Valencia, Spain

    Ascensión Castillo

  11. Hospital Universitario Doctor Josep Trueta, Girona, Spain

    Albert Molins

  12. Hospital Clínico Universitario de Valladolid, Valladolid, Spain

    Dulce Campos

  13. Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

    José Ángel Mauri

  14. Hospital de La Ribera, Alzira, Spain

    Rosario Muñoz

  15. Hospital Arnau de Vilanova, Valencia, Spain

    Macarena Bonet

  16. Complejo Hospitalario Torrecárdenas, Almería, Spain

    Pedro Serrano-Castro

  17. Hospital General Universitario Castellon, Castellón, Spain

    Ana del Villar

  18. Hospital Universitario 12 de Octubre, Madrid, Spain

    Rosa Ana Saiz-Díaz

Authors
  1. Vicente Villanueva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mercedes Garcés
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elena López-Gomáriz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. José María Serratosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Beatriz González-Giráldez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jaime Parra
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juan Rodríguez-Uranga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Manuel Toledo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Francisco Javier López González
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pedro Bermejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Pau Giner
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ascensión Castillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Albert Molins
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Dulce Campos
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. José Ángel Mauri
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Rosario Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Macarena Bonet
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Pedro Serrano-Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Ana del Villar
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Rosa Ana Saiz-Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

REALLY Study Group

Corresponding author

Correspondence to Vicente Villanueva.

Appendix

Appendix

Hospital Universitario y Politécnico La Fe (Valencia, Spain) (Vicente Villanueva, Mercedes Garcés), Hospital Lluis Alcanyis (Xátiva) (Elena López-Gomáriz), Hospital Universitario Fundación Jiménez Díaz, Madrid (José Maria Serratosa, Beatriz González Giráldez), Hospital San Rafael, Madrid (Jaime Parra), Instituto de Especialidades Neurológicas, Hospital Quirón Sevilla (Juan Rodríguez-Uranga), Hospital Universitario Vall d´Hebron, Barcelona(Javier Salas-Puig, Manuel Toledo), Complejo Hospitalario Universitario, Santiago (Francisco Javier López), Hospital Universitario Puerta de Hierro, Madrid (Pedro Bermejo), Hospital Universitario Dr. Peset (Valencia) (Pau Giner, Nerea Torres), Consorcio Hospital General Universitario Valencia (Ascensión Castillo, Javier López-Trigo), Hospital Universitario Dr. Josep Trueta, Girona (Albert Molins), Hospital Clinico Universitario, Valladolid (Dulce Campos), Hospital Clínico Universitario Lozano Blesa, Zaragoza (Jose Angel Mauri), Hospital La Ribera, Alzira (Rosario Muñoz, José Andrés Domínguez), Hospital Arnau de Vilanova, Valencia (Macarena Bonet), Complejo Hospitalario Torrecárdenas, Almeria (Pedro Serrano, Pablo Quiroga), Hospital Clinico Universitario Valencia (Consuelo Santafé), Hospital General Universitario Castellón (Ana del Villar Elena Pajarón), Hospital Universitario 12 de Octubre, Madrid (Pilar de la Peña, Rosana Saiz, Jesús González de la Aleja), Hospital General Universitario, Alicante (Montse Asensio), Hospital Valencia Al Mar (Enrique Noé).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Villanueva, V., Garcés, M., López-Gomáriz, E. et al. Early Add-on Lacosamide in a Real-Life Setting: Results of the REALLY Study. Clin Drug Investig 35, 121–131 (2015). https://doi.org/10.1007/s40261-014-0255-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-014-0255-5

Keywords

Search

Navigation