Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs

• Published in: Seizure (London, England) Vol. 83; pp. 48 - 56
• Main Authors: Santamarina, Estevo, Bertol, Vicente, Garayoa, Vanesa, García-Gomara, María José, Garamendi-Ruiz, Iñigo, Giner, Pau, Aranzábal, Inés, Piera, Anna, Arcos, Carolina, Esteve, Patricia, Marinas, Ainhoa, García-Escrivá, Alejandro, Viloria-Alebesque, Alejandro, Loro, Fernando Ayuga, de Tienda, Alejandro Ponz, Olivan, José Antonio, Bonet, Macarena, Dávila-González, Pablo, Sivera, Rafael, Molins, Albert, Sansa, Gemma, Roche, José Carlos, Martínez, Ana Belén, Monteagudo, Sandra, Casadevall, Teresa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2020
• Subjects: Adult; AMPA receptor antagonist; Anti-seizure drug; Anticonvulsants - administration & dosage; Anticonvulsants - therapeutic use; Epilepsies, Partial - drug therapy; Epilepsy - drug therapy; Female; Humans; Male; Middle Aged; Non-refractory epilepsy; Pharmaceutical Preparations; Pyridones - administration & dosage; Pyridones - therapeutic use; Rational polytherapy; Real-world study; Retrospective Studies; Seizure freedom; Seizures - drug therapy; Treatment Outcome; Non-refractory epilepsy; AMPA; VPA; BRV; TPM; ASD; GBP; AMPA receptor antagonist; CBZ; PHT; ZNS; ESL; Real-world study; IGE; PGB; BZD; Rational polytherapy; PB; SCB; LCM; Seizure freedom; OXC; LEV; PER; Anti-seizure drug; LTG
• ISSN: 1059-1311; 1532-2688
• DOI: 10.1016/j.seizure.2020.09.026

•First add-on PER improves seizure control in patients with focal epilepsy or IGE.•48.3 % of patients experienced an AE over the 12-month observation period.•The tolerability of PER was not affected by the type of concomitant ASD.•Reduced seizure control was observed when PER was administered with strong enzyme-inducing ASDs.•Higher PER doses may optimize seizure control when combined with strong enzyme-inducing ASDs.
To investigate the efficacy and tolerability of perampanel (PER) when administered as a first add-on therapy to patients with focal epilepsy or idiopathic generalized epilepsy (IGE) taking one other antiseizure drug (ASD).
This multicentre, retrospective, one-year observational study collected data from patients (≥12 years) who initiated treatment with PER as first add-on therapy. Patients had to be experiencing inadequate seizure control on ASD monotherapy and tried ≤3 ASD monotherapies before initiating PER. Multivariate logistic regression analyses were performed, adjusted for the number and type of previous seizures, duration and aetiology of epilepsy.
Of the 149 patients included in the study (mean age 41 years; 54.4 % male), 118 (79.2 %) were still receiving PER as first add-on treatment after 12 months. Mean PER dose was 6.2 mg/day. At 12 months, 45.6 % were seizure-free and 84.6 % responders. A significant difference in seizure freedom rate was found between patients with IGE and patients with focal epilepsy, but not in responders. Reduced seizure control was observed when PER was administered with strong enzyme-inducing ASDs; conversely, increased seizure control was seen when the same dose of PER was combined with enzyme-inhibiting ASDs. The most frequent adverse events were dizziness (15.4 %), irritability (14.1 %) and drowsiness (14.1 %); no differences in tolerance were observed among different combinations.
PER demonstrated a good efficacy and safety profile when used as a first add-on therapy in patients who did not respond to monotherapy. PER dose adjustments may optimize seizure control when combined with strong enzyme-inducing or enzyme-inhibiting ASDs.