Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

McKnight D.; Morales A.; Hatchell K.E.; Bristow S.L.; Bonkowsky J.L.; Perry M.S.; Berg A.T.; Borlot F.; Esplin E.D.; Moretz C.; Angione K.; Ríos-Pohl L.; Nussbaum R.L.; Aradhya S.; Haldeman-Englert C.R.; Levy R.J.; Parachuri V.G.; Lay-Son G.; De Montellano D.J.D.-O.; Ramirez-Garcia M.A.; Benítez Alonso E.O.; Ziobro J.; Chirita-Emandi A.; Felix T.M.; Kulasa-Luke D.; Megarbane A.; Karkare S.; Chagnon S.L.; Humberson J.B.; Assaf M.J.; Silva S.; Zarroli K.; Boyarchuk O.; Nelson G.R.; Palmquist R.; Hammond K.C.; Hwang S.T.; Boutlier S.B.; Nolan M.; Batley K.Y.; Chavda D.; Reyes-Silva C.A.; Miroshnikov O.; Zuccarelli B.; Amlie-Wolf L.; Wheless J.W.; Seinfeld S.; Kanhangad M.; Freeman J.L.; Monroy-Santoyo S.; Rodriguez-Vazquez N.; Ryan M.M.; MacHie M.; Guerra P.; Hassan M.J.; Candee M.S.; Bupp C.P.; Park K.L.; Muller E., Ii; Lupo P.; Pedersen R.C.; Arain A.M.; Murphy A.; Schatz K.; Mu W.; Kalika P.M.; Plaza L.; Kellogg M.A.; Lora E.G.; Carson R.P.; Svystilnyk V.; Venegas V.; Luke R.R.; Jiang H.; Stetsenko T.; Dueñas-Roque M.M.; Trasmonte J.; Burke R.J.; Hurst A.C.E.; Smith D.M.; Massingham L.J.; Pisani L.; Costin C.E.; Ostrander B.; Filloux F.M.; Ananth A.L.; Mohamed I.S.; Nechai A.; Dao J.M.; Fahey M.C.; Aliu E.; Falchek S.; Press C.A.; Treat L.; Eschbach K.; Starks A.; Kammeyer R.; Bear J.J.; Jacobson M.; Chernuha V.; Meibos B.; Wong K.; Sweney M.T.; Espinoza A.C.; Van Orman C.B.; Weinstock A.; Kumar A.; Soler-Alfonso C.; Nolan D.A.; Raza M.; Rojas Carrion M.D.; Chari G.; Marsh E.D.; Shiloh-Malawsky Y.; Parikh S.; Gonzalez-Giraldo E.; Fulton S.; Sogawa Y.; Burns K.; Malets M.; Montiel Blanco J.D.; Habela C.W.; Wilson C.A.; Guzmán G.G.; Pavliuk M. · JAMA Neurology (2022) · DOI: 10.1001/jamaneurol.2022.3651

Resumen

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes..