Robert Wapenaar

Time course of adverse events in patients with localization-related epilepsy receiving topiramate added to carbamazepine.

Summary:  Purpose: To explore the time course of treatment‐emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy.

Long-acting injectable risperidone and oral antipsychotics in patients with schizophrenia: results from a prospective, 1-year, non-interventional study (InORS)

Abstract Objective. To explore differences in outcomes for patients with schizophrenia treated with risperidone long-acting treatment (RLAT) or oral antipsychotics (oAP). Methods. The International Observational Registry on Schizophrenia (InORS) explored flexible doses of newly initiated RLAT and oAPs for adults with schizophrenia, exploring 6-month retrospective hospitalization data and 12-month prospective medication use, outcomes, and tolerability. Efficacy outcomes included hospitalizations, the Clinical Global Impression of Schizophrenia (CGI-SCH), and the Global Assessment of Functioning (GAF). Medication switch patterns were also analysed. Results. Data were analysed from 1083 patients (561 RLAT, 522 oAP). At baseline, RLAT patients had higher symptom severity, greater functional impairment, and poorer compliance. Percentages of patients hospitalized were similar between groups, and median duration per hospitalization decreased after RLAT initiation and with oAP. The difference in duration of hospitalization between the retrospective and prospective period was significantly better with RLAT (P = 0.002). Mean CGI-SCH change from baseline was significantly better for RLAT vs. oAP patients for overall, positive, and negative symptom scores (P < 0.05). Mean functional improvement from baseline was significantly higher with RLAT vs. oAP (P < 0.001). Conclusions. Hospitalizations and symptomatic and functional outcomes were better with RLAT vs. oAP; frequent medication switches were associated with less favourable outcomes.

A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS

Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation.A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo.Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies.

1736 – Long-acting injectable risperidone and oral antipsychotics in patients with schizophrenia - a prospective one-year non-interventional study (inors)

Introduction and objectives To explore safety, tolerability, treatment response and hospitalizations in adult patients with schizophrenia treated with long-acting injectable risperidone (RLAI) or oral antipsychotic standard of care (oAP) in routine clinical practice. Methods Prospective one-year open-label non-interventional study exploring flexible doses of RLAI and oAPs. Primary outcome was the number of hospitalizations from baseline to endpoint. Additional outcomes were changes in the Clinical Global Impression of Schizophrenia (CGI-SCH), patient functioning (Global Assessment of Functioning) and treatmentemergent adverse events (TEAEs). Results The intent-to-treat analysis included 561 patients on RLAI and 522 patients on oAPs (44% female gender, mean age (±SD) 42.2±13.1 years). Demographics and baseline characteristics were comparable, yet RLAI-treated patients had higher disease severity, lower baseline functioning and more substance abuse. The number of hospitalizations did not differ between the two groups while median duration of hospitalization was significantly shorter with RLAI (12.3 vs 20.6 days). Positive, negative, cognitive symptoms, disease severity, patient functioning and medication satisfaction improved significantly better with RLAI than oAPs. The most frequently reported TEAEs (=2% in any group) for RLAI and oral APs were increase of body weight (5.0%; 5.6%), psychotic disorder (2.7%; 4.0%), schizophrenia (2.5%; 3.1%), anxiety (2.3%; 2.7%), insomnia (0.9%; 3.1%) and somnolence (0.4%; 2.5%), respectively. Conclusion This one-year non-interventional study supports results of recent randomized controlled trials that treatment with RLAI is associated with less days spent in hospital, better symptomatic and functional outcomes and higher patient satisfaction with medication compared to oral APs.