Effectiveness and tolerability of adjunctive brivaracetam in patients with focal seizures: second interim analysis of 6-month data from a prospective observational study in Europe

Brivaracetam (BRV) is indicated for adjunctive treatment of focal (partial-onset) seizures with or without secondary generalisation in patients 4 years of age and older in the European Union (EU). An ongoing 12-month, prospective, non-interventional post-marketing study (EP0077; NCT02687711) is collecting real-world information on patients receiving treatment with adjunctive BRV in Europe. In this study, BRV is prescribed according to routine clinical practice and the EU Summary of Product Characteristics. This second interim analysis assessed effectiveness, tolerability and health-related quality of life outcomes for up to 6 months of treatment. At the cut-off date (13 April 2018), 266 patients from five countries had attended Visit 1, 24.1% (64/266) had completed the study, 37.6% (100/266) were ongoing, and 38.3% (102/266) had discontinued. In total, 261 patients had at least one dose of BRV and were included in the analyses. Patients had a mean time since epilepsy diagnosis of 23.2 years, a mean of eight lifetime AEDs (sum of AEDs discontinued prior to study entry and concomitant at study entry), and a median of five focal seizures per 28 days during the 3-month retrospective Baseline. 66.3% of patients initiated BRV at a dose within the recommended starting range (50–100 mg/day) and 87.1% of patients received BRV modal doses within the recommended dose range (50–200 mg/day) during the study. Retention rates were 79.1% (N = 239) at 3 months and 62.1% (N = 211) at 6 months. The 50% responder rates for focal seizures were 46.8% (N = 139) at 3 months and 53.6% (N = 97) at 6 months. The proportions of patients who were seizure-free were 10.7% (21/196) and 7.5% (15/199) at 3 and 6 months of treatment, respectively. Median percent reductions in focal seizure frequency per 28 days from Baseline to 3 and 6 months were 34.6% (N = 139) and 53.3% (N = 97), respectively. Overall, 44.2% of patients had an improvement and 15.4% had a worsening in Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 total score from Baseline to 6 months (N = 52). At least one treatment-emergent adverse event (TEAE) was reported in 51.0% (133/261) of patients, and 34.5% (90/261) of patients had drug-related TEAEs. The most common drug-related TEAEs (≥5% of patients) were drug ineffective (7.7%), seizure (6.5%), and fatigue (6.1%). In this 6-month interim analysis, BRV showed effectiveness when used in clinical practice in five European countries. BRV was well tolerated, and no new safety signals were observed

Intra-articular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: Randomized, Double-blind, Placebo-controlled Trial.

Objective. We evaluated in a proof-of-concept double-blind placebo-controlled randomized trial the efficacy and safety of intra-articular sprifermin (recombinant human fibroblast growth factor 18) in patients with symptomatic knee OA. Methods. Sprifermin was evaluated as intra-articular injection at 10, 30, and 100μg. Primary efficacy endpoint was change in central medial femorotibial compartment (cMFTC) cartilage thickness at 6 and 12 months using quantitative MRI (qMRI). Primary safety endpoints were nature, incidence and severity of local and systemic treatment-emergent adverse events, acute inflammatory reactions and laboratory assessments. Secondary endpoints included changes in total and compartment femorotibial cartilage thickness and volume by qMRI, joint space width (JSW) from radiographs, and Western Ontario McMaster Universities (WOMAC) pain. Results. 192 patients were randomized and evaluated for safety, 180 completed the trial, 168 evaluated for primary efficacy endpoint. We found no statistically significant dose-response in change in cMFTC cartilage thickness. Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume, and in JSW narrowing in the lateral femorotibial compartment. All groups improved in WOMAC pain, with statistically significant less improvement at 12 months in patients receiving 100μg sprifermin than placebo. There was no significant difference in SAEs, TEAEs, AIRs between sprifermin and placebo groups. Conclusion. There was no statistically significant relationship between treatment group and reduction in cMFTC cartilage thickness. However, pre-specified structural secondary endpoints showed statistically significant dose-dependent reductions following sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns. Clinicaltrials.gov identification: NCT01033994. © 2014 American College of Rheumatology

Brivaracetam substituting other antiepileptic treatments: Results of a retrospective study in German epilepsy centers

Objective To evaluate the success of initiation of adjunctive brivaracetam in patients who required a change in antiepileptic drug (AED) regimen and substituted at least one AED with brivaracetam. Methods In this retrospective noninterventional study conducted in specialized epilepsy centers across Germany, patients initiated adjunctive brivaracetam between February 15, 2016, and August 31, 2016, as part of an intended change in AED regimen. The primary effectiveness variable was the proportion of patients who continued on brivaracetam after 3 months, and withdrew at least one AED either before or within 6 months after brivaracetam initiation. Results Five hundred and six patients had at least one brivaracetam dose and were included in the safety set (SS). Four hundred and seventy patients started to reduce the dose of one AED before/after brivaracetam initiation, had at least one concomitant AED at brivaracetam initiation, and were included in the full analysis set (FAS) for effectiveness analyses. At baseline, patients had a median of seven lifetime AEDs and a median of 3.8 seizures/28 days. In the SS, 85.2% of patients withdrew one AED before/after initiation of brivaracetam, most commonly levetiracetam (49.4%). 46.2% of patients substituted another AED with brivaracetam within 24 hours (fast withdrawal). The proportions of patients (FAS) who continued on brivaracetam after 3 and 6 months and withdrew one AED were 75.5% and 46.6%, respectively. After 6 months, 32.1% of patients were 50% responders; 13.0% were seizure‐free. In the SS, 34.6% of patients reported treatment‐emergent adverse events (TEAEs); 21.9% had TEAEs that were assessed by the treating physician as drug‐related. Incidences of behavioral AEs before (3‐month baseline) and after brivaracetam initiation in patients who withdrew levetiracetam were 19.2% and 8.0%, respectively (5.0% and 7.7% in patients who withdrew other AEDs). Significance Brivaracetam was effective and well‐tolerated in patients who required a change in AED drug regimen and initiated adjunctive brivaracetam in German clinical practice

Effectiveness and tolerability of lacosamide as add-on therapy in patients with brain tumor–related epilepsy: Results from a prospective, noninterventional study in European clinical practice (VIBES)

Objective: To evaluate the effectiveness and tolerability of lacosamide added to one or two antiepileptic drugs (AEDs) in the treatment of patients with brain tumor–related epilepsy (BTRE), and to evaluate patients’ global impression of change and quality of life (QoL). Methods: This was a prospective, multicenter, single-arm, noninterventional study with a 6-month observation period (EP0045; NCT02276053). Eligible patients (≥16 years old) had active BTRE secondary to low-grade glioma (World Health Organization grade 1 and 2) and were receiving treatment with one or two AEDs at baseline. Lacosamide was initiated by the treating physician in the course of routine clinical practice. Primary outcomes were 50% responders (≥50% reduction in focal seizure frequency from baseline) and Patient's Global Impression of Change (PGIC) at month 6. Secondary outcomes included seizure-free status and Clinical Global Impression of Change (CGIC) at month 6, change in QoL (5-Level EuroQol-5 Dimension Quality of Life Assessment) and symptom outcomes (MD Anderson Symptom Inventory–Brain Tumor) from baseline to month 6, and Kaplan-Meier estimated 6-month retention on lacosamide. Safety variables included adverse drug reactions (ADRs). Results: Patients were recruited from 24 sites in Europe. Ninety-three patients received lacosamide (mean [standard deviation] age = 44.5 [14.7] years; 50 [53.8%] male; median baseline focal seizure frequency = five seizures/28 days [range = 1-280]), of whom 79 (84.9%) completed the study. At 6 months, 66 of 86 (76.7%) patients were 50% responders and 30 of 86 (34.9%) were seizure-free. Improvements on PGIC were reported by 49 of 76 (64.5%) patients. Based on CGIC, 52 of 81 (64.2%) patients improved. QoL and symptoms outcome measures remained stable. Kaplan-Meier estimated 6-month retention rate was 86.0% (N = 93). Fifteen (16.1%) patients reported ADRs; four (4.3%) had ADRs leading to discontinuation (N = 93). Significance: Results of this prospective, noninterventional study suggest that add-on lacosamide is effective and generally well tolerated in patients with BTRE