Search

OBJECTIVE: Fenfluramine has been shown to provide clinically meaningful and statistically significant reductions in convulsive seizure frequency in children and adolescents (aged 2-18 years) with Dravet syndrome in two randomized, placebo-controlled clinical trials. The objective of this analysis was to assess longer-term safety and efficacy of fenfluramine in patients who completed one of the double-blind studies and entered an open-label extension (OLE) study. METHODS: Patients enrolling in the OLE study initiated fenfluramine at 0.2 mg/kg/d regardless of their treatment assignment in the double-blind study. After 4 weeks, the fenfluramine dose could be titrated based on efficacy and tolerability to maximum of 0.7 mg/kg/d (absolute maximum 27 mg/d) or maximum of 0.4 mg/kg/d (absolute maximum 17 mg/d) in patients receiving concomitant stiripentol. The number and type of seizures were recorded daily in an electronic diary, and safety, including echocardiography, was assessed at Months 1, 2, and 3, and at 3-month intervals thereafter. RESULTS: A total of 232 patients were enrolled as of March 13, 2018. During this analysis period, patients were treated for a median 256 days (range = 46-634 days). Over the entire OLE analysis period, the median decrease in convulsive seizure frequency compared to baseline in the double-blind studies was -66.8% (range = -100% to 234.9%; P

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a drug-resistant, childhood onset electroclinical epilepsy syndrome with multiple seizure types and diagnostic electroencephalogram findings. ZX008 (fenfluramine HCl oral solution) was well tolerated and reduced seizure frequency in Dravet syndrome, prompting this phase 2, open-label, dose-finding study of add-on ZX008 in patients with LGS (NCT02655198). METHODS: Eligible treatment-refractory patients with LGS aged 3-18 years with ≥4 documented convulsive seizures (CS) in the prior 4 weeks were administered adjunctive ZX008 twice daily at an initial dose of 0.2 mg/kg/d, with incremental dose escalations up to 0.8 mg/kg/d or 30 mg/d (maximum dose) every 4 weeks in nonresponders (

Richard Radnovich,1 Jeremiah Trudeau,2 Arnold R Gammaitoni3 1Injury Care Medical Center, Boise, ID, USA; 2Analgesic Solutions, Natick, MA, USA; 3Nuvo Research Inc., West Chester, PA, USA Background: Treatment for pain due to shoulder impingement syndrome (SIS) typically begins conservatively with nonsteroidal anti-inflammatory drugs and physical therapy and can include subacromial injection of corticosteroids, particularly in patients unresponsive to conservative measures. The heated lidocaine/tetracaine (HLT) patch has been reported to reduce SIS pain in a small case series. Methods: This was a prospective, randomized, open-label clinical trial in which adult patients with SIS pain lasting at least 14 days, with an average intensity of ≥4 on a 0–10 scale (0= no pain, 10= worst pain) were randomized to treatment with the HLT patch or a single subacromial injection of triamcinolone acetonide (10 mg). Patients in the HLT patch group applied a single HLT patch to the shoulder for 4 hours twice daily, with a 12-hour interval between treatments during the first 14 days, and could continue to use the patch on an as-needed basis (up to twice daily) during the second 14-day period. No treatment was allowed in the final 14-day period. At baseline and at days 14, 28, and 42, patients rated their pain and pain interference with specific activities (0–10 scale). Results: Sixty patients enrolled in the study (average age =51 years, range 18–75, n=21 female). Average pain scores declined from 6.0±1.6 at baseline to 3.5±2.4 at day 42 in the HLT patch group (n=29, P

We reviewed the current literature with respect to the humanistic and financial burdens of Dravet Syndrome (DS) on the caregivers of children with DS, in order to (1) identify key unanswered questions or gaps in knowledge that need to be addressed and then, based on these knowledge gaps, (2) propose a research agenda for the scientific community to address in the coming decade. The findings support the conclusion that caring for a child with DS is associated with significant humanistic burden and direct costs. However, due in part to the paucity of studies, as well as the lack of measures of specific burden domains, there remains much that is not known regarding the burden of caregiving for children with DS. To address the significant knowledge gaps in this area, research is needed that will: (1) identify the specific domains of caregivers' lives that are impacted by caring for a child with DS; (2) identify or, if needed, develop measures of caregiving impact in this area; (3) identify the factors that influence DS caregiving burden; (4) develop and evaluate the efficacy of treatments for reducing the negative impact of DS and its comorbidities on DS caregivers; (5) quantify the direct medical costs associated with DS and DS comorbidities and identify the factors that influence these costs; and (6) quantify and fully explore the indirect costs of DS. Research that addresses these goals will provide the empirical foundation needed for improving the quality of life of children with DS and their families.

Arnold R Gammaitoni,1 Henry T Goitz,2 Stephanie Marsh,2 Thomas B Marriott,3 Bradley S Galer1 1Pain Group, Nuvo Research US, West Chester, PA, USA; 2Sports Medicine, Detroit Medical Center, Warren, MI, USA; 3Pain Group, Nuvo Research US, Salt Lake City, UT, USA Introduction: The pain of patellar tendinopathy (PT) may be mediated by neuronal glutamate and sodium channels. Lidocaine and tetracaine block both of these channels. This study tested the self-heated lidocaine-tetracaine patch (HLT patch) in patients with PT confirmed by physical examination to determine if the HLT patch might relieve pain and improve function. Methods: Thirteen patients with PT pain of ≥14 days' duration and baseline average pain scores ≥4 (on a 0–10 scale) enrolled in and completed this prospective, single-center pilot study. Patients applied one HLT patch to the affected knee twice daily for 2–4 hours for a total of 14 days. Change in average pain intensity and interference (Victorian Institute of Sport Assessment [VISA]) scores from baseline to day 14 were assessed. No statistical inference testing was performed. Results: Average pain scores declined from 5.5 ± 1.3 (mean ± standard deviation) at baseline to 3.8 ± 2.5 on day 14. Similarly, VISA scores improved from 45.2 ± 14.4 at baseline to 54.3 ± 24.5 on day 14. A clinically important reduction in pain score (≥30%) was demonstrated by 54% of patients. Conclusion: The results of this pilot study suggest that topical treatment that targets neuronal sodium and glutamate channels may be useful in the treatment of PT. Keywords: patellar tendinopathy, patellar tendinosis, heated lidocaine/tetracaine patch, topical analgesic patch, knee pain

Background Our objective was to evaluate the effect of background biological disease-modifying anti-rheumatic drugs (bDMARDs) and/or corticosteroids (CS) on response to nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis (RA) patients. Methods The following efficacy endpoints were evaluated using time-weighted change from baseline in a 12-week, randomized controlled clinical trial with etoricoxib: Patient Global Assessment of Pain, Swollen Joint Count, Tender Joint Count, Health Assessment Questionnaire. The following three treatment groups were evaluated: placebo, pooled etoricoxib 10/30/60 mg, and etoricoxib 90 mg. Screening values, values post flare, as well as changes after treatment were analyzed. Results Of the 1014 patients screened, 761 were randomized; 50% were on no background bDMARDs and/or CS therapy, 23% used bDMARDs, 34% used CS, and 8% used both bDMARDs and CS. It was demonstrated that RA patients on bDMARDs or CS had similar pain levels at screening as patients without this co-medication. They experienced flare upon NSAID withdrawal and demonstrated dose-dependent pain improvement with etoricoxib. Conclusion These results support that RA patients receiving bDMARDs or CS may still require the use of concomitant analgesics to treat pain. Clinicians should continue to monitor and treat pain even after initiating a bDMARD and/or CS. Trial Registration [clinicaltrials.gov; NCT00264147]

Background Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs. Methods This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation. Results For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks. Conclusions For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of NNTs and responder analyses provide additional, complementary information beyond population mean responses when assessing efficacy compared to placebo and amongst active therapies.