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Background: We previously demonstrated the efficacy of Japanese cedar (JC) pollen sublingual immunotherapy (SLIT) tablets for treating seasonal allergic rhinitis in a clinical trial (trial no. 206-2-1) that covered 5 pollen dispersal seasons from 2015 to 2019. Objective: Our aim was to perform post hoc analysis of the 206-2-1 trial data to evaluate the efficacy of JC pollen SLIT tablets for patients with rhinitis induced by pollen from Japanese cypress (JCY), a related Cupressaceae species that has a pollen dispersal season overlapping with that of JC. Methods: Data were analyzed for 240 patients who received placebo during the first pollen dispersal season in 2015, were then rerandomized to receive JC SLIT tablets (the PA group) or placebo (the PP group) for 18 months (the 2016 and 2017 dispersal seasons), and were observed untreated for 2 years (the 2018 and 2019 dispersal seasons). The PA and PP groups were assigned to “high” and “low” subgroups if their rhinitis symptoms were exacerbated/did not change or decreased, respectively, during the peak JCY pollen dispersal period in 2015. The mean total nasal symptom and medication scores and other outcomes were compared for the high-PP, high-PA, low-PP, and low-PA groups during the 2016 to 2019 peak JCY pollen dispersal periods. Results: The mean total nasal symptom and medication scores were significantly lower for the high-PA and low-PA groups than for the corresponding PP groups over the 4 years of treatment and observation. JCY pollen–specific IgE levels increased in both PA groups. Conclusion: JC pollen SLIT tablets effectively suppressed JCY pollinosis symptoms, supporting the clinical relevance of immunologic cross-reactivity between JC and JCY allergens.

Abstract Background Haemaphysalis longicornis ticks are reported on dogs from an increasing geographic range. This study aimed to determine the sustained efficacy of Seresto® collars (imidacloprid/flumethrin) against experimental infestations of H. longicornis in dogs. Methods Twenty-four Beagle dogs previously assessed for their suitability to harbor ticks were included in the study and randomized into three groups of eight dogs each. Two of the groups were treated with collars at different time points: at the first tick infestation, dogs in group 1 had already worn collars for 92 days, while dogs in group 2 had received collars only on the previous day, thus allowing evaluation of two different treatment durations at the same point in time. Infestation of the treated groups was conducted at 1, 7, 28, and 56 days (group 2) and 92, 119, 147, 168, 196, 227, and 238 days (group 1) after collar placement. Group 3 served as untreated control and was infested whenever the dogs of the other two groups were infested. Infestations were conducted using 50 viable, adult, unfed female ticks of a US isolate of H. longicornis per dog. Ticks were removed and counted 48 h after each infestation. Health and body weight of the dogs were monitored throughout the study. The efficacy against ticks was calculated for groups 1 and 2 based on arithmetic mean values at each assessment day according to Abbott’s formula. The mean post-treatment H. longicornis tick counts were compared statistically between treatments, using an analysis of variance with a treatment effect untransformed tick count. Results Dogs in the control group were adequately infested at all tick counts. Efficacy was 88.2% on day 3, however well above 90% (i.e., 98.3 to 100%) at all other time points up to day 240. Statistical analysis confirmed significantly different live tick counts (P

Introduction: Rapid onset and sustained efficacy are important for acute migraine treatment. Global phase 3 trials have demonstrated the early onset and sustained efficacy of the 5-HT1F receptor agonist lasmiditan. In this prespecified analysis of the MONONOFU study, we assessed the onset and sustained efficacy of lasmiditan in Japanese patients with migraine. Methods: MONONOFU was a multicenter, randomized, placebo-controlled, phase 2 study conducted in Japan (May 2019–June 2020). Eligible adults with migraine (N = 846; modified intent-to-treat population, N = 682) were randomized 7:3:7:6 to placebo, lasmiditan 50 mg, 100 mg, or 200 mg, taken orally within 4 h of moderate-to-severe migraine onset. Patients recorded headache severity and symptoms predose and 0.5–48 h postdose. Sustained and modified sustained pain freedom were defined as patients who were headache pain-free 2 h postdose and had no pain (sustained pain freedom) or had mild or no pain (modified sustained pain freedom) at 24 or 48 h without rescue/recurrence medications. Efficacy outcomes were analyzed by logistic regression. Patients also recorded the actual time of pain-free and of meaningful pain relief (Kaplan–Meier analysis). Results: Compared with placebo, significantly more lasmiditan-treated (100 or 200 mg) patients were headache pain-free, had pain relief, were free of their most bothersome symptom, or had total migraine freedom (no headache or migraine-associated symptoms) within 30–60 min. Median time to pain-free was 9.26, 6.88, 2.75, and 2.30 h in placebo, 50-mg, 100-mg, and 200-mg lasmiditan groups, respectively. Significantly greater proportions of patients treated with 100 (19.7–29.5%) or 200 mg (21.1–35.7%) lasmiditan had sustained or modified sustained pain freedom at 24 or 48 h compared with placebo (10.4–15.8%). Conclusion: This prespecified analysis of data from MONONOFU has confirmed that the efficacy of lasmiditan is rapid in onset and sustained in patients with moderate-to-severe migraine in Japan. Trial Registration: ClinicalTrials.gov (NCT03962738). [ABSTRACT FROM AUTHOR]

Background: Haemaphysalis longicornis ticks are reported on dogs from an increasing geographic range. This study aimed to determine the sustained efficacy of Seresto® collars (imidacloprid/flumethrin) against experimental infestations of H. longicornis in dogs. Methods: Twenty-four Beagle dogs previously assessed for their suitability to harbor ticks were included in the study and randomized into three groups of eight dogs each. Two of the groups were treated with collars at different time points: at the first tick infestation, dogs in group 1 had already worn collars for 92 days, while dogs in group 2 had received collars only on the previous day, thus allowing evaluation of two different treatment durations at the same point in time. Infestation of the treated groups was conducted at 1, 7, 28, and 56 days (group 2) and 92, 119, 147, 168, 196, 227, and 238 days (group 1) after collar placement. Group 3 served as untreated control and was infested whenever the dogs of the other two groups were infested. Infestations were conducted using 50 viable, adult, unfed female ticks of a US isolate of H. longicornis per dog. Ticks were removed and counted 48 h after each infestation. Health and body weight of the dogs were monitored throughout the study. The efficacy against ticks was calculated for groups 1 and 2 based on arithmetic mean values at each assessment day according to Abbott's formula. The mean post-treatment H. longicornis tick counts were compared statistically between treatments, using an analysis of variance with a treatment effect untransformed tick count. Results: Dogs in the control group were adequately infested at all tick counts. Efficacy was 88.2% on day 3, however well above 90% (i.e., 98.3 to 100%) at all other time points up to day 240. Statistical analysis confirmed significantly different live tick counts (P < 0.001) between the treated groups and the control group at all time points. Conclusions: The 8-month sustained acaricidal efficacy demonstrated by the Seresto® collar (imidacloprid/flumethrin) provides a reliable strategy against H. longicornis infestations in dogs. [ABSTRACT FROM AUTHOR]

Abstract Background Evidence on whether the therapeutic effect and good safety profile of onabotulinumtoxinA (Botox®) in chronic migraine (CM) patients is maintained over long term treatment is still limited. We herein aimed at assessing whether there is a sustained benefit and good safety with repeated onabotulinumtoxinA sessions in CM over more than three years of treatment. Methods We prospectively enrolled 65 CM patients, who were classified as responders after three sessions of onabotulinumtoxinA and were eligible to further continue treatment. Data documenting longitudinal changes from the trimester after the third onabotulinumtoxinA administration (T1) to the trimester after completing two years of treatment (T2) and eventually to the trimester after completing three years of treatment (T3) in (i) mean number of monthly headache days (ii) migraine severity as expressed by the mean number of days with peak headache intensity of > 4/10, and (iii) mean number of days with use of any acute headache medication, were prospectively collected from patients’ headache diaries. Results A total of 56 (86.1%) of 65 patients achieved to attain onabotulinumtoxinA over three years. At T3, a significant reduction in mean monthly headache days was evident, compared to T1 (3.4 ± 1.7 vs 7.2 ± 3.8; P

Background: Tildrakizumab is a high-affinity, humanized, IgG1 κ, anti-interleukin-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis. Objectives: This analysis examined whether tildrakizumab's week-28 efficacy can be sustained or improved to week 52. Methods: Psoriasis patients on the same-dose tildrakizumab (100 or 200 mg) in the first 52 weeks achieving week-28 PASI ≥50 were pooled from two phase-3 randomized controlled trials, and grouped into four mutually exclusive week-28 PASI response groups. Patients' week-52 PASI responses were compared to their week-28 PASI responses. Results: Of 352 patients receiving 100-mg tildrakizumab, 10.5%, 25.3%, 38.4%, and 25.9% achieved PASI 50–74, 75–89, 90–99, and 100 at week 28, respectively. Among patients achieving PASI ≥90, ≥75, or ≥50 at week 28, 89.4%, 91.1%, or 97.4% maintained their week-28 PASI responses at week 52, respectively. Among patients achieving PASI 50–74, 75–89, or 90–99 at week 28, 64.8%, 33.7%, or 25.2% improved their week-28 PASI responses at week 52, respectively. Limitations: This post hoc analysis may be less robust than an a priori analysis. Conclusions: Most tildrakizumab-treated patients with week-28 PASI ≥75 maintained their week-28 PASI improvement at week 52. More than half of week-28 partial responders (PASI 50–74) improved their PASI responses to PASI ≥75 at week 52. Clinicaltrials.gov identifiers: NCT01722331, NCT01729754. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine if mecetronium etilsulfate (MES) contributes to overall efficacy in surgical hand disinfection. Three blinded hand rubs (45% iso-propanol, 30% n-propanol) were applied for 1.5 min and compared with the EN 12791 reference procedure (crossover design). One commercial hand rub contained 0.2% MES, and the two other hand rubs were identical apart from 0.2% MES. None of the formulations had a log10 reduction after 3 h that was significantly better compared with the reference procedure [mean 1.72 (standard deviation 1.15)]. The antimicrobial contribution of MES in hand rubs is questionable. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The aim of the study was to describe effectiveness and safety of percutaneous tibial nerve stimulation (PTNS) at 2 years in women with overactive bladder (OAB) syndrome unresponsive to pharmacotherapy. Methods: Of 30 women who had initial positive response to PTNS, 23 continued to receive maintenance treatment and were reassessed at 2 years using bladder symptom diaries and the Incontinence Impact Questionnaire (IIQ-7). They were also questioned on acceptability and any adverse effects of long-term peripheral neuromodulative treatment. Results: Data from 23 women were available and 7 had been lost to follow-up. With maintenance treatment, the median nocturnal frequency at 2 years had decreased by 57 % (3.5 to 1.5 times/night), while the median IIQ-7 had reduced from 30.4 to 21.5 (both p < 0.01) compared to pre-treatment baseline. Median nocturnal frequency and IIQ-7 scores at 2 years were comparable to those documented after initial response to treatment at 6 weeks, suggesting that maintenance therapy continued to suppress OAB symptoms. Daytime frequency and daily urgency incontinence episodes at 2 years were statistically similar to those documented at 6 weeks and remained lower than pre-treatment baseline (6.5 vs 11.8 and 2.0 vs 3.5, respectively, p < 0.05). The women received a median of 8.42 treatments per year and the median length between treatments was 64.3 days. Apart from hypaesthesia in the toe of one responder lasting for 4 months, there were no reported side effects. Conclusions: Women receiving PTNS for intractable OAB syndrome reported significant symptom relief at 2 years. This remains a safe mode of second-line treatment with excellent durability. [ABSTRACT FROM AUTHOR]

Once-daily hydromorphone extended-release (OROS® hydromorphone ER) and oxycodone controlled-release (CR) are semisynthetic, ER opioid analgesics with established efficacy. An open-label, randomized, 24-week, parallel group, flexible-dose study demonstrated noninferiority of OROS hydromorphone ER vs. twice-daily oxycodone CR in patients with chronic noncancer pain. In total, 112 patients were enrolled in a 28-week, open-label extension study; 60 patients received OROS hydromorphone ER and 52 received oxycodone CR. The primary efficacy measure was the change from baseline to Weeks 38 and 52 in Brief Pain Inventory item 'pain right now.' Global assessments of efficacy, dosing convenience, and tolerability were secondary endpoints. Mean change in 'pain right now' from baseline to Week 38 was −3.0 (OROS hydromorphone ER) vs. −2.8 (oxycodone CR), and from baseline to Week 52 was −2.9 vs. −2.8; these changes were similar to the changes in the core phase (−2.1 vs. −2.1). Similar improvements were demonstrated for secondary assessments, including pain, pain interference, and quality of life. At Week 52, global assessment of efficacy was rated as 'very good' or 'good' by the majority of patients (OROS hydromorphone ER, 91.7%; oxycodone CR, 86.5%). More patients in the OROS hydromorphone ER group (35.0% vs. 21.2%) assessed mode of drug intake as 'very convenient.' The majority of patients receiving OROS hydromorphone ER (88.3%) and oxycodone CR (88.5%) rated tolerability as 'good' or 'very good' at Week 52; few patients discontinued treatment because of an adverse event (1.6% vs. 0.4%, respectively). The effectiveness of OROS hydromorphone ER and oxycodone CR was maintained through 1 year. [ABSTRACT FROM AUTHOR]

Abstract: Dialectical Behaviour Therapy (DBT) is considered one of the most promising treatments for borderline personality disorder (BPD). Recently, we reported significantly positive effects of 12 months DBT on parasuicidal behaviour and impulsivity in a mixed group of female BPD patients with and without substance abuse. Fifty-eight women with BPD were randomly assigned to either 52 weeks of DBT or treatment as usual (TAU). Follow-up assessment took place at 78 weeks, i.e., 6 months after discontinuation of DBT. Participants were clinical referrals from addiction treatment and psychiatric services. Outcome measures included parasuicidal behaviour, impulsivity and substance abuse. Six months after treatment discontinuation, the benefits of DBT over TAU in terms of lower levels of parasuicidal and impulsive behaviours, and in alcohol use, sustained. No differences between the treatment conditions were found for drug abuse. In conclusion, DBT seems to have a sustained effect on some of the core symptoms of BPD and on alcohol problems in a mixed population of female borderline patients with and without substance abuse problems. [Copyright &y& Elsevier]

Purpose: To investigate whether the efficacy of levetiracetam (LEV) is sustained in adult patients with refractory partial seizures over a 3-month period. Methods: Treatment effect was assessed in a post hoc analysis by determining the proportion of seizure-free days during each week of a 3-month period after the initiation of treatment. Pooled data from three randomized, double-blind, placebo-controlled trials (n = 883) were analyzed. Results: The mean proportion of seizure-free days was greater in the LEV group than in the placebo group. The difference, which was statistically significant, was observed as early as the first week after the initiation of treatment. It was higher in the first week of treatment and subsequently was maintained for each week over the 3-month period (p < 0.001 or p = 0.002 at each time point). Patients in the LEV group had on average 74% to 81% days each week without any seizure, compared with 69% to 72% in the placebo group. Conclusions: LEV is efficient in controlling seizures from the first week of drug initiation, during uptitration, and throughout the first 3 months of treatment. An interesting amplification of efficacy occurs in the first week of therapy, which is intriguing and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Japanese cedar (JC) pollinosis is a common allergic rhinitis in Japan. JC pollen sublingual immunotherapy (SLIT) tablets are licensed for the treatment of JC pollinosis., Objective: To assess the disease-modifying effects of JC pollen SLIT tablets over 5 years (2014-2019), comprising a 3-year treatment period and 2-year follow-up., Methods: A total of 1042 patients with JC pollinosis (aged 5-64 years) were included in the study. An optimal dose-finding study was performed in the first 15 months, after which 240 patients in the placebo (P) group and 236 patients in the optimal active dose (A) group (5000 Japanese allergy units) were re-randomized to receive P or A for an additional 18 months (designated AA, AP, PA, and PP groups). Clinical efficacy was evaluated by the total nasal symptom and medication score (TNSMS) during the peak symptom period of each JC pollen season over 3 years of treatment and 2 years of observation after treatment cessation., Results: The AA, AP, and PA groups exhibited significantly reduced TNSMS; however, the largest relative reduction was seen in the AA group both during the treatment period (third season, 46.3% vs PP, P < .001) and during the 2-year follow-up period (fourth and fifth seasons, 45.3% and 34.0% vs PP, respectively; P < .001). The most common adverse drug reactions were mild reactions at the administration site., Conclusions: JC pollen SLIT tablets show sustained clinical efficacy during 3 years of treatment and sustained disease-modifying effects for at least 2 years after treatment cessation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We report the sustained efficacy of the SQ-standardized grass allergy immunotherapy tablet Grazax® (Phleum pratense 75 000 SQ-T/2,800 BAU, ALK, Denmark) from a 5-year randomized, double-blind, placebo-controlled phase III trial. Adults with moderate-to-severe grass pollen allergy inadequately controlled by symptomatic medications were followed for 2 years after the completion of 3 years of treatment. The active group demonstrated a 31% reduction in median rhinoconjunctivitis symptom score over the season compared with placebo. Individual symptom scores favoured active treatment. Combined symptom and medication scores demonstrated a 33% reduction in medians with active treatment. Persistent clinical efficacy was accompanied by prolonged increases in allergen-specific IgG4 antibodies and IgEblocking factor, confirming clinical and immunological tolerance for at least 2 years after the treatment completion. No safety issues were identified during follow-up. [ABSTRACT FROM AUTHOR]

Background: Evidence on whether the therapeutic effect and good safety profile of onabotulinumtoxinA (Botox®) in chronic migraine (CM) patients is maintained over long term treatment is still limited. We herein aimed at assessing whether there is a sustained benefit and good safety with repeated onabotulinumtoxinA sessions in CM over more than three years of treatment.Methods: We prospectively enrolled 65 CM patients, who were classified as responders after three sessions of onabotulinumtoxinA and were eligible to further continue treatment. Data documenting longitudinal changes from the trimester after the third onabotulinumtoxinA administration (T1) to the trimester after completing two years of treatment (T2) and eventually to the trimester after completing three years of treatment (T3) in (i) mean number of monthly headache days (ii) migraine severity as expressed by the mean number of days with peak headache intensity of > 4/10, and (iii) mean number of days with use of any acute headache medication, were prospectively collected from patients’ headache diaries.Results: A total of 56 (86.1%) of 65 patients achieved to attain onabotulinumtoxinA over three years. At T3, a significant reduction in mean monthly headache days was evident, compared to T1 (3.4 ± 1.7 vs 7.2 ± 3.8; P < 0.001) with diminished mean number of monthly days with peak headache intensity of more than 4/10 and a significant change in days using acute headache medications per month between T1 and T3 (2.8 ± 1.3 vs 4.7 ± 3.2; P < 0.001). Significant changes were also noticed in all efficacy variables from T2 to T3. Therapy was safe and well tolerated with low rates of adverse events or drop-outs.Conclusion: The long -term treatment with onabotulinumtoxinA proved effective, safe and well tolerated over three years. Our findings support the strategy to consistently deliver sessions of use of onabotulinumtoxinΑ over long time in CM patients (Trial registration NTC03606356, registered retrospectively, 28 July 2018). [ABSTRACT FROM AUTHOR]

Background: The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials. Objective: To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU, ∗ [∗] SQ-T (standardized quality tablet units) and BAU (biological activity units) are quantitative measures of biological activity; ie, the potency of allergen extracts/vaccines. One grass AIT contains 75,000 SQ-T of timothy (Phleum pratense) grass pollen extract (measure of total biological potency using ALK in-house reference), equivalent to 2,800 BAU (measure of total biological potency, defined by the FDA). ALK, Denmark) or placebo. Methods: A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen–induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters. Results: The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% (P ≤ .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by 20% to 45% (P ≤ .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% (P ≤ .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% (P ≤ .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified. Conclusion: The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis. [Copyright &y& Elsevier]

Background: Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial. Objective: We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abelló, Hørsholm, Denmark). Methods: A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen–specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events. Results: Significant improvements in efficacy were consistently shown during 3 years'' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified. Conclusion: Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment, which is indicative of disease modification and associated long-term benefits. [Copyright &y& Elsevier]