Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne.

BACKGROUND: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied. OBJECTIVES: Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne. METHODS: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator\u27s Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results. RESULTS: In both studies, at week 12 the facial success rates according to the Investigator\u27s Global Assessment and truncal Physician\u27s Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P \u3c .001) in favor of trifarotene when compared with the vehicle. LIMITATIONS: Adjunctive topical or systemic treatments were not studied. CONCLUSION: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne

Bioavailability, Antipsoriatic Efficacy and Tolerability of a New Light Cream with Mometasone Furoate 0.1%

Mometasone furoate, a potent glucocorticoid (class III) with a favorable benefit/risk ratio, has emerged as a standard medication for the treatment of inflammatory skin disorders. The purpose of the investigation presented here was to determine the noninferiority of a topical mometasone formulation, a light cream (O/W 60/40 emulsion) with mometasone furoate 0.1% (water content of 33%) versus marketed comparators. Using the vasoconstrictor assay, a strong blanching effect of the new cream (called Mometasone cream) comparable to that of a mometasone comparator, a fatty cream with mometasone furoate 0.1%, could be demonstrated. Thus, the topical bioavailability of the active ingredient mometasone furoate (0.1%) was regarded to be similar for Mometasone cream and the mometasone comparator. Using the psoriasis plaque test, a strong antipsoriatic effect comparable to that of the mometasone comparator was found for Mometasone cream after 12 days of occlusive treatment. A nearly identical reduction in the mean infiltrate thickness and similar mean AUC values were noted with both formulations confirmed by clinical assessment data. The noninferiority of Mometasone cream to its active comparator with re-spect to the AUC of change to baseline in infiltrate thickness was demonstrated. Both medications were well tolerated. Overall, Mometasone cream and the mometasone comparator showed similar efficacy and tolerability. Mometasone cream, in addition to its high potency and good tolerability, provides the properties of a light cream, which might make this new medication particularly suitable for application on acutely inflamed and sensitive skin. Copyright (C) 2012 S. Karger AG, Base

Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain. An observational analysis

INTRODUCTION: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. METHODS: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0-10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. RESULTS: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. CONCLUSION: OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function

Guideline on the use of onabotulinumtoxinA in chronic migraine. a consensus statement from the European Headache Federation

OnabotulinumtoxinA is being increasingly used in the management of chronic migraine (CM). Treatment with onabotulinumtoxinA poses challenges compared with traditional therapy with orally administered preventatives. The European Headache Federation identified an expert group that was asked to develop the present guideline to provide recommendations for the use of onabotulinumtoxinA in CM. The expert group recommend onabotulinumtoxinA as an effective and well-tolerated treatment of CM. Patients should preferably have tried two to three other migraine prophylactics before start of onabotulinumtoxinA. Patients with medication overuse should be withdrawn from the overused medication before initiation of onabotulinumtoxinA if feasible, if not onabotulinumtoxinA can be initiated from the start or before withdrawal. OnabotulinumtoxinA should be administered according to the PREEMPT injection protocol, i.e. injecting 155 U-195 U to 31-39 sites every 12-weeks. We recommend that patients are defined as non-responders, if they have less than 30% reduction in headache days per month during treatment with onabotulinumtoxinA. However other factors such as headache intensity, disability and patient preferences should also be considered when evaluating response. Treatment should be stopped, if the patient does not respond to the first two to three treatment cycles. Response to continued treatment with onabotulinumtoxinA should be evaluated by comparing the 4 weeks before with the 4 weeks after each treatment cycle. It is recommended that treatment is stopped in patients with a reduction to less than 10 headache days per month for 3 months and that patients are re-evaluated 4-5 months after stopping onabotulinumtoxinA to make sure that the patient has not returned to CM. Questions regarding efficacy and tolerability of onabotulinumtoxinA could be answered on the basis of scientific evidence. The other recommendations were mainly based on expert opinion. Future research on the treatment of CM with onabotulinumtoxinA may further improve the management of this highly disabling disorder

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH)&nbsp;=&nbsp;3.38, p&nbsp;=&nbsp;0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH&nbsp;=&nbsp;3.30, p&nbsp;=&nbsp;0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR)&nbsp;=&nbsp;2.50, p&nbsp;=&nbsp;0.037 for ABC-based triple-therapies, aHR&nbsp;=&nbsp;3.56, p&nbsp;=&nbsp;0.012 for tenofovir-based) and for toxicity (aHR&nbsp;=&nbsp;5.26, p&nbsp;=&nbsp;0.030 for ABC-based, aHR&nbsp;=&nbsp;6.60, p&nbsp;=&nbsp;0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Eletriptan in the management of acute migraine. An update on the evidence for efficacy, safety, and consistent response

Migraine is a multifactorial, neurological and disabling disorder, also characterized by several autonomic symptoms. Triptans, selective serotonin 5-HT1B/1D agonists, are the first-line treatment option for moderate-to-severe headache attacks. In this paper, we review the recent data on eletriptan clinical efficacy, safety, and tolerability, and potential clinically relevant interactions with other drugs. Among triptans, eletriptan shows a consistent and significant clinical efficacy and a good tolerability profile in the treatment of migraine, especially for patients with cardiovascular risk factors without coronary artery disease. It shows the most favorable clinical response, together with sumatriptan injections, zolmitriptan and rizatriptan. Additionally, eletriptan shows the most complex pharmacokinetic/dynamic profile compared with the other triptans. It is metabolized primarily by the CYP3A4 hepatic enzyme and therefore the concomitant administration of CYP3A4-potent inhibitors should be carefully evaluated. A relatively low risk of serotonin syndrome is given by the co-administration with serotoninergic drugs. No clinically relevant interaction has been found with drugs used for migraine prophylactic treatment or other acute drugs, with the exception of ergot derivatives that should not be co-administered with eletriptan

Long-term safety and efficacy of trifarotene 50 μg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne.

BackgroundTreatment for both facial and truncal acne has not sufficiently been studied.ObjectivesTo evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne.MethodsIn a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 μg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET.ResultsOf 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit.ConclusionIn this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne

Levetiracetam in clinical practice: efficacy and tolerability in epilepsy.

BACKGROUND: The aim of this study was to evaluate efficacy and tolerability of levetiracetam (LEV) in patients with different epilepsy syndromes. METHODS: We evaluated epileptic patients seen in the previous 18 months, including all patients with present or past exposure to LEV. Tolerability of LEV therapy was evaluated in all patients; efficacy was evaluated only in patients who had received LEV for at least six months. Two hundred and two patients were included in the study. Patients were considered responsive when showing a > 50% reduction in seizures frequency and non-responders when seizure frequency was unchanged, worsened or showed a reduction < 50%. RESULTS: Thirty patients did not complete six months of LEV treatment and dropped out. 57.4% of the patients with uncontrolled seizures treated for at least six months were responders, with 27.7% seizure free. Adverse effects were observed in 46 patients (23%) and were responsible for early drop out in 26. Adverse effects occurred significantly more often in females than in males (30.6% vs 13.2%); moreover, nearly 30% of women with adverse effects complained of more than one adverse effect, while this was never observed in male patients. CONCLUSIONS: Our study shows LEV as a well tolerated and effective treatment, both in monotherapy and as an add-on. Further investigations on larges samples are needed to investigate the issue of gender-related tolerability

Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM-HFpEF study.

BackgroundApproximately half of the patients presenting with new-onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid-range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta-blockers and angiotensin-converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease.MethodsThe Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM-HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post-titration follow-up period of at least 12 months.ConclusionsThe ANTHEM-HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF

A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.

BackgroundDFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms.MethodsThis was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months.ResultsA total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period.ConclusionDFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely