Patients Achieved Treatment Success Research Articles

Comparative analysis of two custom-made mandibular advancement devices with varied designs for treating moderate to severe obstructive sleep apnea

IntroductionCustom-made titratable mandibular advancement device (MAD) treatment can nowadays be considered a promising first-line treatment in patients with mild to severe obstructive sleep apnea (OSA). Specific manufacturing designs and titration mechanisms of MAD are on the market, characterized by their titration approach, vertical opening, and materials selection.The wing-designed MAD (SomnoDent® Flex™, SomnoMed Ltd, Sydney, Australia) has a lateral screw mechanism to advance the lower jaw in incremental steps of 0.1 up to 6.0 mm. The newer uniquely designed custom-made MAD with passive mouth closing (SomnoDent® Avant™ SomnoMed Ltd, Sydney, Australia) has a frontal exchangeable advancement strap of fixed lengths as a specific titration mechanism, all supporting freedom of lateral movement.We aimed to assess the associations between the type of MAD prescribed and OSA treatment outcome. MethodsData from 209 patients (165 male, mean age 53.9 (±10.9) years, median baseline BMI and AHI 27.02 [24.8; 29.7] kg/m2 and 22.8 [17.7; 31.6]/hour sleep, respectively) were collected.Of this cohort, 91 patients with the traditional, wing-based SomnoDent® Flex™ and 118 patients with SomnoDent® Avant™. All patients were diagnosed with a type 1 polysomnography demonstrating moderate to severe OSA (15 ≤ AHI ≤65 per hour sleep). The selected MAD was fitted in the so-called maximal comfortable protrusion.After 3 months of subjective titration until resolution of subjective symptoms and/or achieving physical limits, a checkup with validated home sleep monitoring was conducted. Treatment success was defined as “AHI reduction ≥50% with MAD compared to baseline AHI and AHI with MAD <10 events per hour”. ResultsThese real-world data set showed that 67% of patients achieved treatment success, with a statistically significant reduction in AHI from 22.8 [17.7; 31.6] to 7.45 [3.4; 15.0]/h sleep. The SomnoDent® Avant™ achieved 75% treatment success versus 56% for the traditional, wing-based SomnoDent® Flex™ (P < 0.05). Overall, AHI reduction was 70% for SomnoDent® Avant™ (P < 0.05) vs. 63% for SomnoDent® Flex™ (P < 0.05). ConclusionsThis study shows that choice of MAD design can impact the treatment outcome and could become an important consideration in selecting the type of MAD for personalized treatment for OSA patients. While the results of the traditional wing-based MAD design were comparable to the therapeutic outcome with other titratable, custom-made MADs, the MAD with the passive mouth closing feature showed significantly greater reduction in total AHI potentially due to encouraged nasal breathing, reduced mouth breathing and lesser vertical opening thereby decreasing the probability of tongue base collapse.

Nasal Glucagon Reverses Insulin-induced Hypoglycemia With Less Rebound Hyperglycemia: Pooled Analysis of Clinical Trials.

Rebound hyperglycemia may occur following glucagon treatment for severe hypoglycemia. We assessed rebound hyperglycemia occurrence after nasal glucagon (NG) or injectable glucagon (IG) administration in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). This was a pooled analysis of 3 multicenter, randomized, open-label studies (NCT03339453, NCT03421379, NCT01994746) in patients ≥18 years with T1D or T2D with induced hypoglycemia. Proportions of patients achieving treatment success [blood glucose (BG) increase to ≥70 mg/dL or increase of ≥20 mg/dL from nadir within 15 and 30 minutes]; BG ≥70 mg/dL within 15 minutes; in-range BG (70-180 mg/dL) 1 to 2 and 1 to 4 hours postdose; and BG >180 mg/dL 1 to 2 and 1 to 4 hours postdose were compared. Incremental area under curve (iAUC) of BG >180 mg/dL and area under curve (AUC) of observed BG values postdose were analyzed. Safety was assessed in all studies. Higher proportions of patients had in-range BG with NG vs IG (1-2 hours: P = .0047; 1-4 hours: P = .0034). Lower proportions of patients had at least 1 BG value >180 mg/dL with NG vs IG (1-2 hours: P = .0034; 1-4 hours: P = .0068). iAUC and AUC were lower with NG vs IG (P = .025 and P < .0001). As expected, similar proportions of patients receiving NG or IG achieved treatment success at 15 and 30 minutes (97-100%). Most patients had BG ≥70 mg/dL within 15 minutes (93-96%). The safety profile was consistent with previous studies. This study demonstrated lower rebound hyperglycemia risk after NG treatment compared with IG. NCT03421379, NCT03339453, NCT01994746.

Efficacy and Safety of Fractional CO2 Laser Combined with Halometasone Cream for Treatment of Moderate-to-Severe Chronic Hand Eczema: A Prospective, Single-Center, Parallel-Group, Open-Label Randomized Trial.

The purpose of this study was to assess the efficacy and safety of fractional CO2 laser combined with halometasone cream in patients with moderate-to-severe chronic hand eczema (CHE). A prospective, single-center, parallel-group, open-label randomized trial including 67 patients with moderate-to-severe CHE was carried out. Patients were randomly assigned to group A (n = 33, fractional CO2 laser once every 4weeks 1-2 times and halometasone cream twice daily for 8weeks) or group B (n = 34, halometasone cream alone twice daily for 8weeks). The primary endpoint was the proportion of patients achieving treatment success at week12 in each group. Secondary endpoints included differences between groups in the change of hand eczema severity index (HECSI), patient global assessment (PaGA), dermatology life quality index (DLQI), and quality of life in hand eczema questionnaire (QOLHEQ) from baseline to week12. Relapse rate and adverse effects were also recorded. A total of 29 patients in each group completed the trial. At week12, the treatment success rate was 62.1% (18/29) in group A and 27.6% (8/29) in group B (p = 0.009). At week12, HECSI, PaGA, DLQI, and QOLHEQ all decreased compared with baseline in both groups (p < 0.05). HECSI, DLQI, and QOLHEQ decreased more in group A than group B (p = 0.014, 0.010, and 0.014, respectively), but there was no significant difference in change of PaGA between the two groups (1.0 versus 3.0, p = 0.419). Among patients achieving treatment success, 11.1% (2/18) patients in group A and 50.0% (4/8) patients in group B relapsed at week24 (p = 0.011). Skin pigmentation was the most common adverse effect. For patients with moderate-to-severe CHE, fractional CO2 laser combined with halometasone cream is more effective than halometasone cream alone, with few adverse effects. ChiCTR2100051948.

430 Comparison of effectiveness of topical treatments for atopic dermatitis

Abstract Atopic dermatitis (AD) is a chronic inflammatory condition that affects 15% of children and 7.3% of adults in the USA. While topical corticosteroids (TCs) and topical calcineurin inhibitors (TCIs) are considered the mainstay of topical treatments for AD management, long-term use is cautioned due to possible adverse effects (AEs). We present and review the efficacy and safety of new FDA-approved topical agents, topical agents currently in clinical trials, and TCs and TCIs that are currently available for AD management. We also present and compare the safety and efficacy of new and old FDA-approved topical agents, along with other topical treatments that are currently in clinical trials for AD management. An extensive review of the literature was performed using the PubMed, Cochrane, Scopus and ClinicalKey databases with year parameters set between 2014 and 2022. Search keywords included ‘atopic dermatitis’, ‘topical treatments’, ‘comparison’, ‘effectiveness’, ‘new topical treatments for AD’, ‘JAK inhibitors’, ‘PDE-4 inhibitors’, ‘delgocitinib’, ‘crisaborole’ and ‘tapinarof’. We identified four topical drug classes that are efficacious in treating AD: corticosteroids, calcineurin inhibitors, phosphodiesterase-4 (PDE-4) inhibitors and aryl hydrocarbon receptor agonists. Criteria for treatment success were an IGA score of 0 or 1 and improvement ≥2 grades from baseline. Treatment varied among studies from 2 to 24 weeks. Topical corticosteroids were the most effective after adjusting for vehicle (0.05% clobetasol propionate emulsion foam, 38%; 0.1% clocortolone pivalate, 31.6% IGA reduction), followed by tapinarof 1% cream with 29% of patients achieving treatment success, TCIs (0.03% tacrolimus ointment, 24.8%; 1% pimecrolimus cream, 32.1% vehicle-adjusted achieving IGA of ≤2) and PDE-4 inhibitors (2% crisaborole ointment, 10.4%). Tapinarof was the most efficacious in treating AD. There is a lack of head-to-head trials for topical treatments for AD. Due to the tremendous burden of AD on patients’ physical and mental health, there is a need for additional therapies.

S189 Efficacy and Safety of RBX2660 in Patients After First Recurrence of Clostridioides difficile Infection – Results From a Phase 3, Randomized, Placebo-Controlled Study

Introduction: Antibiotics used to treat Clostridioides difficile infection (CDI) can predispose patients to recurrent CDI (rCDI). Gut microbiome restoration by fecal microbiota transplantation is recommended by multiple guidelines after ≥2 rCDI, with no guideline recommended options to restore the microbiome earlier in the course of CDI. A prespecified analysis of a prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 trial, PUNCH CD3 (NCT03244644), showed consistent efficacy of microbiota-based live biotherapeutic RBX2660 in participants with ≤3 (treatment success: placebo, 67%; RBX2660, 72%) and >3 (placebo, 54%; RBX2660, 70%) episodes of CDI prior to enrollment. In the present post-hoc analysis, we report the efficacy and safety of RBX2660 in a subgroup of patients with only 1 rCDI episode prior to enrollment. Methods: Patients enrolled in PUNCH CD3 were ≥18 years old with ≥1 rCDI episode as determined by the treating physician and assessed with current standard-of-care (SOC) diagnostic methods. After completing SOC antibiotic therapy for the enrolling CDI episode, patients received a single blinded dose of RBX2660 or placebo. Treatment success was defined as remaining free of CDI recurrence for 8 weeks after treatment. Patients were monitored for recurrence through 6 months. Treatment-emergent adverse events (TEAEs) were summarized for the double-blind treatment period within 8 weeks. Results: In the modified intent-to-treat population, 86 of 276 patients (32.2%) were enrolled after 1 rCDI. Patients were mostly white (93%) and female (66.3%) with a mean age of 58 years. At week 8, 79.2% (42/53) of RBX2660-treated patients and 60.6% (20/33) of placebo-treated patients achieved treatment success. Of responders, 90.5% (38/42) treated with RBX2660 and 85% (17/20) treated with placebo remained recurrence-free at 6 months. TEAEs were reported by 54.7% (29/53) of RBX2660-treated patients and 33.3% (11/33) of placebo-treated patients; mild events, mostly gastrointestinal, accounted for the difference. Serious adverse events were reported by 5.7% (3/53) of RBX2660-treated and 6.1% (2/33) of placebo-treated patients. No potentially life-threatening TEAEs or TEAEs leading to discontinuation or death were reported. Conclusion: After 1 rCDI episode, RBX2660-treated patients had numerically higher treatment success at week 8 and sustained response at 6 months compared to placebo. These results support the efficacy and safety of RBX2660 in reducing rCDI.

Determinants of Response at 2 Months of Treatment in a Cohort of Pakistani Patients with Pulmonary Tuberculosis.

Mycobacterium tuberculosis infection continues to be a major global challenge. All patients with pulmonary tuberculosis are treated with a standard 6-month treatment regimen. Historical data suggest that even with shortened treatment, most patients achieve long-term remission. Risk stratification is a goal for reducing potentially toxic prolonged treatment. This study aimed to determine the factors associated with the early clearance of sputum acid-fast bacilli (AFB). A total of 297 freshly diagnosed patients with pulmonary tuberculosis were included and enrolled in this study. Information related to their ethno-demographic and anthropometric characteristics was collected. We also assessed their complete blood counts, and blood iron, folate, and vitamin B12 levels. We found that the presence of higher levels of acid-fast bacilli (AFB) in diagnostic sputum microscopy was the single most significant prognostic factor associated with early clearance of sputum AFB after 2 months of treatment. All of our patients achieved treatment success after 6 months of treatment and were disease free. Our results support the data obtained from previous studies indicating that AFB clearance at 2 months is unlikely to be a clinically useful biomarker or indicator for therapeutic stratification. Furthermore, demographic, anthropometric, and nutritional factors are not clinically useful biomarkers.

IStent Trabecular Micro-bypass Stent Implantation Combined with Phacoemulsification for Open-Angle Glaucoma: A 2-Year Post-marketing Surveillance Study in Japan.

IntroductionWe report 2-year outcomes after implantation of iStent trabecular micro-bypass stent with phacoemulsification, in Japanese patients with mild–moderate open-angle glaucoma (OAG).MethodsThis was a 24-month, prospective, longitudinal, observational, post-marketing study conducted between July 2017 and September 2020. Patients consisted of adults with OAG on antiglaucoma medications who had cataract surgery combined with one iStent implantation. Outcome measures included intraocular pressure (IOP), antiglaucoma medications, treatment success rates (defined as eyes having lower IOP with same or reduced number of medications from baseline, or same IOP with reduced number of medications from baseline, and not requiring secondary glaucoma surgeries postoperatively), and safety. Outcomes were analyzed in the overall cohort and in glaucoma subtypes: primary OAG, normal-tension glaucoma, and exfoliative glaucoma.ResultsOverall, 232 eyes were enrolled. At 24 months, mean ± standard deviation IOP decreased from 17.6 ± 4.0 mmHg preoperatively to 14.3 ± 3.0 mmHg (p < 0.05), and mean number of medications reduced from 2.2 ± 1.2 preoperatively to 0.7 ± 1.2 (p < 0.05). Similar trends were observed across glaucoma subtypes. In the overall cohort, 96.7%, 95.3%, and 93.7% of patients achieved treatment success at 6, 12, and 24 months, respectively. There were 67.6% medication-free eyes at 24 months compared to 3.2% medication-free eyes preoperatively (p < 0.0001). Safety profile was favorable over the 2-year period.ConclusionsFollowing iStent implantation with phacoemulsification, clinically relevant and statistically significant reductions in IOP and number of medications were observed in Japanese eyes with OAG over 2 years, with favorable safety profile. These reductions were observed across all glaucoma subtypes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02207-0.

Sub-population analysis of patients with plaque psoriasis treated with calcipotriol/betamethasone aerosol foam; effectiveness and patient satisfaction, according to baseline disease severity and prior psoriasis treatment experience, in a Greek population.

Fixed combination calcipotriol/betamethasone (Cal/BD) aerosol foam has been shown to be effective in psoriasis treatment in clinical trials, but real-world evidence is currently sparse. The real-world CELSUS study in Greece found that Cal/BD aerosol foam treatment was effective and associated with satisfaction in psoriasis patients. Patients from the CELSUS study (N=400) were stratified by baseline disease severity according to physician's global assessment (PGA) score (mild vs. moderate vs. severe) and by previous psoriasis treatment (naïve vs. treatment-experienced). Proportions of patients achieving treatment success (clear/almost clear [PGA 0/1]) after 4 weeks' treatment with Cal/BD aerosol foam were reported for each subgroup. Psoriasis area and severity index (PASI) and patient-reported itch, itch-related sleep loss, scaling, dry skin, and erythema numerical rating scores were reported by subgroup. At baseline, 216 (54%) patients were systemic-or-topical psoriasis treatment-naïve and 184 (46%) were treatment experienced. By disease severity, there were 135 versus 89 patients with mild, 69 versus 83 with moderate and 12 versus 12 with severe disease in the treatment-naïve versus treatment-experienced groups, respectively. In the treatment-naïve group, treatment success was achieved by 72.6%, 56.5%, and 66.7% of patients with mild, moderate, and severe disease, respectively, while the proportions in the treatment-experienced group were 60.7%, 42.2%, and 25%, respectively. Reduction from baseline in psoriasis symptoms was observed in all patient groups. The greatest reductions were observed in treatment-naïve patients with severe disease. Clinically relevant benefits were observed with Cal/BD aerosol foam in psoriasis patients, regardless of prior treatment-experience and disease severity at baseline.

Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia Is Associated With Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study.

BackgroundDeutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal studies, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores, with favorable safety/tolerability in TD patients. This study reports long-term efficacy and safety of deutetrabenazine in a 3-year, single-arm, open-label extension (OLE) study.MethodsPatients who completed the pivotal studies could enroll in this single-arm OLE study, titrating up to 48 mg/day based on dyskinesia control and tolerability. Efficacy was assessed based on change from baseline in total motor AIMS score, Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC), and quality of life (QOL) assessments. Safety evaluation included adverse event (AE) incidence, reported using exposure-adjusted incidence rates, and safety scales.Results343 patients enrolled in the study (6 patients were excluded). At Week 145 (mean dose: 39.4 ± 0.83 mg/day), mean ± SE change from baseline in total motor AIMS score was −6.6 ± 0.37 and 67% of patients achieved ≥50% improvement in total motor AIMS score. Based on CGIC and PGIC, 73% and 63% of patients achieved treatment success, respectively. QOL improvements were also observed. Deutetrabenazine was generally well tolerated, with low rates of mild-to-moderate AEs and no new safety signals; most safety scales remained unchanged over time.ConclusionsLong-term deutetrabenazine treatment was associated with sustained improvement in AIMS scores, indicative of clinically meaningful long-term benefit, and was generally well tolerated. Results suggest deutetrabenazine may provide increasing benefit over time without increases in dose.

Long-Term Safety and Efficacy of Deutetrabenazine in Younger and Older Patients With Tardive Dyskinesia

Tardive dyskinesia (TD) is an involuntary movement disorder that is more prevalent in older patients. However, there is limited information on TD treatment for this population. In two 12-week pivotal trials (ARM-TD and AIM-TD), TD patients demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) score with deutetrabenazine versus placebo. Patients who completed ARM-TD or AIM-TD enrolled in an open-label extension (OLE) study. This post hoc analysis assessed change and percent change from baseline in AIMS score, response rates for ≥50% AIMS improvement, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety in younger (<55years) and older (≥55 years) patients. This analysis included 119 younger and 218 older patients enrolled in the OLE. Data presented at Week 145 (mean±SE): total deutetrabenazine dose was 39.4±1.39mg/day and 39.5±1.04mg/day in younger and older patients, respectively. Changes from baseline in AIMS score were -6.7±0.62 and -6.5±0.47, respectively (percent changes of -61.4%±4.10% and -54.6%±3.01%). The majority of younger and older patients achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%) and achieved ≥50% AIMS response (76% and 62%). Deutetrabenazine was generally well tolerated in both groups. Exposure-adjusted incidence rates (incidence/patient-years) were <0.01 and 0.02 for akathisia, 0.07 (both) for somnolence and sedation, 0.04 and 0.11 for parkinson-like events, and 0.06 and 0.09 for depression in younger and older patients, respectively. Deutetrabenazine treatment was associated with sustained improvements in AIMS score and was well tolerated in both younger and older TD patients. Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.

Four-Week Daily Calcipotriene/Betamethasone Dipropionate Foam Is Highly Efficacious in Patients With Psoriasis (PSO-LONG Lead-in Phase)

Background: Psoriasis is a chronic disease requiring long-term treatment strategies. Optimal strategies should include initial rapid relief of symptoms followed by long-term management to maintain remission. This 4-week open-label phase of a long-term proactive management phase 3 trial aimed to select responders to once daily, fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% (Cal/BD) foam in adults with psoriasis and assess patient-reported outcomes.Method: This phase 3 trial in adults with psoriasis included a 4-week open-label lead-in phase to determine treatment success prior to entering the randomized maintenance phase. Success was defined as Physician Global Assessment (PGA) score ‘clear’/‘almost clear’ (PGA <2) with ≥2-grade improvement from baseline. Those achieving treatment success at week 4 entered the maintenance phase; non-responders were withdrawn from the trial. Results: 650 patients enrolled in the open-label phase, and 623 were treated with Cal/BD foam for 4 weeks; 521 (80%) patients achieved treatment success and were included in the maintenance phase. In those patients achieving success (responders), 21.1% and 78.9% achieved a PGA score of ‘clear’ and ‘almost clear’, respectively. Mean change from baseline in modified Psoriasis Area and Severity Index (± standard deviation [SD]) and body surface area (± SD) in responders at week 4 was −82.1% (16.4%) and −56.6% (38.3%), respectively. Mean Dermatology Life Quality Index score reduced by 6.0 from baseline to week 4 (n=521). 17.7% of patients experienced AEs; with only one severe AE reported. Conclusion: Cal/BD foam was highly efficacious and well tolerated during the 4-week lead-in phase of PSO-LONG. J Drugs Dermatol. 2021;20(4):436-441, doi:10.36849/JDD.5728Visit the Psoriasis Resource Center.

A Case Series Exploring the Efficacy, Secondary Failure, Paradoxical Event &amp; Relapse with Ustekinumab Therapy in Chronic Plaque Psoriasis

Ustekinumab is an anti-IL12/23 biologic agent used for treatment of psoriasis with excellent efficacy. However, there are therapeutic obstacles such as secondary failure and paradoxical event. Disease relapse upon discontinuation of therapy is common. A case series was performed on patients with chronic plaque psoriasis who received ustekinumab between 2013 to 2018 at a tertiary referral centre. Demographics, clinical characteristics, duration of therapy, efficacy, treatment complications, rate and pattern of relapses were determined from the patients’ medical records. Out of 8 patients, 6 (75%) patients were males. There were 6 (75%) biologic-naïve patients. Median age was 41.5 years (IQR26.8-48.3), median duration of psoriasis was 16.5 years (IQR6.5-23.0). Median duration to achieve Psoriasis Activity and Severity Index (PASI)75 was 16 weeks and median total duration of treatment was 102 weeks. All patients achieved treatment success. PASI75 at week 12 was achieved by 37.5%, a median of 16 weeks was required to achieve at least PASI 75 but 6 (75%) attained PASI 90 by then. One patient (12.5%) developed paradoxical event with pustular and plaques. Secondary failure occurred in 2 (25%) patients. All patients relapsed after treatment discontinuation, relapse occurred at median of 40 weeks. Most (71%) developed plaques on relapse but 25% developed plaques and pustules. All but one patient required further biological agent for treatment of relapse. Ustekinumab was efficacious in all patients. Treatment success was achieved slightly later than standard duration. The rare occurrences of secondary failure and paradoxical were observed. Relapse was inevitable, new onset pustular eruptions featured in relapses.

12797 Safety of long-term proactive management with fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam in patients with psoriasis vulgaris: Results of a phase III, multicenter, randomized, 52-week, vehicle-controlled trial

Patients achieving treatment success (physician’s global assessment of disease severity [PGA] score ‘clear’/‘almost clear’ with ≥2-grade improvement from baseline) following once-daily Cal/BD for 4 weeks, were randomized 1:1 to twice-weekly Cal/BD or vehicle for 52 weeks. Eligibility criteria: ≥18 years; truncal and/or limb psoriasis at least ‘mild’ by PGA; involving 2%-30% body surface area (BSA); modified Psoriasis Area and Severity Index score (mPASI) ≥2. Additional criteria for HPA axis subgroup: truncal and/or limb psoriasis at least ‘moderate’ by PGA; involving 10%-30%, BSA; normal HPA axis function. Safety end points: adverse events (AEs); rebounds (mPASI ≥12 and increase from baseline in mPASI ≥125% or development of more inflammatory disease); effect on calcium homeostasis and HPA axis. 545 patients were randomized to Cal/BD (n = 272) or vehicle (n = 273). Characteristics at randomization were similar between groups. Rate of AEs per 100 patient-years was 165.1 and 156.1, Cal/BD and vehicle groups, respectively. Rate of serious AEs per 100 patient-years was low and comparable (8.2 Cal/BD; 7.8 vehicle), as was rate of treatment-related AEs (2.7 Cal/BD; 4.5 vehicle). Two AEs (chorioretinopathy and pain of skin) were adjudicated as related to long-term corticosteroid use. Three patients (2 Cal/BD [0.7%]; 1 vehicle [0.4%]) experienced AEs leading to discontinuation. Rebound within two months of entering the proactive-management phase occurred in six and seven patients, Cal/BD and vehicle, respectively. Rebound was four times as likely with vehicle (n = 17) compared with Cal/BD (n = 4) following relapse. No clinically relevant effect on calcium metabolism or HPA axis by subgroup analysis was observed.

15211 Treatment of moderate to severe acne with once-daily tazarotene 0.045% lotion in males: Pooled analysis of two phase 3 studies

Acne vulgaris has been reported in 85% of adolescents, with moderate to severe acne occurring more frequently in adolescent/adult males than females. Tazarotene is a potent topical retinoid for acne treatment, but irritation with existing formulations may limit its use. An innovative tazarotene 0.045% lotion formulation was developed by utilizing polymeric emulsion technology. In two phase 3, double-blind, vehicle-controlled 12-week studies, eligible patients aged ≥9 years with moderate to severe acne were randomized (1:1) to receive once-daily tazarotene 0.045% lotion or vehicle. Data for male patients were summarized descriptively at week 12 in this analysis. Efficacy assessments included reductions in inflammatory/noninflammatory lesion counts and percent of patients achieving ≥2-grade reduction in Evaluator Global Severity Scores (EGSS) and a clear/almost clear score (treatment success). Adverse events (AEs) and cutaneous safety/tolerability were also assessed. Of 1614 total pooled participants, 550 were males (n = 268 tazarotene 0.045%; n = 282 vehicle). Changes from baseline in absolute lesion counts were higher with tazarotene (least-squares mean [standard deviation] inflammatory: −15.9 [10.5]; noninflammatory −22.4 [16.1]) versus vehicle (−11.3 [10.5]; −14.4 [17.8]). More patients achieved treatment success with tazarotene (25.1%) versus vehicle (12.7%). The percent of males reporting treatment-emergent AEs (TEAEs) was similar between tazarotene (19.0%; 50/263) and vehicle (19.3%; 53/275). In both groups, most TEAEs were of mild-moderate severity. Serious AEs occurred in 1 patient in each group (not treatment-related). The most common administration-related TEAE was application site pain (2.7% tazarotene; 0% vehicle). The novel tazarotene 0.045% lotion was efficacious and well tolerated in male patients with moderate to severe acne.

16830 Results from the open-label treatment period of a long-term proactive management phase III trial using fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam

Patients received Cal/BD once daily for 4 weeks during the open-label period of this phase III long-term proactive management trial. Patients who achieved treatment success (PGA score ‘clear’/‘almost clear’ with ≥2 grade improvement from baseline) were randomized 1:1 in a double-blind fashion to Cal/BD or vehicle twice weekly for 52 weeks. Patients who did not achieve treatment success were withdrawn from the study. Eligible patients: ≥18 years; truncal and/or limb psoriasis at least ‘mild’ by PGA; covering 2%-30% of body surface area (BSA); with a modified psoriasis area and severity index (m-PASI) of ≥2. End points included: change from baseline in PGA, m-PASI and, BSA, and number of adverse events (AEs). 650 patients entered the open-label phase; 521 (80.2%) achieved treatment success at week 4. More than 90% of patients achieving success had PGA score moderate or severe at baseline (moderate, n = 444 [85.2%]; severe, n = 34 [6.5%]). PGA at week 4 was ‘clear’ (n = 110, 21.1%) and ‘almost clear’ (n = 411, 78.9%) in those achieving success. Mean (SD) m-PASI and mean (SD) BSA at baseline were 7.8 (3.8) and 8.2% (6.2%), respectively, in patients achieving treatment success. Change in mean (SD) m-PASI and BSA from baseline to week 4 was −0.8% (0.2%) and −0.6% (0.4%), respectively, in successful patients. Of the 650 patients assigned to treatment, 115 (17.7%) experienced 157 AEs; 5 patients (0.8%) experienced AEs possibly or probably related to the study drug; and 2 patients (0.3%) withdrew during the open-label phase due to an AE.

Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan.

BackgroundIn 2016, World Health Organization guidelines conditionally recommended standardised shorter 9–12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.MethodsConsecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.ResultsOf 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8–44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression.ConclusionsOverall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility.

Twice-weekly topical calcipotriene/betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial)

Topical psoriasis treatment relies on a reactive rather than a long-term proactive approach to disease relapse. Assess long-term efficacy and safety of proactive psoriasis management with twice-weekly calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam. Phase III trial (NCT02899962) included a 4-week open-label lead-in phase (Cal/BD foam once daily) and a 52-week, randomized, double-blind, maintenance phase. A total of 545 patients achieved treatment success (physician's global assessment "clear"/"almost clear," ≥2-grade improvement from baseline) and were randomized to proactive management (Cal/BD foam; n=272) or reactive management (vehicle foam; n=273) twice-weekly, with rescue treatment of Cal/BD foam once daily for 4weeks upon relapse. Primary endpoint was time to first relapse (physician's global assessment "mild" or higher). A total of 251 randomized patients (46.1%) completed the trial. Median time to first relapse was 56days (proactive) and 30days (reactive). Patients in the proactive group had an additional 41days in remission compared with the reactive group over 1year (P<.001). Number of relapses per year of exposure was 3.1 (proactive) and 4.8 (reactive). Cal/BD foam was well tolerated. Maintenance phase dropout rate (53.9%) was within the expected range but provides challenges in statistical analysis. Long-term proactive management with Cal/BD foam demonstrated superior efficacy vs reactive management.

Efficacy and safety of selective laser trabeculoplasty and pattern scanning laser trabeculoplasty: a randomised clinical trial

AimsTo compare the intraocular pressure (IOP) lowering effect and safety profile between pattern scanning laser trabeculoplasty (PSLT) and selective laser trabeculoplasty (SLT) in patients with primary open-angle glaucoma (POAG) or...

Sa1312 CLINICAL OUTCOME OF PERORAL ENDOSCOPIC MYOTOMY IN ADVANCED ACHALASIA TREATMENT STRATIFIED BY MORPHOLOGICAL SUBTYPES

Peroral endoscopic myotomy (POEM) has been first-line treatment of achalasia. However, the efficacy and safety of POEM on advanced achalasia remains to be clarified. Our purpose was to evaluate the feasibility and clinical outcome of POEM for advanced AC with various esophageal morphological changes. From June 2015 to March 2019, a total of 50 patients were enrolled with advance achalasia (megaesophagus type in 23 patients, sigmoid type in 19 patients and both type in 8 patients). Primary endpoint was symptomatic relief during follow-up, defined as an Eckardt score ≤3. Secondary endpoints were intra-procedural details such as operation time, length of myotomy, post-treatment adverse events, hospital stay, as well as delayed AE, named gastroesophageal reflux disease (GERD). All patients successfully received endoscopic myotomy, with a mean procedure time of 38.5±26.3 (range, 10.7-162.6) min. In 10 patients (20%) adverse events were encountered, including mild (n=8) and moderate (n=6) without conversion to surgery and ICU admission. During a mean follow-up of 23.8 months, despite 41 (89.1%) patients achieved treatment success with a decrease in mean Eckardt score from 7.2 to 1.7 (P=6.7×10-9), only 4 (57.1%) patients in subgroup 3 (dilation and sigmoid esophagus) obtained clinical success. Symptomatic reflux occurred in 13 patients (13/46, 28.3%), and all reflux symptoms were easily controlled by intermittent oral medication with PPIs. In advanced achalasia patients with various esophageal morphological changes, POEM was a technically feasible, safe and effective option. POEM appears to be less effective in patients with significant dilated and distorted esophagus, which should be paid more attention in future managements.

1074-P: Nasal Glucagon Reversed Insulin-Induced Hypoglycemia in Adults with Diabetes: A Pooled Analysis

Background: Nasal glucagon (NG), a ready-to-use drug-device combination for treatment of severe hypoglycemia, contains 3 mg glucagon dry powder that is absorbed passively through nasal mucosa. We examined the efficacy and safety of NG compared to 1 mg injectable glucagon (IG) in reversing insulin-induced hypoglycemia in a global population of adults with T1D or T2D. Notably, this is the first analysis including pooled T2D data. Methods: Post-hoc analyses used data from 3 randomized, cross-over studies. Treatment success was defined as an increase in BG to ≥70 mg/dL or an increase of ≥20 mg/dL from nadir BG within 30 min of receiving glucagon. Tolerability was assessed using treatment-emergent adverse events and a symptom questionnaire. Results: In the T1D+T2D pooled analysis, 99.5% (213/214) of NG and 100% (214/214) of IG patients achieved treatment success in a mean time (preparation time excluded) of 13 and 11 min, respectively. All NG T2D patients (N=41) achieved treatment success. NG and IG induced similar BG changes (Figure). NG and IG had similar incidences of nausea and vomiting, with NG having a higher rate of side effects related to nasal administration [headache (13% NG, 7% IG), nasal discomfort (4% NG, 1% IG), etc.]. Separate T1D and T2D analyses showed similar results as T1D+T2D. Conclusion: NG was efficacious and well-tolerated in reversing insulin-induced hypoglycemia in adults with T1D or T2D. Disclosure E.R. Seaquist: Advisory Panel; Self; MannKind Corporation, Zucara Therapeutics Inc. Other Relationship; Self; American Board of Internal Medicine, Endocrine Society, International Hypoglycemia Study Group. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. M.X. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. Y. Takita: Employee; Self; Eli Lilly Japan K.K. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Y. Nagai: Employee; Self; Eli Lilly Japan K.K. Stock/Shareholder; Self; Eli Lilly and Company. Y. Yan: Employee; Self; Eli Lilly and Company. M. Matsuhisa: Research Support; Self; Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., Sanofi, Sysmex Corporation. Speaker’s Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Sanofi K.K., Takeda Pharmaceutical Company Limited. Funding Eli Lilly and Company