scholarly journals FC 035VOCLOSPORIN INCREASES RENAL RESPONSE AT COMMONLY USED UPCR THRESHOLDS IN PATIENTS WITH LUPUS NEPHRITIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Maria Dall'Era ◽  
Paola Mina-Osorio ◽  
Vanessa Birardi ◽  
Simrat Randhawa
Keyword(s):  
Lupus Nephritis ◽  
Primary Endpoint ◽  
Low Dose ◽  
Therapeutic Drug ◽  
Phase 3 ◽  
Renal Response ◽  
Dose Concentration ◽  
Dose Oral ◽  
One Year ◽  
Post Hoc

Abstract Background and Aims Voclosporin is a novel calcineurin inhibitor with a favorable metabolic profile and a consistent dose-concentration relationship, potentially eliminating the need for therapeutic drug monitoring. We have previously reported the primary endpoint of the Phase 3 AURORA trial showing the addition of voclosporin to mycophenolate mofetil (MMF) and a low-dose glucocorticoid regimen results in significantly higher renal response (RR) rates at one year of treatment compared to MMF and low-dose glucocorticoids alone in patients with lupus nephritis (LN). For the primary endpoint, RR was defined as ≤0.5 mg/mg UPCR with stable renal function in the presence of low-dose glucocorticoids and no use of rescue medication. Several studies have demonstrated that proteinuria represents the best single predictor for long-term renal outcomes.1,2 Given the efficacy of voclosporin in terms of proteinuria reduction, we conducted a sensitivity analysis evaluating RR with additional UPCR targets. Method A total of 179 participants in the voclosporin (23.7 mg BID) arm and 178 participants in the control arm from the AURORA trial were included in this analysis. All participants received MMF (target 1 g BID) and low-dose oral glucocorticoids (initiated at 20-25 mg/day and tapered to 2.5 mg/day at 16 weeks). For this post hoc analysis, the UPCR component of RR was revised to include UPCR targets at 0.2 mg/mg intervals above and below the original ≤0.5 target used for the primary endpoint in AURORA (i.e., ≤0.7 mg/mg or ≤0.3 mg/mg, respectively). Odds ratios for RR at six months and one year of treatment were analyzed using a logistic regression model with terms for treatment, baseline UPCR, biopsy class, and MMF use at baseline and region. Results RR with UPCR ≤0.7 mg/mg was achieved by 46.9% of participants in the voclosporin arm vs 32.0% of participants in the control arm at one year of treatment (OR 2.07, p<0.0014) and 39.1% of participants in the voclosporin arm vs 24.7% of participants in the control arm at six months of treatment (OR 2.10, p=0.0020). RR with UPCR ≤0.3 mg/mg was achieved by 28.5% of participants in the voclosporin arm vs 15.7% of participants in the control arm at one year (OR 2.27, p=0.0023 and 22.9% of participants in the voclosporin arm vs 14.0% of participants in the control arm at six months of treatment (OR 1.90, p=0.0238; Table 1). Conclusion Participants treated with voclosporin in addition to MMF and low-dose glucocorticoids achieved statistically significantly increased renal response rates regardless of the level of UPCR used, including at an even more stringent ≤0.3 mg/mg target. This analysis further supports the efficacy observed with voclosporin in the Phase 3 AURORA and the prior Phase 2 AURA-LV global trials.

MO019AURORA PHASE 3 TRIAL DEMONSTRATES VOCLOSPORIN STATISTICAL SUPERIORITY OVER STANDARD OF CARE IN LUPUS NEPHRITIS (LN)

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dawn J Caster ◽  
Neil Solomons ◽  
Simrat Randhawa ◽  
Robert B Huizinga
Keyword(s):  
Primary Endpoint ◽  
Standard Therapy ◽  
Low Dose ◽  
Statistical Significance ◽  
Standard Of Care ◽  
Therapeutic Drug ◽  
Control Group ◽  
Phase 3 ◽  
Double Blind ◽  
Renal Response

Abstract Background and Aims Voclosporin (VCS) is a novel high potency calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring. The Aurinia Renal Response in Active Lupus with Voclosporin (AURORA) study, involving 357 patients with active LN, was a Phase 3 global, double-blind, placebo-controlled RCT designed to evaluate the efficacy and safety of VCS (23.7mg BID) vs placebo in combination with mycophenolate (MMF, 2 g/day) and rapidly tapered low dose oral steroids. Method The primary endpoint was renal response (RR) at 52 weeks. RR was defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of > 20%, presence of sustained, low dose steroids and no administration of rescue medication. Results AURORA met its primary endpoint, achieving statistically superior RR rates of 40.8% for voclosporin vs. 22.5% for the control (OR 2.65, 95% CI; p < 0.001). The benefits of VCS were also seen for all predetermined secondary endpoints, achieving statistical significance in favor of VCS for RR at 24 weeks, partial renal response (PRR) at 24 and 52 weeks, time to achieve UPCR ≤ 0.5, and time to 50% reduction in UPCR. Prespecified confirmed eGFR decreases >30% were similar in both groups, with 10.1% reported in the VCS group and 10.2% in the control arm (p= 0.971). No significant differences were seen at any timepoints in the study. Furthermore, all pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) also favored VCS. VCS was well tolerated with no unexpected safety signals. Similar SAEs were reported in the VCS group (20.8%) and in the control arm (21.3%). Infection was the most commonly reported SAE with 10.1% of VCS patients versus 11.2% of patients in the control arm. Overall mortality in the trial was low, with 6 deaths observed; 1 in the VCS arm and 5 in the control group. Additionally, the VCS arm showed no significant decrease at week 52 in eGFR or increase in BP, lipids or glucose. Conclusion While maintaining a comparable safety profile, VCS plus standard therapy achieved a statistically superior RR over one year compared to placebo plus standard therapy in adults with active LN.

scholarly journals OP0277 AURORA PHASE 3 STUDY DEMONSTRATES VOCLOSPORIN STATISTICAL SUPERIORITY OVER STANDARD OF CARE IN LUPUS NEPHRITIS (LN)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 172.2-173 ◽  
Author(s):  
C. Arriens ◽  
S. Polyakova ◽  
I. Adzerikho ◽  
S. Randhawa ◽  
N. Solomons
Keyword(s):  
Primary Endpoint ◽  
Research Funding ◽  
Standard Of Care ◽  
Phase Iii ◽  
Therapeutic Drug ◽  
Phase 3 ◽  
Double Blind ◽  
Renal Response ◽  
Subgroup Analyses ◽  
And Control

Background:Voclosporin (VCS) is a novel high potency calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring. LN occurs more frequently and is more severe in Hispanic/Latino ethnicity SLE patients. The recently completed phase 3 AURORA study builds on the favorable efficacy seen in the Phase IIb AURA-LV study in patients with active LN.Objectives:Document efficacy and safety of VCS vs placebo over one year when used with 2 grams of MMF daily and a rapid steroid taper in patients with active LN.Methods:AURORA is a Phase III multicenter, randomized, double-blind, placebo-controlled 52-week study of active LN patients. Patients were randomized 1:1 to VCS (23.7 mg BID) or placebo in combination with mycophenolate (MMF, 1 g BID) and rapidly tapered oral steroids. The primary endpoint was renal response (RR) at 52 weeks, defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of > 20%, presence of sustained, low dose steroids and no administration of rescue medication. Ethnicity subgroup analyses of RR was also undertaken given the higher severity of disease in the Hispanic/Latino LN patients.Results:There were 357 patients enrolled, 88% female, median age of 31 and 33% of Hispanic/Latino ethnicity. Renal response by intention to treat analysis at 52 weeks was 40.8% for the voclosporin arm and 22.5% for the control arm (OR: 2.65; 95% CI: 1.64, 4.27; p< 0.001); therefore, AURORA met its primary endpoint. These findings were consistent with those observed in the previously completed pivotal AURA-LV study. Ethnicity subgroup analysis of RR at 52 weeks noted benefit of VCS in both Hispanic/Latino (VCS 38.6% and control 18.6%, p=0.0062, OR 3.45) and non-Hispanic/Latino patients (VCS 41.8% and control 24.6%, p=0.0045, OR 2.29). The benefits of VCS were also seen for all pre-specified hierarchical secondary endpoints: RR at 24 weeks, partial renal response (PRR) at 24 and 52 weeks, time to achieve UPCR ≤ 0.5, and time to 50% reduction in UPCR. Furthermore, all pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) favored VCS. VCS was well tolerated with no unexpected safety signals. The overall incidence of SAEs were similar in both groups (VCS 20.8% and control 21.3%); with infection most commonly reported (VCS 10.1% and control 11.2%). Overall mortality in the trial was low, with one death in the voclosporin arm and five in the control arm. Additionally, the VCS arm showed no significant decrease at week 52 in eGFR or increase in BP, lipids, or glucose.Conclusion:The AURORA study met its primary endpoint and VCS was efficacious in Hispanic/Latino ethnicity patients, a difficult to treat group.Disclosure of Interests:Cristina Arriens Grant/research support from: - BMS: Investigator Initiated Trial Research Funding, GSK: Investigator Initiated Trial Research Funding, Exagen: Research Grant, Consultant of: AstraZeneca (Sci Ad Board Dec 2017), GSK (Sci Ad Board Oct 2018), BMS (Sci Ad Board April 2019), Svetlana Polyakova: None declared, Igor Adzerikho: None declared, Simrat Randhawa Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Aurinia Pharmaceuticals, Inc., Neil Solomons Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Aurinia Pharmaceuticals.

scholarly journals LB001EFFICACY AND SAFETY OF BELIMUMAB IN PATIENTS WITH ACTIVE LUPUS NEPHRITIS: A PHASE 3, RANDOMISED, PLACEBO-CONTROLLED TRIAL

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Brad Rovin ◽  
Frédéric A Houssiau ◽  
Richard Furie ◽  
Ana Malvar ◽  
Y K O Teng ◽  
...  
Keyword(s):  
Treatment Group ◽  
Lupus Nephritis ◽  
Renal Disease ◽  
Rescue Therapy ◽  
High Dose ◽  
Related Event ◽  
Phase 3 ◽  
Renal Response ◽  
Induction Regimen ◽  
Post Hoc

Abstract Background and Aims Belimumab (BEL), an anti-B-cell-activating factor (BAFF) monoclonal antibody, is approved in patients (pts) ≥5 years of age with active systemic lupus erythematosus (SLE). Post hoc analyses of pooled renal outcomes data from two Phase 3 SLE studies showed favourable trends of greater reduction in proteinuria, haematuria, pyuria and lower renal flare rates in BEL-treated pts vs placebo (PBO).1 This is the largest study in acute lupus nephritis (LN) to date that evaluated efficacy and safety of intravenous (IV) BEL plus standard therapy (ST) in pts with active LN. Method BLISS-LN is a Phase 3, randomised, double-blind, placebo-controlled, 104-week study (GSK study BEL114054, NCT01639339); eligible pts (≥18 years) with autoantibody-positive SLE and active, biopsy-proven LN (classes III, IV and/or V) were randomised (1:1) to monthly BEL 10 mg/kg IV or PBO, plus ST. Randomisation was stratified by induction regimen: high dose corticosteroids [HDCS] plus either cyclophosphamide (CyC), followed by azathioprine + low dose corticosteroids (LDCS), or mycophenolate mofetil (MMF), followed by MMF + LDCS. Primary endpoint: primary efficacy renal response (PERR; defined as urine protein creatinine ratio [uPCR] ≤0.7; estimated glomerular filtration rate [eGFR] no more than 20% below pre-flare value or ≥60 ml/min/1.73m2; no rescue therapy) at Week (Wk) 104. Key secondary endpoints: complete renal response (CRR; defined as uPCR &lt;0.5; eGFR no more than 10% below pre-flare value or ≥90 ml/min/1.73m2; no rescue therapy) at Wk 104; PERR at Wk 52; risk of renal-related event (defined as end-stage renal disease/doubling of serum creatinine/renal worsening/renal disease-related treatment failure) or death at any time up to Wk 104. Other endpoints: PERR and CRR at Wk 104 by induction regimen; proportions of pts with baseline uPCR ≥0.5 with uPCR shift to &lt;0.5 while on study. Results Overall, 448 pts were randomised (efficacy: 223/treatment group; safety: 224/treatment group); 118 pts received CyC induction and 328 MMF induction; 278 (62.3%) completed the treatment. At Wk 104, 43.0% BEL and 32.3% PBO pts achieved PERR (OR [95% CI] vs PBO 1.55 [1.04, 2.32], p=0.0311); 30.0% BEL and 19.7% PBO pts achieved CRR (OR [95% CI] vs PBO 1.74 [1.11, 2.74], p=0.0167). Over 104 weeks, more BEL than PBO pts achieved CRR at each visit (Figure 1A). PERR at Wk 52 was achieved by 46.6% BEL and 35.4% PBO pts (OR [95% CI] vs PBO 1.59 [1.06, 2.38], p=0.0245). The risk of a renal-related event or death was 49% lower with BEL than PBO (HR [95%CI] 0.51 [0.34, 0.77]; p=0.0014) at any time point during the study. Overall, 15.7% of BEL and 28.3% of PBO pts experienced a renal-related event or death. When analysed by induction regimen, PERR at Wk 104 was achieved by 33.9% BEL and 27.1% PBO CyC-induced pts (OR [95% CI] vs PBO 1.52 [0.66, 3.49], p=0.3272), and by 46.3% BEL and 34.1% PBO MMF-induced pts (OR [95% CI] vs PBO 1.58 [1.00, 2.51], p=0.0501). CRR at Wk 104 was achieved by 18.6% BEL and 18.6% PBO CyC-induced pts (OR [95% CI] vs PBO 1.07 [0.41, 2.78], p=0.8843), and by 34.1% BEL and 20.1% PBO MMF-induced pts (OR [95% CI] vs PBO 2.01 [1.19, 3.38], p=0.0085). Proportions of pts with uPCR shift from ≥0.5 at baseline to &lt;0.5 while on study (calculated post hoc) are presented in the Figure 1B. Overall, 95.5% BEL and 94.2% PBO pts had ≥1 adverse event (AE); 25.9% BEL and 29.9% PBO pts had ≥1 serious AE; 13.8% BEL and 17.0% PBO pts had serious infections; 12.9% pts in each group had ≥1 AE resulting in study treatment discontinuation; on-treatment fatal AEs were reported in 1.8% BEL and 1.3% PBO pts. Conclusion BEL demonstrated improved renal responses vs PBO in pts with active LN, with a safety profile consistent with previous BEL trials.

scholarly journals POS0681 VOCLOSPORIN FOR LUPUS NEPHRITIS: INTERIM ANALYSIS OF THE AURORA 2 EXTENSION STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 585.2-586
Author(s):  
A. Saxena ◽  
P. Mina-Osorio ◽  
C. Mela ◽  
V. Berardi
Keyword(s):  
Lupus Nephritis ◽  
Treatment Period ◽  
Interim Analysis ◽  
Low Dose ◽  
Extension Study ◽  
Creatinine Ratio ◽  
Urine Protein ◽  
Pre Treatment ◽  
One Year ◽  
Change In Mean

Background:Voclosporin, a novel calcineurin inhibitor (CNI), has been tested successfully in two pivotal trials in adult patients with lupus nephritis.Previously reported results from the Phase 3 AURORA 1 study and the Phase 2 AURA-LV study showed that compared with mycophenolate mofetil (MMF) and low-dose steroids alone, the addition of voclosporin significantly increased the renal response rate and reduced proteinuria, as measured by urine protein creatinine ratio (UPCR), in patients with lupus nephritis (LN) at approximately one year of treatment (48 weeks in AURA-LV and 52 weeks in AURORA 1).Objectives:Patients that completed one year of treatment in the AURORA 1 study were eligible to enroll into the two-year, blinded, controlled extension study, AURORA 2. Here we report the first interim analysis of the ongoing AURORA 2 study.Methods:Patients completing AURORA 1 were eligible to continue the same randomized treatment of voclosporin (23.7 mg BID) or placebo, in combination with MMF (1 g BID) and low-dose oral steroids in the AURORA 2 extension. This interim analysis evaluated UPCR and estimated glomerular filtration rate (eGFR) in patients with up to two years of total treatment: one year from AURORA 1 and up to one year in AURORA 2.Results:116 patients in the voclosporin arm and 100 patients in the control arm enrolled in the extension study, of which 73 patients in the voclosporin arm and 51 patients in the control arm had received two years of treatment at the time of this interim analysis. Mean UPCR at pre-treatment (AURORA 1) baseline was 3.94 mg/mg in the voclosporin arm (n=116) and 3.87 mg/mg in the control arm (n=100). The LS mean change in UPCR from pre-treatment baseline to year two was -3.1 mg/mg for the voclosporin arm (n=73) and -2.1 mg/mg for control arm (n=51; Table 1). Mean eGFR at pre-treatment (AURORA 1) baseline was 79.6 mL/min for the voclosporin arm (n=116) and 78.9 mL/min for the control arm (n=100) and at year two, was 79.0 mL/min for the voclosporin arm (n=73) and 82.9 mL/min for the control arm (n=51). There was a small early decrease in mean eGFR in the first four weeks of treatment (in AURORA 1) after which eGFR remained stable throughout year one and year two. Additionally, there were no unexpected new AEs observed in patients who continued with voclosporin treatment compared to control-treated patients for more than one year.Table 1.UPCRControl (n=100)Voclosporin (n=116)Treatment Comparison of Voclosporin to ControlnUPCR (mg/mg)nUPCR (mg/mg)UPCR (mg/mg)p-valuePre-treatment baseline, mean1003.871163.94NCNCChange from pre-treatment baseline, LS mean Year 1100-2.4116-3.0-0.60.0080 Year 251-2.173-3.1-1.00.0004LS, least squares; NC, not calculated; UPCR, urine protein creatinine ratio.Mixed effects model for repeated measures (MMRM) analysis of LS mean change from pre-treatment baseline for UPCR included terms for baseline covariate, treatment, visit and treatment by visit interaction. Integrated results include data from pre-treatment baseline of AURORA 1, the one-year treatment period in AURORA 1 and up to a one-year treatment period in AURORA 2.Conclusion:Patients in the voclosporin treatment arm maintained meaningful reductions in proteinuria with no change in mean eGFR at two years of treatment. Additional AURORA 2 efficacy and safety data will be provided at the conclusion of the study.Disclosure of Interests:Amit Saxena: None declared, Paola Mina-Osorio Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Christopher Mela Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Vanessa Berardi Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc.

scholarly journals Effects of hormone therapy on the endometrium in postmenopausal women: a one year randomized trial of low dose oral estradiol in association with a levonorgestrel-releasing intrauterine system or drospirenone

2013 ◽  
Vol 13 (3) ◽  
pp. 259-266
Author(s):  
Luiza Schvartzman ◽  
José Antônio Magalhães ◽  
Fernando Monteiro de Freitas ◽  
Carolina Pereira ◽  
Julia Azevedo ◽  
...  
Keyword(s):  
Low Dose ◽  
Endometrial Thickness ◽  
Transvaginal Ultrasound ◽  
Histological Evaluation ◽  
Categorical Variables ◽  
Kupperman Index ◽  
Dose Oral ◽  
Student’S T ◽  
One Year ◽  
Student’S T Test

OBJECTIVES: to compare the endometrial effects and uterine bleeding patterns associated with treatment using (1) levonorgestrel-releasing intrauterine system (LNG-IUS) and estradiol (1 mg/day, p.o.) or (2) orally administered drospirenone (2 mg/day) andestradiol (1 mg/day). METHODS: thirty-four patients (aged 52.53 ± 4.44 in the LNG-IUS group and 53.15 ± 4.018 in the DRSP group) were randomized. The severity of menopausal symptoms was evaluated using the Kupperman index every three months. Transvaginal ultrasound, hysteroscopy and histological evaluation were repeated after 12 months. During this period, patients kept menstrual calendars. All categorical variables were described as percentages. Variables were tested for normal distribution and Student's t test was applied for independent samples and ANOVA forrepeated measures when appropriate. Data were considered to be significant when p<0.05. RESULTS: slight vaginal bleeding was reported in the first month of treatment by 53.3% of patients from the LNG-IUS/estradiol group compared with 7.7% of patients from the drospirenone/estradiol group. There were no differences in endometrial thickness between the two groups throughout the study period. End-of-study histological findings showed atrophic endometrium in 53.3% of patients in the LNG-IUS/estradiol group compared with 76.9% of patients in the drospirenone/estradiol group. CONCLUSIONS: our results suggest good endometrial protection with both HT regimens.

scholarly journals 0535 Evaluation of Insomnia Symptoms in a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial of Sage-217 in Postpartum Depression

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A204-A205
Author(s):  
A Mittal ◽  
K Deligiannidis ◽  
M Huang ◽  
E Suthoff ◽  
S Acaster ◽  
...  
Keyword(s):  
Postpartum Depression ◽  
Primary Endpoint ◽  
Repeated Measures ◽  
Rating Scale ◽  
Depression Symptoms ◽  
Upper Respiratory Tract ◽  
Major Depressive ◽  
Phase 3 ◽  
Post Hoc ◽  
Insomnia Symptoms

Abstract Introduction Postpartum depression (PPD) is a specifier of major depressive disorder (MDD) with peripartum onset. SAGE-217, an investigational, oral neuroactive steroid GABAA receptor positive allosteric modulator, demonstrated improvements in depressive and anxiety symptoms versus placebo in a Phase 3 trial in PPD (NCT02978326; ROBIN) and a pivotal trial in MDD (NCT03000530). In PPD and MDD, insomnia symptoms are key diagnostic features, comorbid sleep disorders are frequent, and insomnia is a common residual symptom. Here we conducted post-hoc analyses to assess insomnia symptoms in the ROBIN trial. Methods Women (n=151) ages 18-45, ≤6 months postpartum, with PPD (major depressive episode beginning in 3rd trimester or ≤4 weeks postpartum) and a Hamilton Rating Scale for Depression (HAM-D) total score ≥26, were randomized 1:1 to receive outpatient SAGE-217 30mg or placebo for two weeks, with 4 weeks follow-up. Change from baseline (CFB) in HAM-D score at Day 15 was the primary endpoint. Secondary endpoints included CFB in HAM-D at other time points and the Montgomery-Åsberg Depression Rating Scale (MADRS). Post-hoc analyses assessed HAM-D insomnia subscale (HAM-D-Ins) and MADRS individual insomnia item (MADRS-Ins) scores. HAM-D and MADRS measures were evaluated using a mixed-effects model for repeated measures. Safety and tolerability were assessed by adverse event (AE) reporting. Results SAGE-217 demonstrated statistically significant Day 15 CFB versus placebo in HAM-D (primary endpoint: -17.8 vs. -13.6, p=0.0028), MADRS (-22.1 vs. -17.6, p=0.0180), and associated insomnia sub-scales/items (difference SAGE-217 vs. placebo; HAM-D-Ins: -1.003, p=0.0038; MADRS-Ins: -0.773, p=0.0116). Significant CFB in insomnia sub-scales/items favoring SAGE-217 were observed by Day 3 (HAM-D-Ins: -0.841, p=0.0142; MADRS-Ins: -0.710, p=0.017) and at Day 45 (HAM-D-Ins: -0.730, p=0.0207; MADRS-Ins: -0.636, p=0.0221). Most common (≥5%) AEs were somnolence, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation. Conclusion SAGE-217 demonstrated improvements in depression symptoms, including insomnia symptoms, and was generally well tolerated. Support This study was sponsored by Sage Therapeutics, Inc.

Comparison of Lupus Nephritis Induction Treatments in a Hispanic Population: A Single-center Cohort Analysis

2015 ◽  
Vol 42 (11) ◽  
pp. 2082-2091 ◽  
Author(s):  
Juan Manuel Mejía-Vilet ◽  
José Manuel Arreola-Guerra ◽  
Bertha M. Córdova-Sánchez ◽  
Luis Eduardo Morales-Buenrostro ◽  
Norma O. Uribe-Uribe ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Primary Endpoint ◽  
Cohort Analysis ◽  
Vascular Lesions ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Free Survival ◽  
Renal Response ◽  
Renal Flare

Objective.To evaluate response rates in an adult lupus nephritis (LN) cohort in Mexico City, Mexico.Methods.We analyzed 165 patients with biopsy-proven LN histological International Society of Nephrology/Renal Pathology Society classes III, IV, or V, distributed by treatment drug in 3 groups: mycophenolate mofetil (MMF; dosage > 2 g/day per 6 mos, n = 63), intravenous cyclophosphamide (IVC; 0.7 g/m2 body surface area monthly per 6 pulses, n = 66), or azathioprine (AZA; dosage > 1.5 mg/kg/day per 6 mos, n = 36). Median followup was 31 ± 18 months. The primary endpoint was the proportion of patients achieving complete renal response (CR). Secondary endpoints included the proportion of patients achieving renal response (complete or partial), renal flare–free survival, doubling of serum creatinine, and progression to endstage renal disease (ESRD).Results.MMF induction was superior to IVC (HR 2.00, 95% CI 1.23–3.25, p = 0.005) and AZA (HR 2.12, 95% CI 1.23–3.66, p = 0.007) in the primary endpoint. Censored CR rates at 6, 12, 24, and 36 months were 32.6%, 56.1%, 76.6%, and 94.1% for MMF; 24.2%, 34.4%, 57.9%, and 62.1% for IVC; and 8.4%, 39.8%, 49.7%, and 49.7% for AZA. MMF was also superior in renal response to treatment and renal flare–free survival outcomes. There were no differences between groups in doubling of serum creatinine or progression to ESRD. The induction treatment with MMF (HR 2.04, 95% CI 1.25–3.33, p = 0.005) and absence of vascular lesions on renal biopsy (HR 2.05, 95% CI 1.25–3.37, p = 0.004) were associated with CR, whereas proteinuria at the time of presentation was negatively associated with CR (HR 0.91, 95% CI 0.84–0.98, p = 0.013).Conclusion.MMF induction therapy is superior to IVC and AZA in patients with LN of Mexican-mestizo race.

scholarly journals S1342 Efficacy of H. pylori Eradication by Low-Dose Rifabutin Triple Therapy (RHB-105) Is Unaffected by BMI: Post-hoc Analysis From Two Phase 3 Trials

2020 ◽  
Vol 115 (1) ◽  
pp. S677-S677
Author(s):  
Kely L. Sheldon ◽  
Steven Moss ◽  
Mohd Amer Al Samman ◽  
Elliot Offman ◽  
Raymond M. Panas ◽  
...  
Keyword(s):  
Triple Therapy ◽  
Low Dose ◽  
Phase 3 ◽  
Two Phase ◽  
Post Hoc Analysis ◽  
H Pylori ◽  
Post Hoc

scholarly journals B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial

2021 ◽  
Vol 81 (1) ◽  
pp. 100-107
Author(s):  
Richard A Furie ◽  
Gustavo Aroca ◽  
Matthew D Cascino ◽  
Jay P Garg ◽  
Brad H Rovin ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
B Cell ◽  
Primary Endpoint ◽  
Cell Depletion ◽  
Type I ◽  
B Cell Depletion ◽  
Renal Response ◽  
Percentage Difference ◽  
Proliferative Lupus Nephritis ◽  
Anti Cd20

ObjectiveRandomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies.MethodsPatients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104. The primary endpoint was complete renal response (CRR) at week 52. Exploratory analyses through week 104 were conducted. The prespecified alpha level was 0.2.ResultsA total of 125 patients were randomised and received blinded infusions. Achievement of CRR was greater with obinutuzumab at week 52 (primary endpoint, 22 (35%) vs 14 (23%) with placebo; percentage difference, 12% (95% CI −3.4% to 28%), p=0.115) and at week 104 (26 (41%) vs 14 (23%); percentage difference, 19% (95% CI 2.7% to 35%), p=0.026). Improvements in other renal response measures, serologies, estimated glomerular filtration rate and proteinuria were greater with obinutuzumab. Obinutuzumab was not associated with increases in serious adverse events, serious infections or deaths. Non-serious infusion-related reactions occurred more frequently with obinutuzumab.ConclusionsImproved renal responses through week 104 were observed in patients with LN who received obinutuzumab plus standard therapies compared with standard therapies alone. Obinutuzumab was well tolerated and no new safety signals were identified.Trial registration numberNCT02550652.

Sign in / Sign up

Export Citation Format

Share Document