scholarly journals Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world

2019 ◽  
Vol 7 (1) ◽  
pp. e000581 ◽  
Author(s):  
George Dailey ◽  
Harpreet S Bajaj ◽  
Terry Dex ◽  
Melanie Groleau ◽  
William Stager ◽  
...  
Keyword(s):  
Adverse Events ◽  
Insulin Glargine ◽  
Fixed Ratio ◽  
Composite Endpoint ◽  
Postprandial Glucose ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Two Phase ◽  
Link Type ◽  
Post Hoc

ObjectiveTo assess the efficacy and safety of iGlarLixi (titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide) in patients with type 2 diabetes (T2D) living in North America (NA; USA and Canada) compared with the rest of the world (RoW).Research design and methodsPost hoc analysis included patient-level data from 509 sites/centers across two phase III trials: LixiLan-O (NCT02058147; insulin-naive patients; NA, n=371; RoW, n=796) and LixiLan-L (NCT02058160; inadequately controlled patients on basal insulin; NA, n=196; RoW, n=535). Efficacy outcomes were: change from baseline to Week 30 in glycated hemoglobin (HbA1c), postprandial glucose (PPG), PPG excursions, fasting plasma glucose (FPG) and body weight; proportion of patients achieving HbA1c <42 mmol/mol (<7.0%); proportion of patients achieving composite endpoint: HbA1c <42 mmol/mol (<7.0%), no weight gain or symptomatic hypoglycemia (blood glucose ≤3.9 mmol/L (≤70 mg/dL)). Safety endpoints included incidence of documented symptomatic hypoglycemia and gastrointestinal (GI) adverse events.ResultsSignificantly larger reductions (p≤0.003) in HbA1c from baseline to Week 30 were achieved with iGlarLixi, compared with iGlar or lixisenatide, in NA and RoW patients in LixiLan-O (iGlarLixi vs iGlar: −0.31 and −0.29, respectively; iGlarLixi vs lixisenatide: −0.84 and −0.69, respectively) and in LixiLan-L (iGlarLixi vs iGlar: −0.5 and −0.51, respectively). Documented symptomatic hypoglycemia was similar between NA and RoW patients. iGlarLixi resulted in significant weight benefits versus iGlar (change from baseline –1.58 and –1.29 kg for NA and RoW patients, respectively; p<0.001). GI adverse events were similar for iGlarLixi and iGlar, but significantly higher for lixisenatide.ConclusionsiGlarLixi improved glycemic parameters versus iGlar or lixisenatide alone in both NA and RoW patients, with beneficial weight effects versus iGlar. iGlarLixi treatment responses, hypoglycemia risk and GI adverse events in NA patients were comparable with patients in the RoW.Trial registryClinicaltrials.govNCT02058147andNCT02058160.-

Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2)

2016 ◽  
Vol 75 (11) ◽  
pp. 1984-1988 ◽  
Author(s):  
Arthur Kavanaugh ◽  
Lluis Puig ◽  
Alice B Gottlieb ◽  
Christopher Ritchlin ◽  
Yin You ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Activity Index ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Peripheral Arthritis ◽  
Link Type ◽  
Study Results ◽  
Post Hoc

ObjectiveTo evaluate ustekinumab efficacy and safety in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (termed the ‘spondylitis subset’).MethodsAdults with active PsA (PSUMMIT-1/PSUMMIT-2, n=615/312) were randomised to ustekinumab 45 mg, 90 mg or placebo at week 0/week 4/q12 week. At week 16, patients with <5% improvement in tender and swollen joints entered blinded early escape. A subset of patients with physician-identified spondylitis was evaluated with spondylitis-specific assessments, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score employing C reactive protein (ASDAS-CRP), through week 24.Results256/927 (27.6%) PSUMMIT-1/PSUMMIT-2 patients (placebo/ustekinumab, n=92/164) comprised the evaluable spondylitis subset. At week 24, in this analysis subset, significantly more patients achieved BASDAI20/50/70 responses (54.8%/29.3%/15.3% vs 32.9%/11.4%/0%; p≤0.002), improvement in BASDAI question 2 concerning axial pain (1.85 vs 0.24; p<0.001) and mean per cent ASDAS-CRP improvements (27.8% vs 3.9%; p<0.001) for ustekinumab versus placebo recipients, respectively. Comparable to the overall study population, significant improvements were also achieved in psoriasis, peripheral arthritis, enthesitis, dactylitis, physical function and peripheral joint radiographs in the spondylitis subset.ConclusionsIn this post-hoc analysis of PsA patients with baseline peripheral arthritis and physician-reported spondylitis, ustekinumab-treated patients demonstrated significant improvements in axial signs and symptoms through week 24.Trial registration numberPSUMMIT-1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT-2 (NCT01077362, EudraCT 2009-012265-60); post-study results.

scholarly journals Efficacy and safety of tofacitinib by background methotrexate dose in psoriatic arthritis: post hoc exploratory analysis from two phase III trials

2021 ◽  
Author(s):  
Alan J. Kivitz ◽  
Oliver FitzGerald ◽  
Peter Nash ◽  
Shirley Pang ◽  
Valderilio F. Azevedo ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Small Sample ◽  
Janus Kinase ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Two Phase ◽  
Double Blind ◽  
Methotrexate Dose ◽  
Post Hoc ◽  
The Impact

Abstract Objective Analyze tofacitinib efficacy and safety by background methotrexate (MTX) dose in patients with psoriatic arthritis (PsA). Methods This post hoc analysis pooled data from two phase III, double-blind trials (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) including patients receiving tofacitinib 5 or 10 mg twice daily (BID), or placebo, with stable MTX. Efficacy outcomes at month 3 stratified by MTX dose (≤ 15 month 3 stratified by MTX dose vs > 15 mg/week) were American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire-Disability Index (HAQ-DI); Psoriasis Area and Severity Index (PASI)50/75; change from baseline in HAQ-DI; physician’s global assessment of PsA (PGA-PsA-visual analog scale [VAS]); patient’s global joint and skin assessment (PGJS-VAS), Leeds Enthesitis Index (LEI); and Dactylitis Severity Score (DSS). Safety assessments included adverse events and laboratory parameters. Results Five hundred fifty-six patients received tofacitinib 5 mg BID (n = 186), 10 mg BID (n = 178), or placebo (n = 192), plus MTX (≤ 15 mg/week, n = 371; > 15 mg/week, n = 185). At month 3, tofacitinib efficacy was generally greater than placebo. Patients receiving tofacitinib 5 mg BID demonstrated greater numerical improvements in efficacy outcomes at month 3 with MTX > 15 mg/week vs MTX ≤ 15 mg/week; patients receiving tofacitinib 10 mg BID displayed the opposite. The safety profile was generally consistent between groups; headache was associated with MTX > 15 mg/week; decreased hemoglobin levels were observed in patients receiving tofacitinib 10 mg BID and MTX ≤ 15 mg/week. Conclusion Efficacy of tofacitinib was generally numerically greater than placebo, regardless of MTX dose. Tofacitinib 5 mg BID was generally more efficacious with MTX > 15 mg/week vs ≤ 15 mg/week; the opposite was observed for tofacitinib 10 mg BID. Headache was more frequent with MTX > 15 mg/week. Trial registration ClinicalTrials.gov. Identifier: NCT01877668 (registration: June 14, 2013) and NCT01882439 (registration: June 20, 2013). Key Points• Methotrexate is widely used in the treatment of psoriatic arthritis; however, there are limited data on the impact of varying background methotrexate doses on the efficacy and safety of Janus kinase inhibitors in patients with psoriatic arthritis.• This post hoc analysis assessed the impact of background methotrexate dose (≤ 15 or > 15 mg/week) on tofacitinib efficacy and safety in patients with psoriatic arthritis.• Results indicated that tofacitinib efficacy was generally numerically greater than placebo, regardless of methotrexate dose. Tofacitinib 5 mg twice daily, in combination with a higher dose of background methotrexate, was more efficacious compared with a lower dose of background methotrexate; the opposite was observed for tofacitinib 10 mg twice daily.• Headache was more frequent with the higher methotrexate dose. Data should be interpreted with caution due to the small sample sizes.

scholarly journals Rationale, design and objectives of two phase III, randomised, placebo-controlled studies of GLPG1690, a novel autotaxin inhibitor, in idiopathic pulmonary fibrosis (ISABELA 1 and 2)

2019 ◽  
Vol 6 (1) ◽  
pp. e000422 ◽  
Author(s):  
Toby M Maher ◽  
Michael Kreuter ◽  
David J Lederer ◽  
Kevin K Brown ◽  
Wim Wuyts ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Composite Endpoint ◽  
Phase Iii ◽  
Two Phase ◽  
Link Type ◽  
All Cause Mortality

IntroductionWhile current standard of care (SOC) for idiopathic pulmonary fibrosis (IPF) slows disease progression, prognosis remains poor. Therefore, an unmet need exists for novel, well-tolerated agents that reduce lung function decline and improve quality of life. Here we report the design of two phase III studies of the novel IPF therapy, GLPG1690.Methods and analysisTwo identically designed, phase III, international, randomised, double-blind, placebo-controlled, parallel-group, multicentre studies (ISABELA 1 and 2) were initiated in November 2018. It is planned that, in each study, 750 subjects with IPF will be randomised 1:1:1 to receive oral GLPG1690 600 mg, GLPG1690 200 mg or placebo, once daily, on top of local SOC, for at least 52 weeks. The primary endpoint is rate of decline of forced vital capacity (FVC) over 52 weeks. Key secondary endpoints are week 52 composite endpoint of disease progression or all-cause mortality (defined as composite endpoint of first occurrence of ≥10% absolute decline in per cent predicted FVC or all-cause mortality at week 52); time to first respiratory-related hospitalisation until end of study; and week 52 change from baseline in the St George’s Respiratory Questionnaire total score (a quality-of-life measure).Ethics and disseminationStudies will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and local ethical and legal requirements. Results will be reported in a peer-reviewed publication.Trial registration numbersNCT03711162; NCT03733444.

scholarly journals Similar glycaemic control and risk of hypoglycaemia with patient- versus physician-managed titration of insulin glargine 300 U/mL across subgroups of patients with T2DM: a post hoc analysis of ITAS

2021 ◽  
Author(s):  
Andrea Giaccari ◽  
R. C. Bonadonna ◽  
R. Buzzetti ◽  
G. Perseghin ◽  
D. Cucinotta ◽  
...  
Keyword(s):  
Glycaemic Control ◽  
Insulin Glargine ◽  
Patient Characteristics ◽  
Efficacy And Safety ◽  
Clinical Trial Registration ◽  
Post Hoc Analysis ◽  
Almost All ◽  
Antihyperglycaemic Drugs ◽  
Post Hoc ◽  
Patient Subgroups

Abstract Aims The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. Methods This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. Results HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00–pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p < 0.05). Conclusions Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. Clinical trial registration EudraCT 2015-001167-39

scholarly journals Efficacy and safety associated with the infusion speed of intravenous immunoglobulin for the treatment of Kawasaki disease: a randomized controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Saori Fukui ◽  
Mitsuru Seki ◽  
Takaomi Minami ◽  
Kazuhiko Kotani ◽  
Kensuke Oka ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Adverse Events ◽  
Intravenous Immunoglobulin ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Link Type ◽  
Cell Counts ◽  
Infusion Speed ◽  
Ivig Administration

Abstract Background High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10–24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds. Methods This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration. Results A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01). Conclusion The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed). Trial registration University Hospital Medical Information Network (UMIN000014665). Registered 27 July 2014 – Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058

scholarly journals Efficacy and Safety of Teriflunomide in Multiple Sclerosis across Age Groups: Analysis from Pooled Pivotal and Real-world Studies

2021 ◽  
Vol 13 ◽  
pp. 117957352110287
Author(s):  
Jiwon Oh ◽  
Sandra Vukusic ◽  
Klaus Tiel-Wilck ◽  
Jihad Said Inshasi ◽  
David Rog ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Age Groups ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Additional Group ◽  
Disability Status ◽  
Scale Scores ◽  
Post Hoc ◽  
Phase Ii And Iii

Background: Evidence suggests that efficacy and safety of disease-modifying treatments for multiple sclerosis may differ with age. We evaluate efficacy and safety of teriflunomide across age subgroups of patients from pooled clinical trials and real-world studies. Methods: Post hoc analyses of patients who received teriflunomide 14 mg in the pooled phase II and III TEMSO, TOWER, TENERE, and TOPIC core and extension studies (n = 1978), and the real-world Teri-PRO (n = 928) and TAURUS-MS I (n = 1126) studies were conducted. Data were stratified by age at study entry: ⩽25, >25 to ⩽35, >35 to ⩽45, and >45 years. In Teri-PRO and TAURUS-MS I, an additional group, >55 years, was assessed. Results: In the pooled core studies, teriflunomide reduced annualized relapse rate (ARR) versus placebo across all ages. Unadjusted ARRs remained low across age groups in pooled extensions (0.18-0.30), Teri-PRO (0.10-0.35), and TAURUS-MS I (0.14-0.35). Baseline Expanded Disability Status Scale scores were higher with age, but stable through core and extension studies (mean increases over 7 years: ⩽25 years, +0.59; >25 to ⩽35 years, +0.46; >35 to ⩽45 years, +0.35; >45 years, +0.81). Across age groups, adverse event (AE) incidences were 78.4% to 90.7% in pooled core and extension studies and Teri-PRO, and 29.2% to 37.7% in TAURUS-MS I; serious AE incidences were ⩽21.3% in all studies. In pooled phase III and Teri-PRO studies, lymphocyte count decreases over 1 year after initiating teriflunomide, and proportions of patients developing lymphopenia, were small across age groups. Conclusions: Teriflunomide efficacy was demonstrated regardless of age. Safety was generally consistent across age groups.

scholarly journals Utility of the Mini-Cog for Detection of Cognitive Impairment in Primary Care: Data from Two Spanish Studies

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Cristóbal Carnero-Pardo ◽  
Isabel Cruz-Orduña ◽  
Beatriz Espejo-Martínez ◽  
Carolina Martos-Aparicio ◽  
Samuel López-Alcalde ◽  
...  
Keyword(s):  
Primary Care ◽  
Cognitive Impairment ◽  
Characteristic Curve ◽  
Total Sample ◽  
Phase Iii ◽  
Kappa Index ◽  
Two Phase ◽  
Clock Drawing Test ◽  
Pooled Data ◽  
Post Hoc

Objectives. To study the utility of the Mini-Cog test for detection of patients with cognitive impairment (CI) in primary care (PC).Methods. We pooled data from two phase III studies conducted in Spain. Patients with complaints or suspicion of CI were consecutively recruited by PC physicians. The cognitive diagnosis was performed by an expert neurologist, after formal neuropsychological evaluation. The Mini-Cog score was calculatedpost hoc, and its diagnostic utility was evaluated and compared with the utility of the Mini-Mental State (MMS), the Clock Drawing Test (CDT), and the sum of the MMS and the CDT (MMS+CDT) using the area under the receiver operating characteristic curve (AUC). The best cut points were obtained on the basis of diagnostic accuracy (DA) and kappa index.Results. A total sample of 307 subjects (176 CI) was analyzed. The Mini-Cog displayed an AUC (±SE) of0.78±0.02, which was significantly inferior to the AUC of the CDT (0.84±0.02), the MMS (0.84±0.02), and theMMS+CDT(0.86±0.02). The best cut point of the Mini-Cog was 1/2 (sensitivity 0.60, specificity 0.90, DA 0.73, and kappa index0.48±0.05).Conclusions. The utility of the Mini-Cog for detection of CI in PC was very modest, clearly inferior to the MMS or the CDT. These results do not permit recommendation of the Mini-Cog in PC.

scholarly journals POS0928 NETAKIMAB EFFICACY IN ANTI-TNF-NAIVE AND ANTI-TNF-EXPERIENCED PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: RESULTS OF SUBANALYSIS OF PHASE 3 ASTERA TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 726.2-727
Author(s):  
S. Erdes ◽  
V. Mazurov ◽  
T. Dubinina ◽  
I. Gaydukova ◽  
A. Kundzer ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Phase Iii ◽  
P Value ◽  
Interleukin 17 ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Two Phase ◽  
Double Blind ◽  
Asas Criteria

Background:According to previous studies, the effectiveness of interleukin-17 (IL-17) inhibitors was higher in anti-TNF-naïve patients with ankylosing spondylitis (AS) [1,2]. Netakimab (NTK) is a humanized anti-IL-17A antibody approved for the treatment of AS, psoriatic arthritis, moderate-to-severe plaque psoriasis in Russia and Belarus.Objectives:To compare the efficacy of NTK in anti-TNF-naïve patients with anti-TNF-experienced patients with active AS at week 16 of therapy.Methods:ASTERA (NCT03447704) is an ongoing phase 3 placebo (PBO)-controlled clinical study, aimed at evaluating NTK efficacy in AS [3]. 228 adult patients with active AS (BASDAI ≥ 4) were randomly assigned (1:1) to receive 120 mg NTK or PBO subcutaneously at week 0,1,2 and then q2w. This analysis includes 112 patients in NTK group. Efficacy endpoints included ASAS20/40, ASAS5/6 and ASAS partial remission (PR) at week 16 of therapy.Results:28 (25.0%) of 112 patients in NTK group had previous inadequate response/intolerance to anti-TNF (anti-TNF-IR): 24 (21.4%) – one anti-TNF, and 4 (3.6%) – two anti-TNF. 84 (75.0%) patients were TNF-naive. Achievement of ASAS criteria response at week 16 was similar in both groups (Table 1).Table 1.Efficacy of NTK at week 16ParameterTNF-naïve (n = 84)anti-TNF-IR (n = 28)p-value*ASAS20, n (%)52 (61.9%)17 (60.7%)0.91ASAS40, n (%)35 (41.7%)11 (39.3%)0.82ASAS5/6, n (%)39 (46.4%)11 (39.3%)0.51ASAS(PR), n (%)15 (17.9%) 4 (14.3%)0.78*- Fisher’s exact testConclusion:NTK 120 mg provided sustained improvements in signs and symptoms of AS in anti-TNF-naive and anti-TNF-IR patients at 16 weeks of therapy.References:[1]Blair HA, Dhillon S. Secukinumab: A Review in Ankylosing Spondylitis. Drugs. 2016;76(10):1023-30.[2]Dougados M, et al. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis. 2020;79(2):176-185.[3]Mazurov VI, et al. Efficacy and safety of Netakimab, anti-IL-17A monoclonal antibody, in patients with ankylosing spondylitis. Results of phase III international, multicenter, randomized double-blind clinical trial BCD-085-5/ASTERA. Nauchno-Practicheskaya Revmatologia=Rheumatology Science and Practice. 2020;58 (4):376–386 (In Russ).Acknowledgements:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Shandor Erdes: None declared, V Mazurov: None declared, Tatiana Dubinina: None declared, Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Anna Eremeeva Employee of: Biocad

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