Faculty Opinions recommendation of Efficacy and safety of tofacitinib by background methotrexate dose in psoriatic arthritis: post hoc exploratory analysis from two phase III trials.

2021 ◽  
Author(s):  
Dafna Gladman ◽  
Vinod Chandran
Keyword(s):  
Psoriatic Arthritis ◽  
Exploratory Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Two Phase ◽  
Phase Iii Trials ◽  
Methotrexate Dose ◽  
Post Hoc

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.

Phase Ib study of sintilimab in combination with chemotherapy for 1L advanced or metastatic non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20546-e20546 ◽  
Author(s):  
Nong Xu ◽  
Kejing Ying ◽  
Ziping Wang ◽  
Yunpeng Liu ◽  
Haiping Jiang ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Efficacy And Safety ◽  
Two Phase ◽  
Phase Ib ◽  
Biomarker Analysis ◽  
Phase Iii Trials ◽  
Treatment Naïve

e20546 Background: Anti-programmed death-1 antibodies (PD-1 Abs) have shown benefits in advanced NSCLC. The efficacy and safety of sintilimab, a PD-1 Ab, in combination with chemotherapy for 1L NSCLC is evaluated in this phase Ib study (NCT02937116). Methods: The study enrolled treatment-naïve unresectable locally advanced or metastatic non-squamous (nsq-) and squamous (sq-) NSCLC patients with neither EGFR mutations nor ALK rearrangements in cohort D and E respectively. Patients received sintilimab 200mg IV q3w in combination with pemetrexed 500mg/m2 and cisplatin 75mg/m2 IV q3w (4 cycles) in cohort D, or gemcitabine 1250mg/m2 D1,8 and cisplatin 75mg/m2 D1 IV q3W (6 cycles) in cohort E until disease progression, unacceptable toxicity or death. The primary objective was to evaluate the efficacy and safety of the combination. Results: As data cutoff (15 Jan 2019), 21 and 20 patients were enrolled in cohort D and E respectively. ORR in nsq- and sq-NSCLC were 68.4% (95%CI, 43.4 to 87.4) and 64.7% (95%CI, 38.3 to 85.8) respectively based on data of 19 and 17 patients with at least one radiological assessment. Median PFS was 11.4 months (95%CI, 3.1 to NA) and 6.5 months (95%CI, 5.3 to 8.0) respectively (Table). Totally 38 (92.7%) patients experienced at least one treatment emergent adverse event (TEAE). Treatment-related AEs (TRAEs) occurred in 28 (68.3%) patients. TRAE ≥grade 3 occurred in 4 (9.8%) patients. Immune related AEs occurred in 10 patients (24.4%), the most common of which were skin rash (N = 5), pneumonitis (N = 3) and hypothyroidism (N = 2). There was no AEs leading to death. The biomarker analysis was ongoing. Conclusions: The combination of sintilimab and chemotherapy showed efficacy with an acceptable safety profile in 1L nsq- and sq-NSCLC. Two phase III trials are ongoing to evaluate the combination in 1L nsq- (NCT03607539) and sq-NSCLC (NCT03629925) respectively. Clinical trial information: NCT02937116. [Table: see text]

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.

Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials

2004 ◽  
Vol 5 (2) ◽  
pp. 107-117 ◽  
Author(s):  
Vincent Meininger ◽  
Gilbert Bensimon ◽  
Walter G Bradley ◽  
Benjamin R Brooks ◽  
Patrice Douillet ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Two Phase ◽  
Phase Iii Trials ◽  
Lateral Sclerosis

Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials

2021 ◽  
Vol 147 (2) ◽  
pp. AB56
Author(s):  
Mark Liu ◽  
Camille Taillé ◽  
Jason Lee ◽  
Steven Smith ◽  
Steve Mallett ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Trials ◽  
Post Hoc ◽  
Clinical Asthma

Abstract #999926: Effect of Dosing and Titration of Osilodrostat on Efficacy and Safety in Patients With Cushing's Disease (CD): Results From Two Phase III Trials (LINC3 and LINC4)

2021 ◽  
Vol 27 (6) ◽  
pp. S112
Author(s):  
Maria Fleseriu ◽  
Richard J. Auchus ◽  
Peter J. Snyder ◽  
André Lacroix ◽  
Anthony P. Heaney ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Phase Iii ◽  
Cushing's Disease ◽  
Efficacy And Safety ◽  
Two Phase ◽  
Phase Iii Trials

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.-

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