scholarly journals A close association of freedom from pain, migraine-related functional disability, and other outcomes: Results of a post hoc analysis of randomized lasmiditan studies SAMURAI and SPARTAN

2021 ◽  
Author(s):  
Richard B Lipton ◽  
Simin K Baygani ◽  
Stewart J Tepper ◽  
John H Krege ◽  
Raghavendra Vasudeva ◽  
...  
Keyword(s):  
Functional Disability ◽  
Close Association ◽  
Two Phase ◽  
Mild Pain ◽  
Post Hoc Analysis ◽  
Head Pain ◽  
Level Data ◽  
Bothersome Symptom ◽  
Global Impression Of Change ◽  
Post Hoc

Abstract BackgroundWhile pain freedom at 2h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2h post dosing.MethodsPatient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2h pain freedom compared to those who experienced 2h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom.ResultsParticipants who achieved 2h pain freedom (N = 913), in comparison with those with 2h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2h MBS freedom and 2h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom was lower (4.6%) than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time.ConclusionsThis study demonstrated that, at 2h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2h pain freedom is more robustly associated with other clinical outcomes than the 2h mild pain endpoint.Trial RegistrationSAMURAI (NCT02439320); SPARTAN (NCT02605174).

scholarly journals A close association of freedom from pain, migraine-related functional disability, and other outcomes: results of a post hoc analysis of randomized lasmiditan studies SAMURAI and SPARTAN

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Richard B. Lipton ◽  
Simin K. Baygani ◽  
Stewart J. Tepper ◽  
John H. Krege ◽  
Raghavendra Vasudeva ◽  
...  
Keyword(s):  
Functional Disability ◽  
Close Association ◽  
Two Phase ◽  
Mild Pain ◽  
Post Hoc Analysis ◽  
Head Pain ◽  
Link Type ◽  
Bothersome Symptom ◽  
Global Impression Of Change ◽  
Post Hoc

Abstract Background While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing. Methods Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom. Results Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time. Conclusions This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint. Trial Registration SAMURAI (NCT02439320); SPARTAN (NCT02605174).

scholarly journals Four-Factor Prothrombin Complex Concentrate Reduces Time to Procedure in Vitamin K Antagonist-Treated Patients Experiencing Gastrointestinal Bleeding: A Post Hoc Analysis of Two Randomized Controlled Trials

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Majed A. Refaai ◽  
Truptesh H. Kothari ◽  
Shana Straub ◽  
Jacob Falcon ◽  
Ravi Sarode ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Invasive Procedure ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Two Phase ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
The Impact

Introduction. To investigate the impact of a 4-factor prothrombin complex concentrate (4F-PCC [Beriplex®/Kcentra®]) versus plasma on “time to procedure” in patients with acute/severe gastrointestinal bleeding requiring rapid vitamin K antagonist (VKA) reversal prior to invasive procedure. Methods. A post hoc analysis of two phase III trials of 4F-PCC versus plasma in patients with acute/severe gastrointestinal bleeding. The treatment arms were compared for study treatment volume, infusion times, and time from start of study treatment to procedure. Results. Analysis included 42 patients (plasma, n=20; 4F-PCC, n=22). Median (interquartile range) infusion time was significantly shorter for the 4F-PCC group than for the plasma group (16 [13, 26] min versus 210 [149, 393] min; P<0.0001). Median infusion volumes were significantly smaller (103 [80, 130] mL versus 870 [748, 1001] mL; P<0.0001) and median time from study treatment initiation to first procedure was significantly shorter in the 4F-PCC group than in the plasma group (17.5 [12.8, 22.8] versus 23.9 [18.5, 62.0] h; P=0.037). Conclusions. In this analysis of patients with acute/severe gastrointestinal bleeding requiring urgent VKA reversal prior to an invasive procedure, 4F-PCC (compared with plasma) was associated with smaller infusion volumes, shorter infusion times, and reduced time to procedure.

scholarly journals Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis

2021 ◽  
Vol 7 (3) ◽  
pp. 205521732110242
Author(s):  
Jiwon Oh ◽  
Bryan Walker ◽  
Gavin Giovannoni ◽  
Dominic Jack ◽  
Fernando Dangond ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Initiation ◽  
Treatment Discontinuation ◽  
Clear Understanding ◽  
Phase 3 ◽  
Two Phase ◽  
Post Hoc Analysis ◽  
Low Incidence ◽  
Post Hoc ◽  
Common Teaes

Background Treatment-emergent adverse events (TEAEs) that occur close to treatment initiation may negatively affect overall tolerability and adherence. It is important to develop a clear understanding of potential early TEAEs after initiating treatment with cladribine tablets. Objective To identify TEAEs that begin early in the course of treatment in patients enrolled in CLARITY and ORACLE-MS studies. Methods This post hoc analysis of CLARITY and ORACLE-MS safety populations assessed the incidence of TEAEs, serious TEAEs, drug-related TEAEs, and TEAEs leading to discontinuation in patients receiving cladribine tablets or placebo within 2, 6, and 12 weeks after treatment initiation. Results By Week 12, 61.3% of patients treated with cladribine tablets 3.5 mg/kg and 55.2% treated with placebo experienced a TEAE. More patients receiving cladribine tablets versus placebo experienced a drug-related TEAE by Week 12 (34.7% vs. 23.2%). The most common TEAEs reported with cladribine tablets were: headache (7.2%), lymphopenia (6.8%), and nausea (6.0%). Patients receiving cladribine tablets and placebo reported similar proportions of serious TEAEs (2.2% vs. 1.7%) and TEAEs leading to treatment discontinuation (1.6% vs. 1.4%). Conclusion Cladribine tablets were well tolerated during the first 12 weeks as evidenced by a low incidence of TEAEs leading to treatment discontinuation.

scholarly journals Sustained responses to lasmiditan: Results from post-hoc analyses of two Phase 3 randomized clinical trials for acute treatment of migraine

Cephalalgia ◽  
2019 ◽  
Vol 39 (12) ◽  
pp. 1569-1576 ◽  
Author(s):  
Erin Gautier Doty ◽  
John H Krege ◽  
Leah Jin ◽  
Joel Raskin ◽  
Rashmi B Halker Singh ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Study Drug ◽  
Published Data ◽  
Phase 3 ◽  
Two Phase ◽  
Post Dose ◽  
Double Blind ◽  
Bothersome Symptom ◽  
Post Hoc ◽  
Sustained Responses

Background Sustained pain freedom is an important attribute of acute migraine therapies for patients and physicians. Here we report efficacy of the centrally penetrant, highly selective, 5-HT1F agonist lasmiditan on sustained pain freedom and other outcomes at 24 and 48 hours post-dose. Study design and methods Data from the similarly designed, Phase 3, double-blind studies SAMURAI (NCT02439320) and SPARTAN (NCT02605174) were pooled to more precisely estimate efficacy effects in these post-hoc analyses. In both studies, inclusion criteria were 3–8 migraine attacks per month and Migraine Disability Assessment Score of ≥ 11 (at least moderate disability). Patients were randomized equally to lasmiditan 200 mg, 100 mg, 50 mg (50 mg only in SPARTAN), or to placebo. The study drug was to be taken within 4 hours of onset of pain for non-improving headache of at least moderate severity. Sustained pain freedom was defined as being pain free at 2 hours and at the given time point (24 or 48 hours) post-dose without use of additional study drug or migraine medications. Sustained responses were assessed similarly for most bothersome symptom-free, total migraine-free, and disability-free outcomes. For comparisons with previously published data on other acute medications, an additional endpoint of modified sustained pain freedom at 24 hours was defined as being pain free at 2 hours and no moderate-to-severe headache at 24 hours post-dose without use of additional study drug or migraine medications. Results Significantly higher proportions of patients treated with lasmiditan versus placebo achieved headache pain freedom at 2 hours post-dose: 200 mg: 35.6%; 100 mg: 29.9%; 50 mg: 28.6%; placebo: 18.3% (all p < 0.001). Sustained pain freedom was significantly higher in patients treated with lasmiditan versus placebo at 24 hours: 200 mg: 21.2%; 100 mg: 16.9%; 50 mg: 17.4%; placebo: 10.3% (all p < 0.01); and at 48 hours: 200 mg: 18.4%; 100 mg: 15.2%; 50 mg: 14.9%; placebo: 9.6% (all p < 0.05). Similar sustained benefits of lasmiditan versus placebo at 24 and 48 hours were noted for most bothersome symptom-free, total migraine-free and disability-free responses. Modified sustained pain freedom at 24 hours was also observed in significantly higher proportions of lasmiditan-treated patients versus placebo: 200 mg: 27.0%; 100 mg: 21.7%; 50 mg: 21.7%; placebo: 12.9% (all p < 0.01). Conclusion Sustained responses at 24 and 48 hours were noted in significantly more patients treated with lasmiditan versus placebo for several efficacy outcomes including pain freedom, most bothersome symptom-free, total migraine-free and disability-free responses. Clinicaltrials.gov identifier numbers SAMURAI: NCT02439320; SPARTAN: NCT02605174.

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