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 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 POS1025 TOFACITINIB TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS AND PROBABLE DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF TWO PHASE 3 CLINICAL TRIALS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 782.1-782
Author(s):  
L. Gossec ◽  
G. Citera ◽  
A. Sellas-Fernández ◽  
D. C. Gruben ◽  
M. Valderrama ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Research Support ◽  
Phase 3 ◽  
Two Phase ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Sf 36 ◽  
Global Pain ◽  
Post Hoc

Background:Depression and anxiety are highly prevalent in patients (pts) with psoriatic arthritis (PsA),1 with inflammation a key pathogenic feature of depression in these pts.2 Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. It acts by modulating immune and inflammatory responses. The link between major depressive disorder/generalised anxiety disorder (MDD/GAD), inflammation and tofacitinib effectiveness has not been fully explored.Objectives:Analyse the prevalence of probable MDD/GAD in pts with PsA initiating tofacitinib treatment and the impact of baseline (BL) probable MDD/GAD status on tofacitinib efficacy in these pts.Methods:This was a post hoc analysis of data from pts who received tofacitinib 5 or 10 mg twice daily (BID), or placebo (PBO), pooled from two Phase 3 trials (12-month OPAL Broaden [NCT01877668];3 6-month OPAL Beyond [NCT01882439]4). Pts with BL probable MDD and/or GAD were identified by a Short Form-36 Health Survey (SF-36) Mental Component Summary score (MCS) ≤38. Pt demographics/BL characteristics and outcomes were stratified by the presence (SF-36 MCS ≤38) or absence (SF-36 MCS >38) of BL probable MDD/GAD. At Months (M)3/6/9/12, changes from BL in SF-36 MCS were evaluated, and efficacy assessed by the proportions of pts who achieved: Psoriatic Arthritis Disease Activity Score (PASDAS) ≤3.2, Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement ≥0.35 and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) improvement ≥4. BL global pain was measured via visual analogue scale.Results:Of the 706 pts included in this analysis, BL probable MDD/GAD was identified in 46.2%, 44.9% and 46.2% of pts in the tofacitinib 5 mg BID (108/234), tofacitinib 10 mg BID (106/236) and PBO (109/236) groups, respectively. BL disease activity was similar across the three treatment groups, independent of probable MDD/GAD status (mean PASDAS: 6.1–6.4 in pts with vs 5.8–6.1 in pts without probable MDD/GAD). In the tofacitinib 5 mg BID group, mean BL scores for HAQ-DI (1.4 vs 1.0), FACIT-F total score (20.5 vs 32.4) and global pain (61.3 vs 51.5) indicated worse disability, fatigue and pain, respectively, for pts with vs without BL probable MDD/GAD. Similar findings were seen in the tofacitinib 10 mg BID and PBO groups. At M3, improvements from BL in SF-36 MCS in pts with probable MDD/GAD were numerically, but not significantly, greater with tofacitinib 5 and 10 mg BID vs PBO, and these changes were largely sustained to M12 (Figure 1a). At M3, numerically greater proportions of pts achieved improvements in PASDAS, HAQ-DI and FACIT-F with tofacitinib 5 or 10 mg BID vs PBO, regardless of BL probable MDD/GAD status (Figure 1b–d). Through M3–12, the proportions of pts who achieved PASDAS ≤3.2 with tofacitinib 5 or 10 mg BID were generally significantly greater in pts without vs with probable MDD/GAD (Figure 1b). At all timepoints, rates of improvement in HAQ-DI with tofacitinib 5 mg BID were numerically greater in pts with vs without probable MDD/GAD, whereas the opposite was true for tofacitinib 10 mg BID (Figure 1c). FACIT-F improvement rates with tofacitinib 10 mg BID were consistently numerically greater in pts with vs without probable MDD/GAD, while findings were mixed for tofacitinib 5 mg BID (Figure 1d).Conclusion:Around 46% of pts with PsA treated with tofacitinib had BL probable MDD/GAD (SF-36 MCS ≤38). Pts with BL probable MDD/GAD treated with tofacitinib had sustained changes in SF-36 MCS. Rates of clinical improvement with tofacitinib were generally greater in pts without vs with probable MDD/GAD, whereas findings for disability and fatigue improvements varied between tofacitinib doses. Further research is required to evaluate the relationship between PsA and depression, to improve treatment targets and the quality of life of pts with PsA.References:[1]Zhao et al. Clin Rheumatol 2020; 39: 217-225.[2]Mathew & Chandran. Rheumatol Ther 2020; 7: 287-300.[3]Mease et al. N Engl J Med 2017; 377: 1537-1550.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Deeks, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Laure Gossec Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Roche, UCB, Gustavo Citera Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Agustí Sellas-Fernández: None declared, David C Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Monica Valderrama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Susana Gómez Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

scholarly journals Post hoc analysis of ellipsoid zone changes beyond the central subfield in symptomatic vitreomacular adhesion patients from the OASIS trial

2021 ◽  
Vol 6 (1) ◽  
pp. e000648
Author(s):  
Swetha Bindu Velaga ◽  
Muneeswar Gupta Nittala ◽  
Michael S Ip ◽  
Luc Duchateau ◽  
SriniVas R Sadda
Keyword(s):  
Time Course ◽  
Vitreomacular Adhesion ◽  
Ellipsoid Zone ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Phase Iiib ◽  
The Status ◽  
Registration Number ◽  
Post Hoc ◽  
And Control

Background/aimsOASIS is a Phase IIIb trial (NCT01429441) assessing long-term outcomes in subjects with symptomatic vitreomacular adhesion (VMA). The purpose of this study is to report on the frequency, severity, location and time course of ellipsoid zone (EZ) alterations in ocriplasmin-treated and sham control eyes in the OASIS study.Methods220 patients (146 ocriplasmin, 74 sham) subjects with VMA were enrolled in this masked post hoc analysis phase IIIb, randomised, sham-controlled double-masked multicentre clinical trial. A masked post hoc analysis of OCT images was performed at the Doheny Image Reading Center from subjects enrolled in the OASIS trial. The status of the EZ band was assessed in three different macular regions: the central subfield (CS) (≤1 mm diameter), the parafoveal area (PAA) (>1 to ≤3 mm) and the perifoveal area (PEA) (>3 to ≤6 mm). The EZ band was rated as normal/intact, full thickness macular hole (FTMH), abnormal but continuous, discontinuous/disrupted or absent at visits from baseline (pretreatment) to week 1 (day 7), month 1 (day 28), month 3, month 6, month 12 and the final follow-up at month 24. EZ band status was compared in both study and control eyes.ResultsA total of 208 patients (138 ocriplasmin, 70 sham) were included in this analysis. At baseline, FTMH was present in 48.6%, 8.0%, 0% and 52.8%, 2.9%, 0% in the CS, PAA and PEA of the ocriplasmin and sham groups, respectively. The EZ was graded to be abnormal but continuous, discontinuous/disrupted or absent at Baseline in 21.0%, 4.3%, 2.8% in the CS, PAA and PEA, respectively, of the ocriplasmin group; and 12.9%, 10.0%, 4.3% in the CS, PAA and PEA of the sham group. For the ocriplasmin group in the PAA, this frequency increased to 6.6% at week 1, was 9.8% at month 1, but improved to 3.8% at month 3, and remained stable to 1.6% at month 24. These differences, however, were not statistically significant.ConclusionsOcriplasmin treatment for symptomatic VMA was associated with EZ abnormalities in a small percentage of patients that was best assessed in regions (PEA) relatively unaffected by the VM interface disease at baseline. The EZ abnormalities were apparent by week 1, persisted at month 1, and appeared to resolve in the majority of cases by month 3.Trial registration numberNCT01429441

scholarly journals Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Laura C. Coates ◽  
Johan K. Wallman ◽  
Dennis McGonagle ◽  
Georg A. Schett ◽  
Iain B. McInnes ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Pooled Analysis ◽  
Search Query ◽  
Two Phase ◽  
Pooled Data ◽  
Link Type ◽  
Full Resolution ◽  
Shift Analysis ◽  
Post Hoc ◽  
Future 2

Abstract Background Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. Method Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3–6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. Results A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3–6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg. Conclusion Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis. Trial registration FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013)

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.

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