scholarly journals Erenumab for Migraine Prevention in a 1-Year Compassionate Use Program: Efficacy, Tolerability, and Differences Between Clinical Phenotypes

2021 ◽  
Vol 12 ◽  
Author(s):  
Jean Schoenen ◽  
Gregory Timmermans ◽  
Romain Nonis ◽  
Maïté Manise ◽  
Arnaud Fumal ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Prophylactic Treatment ◽  
Episodic Migraine ◽  
Responder Rate ◽  
Compassionate Use ◽  
Serious Adverse Events ◽  
Headache Severity ◽  
Acute Medication ◽  
Significant Efficacy ◽  
Monthly Dose

During a 1-year compassionate use program, 156 patients with migraine self-administered a monthly dose of erenumab 140 mg with a subcutaneous autoinjector. Main inclusion criteria were: ≥ 4 migraine days/month and ≥two prior prophylactic treatment failures. The patients covered the migraine severity spectrum from episodic migraine (EM) (n = 80) to chronic migraine (CM) (n = 76). During the 3rd month of treatment, monthly headache days decreased by 45.7% in EM and 35.5% in CM. The 50% responder rate for reduction in monthly headache days was significantly higher in EM (55%) than in CM (43%) (p = 0.05). In both the migraine subgroups, the clinical improvement vs. baseline was already significant during the 1st month of treatment (p < 0.001). There were also significant reductions in mean headache severity, duration, and monthly days with acute drug intake. The 30% responder rate at 3 months was 60% in CM and 54.1% of patients reversed from CM to EM. The therapeutic effect was maintained at 12 months when 50% responder rates, considering discontinuation for lack of efficacy or adverse effects as 0% response, still were 51% in EM and 41% in CM. A total of 10 patients with EM (12.5%) and 23 patients with CM (30.3%) had discontinued treatment, considering the treatment as ineffective. At 3 months, 48% of patients reported non-serious adverse events among which the most frequent was constipation (20.5%); corresponding figures at 12 months were 30 and 15%. Discontinuation due to an adverse effect for the entire 12 month period was rare (3.8%). The lower efficacy in CM than in EM was mainly due to a very low 50% responder rate in patients with CM with continuous pain (13%) as compared to CM with pain-free periods (58%) (p < 0.001). Similarly, the 50% responder rate was lower in patients with ≥two prior prophylactic treatment failures (40.5%) compared to those with two failures (70%) (p < 0.05). There was no significant efficacy difference between low (4–7 migraine days/month, n = 22) and high frequency (8–14 days, n = 59) EM nor between patients with CM with (n = 50) or without (n = 26) acute medication overuse. Erenumab had no effect on the frequency of auras. Taken together, erenumab 140 mg monthly was highly effective for migraine prophylaxis over the whole severity spectrum of the disease, except in patients with continuous headaches. Its effect is significant after the first injection, quasi-maximal after the second injection, and does not wear off after 12 months. The most frequent adverse effect was constipation. These results are compared to those published for erenumab in the pivotal randomized placebo-controlled trials and to those reported in several recent real-world studies.

Safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine – a meta-analysis of randomized controlled trials

Cephalalgia ◽  
2019 ◽  
Vol 39 (9) ◽  
pp. 1164-1179 ◽  
Author(s):  
Da Xu ◽  
Deng Chen ◽  
Li-na Zhu ◽  
Ge Tan ◽  
Hai-jiao Wang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Adverse Events ◽  
Injection Site ◽  
Meta Analysis ◽  
Peptide Binding ◽  
Episodic Migraine ◽  
Calcitonin Gene Related Peptide ◽  
Serious Adverse Events ◽  
Related Peptide ◽  
Calcitonin Gene

Aim To systematically evaluate the safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies from the results of randomized controlled trials. Methods Online databases were searched on calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine. Overall withdrawal, withdrawal due to adverse events, adverse events, serious adverse events and specific adverse events were extracted from the included studies. A meta-analysis was performed with Revman 5.3.0 software. Results Ten studies that investigated four drugs (galcanezumab, erenumab, fremanezumab and eptinezumab) with 5817 participants were included in this study. Serious adverse events, overall withdrawals, withdrawal due to adverse events and any adverse events were not significantly associated with monoclonal antibody treatment. Injection site pain and erythema were significantly higher in the calcitonin-gene-related peptide binding monoclonal antibodies treatment group than in the placebo group. The rates of serious adverse events were significantly higher in the galcanezumab 120 mg group. Injection site erythema was associated with galcanezumab 120 mg and 240 mg. Injection site pain and nasopharyngitis were associated with galcanezumab 150 mg and 5 mg, respectively. Overall adverse events were significantly higher with erenumab 70 mg and 140 mg. Treatment-related adverse events were significantly higher with fremanezumab 225 mg/month and 675 mg/quarter. Conclusions This study provides data on the safety and tolerability profiles of calcitonin-gene-related peptide binding monoclonal antibodies and confirms their potential use as preventive treatments for episodic migraine. In addition to the acceptable withdrawal rates, serious adverse events were rare, and the severity of most adverse events was mild to moderate. Injection site reaction may be the major adverse event associated with galcanezumab.

scholarly journals A Prospective Observational Cohort Study on Pharmacological Habitus, Headache-Related Disability and Psychological Profile in Patients with Chronic Migraine Undergoing OnabotulinumtoxinA Prophylactic Treatment

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 504 ◽  
Author(s):  
Gandolfi ◽  
Donisi ◽  
Marchioretto ◽  
Battista ◽  
Smania ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Psychological Distress ◽  
Coping Strategies ◽  
Chronic Migraine ◽  
Prophylactic Treatment ◽  
Moderate Intensity ◽  
Psychological Profile ◽  
Factors Affecting ◽  
Acute Medication

Chronic Migraine (CM) is a disabling neurologic condition with a severe impact on functioning and quality of life. Successful therapeutic management of patients with CM is complex, and differences in therapeutic response could be attributable to genetically determined factors, sensitivity to pharmacological treatment, psychosocial and relational factors affecting the patient’s compliance and approach on the therapeutic treatment. The aim of this prospective observational study was to explore self-efficacy, coping strategies, psychological distress and headache-related disability in a cohort of 40 patients with CM (mean age: 46.73; standard deviation 13.75) treated with OnabotulinumtoxinA and the relationship between these clinical and psychological aspects and acute medication consumption during OnabotulinumtoxinA prophylactic treatment. Patients presented an overall significant reduction in the Headache Index (HI) (p < 0.001), HI with severe intensity (p = 0.009), and total analgesic consumption (p = 0.003) after the prophylactic treatment. These results are in line with the literature. Despite this, higher nonsteroidal anti-inflammatory drugs consumption was associated with higher psychological distress, higher HI with severe and moderate intensity, and worse quality of life. Conversely, triptans consumption was correlated with HI of mild intensity, and problem-focused coping strategies. To conclude, the psychological profile, and in particular, the psychological distress and specific coping strategies might influence the self-management of acute medication.

Effect of coadministration of propranolol and etodolac (VT-122) plus sorafenib for patients with advanced hepatocellular carcinoma (HCC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 390-390 ◽  
Author(s):  
Andrew N de la Torre ◽  
Ismael Castaneda ◽  
Aram F. Hezel ◽  
Newell F. Bascomb ◽  
Gouri Shankar Bhattacharyya ◽  
...  
Keyword(s):  
Hepatitis Virus ◽  
Small Sample Size ◽  
Small Sample ◽  
Controlled Study ◽  
Advanced Hepatocellular Carcinoma ◽  
Separate Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Duration Of Therapy ◽  
Significant Efficacy

390 Background: Propranolol and etodolac (designated VT-122) target the adrenergic and prostaglandin stress systems activated in HCC. These stress-induced systems are proposed to induce changes in the tumor microenvironment and immune system leading to tumor promotion and immune tolerance. In a separate study, administration of VT-122 prior to sorafenib showed an increase in median overall survival (OS) of 21 months when VT-122 is administered before sorafenib compared to 10 months OS for sorafenib alone. The aim of the current study was to evaluate the effect of administering VT-122 at least 30 days after starting sorafenib. Methods: Patients with HCC receiving sorafenib for at least 30 days were eligible for this double-blind, placebo-controlled study. Patients were randomized to receive sorafenib with either VT-122 or placebo. Patients received therapy for up to 12 months or until treatment failure. VT-122 was administered twice daily. The primary endpoint was duration of therapy (DoT) and the secondary endpoint was OS. Results: Twenty patients were randomized, 11 and 9 patients to the VT122 and placebo arm, respectively. Each arm was balanced with regards to age (mean of 60.4 years), Child Pugh status (9 Child Pugh A, 11 Child Pugh B7), hepatitis virus status (6 HBV and 1 HCV positive) and C-reactive protein (CRP) (20.4 mg/L). VT122 with sorafenib was well tolerated with no unexpected serious adverse events reported. Mean OS was 13.9 months and 9.6 months in the VT-122 and placebo arms, respectively. Mean DoT (unvalidated) was 10.1 months and 7.5 months in the VT-122 and placebo arms, respectively. Conclusions: Co-administration of VT-122 with sorafenib was well tolerated and showed an increase in duration of therapy and OS versus sorafenib alone. The small sample size and number of events precludes the ability to make any significant efficacy conclusions. The increase in survival was not as great as that seen in a separate study in which VT122 was started prior to sorafenib. A further Phase 3 study of VT122 administered prior to sorafenib in patients with HCC is warranted. Clinical trial information: NCT01265576.

Acetyl-l-carnitine versus placebo for migraine prophylaxis: A randomized, triple-blind, crossover study

Cephalalgia ◽  
2015 ◽  
Vol 35 (11) ◽  
pp. 987-995 ◽  
Author(s):  
Knut Hagen ◽  
Eiliv Brenner ◽  
Mattias Linde ◽  
Gøril Bruvik Gravdahl ◽  
Erling Andreas Tronvik ◽  
...  
Keyword(s):  
Crossover Study ◽  
Primary Outcome ◽  
Prophylactic Treatment ◽  
Episodic Migraine ◽  
Secondary Outcome ◽  
Complete Case ◽  
Preventive Medication ◽  
Prophylactic Drug ◽  
To Receive ◽  
Blind Crossover Study

Background Preventive medication is indicated for many migraine patients, but is used in relatively few. The aim of the present study was to evaluate the efficacy of acetyl-l-carnitine as a prophylactic drug in migraine patients. Methods A single-center, randomized, triple-blind, placebo-controlled, crossover study was carried out. Men and women, age 18–65 years, with episodic migraine but otherwise healthy, were recruited mostly through advertisements. After a four-week run-in-phase, 72 participants were randomized to receive either placebo or 3 g acetyl-l-carnitine for 12 weeks. After a four-week washout, treatment was switched. The primary outcome was days with moderate or severe headache per four weeks. Secondary outcomes were days with headache, hours with headache, proportion of responders (>50% reduction in migraine days from baseline) and adverse events. Results In the complete case analyses, no statistically significant differences were found between acetyl-l-carnitine and placebo in severe or moderate headache days per month (3.0 versus 3.1, p = 0.80), headache days per month (5.1 versus 5.2, p = 0.73) or for the other secondary outcome measures. Conclusion In this triple-blind crossover study no differences were found in headache outcomes between acetyl-l-carnitine and placebo. Our results do not provide evidence of benefit for efficacy of acetyl-l-carnitine as prophylactic treatment for migraine. Trial registration: EUDRACT (2012-001624-36), ClinicalTrials.gov (NCT01695317).

scholarly journals Reversal of SARS-CoV2 Induced Hypoxia by Nebulized Sodium-Ibuprofen in a Compassionate Use Program

2021 ◽  
Author(s):  
Oscar Salva ◽  
Pablo Alexis Doreski ◽  
Celia Sara Giler ◽  
Dario Conrado Quinodoz ◽  
Lucia Guadalupe Guzman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Average Length ◽  
Vital Signs ◽  
Standard Of Care ◽  
Ambient Air ◽  
Outcome Data ◽  
Compassionate Use ◽  
Rapid Improvement ◽  
Serious Adverse Events ◽  
Average Length Of Stay

Abstract BackgroundSodium-ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients.MethodsNaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care to hospitalized Covid-19 patients until oxygen saturation levels of >94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 04, 2020, through October 31, 2020 are summarized.Results383 patients were treated, including 327 not on mechanical ventilation at baseline (MV) and 56 ICU patients receiving MV. For those not on baseline MV (59±0.8 years), 64% were male, most with at least one recognized risk factor for disease severity, and mean NEWS2 score prior to treatment initiation of 7.0±0.1. The average length of stay (ALOS) was 11.5±0.3 days and length of treatment (LOT) 9.0±0.2 days. In patients on baseline MV (60.6±2.2 years), 69.9% were male, baseline mean NEWS2 Score was 8.8±0.4, ALOS 15.5±1.4 days and LOT 10.5±0.7 days. Reversal of deterioration in oxygenation and NEWS2 scores was observed acutely following initiation of therapy. Overall in-hospital mortality was 10.7% among patients not on MV at baseline, and 19.6% among patients receiving MV at baseline. No serious adverse events were considered related to ibuprofen therapy.ConclusionsTreatment of COVID-19 pneumonitis with inhalational nebulized NaIHS was associated with rapid improvement in hypoxia and vital signs, with no serious adverse events attributed to therapy. Nebulized NaIHS is worthy of further study in randomized, placebo-controlled trials.(ClinicalTrials.gov:NCT04382768).

scholarly journals Sensory Processing Patterns affect Headache Severity among Adolescents with Migraine

2020 ◽  
Author(s):  
Jacob Genizi ◽  
Ayelet Halevy ◽  
Mitchell Schertz ◽  
Khaled Osman ◽  
Nurit Assaf ◽  
...  
Keyword(s):  
Sensory Processing ◽  
Sensory Input ◽  
Pain Catastrophizing ◽  
Episodic Migraine ◽  
Healthy Controls ◽  
Sensory Sensitivity ◽  
Headache Severity ◽  
Sensory Processing Patterns ◽  
The Relationship ◽  
Disability Level

Abstract Objective : To evaluate the relationship between pain catastrophizing level, sensory processing patterns, and headache severity among adolescents with episodic migraine. Background : Catastrophizing about pain is a critical variable in how we understand adjustment to pain and has a unique contribution in predicting pain intensity. Recent reports found that migraine is also related to enhanced sensory sensitivity. However, the relationship between pain severity, pain catastrophizing level and sensory sensitivity requires greater study especially among adolescents. Methods : Participants were 92 adolescents aged 13-18 years, 40 with episodic migraine and 52 healthy controls. The migraine patients were prospectively recruited from outpatient pediatric neurology clinics. All participants completed the Short Sensory Profile (SSP), and the Pain Catastrophizing Scale for children (PCS-ch). The migraine groups also completed the PedMIDAS, which measures Headache related disability. Results : Adolescents with migraine had significantly lower tendency to seek sensory input than healthy controls. Elevated rumination and helplessness correlated with higher migraine pain severity. Tendency to avoid sensory input predicted the migraine related disability level. They also significantly higher pain catastrophizing level than healthy controls, as seen in enhanced rumination (p ≤ 0.001) and helplessness (p ≤ 0.05). Conclusions : Sensory processing difficulties are common among adolescents with episodic migraine. Sensory avoidance may be related to pain experience, and pain catastrophizing and disability level.

scholarly journals Anti-CGRP monoclonal antibodies: a breakthrough in the treatment of migraine

2019 ◽  
Vol 9 (5) ◽  
pp. 262-267
Author(s):  
Julia Azimova ◽  
Yaroslav Ashikhmin ◽  
Mikhail Kukushkin ◽  
Aleksandr Amelin ◽  
Kirill Skorobogatykh
Keyword(s):  
Monoclonal Antibodies ◽  
Adverse Effects ◽  
Adverse Reactions ◽  
Prophylactic Treatment ◽  
Botulinum Toxin A ◽  
Beta Blockers ◽  
Episodic Migraine ◽  
New Class ◽  
Humanized Monoclonal Antibodies ◽  
Severe Adverse Reactions

To date, the prophylactic treatment of migraine has included only nonspecific drugs of various pharmacological groups: the beta-blockers propranolol and metoprolol, the anticonvulsants topiramate and valproic acid, the antidepressants amitriptyline and venlafaxine, candesartan, and Ona botulinum toxin A. As these drugs were developed for treatment of other diseases, their use was associated with adverse effects: decreased blood pressure, mental retardation, weight increase, nausea, and some others. CGRP is a neuropeptide that was regarded as the main biomarker of migraine as its level in this disease rise. The emergence of humanized monoclonal antibodies has opened up the possibility of blocking the action of CGRP and developing a new class of drugs that includes fremanezumab, erenumab, galcanezumab, and eptinezumab. Anti-CGRP monoclonal antibodies can be prescribed to patients with chronic and episodic migraine. The use of anti-CGRP monoclonal antibodies in clinical studies was associated with a small number of adverse effects, with severe adverse reactions being extremely rare.

scholarly journals Two-year efficacy and safety of erenumab in participants with episodic migraine and 2–4 prior preventive treatment failures: results from the LIBERTY study

2021 ◽  
pp. jnnp-2021-327480
Author(s):  
Michel Dominique Ferrari ◽  
Uwe Reuter ◽  
Peter J Goadsby ◽  
Gabriel Paiva da Silva Lima ◽  
Subhayan Mondal ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Responder Rate ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Registration Number

ObjectiveTo evaluate individual and group long-term efficacy and safety of erenumab in individuals with episodic migraine (EM) for whom 2–4 prior preventatives had failed.MethodsParticipants completing the 12-week double-blind treatment phase (DBTP) of the LIBERTY study could continue into an open-label extension phase (OLEP) receiving erenumab 140 mg monthly for up to 3 years. Main outcomes assessed at week 112 were: ≥50%, ≥75% and 100% reduction in monthly migraine days (MMD) as group responder rate and individual responder rates, MMD change from baseline, safety and tolerability.ResultsOverall 240/246 (97.6%) entered the OLEP (118 continuing erenumab, 122 switching from placebo). In total 181/240 (75.4%) reached 112 weeks, 24.6% discontinued, mainly due to lack of efficacy (44.0%), participant decision (37.0%) and adverse events (AEs; 12.0%). The ≥50% responder rate was 57.2% (99/173) at 112 weeks. Of ≥50% responders at the end of the DBTP, 36/52 (69.2%) remained responders at ≥50% and 22/52 (42.3%) at >80% of visits. Of the non-responders at the end of the DBTP, 60/185 (32.4%) converted to ≥50% responders in at least half the visits and 24/185 (13.0%) converted to ≥50% responders in >80% of visits. Change from baseline at 112 weeks in mean (SD) MMD was −4.2 (5.0) days. Common AEs (≥10%) were nasopharyngitis, influenza and back pain.ConclusionsEfficacy was sustained over 112 weeks in individuals with difficult-to-treat EM for whom 2–4 prior migraine preventives had failed. Erenumab treatment was safe and well tolerated, in-line with previous studies.Trial registration numberNCT03096834

scholarly journals A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Duliang Soft Capsule in Patients with Chronic Daily Headache

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shengyuan Yu ◽  
Yueqing Hu ◽  
Qi Wan ◽  
Jiying Zhou ◽  
Xinfeng Liu ◽  
...  
Keyword(s):  
Chronic Daily Headache ◽  
Prophylactic Treatment ◽  
Controlled Trial ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Headache Severity ◽  
Efficacy Measure ◽  
Daily Headache ◽  
Efficacy Measures ◽  
Accompanying Symptoms

Objective. To investigate the efficacy and safety of traditional Chinese medicine Duliang soft capsule (DSC) in prophylactic treatment for patients with chronic daily headache (CDH). Methods. A multicenter, double-blind, randomized, placebo-controlled clinical study was conducted at 18 Chinese clinical centers. The participants received either DSC or placebo for 4 weeks. The primary efficacy measure was headache-free rate (HFR) in a 4-week period between the pretreatment and posttreatment stages. The secondary efficacy measures were the decrease of headache days, the duration of headache attacks, the frequency of analgesic usage, quality of life, disability, and the headache severity (VAS scores). The accompanying symptoms and adverse events were also assessed. Results. Of 584 CDH patients assessed, 468 eligible patients were randomized. 338 patients received DSC, while 111 patients were assigned in the placebo group. Following treatment, there was a 16.56% difference in HFR favoring DSC over placebo (P<0.01). Significant differences were also observed between DSC and placebo groups in the secondary measures. However, no statistical difference was found between the two groups in the associated symptoms. No severe adverse effects were observed in the study. Conclusions. DSC might be an effective and well-tolerated option for the prophylactic treatment of patients with CDH.

Acupuncture versus topiramate in chronic migraine prophylaxis: A randomized clinical trial

Cephalalgia ◽  
2011 ◽  
Vol 31 (15) ◽  
pp. 1510-1521 ◽  
Author(s):  
C-P Yang ◽  
M-H Chang ◽  
P-E Liu ◽  
T-C Li ◽  
C-L Hsieh ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Prophylactic Treatment ◽  
Medication Overuse ◽  
Severe Headache ◽  
Migraine Prophylaxis ◽  
Acupuncture Group ◽  
Maintenance Period ◽  
Acute Medication ◽  
Group A ◽  
The Mean

Background: The aim of this study was to investigate the efficacy and tolerability of acupuncture compared with topiramate treatment in chronic migraine (CM) prophylaxis. Methods: A total of 66 consecutive and prospective CM patients were randomly divided into two treatment arms: 1) acupuncture group: acupuncture administered in 24 sessions over 12 weeks (n = 33); and 2) topiramate group: a 4-week titration, initiated at 25 mg/day and increased by 25 mg/day weekly to a maximum of 100 mg/day followed by an 8-week maintenance period (n = 33). Results: A significantly larger decrease in the mean monthly number of moderate/severe headache days (primary end point) from 20.2 ± 1.5 days to 9.8 ± 2.8 days was observed in the acupuncture group compared with 19.8 ± 1.7 days to 12.0 ± 4.1 days in the topiramate group (p < .01) Significant differences favoring acupuncture were also observed for all secondary efficacy variables. These significant differences still existed when we focused on those patients who were overusing acute medication. Adverse events occurred in 6% of acupuncture group and 66% of topiramate group. Conclusion: We suggest that acupuncture could be considered a treatment option for CM patients willing to undergo this prophylactic treatment, even for those patients with medication overuse.

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