Search

In the phase 3b, randomized, double-blind, placebo-controlled DELIVER clinical trial, eptinezumab reduced migraine frequency and headache in adults with two to four prior preventive treatment failures. Here the effect of eptinezumab on coinciding patient-reported outcomes is reported.Adults were randomized to receive eptinezumab 100 mg, 300 mg, or placebo IV at weeks 12 and 24. The EQ-5D-5L, measuring overall patient health, and 6-item Headache Impact Test (HIT-6) were completed every four weeks. The Patient Global Impression of Change (PGIC) was completed at weeks 4, 12 and 24. Patient-identified most bothersome symptom (PI-MBS) and the Migraine-Specific Quality of Life Questionnaire (MSQ) were administered at weeks 12 and 24.Eptinezumab improved patient-reported outcomes more than placebo, starting at week 4 and at all subsequent time points. By week 12, patients' overall health, (EQ-5D-5L visual analog scale score) improved with eptinezumab treatment (difference from placebo in change from baseline [95% CI]: 100 mg, 5.1 [2.2, 8.1], P0.001; 300 mg, 7.5 [4.5, 10.4], P0.0001). At week 12, eptinezumab improved headache-related quality of life (difference from placebo in change from baseline in HIT-6 total score: 100 mg, -3.8 [-5.0, -2.5], P0.0001; 300 mg, -5.4 [-6.7, -4.2], P0.0001), including each MSQ domain (P ≤0.0001, all comparisons). Over twice as many patients receiving eptinezumab than placebo reported much or very much improvement on the PGIC and PI-MBS.Patients with two to four prior preventive treatment failures receiving eptinezumab vs placebo reported greater improvements in well-being, quality of life, , and most bothersome symptoms compared to placebo.

The monoclonal antibody eptinezumab, which targets calcitonin gene-related peptide, has shown migraine preventive effects starting the day following infusion and acceptable safety and tolerability in phase 3 trials, but benefits in the subpopulations of patients with previous preventive treatment failures were not examined. We aimed to investigate the safety and efficacy of eptinezumab for migraine prevention in adults with migraine and two-to-four previous preventive treatment failures.DELIVER was a multicentre, multi-arm, phase 3b trial comprising a 24-week double-blind, placebo-controlled period and a 48-week dose-blinded extension. We recruited adults with episodic or chronic migraine with at least 4 monthly migraine days (as per International Headache Society guidelines) and documented evidence of two-to-four previous preventive treatment failures within the past 10 years, from 96 study locations across Europe (n=93) and the USA (n=3). Patients were randomly assigned (1:1:1) via a centralised randomisation system, stratified by baseline monthly headache days and country, to eptinezumab 100 mg, eptinezumab 300 mg, or placebo. The primary efficacy endpoint was the change from baseline in mean monthly migraine days (captured using a daily electronic diary) in weeks 1-12, assessed in the full analysis set. All participants and study personnel were masked to study drug assignments. The dose-blinded extension period is ongoing. The trial is registered with ClinicalTrials.gov, NCT04418765, and EudraCT, 2019-004497-25.Between June 1, 2020, and Oct 7, 2021, 891 individuals were randomly assigned and received at least one dose of study drug (safety population; eptinezumab 100 mg n=299 [34%], eptinezumab 300 mg n=294 [33%], placebo n=298 [33%]). 865 patients completed the placebo-controlled period. The change from baseline to weeks 1-12 in mean monthly migraine days was -4·8 (SE 0·37) with eptinezumab 100 mg, -5·3 (0·37) with eptinezumab 300 mg, and -2·1 (0·38) with placebo. The difference from placebo in change in mean monthly migraine days from baseline was significant with eptinezumab 100 mg (-2·7 [95% CI -3·4 to -2·0]; p0·0001) and eptinezumab 300 mg (-3·2 [-3·9 to -2·5]; p0·0001). Treatment-emergent adverse events occurred in 127 (42%) of 299 patients in the eptinezumab 100 mg group, in 120 (41%) of 294 in the eptinezumab 300 mg group, and in 119 (40%) of 298 in the placebo group. The most common treatment-emergent adverse event was COVID-19 (20 [7%] of 299 patients in the eptinezumab 100 mg group, 17 [6%] of 294 in the eptinezumab 300 mg group, and 16 [5%] of 298 in the placebo group). Serious adverse events were uncommon (five [2%] of 299 in the eptinezumab 100 mg group, seven [2%] of 294 in the eptinezumab 300 mg group, four [1%] of 298 in the placebo group) and included anaphylactic reaction (eptinezumab 300 mg n=2) and COVID-19 (eptinezumab 100 mg n=1 and eptinezumab 300 mg n=1).In adults with migraine and two-to-four previous preventive treatment failures, eptinezumab provided significant migraine preventive effects compared with placebo, with acceptable safety and tolerability, indicating that eptinezumab might be an effective treatment option for this patient population. The dose-blinded extension period will provide additional long-term safety data in patients with migraine and previous preventive treatment failures.H Lundbeck.

Chronic migraine; Episodic migraine; Eptinezumab Migraña crónica; Migraña episódica; Eptinezumab Migranya crònica; Migranya episòdica; Eptinezumab Background Migraine is a disabling neurological disease adversely affecting many aspects of life. Most patients are still required to have failed several older oral preventive therapies before being reimbursed for a preventive, migraine-specific anti-calcitonin gene-related peptide treatment. In the 24-week placebo-controlled portion of DELIVER, eptinezumab was shown to reduce migraine frequency and resulted in higher migraine responder rates compared with placebo in patients with two to four previous preventive treatment failures. This subgroup analysis assessed if demographic or clinical characteristics were associated with differences in preventive benefits. Methods Migraine frequency reductions and responder rates (i.e., the proportion of patients reaching a ≥50% and ≥75% reduction in monthly migraine days relative to baseline) were determined in the total population and predefined subgroups by sex, age, migraine frequency (chronic migraine, episodic migraine, high-frequency episodic migraine, low-frequency episodic migraine), medication overuse, medication-overuse headache, and previous preventive treatment failures (2, >2). The primary endpoint was change from baseline in monthly migraine days over weeks 1–12. Results Eptinezumab 100 and 300 mg reduced monthly migraine days more than placebo over weeks 1–12 (−4.8 and −5.3 vs –2.1, respectively; p

Carlos Cuevas,1 Florian Deisenhammer,2 Xiaojun You,3 Mariano Scolnik,4 Regine Buffels,3 Bjørn Sperling,3 Francisco Flores-Ramírez,5 Miguel Macías-Islas,6 Sergio Sauri-Suárez7 On behalf of the MATRIX Investigator Group 1Specialty Hospital, Department of Neurology, National Medical Center Siglo XXI, Mexican Institute of Social Security, Mexico City, Mexico; 2Department of Neurology, University of Innsbruck, Innsbruck, Austria; 3Biogen, Cambridge, MA, USA; 4Biogen, Argentina, Buenos Aires, Argentina; 5Department of Internal Medicine–Neurology, Hospital Regional ISSSTE Monterrey, Monterrey, 6University Center for Health Sciences, University of Guadalajara, Guadalajara, 7Internal Medicine/Department of Neurology, National Medical Center, Mexico City, Mexico Abstract: MATRIX (Measuring neutralizing Antibodies in patients TReated with Interferon beta-1a IM in MeXico) was primarily a cross-sectional phase 4 study of patients with relapsing multiple sclerosis (RMS) that evaluated neutralizing antibody (NAb) frequency in Mexican and Colombian patients treated with intramuscular interferon (IFN) beta-1a in the form of Avonex® or the biosimilar drug Jumtab®. A secondary long-term retrospective observational evaluation of safety, tolerability, and relapses was also performed for patients in each arm of the study. In the cross-sectional portion of the study, patients with multiple sclerosis who had been treated with once-weekly Avonex (n=36) or Jumtab (n=29) self-injections as their first and only disease-modifying therapy for 1–3 years were retrospectively identified. The primary and secondary endpoints were proportion of patients with NAb levels >100 tenfold reduction units (TRU) and >20 TRU. The biological response to IFN beta-1a injections was assessed by change in serum neopterin levels and by pre- versus post-dose concentration difference. Safety, tolerability, and relapse-related information were also retrospectively assessed. No patients developed NAb levels >100 TRU. Neopterin levels were significantly higher relative to baseline with Avonex than with Jumtab. Supporting this result, flu-like symptoms were reported in a greater proportion of Avonex-treated than Jumtab-treated patients. No unexpected adverse events or significant differences in relapses were observed. In conclusion, Avonex and Jumtab exhibited minimal immunogenicity; Jumtab was associated with significantly lower neopterin activation and flu-like symptom frequency compared with Avonex, suggesting less IFN bioactivity with Jumtab. Keywords: multiple sclerosis, neutralizing antibodies, flu-like symptoms, neopterin, follow-on biologics, biosimilars

Background . Postoperative cognitive dysfunction after cardiac surgery has been attributed both to embolic events and periods with reduced cerebral perfusion. We investigated whether cognitive dysfunction after coronary surgery is associated with changes in regional cerebral blood flow (CBF) using single photon emission computed tomography. Methods . Before surgery and at discharge, 15 coronary surgery patients were studied. Global and regional CBF were measured using a brain-dedicated single photon emission computed tomography scanner, and neuropsychological testing with seven subtests was performed. Postoperative cognitive dysfunction was defined as a Z score above 2. Normative single photon emission computed tomography data were available from 26 healthy age-matched controls. Results . Preoperative global CBF was significantly lower in patients compared with controls (53.7 versus 46.1 mL/100 g/min, p = 0.006). After surgery, global CBF significantly decreased in the patient group (46.1 versus 38.6 mL/100 g/min, p = 0.0001). No significant differences were detected in regional CBF. Cognitive dysfunction was identified in 4 of the 15 patients (26.7%, 95% CI 7.8% to 55.1%). No correlation was found between the neuropsychological Z score and global or regional CBF. Conclusions . The significant decrease in CBF after coronary surgery was uniformly distributed and was not correlated to postoperative cognitive dysfunction.

Background The concept of selective vulnerability or selective loss of individual neurons, with survival of glial and vascular elements as one of the consequences of a systemic ischemic-hypoxic insult (eg, transient cardiac arrest or severe hypotension), has been recognized for decades. In contrast, selective neuronal death as one of the lesions that may develop in the brain after occluding an intracranial artery is an idea not readily acknowledged in the current medical literature dealing with human stroke. Summary of Review A review of pertinent publications reveals that selective neuronal injury after middle cerebral artery occlusion was observed in autopsy specimens over 40 years ago, although its pathogenesis remains unclear. Recent observations in both humans and animals suggest that selective neuronal necrosis (rather than infarct) is the consequence of either a short-term arterial occlusion or permanent occlusion accompanied by ischemia of moderate severity. During the acute and subacute stages of an ischemic stroke, the loss of a limited number of neurons (ie, incomplete infarction) does not result in structural changes discernible by either CT or conventional MRI. However, the loss of a selected number of neurons may be demonstrable in vivo by calculating the corresponding loss of benzodiazepine receptors. The use of specific radiotracers in combination with single-photon emission CT or positron emission tomography allows demonstration of a decrease in γ-aminobutyric acid–ergic receptor sites at places where many neurons have been lethally injured. Conclusions We aim to alert physicians to the potential development of incomplete brain infarctions in patients with intracranial arterial occlusions. Recognizing incomplete infarcts is particularly important in the context of stroke therapy with thrombolytic and neuroprotective agents. This brain lesion is likely to be the consequence of an arterial occlusion with a resultant ischemia of moderate severity (eg, regional blood flows in the range of 15 to 20 mL·100 g −1 ·min −1 ).

Gary Bloomgren, Bjørn Sperling, Kimberly Cushing, Madé WentenBiogen Idec Inc., Weston, MA, USABackground: Intramuscular interferon beta-1a (IFNβ-1a), a multiple sclerosis (MS) therapy that has been commercially available for over a decade, provides a unique opportunity to retrospectively assess postmarketing data for evidence of malignancy risk, compared with relatively limited data available for more recently approved therapies. Postmarketing and claims data were analyzed to determine the risk of malignancy in MS patients treated with intramuscular IFNβ-1a.Materials and methods: The cumulative reporting rates of suspected adverse drug reactions coded to malignancy in the intramuscular IFNβ-1a global safety database were compared with malignancy incidence rates in the World Health Organization GLOBOCAN database. In addition, using data from a large US claims database, the cumulative prevalence of malignancy in MS patients treated with intramuscular IFNβ-1a was compared with non-MS population controls, MS patients without intramuscular IFNβ-1a use, and untreated MS patients. Mean follow-up was approximately 3 years for all groups, ie, 3.1 years for the intramuscular IFNβ-1a group (range 0.02–6.0 years), 2.6 years for non-MS population controls (range 0–6.0 years), 2.6 years for the intramuscular IFNβ-1a nonuse group (range 0.01–6.0 years), and 2.4 years for the untreated MS group (range 0.01–6.0 years).Results: An estimated 402,250 patients received intramuscular IFNβ-1a during the postmarketing period. Cumulative reporting rates of malignancy in this population were consistent with GLOBOCAN incidence rates observed within the general population. The claims database included 12,894 MS patients who received intramuscular IFNβ-1a. No significant difference in malignancy prevalence was observed in intramuscular IFNβ-1a users compared with other groups.Conclusion: Results from this evaluation provide no evidence of an increased risk of malignancy with intramuscular IFNβ-1a use.Keywords: multiple sclerosis, malignancy, safety, intramuscular interferon beta-1a, postmarketing surveillance, claims&nbsp