Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial.

BACKGROUND: No acute treatments targeting calcitonin gene-related peptide (CGRP) have been approved for use in China or South Korea. We aimed to compare the efficacy and safety of rimegepant-an orally administered small molecule CGRP antagonist-with placebo in the acute treatment of migraine among adults in these countries. METHODS: This double-blind, randomised, placebo-controlled, multicentre phase 3 trial was done at 86 outpatient clinics at hospitals and academic medical centres (73 in China and 13 in South Korea). Participants were adults (≥18 years) with at least a 1-year history of migraine who had two to eight moderate or severe attacks per month and fewer than 15 headache days per month within the 3 months before the screening visit. Participants were randomly assigned (1:1) to 75 mg rimegepant or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use of preventive medication and by country. The allocation sequence was generated and implemented by study personnel using an interactive web-response system accessed online from each study centre. All participants, investigators, and the sponsor were masked to treatment assignment. The coprimary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, phonophobia, or photophobia) 2 h after dosing were assessed in the modified intention-to-treat (mITT) population (randomly assigned participants who took study medication for a migraine attack of moderate or severe pain intensity, and provided at least one efficacy datapoint after treatment) using Cochran-Mantel Haenszel tests. Safety was assessed in all participants who received rimegepant or placebo. The study is registered with ClinicalTrials.gov, number NCT04574362, and is completed. FINDINGS: 1431 participants were randomly assigned (716 [50%] to rimegepant and 715 [50%] to placebo). 668 (93%) participants in the rimegepant group and 674 (94%) participants in the placebo group received treatment. 1340 participants were included in the mITT analysis (666 [93%] in the rimegepant group and 674 [94%] in the placebo group). 2 h after dosing, rimegepant was superior to placebo for pain freedom (132 [20%] of 666 vs 72 [11%] of 674, risk difference 9·2, 95% CI 5·4-13·0; p<0·0001) and freedom from the most bothersome symptom (336 [50%] of 666 participants vs 241 [36%] of 674 participants, 14·8, 9·6-20·0; p<0·0001). The most common (≥1%) adverse events were protein in urine (8 [1%] of 668 participants in the rimepegant group vs 7 [1%] of 674 participants in the placebo group), nausea (7 [1%] of 668 vs 18 [3%] of 674), and urinary tract infection (5 [1%] of 668 vs 8 [1%] of 674). There were no rimegepant-related serious adverse events. INTERPRETATION: Among adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population. FUNDING: BioShin Limited. TRANSLATIONS: For the Chinese and Korean translations of the abstract see Supplementary Materials section.

Evaluation of the Effect of Garlic Tablet as a Complementary Treatment for Patients with Diabetic Retinopathy.

Purpose: The aim of this study was to investigate the effectiveness of garlic (Allium sativum L.) tablets as a complimentary herbal medication in diabetic macular edema. Methods: A total of 91 diabetic participants (117 eyes) with central involved macular edema underwent a double-blind randomized trial. The patients used garlic tablets (500 mg) (2 tab/day) or placebo for 4 weeks and subsequently were examined by an expert ophthalmologist. Clinical manifestations including the best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), and intraocular pressure (IOP) were measured as the main outcomes. Results: BCVA was significantly improved by a 0.18 decrease in mean logMAR value in the garlic-treated patients in comparison with 0.06 in the control ones (P value = 0.027). CMT was decreased in both groups by a 102.99 µm decrease in the garlic group compared to 52.67 µm in the placebo group, albeit in a nonsignificant manner (P value: 0.094). IOP was decreased in the garlic group by 1.03 mmHg (P value: 0.024) and increased by 0.3 mmHg (P value: 0.468) in the placebo group. Conclusion: Our trial suggests that garlic supplements can improve visual acuity, decrease the CMT and lower the IOP, and can be considered as an adjuvant treatment in patients with diabetic macular edema. Garlic was satisfactorily tolerated in diabetic patients, and no significant adverse effect interrupting the safety profile was observed.

Real-world evidence for cladribine tablets in multiple sclerosis: further insights into efficacy and safety.

Cladribine (CLAD) is a purine nucleoside analog approved in tablet form to treat highly active multiple sclerosis (MS). CLAD tablets are the first oral therapy with an infrequent dosing schedule, administered in two annual treatment courses, each divided into two treatment cycles comprising 4-5 days of treatment. The efficacy and safety of CLAD tablets have been verified in randomized controlled clinical trials. Clinical observational studies are performed in more representative populations and over more extended periods, and thus provide valuable complementary insights. Here, we summarize the available evidence for CLAD tablets from post-marketing trials, including two observational, four long-term extensions, and two comparative studies. The patients in the post-marketing setting differed from the cohort recruited in the pivotal phase III trials regarding demographics and MS-related disability. The limited number of studies with small cohorts corroborate the disease-modifying capacity of oral CLAD and report on a durable benefit after active treatment periods. Skin-related adverse events were common in the studies focusing on safety aspects. In addition, single cases of CLAD-associated autoimmune events have been reported. Lastly, CLAD tablets appear safe regarding COVID-19 concerns, and patients mount a robust humoral immune response to SARS-CoV­2 vaccination. We conclude that the current real-world evidence for CLAD tablets as immune reconstitution therapy for treatment of MS is based on a small number of studies and a population distinct from the cohorts randomized in the pivotal phase III trials. Further research should advance the understanding of long-term disease control after active treatment periods and the mitigation of adverse events.

Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study.

BACKGROUND: Functional iron deficiency facilitates allergy development and amplifies the symptom burden in people experiencing allergies. Previously we selectively delivered micronutrients to immune cells with ß-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention. OBJECTIVE: The clinical efficacy of a food for special medical purposes-lozenge containing ß-lactoglobulin with iron, polyphenols, retinoic acid, and zinc (holoBLG lozenge) was assessed in allergic women. METHODS: In a randomized, double-blind, placebo-controlled pilot study, grass- and/or birch pollen-allergic women (n = 51) were given holoBLG or placebo lozenges over 6 months. Before and after dietary supplementation, participants were nasally challenged and the blood was analyzed for immune and iron parameters. Daily symptoms, medications, pollen concentrations, and well-being were recorded by an electronic health application. RESULTS: Total nasal symptom score after nasal provocations improved by 42% in the holoBLG group versus 13% in the placebo group. The combined symptom medication score during the birch peak and entire season as well as the entire grass pollen season improved in allergic subjects supplemented with the holoBLG lozenge by 45%, 31%, and 40%, respectively, compared with the placebo arm. Participants ingesting the holoBLG lozenge had improved iron status with increased hematocrit values, decreased red cell distribution width, and higher iron levels in circulating CD14+ cells compared with the placebo group. CONCLUSIONS: Targeted micronutrition with the holoBLG lozenge seemed to be effective in elevating the labile iron levels in immune cells and reducing the symptom burden in allergic women in this pilot study. The underlying allergen-independent mechanism provides evidence that dietary nutritional supplementation of the immune system is one of the ways to combat atopy.