Efficacy and Safety of Erenumab in Participants With Episodic Migraine in Whom 2-4 Prior Preventive Treatments Had Failed: LIBERTY 3-Year Study.

Background And Objectives: The LIBERTY study assessed the efficacy and safety of erenumab in participants with episodic migraine (EM) and 2-4 prior preventive treatment failures. The results have been presented after 3 years of erenumab exposure in its open-label extension phase (OLEP).

Methods: Participants completing the 12-week double-blind treatment phase (DBTP) of the LIBERTY study could enter the OLEP and receive 140 mg of erenumab once monthly for 3 years.

Early Use of Erenumab vs Nonspecific Oral Migraine Preventives: The APPRAISE Randomized Clinical Trial.

Importance: Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden.

Objective: To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments.

Design, Setting, And Participants: The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021.

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

Objective: To 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.

Methods: Participants 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.

Effect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: results from the phase 3 PARADIG study.

Objective: PARADIG demonstrated superior efficacy and comparable safety of fingolimod versus interferon β-1a (IFN β-1a) in paediatric-onset multiple sclerosis (PoMS). This study aimed to report all predefined MRI outcomes from this study.

Methods: Patients with multiple sclerosis (MS) (aged 10-<18 years) were randomised to once-daily oral fingolimod (n=107) or once-weekly intramuscular IFN β-1a (n=108) in this flexible duration study.

Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIG.

Background: In PARADIG, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a.

Objectives: To investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.

Methods: ARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations.

Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis.

Background: Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.

Methods: In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.

Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study.

Objective: The 12-month (M), phase 3, double-blind, randomised TRANSFORMS study demonstrated significant benefits of fingolimod 0.5 or 1.25 mg over interferon β-1a (IFNβ-1a) in patients with relapsing-remitting multiple sclerosis.

Fingolimod and CSF neurofilament light chain levels in relapsing-remitting multiple sclerosis.

Objective: We assessed CSF levels of the light chain subunit of neurofilaments (NfL) at baseline and after fingolimod therapy or placebo in patients with relapsing-remitting multiple sclerosis (RRMS). Changes in NfL levels were also correlated with relapse and MRI outcomes.

Methods: CSF samples were available, at baseline and 12 months after treatment initiation, from a subset of 36 patients with RRMS (fingolimod 0.

Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial.

Background: Fingolimod has shown reductions in clinical and MRI disease activity in patients with relapsing-remitting multiple sclerosis. We further assessed the efficacy and safety of fingolimod in such patients.

Methods: We did this placebo-controlled, double-blind phase 3 study predominantly in the USA (101 of 117 centres).

Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study.

Background: In a 12-month phase 3 study in patients with relapsing-remitting multiple sclerosis (RRMS), TRANSFORMS, fingolimod showed greater efficacy on relapse rates and MRI outcomes compared with interferon beta-1a. We had two aims in our extension: to compare year 2 with year 1 in the switched patients to assess the effect of a change from interferon beta-1a to fingolimod, and to compare over 24 months the treatment groups as originally randomised to assess the effect of delaying the start of treatment with fingolimod.

Methods: Patients randomly assigned to receive 0.

Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.

Background: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis.

Methods: In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.

Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice.

When pyrroloquinoline quinone (PQQ) is added to an amino acid-based, but otherwise nutritionally complete basal diet, it improves growth-related variables in young mice. We examined PQQ and mitochondrial function based on observations that PQQ deficiency results in elevated plasma glucose concentrations in young mice, and PQQ addition stimulates mitochondrial complex 1 activity in vitro. PQQ-deficient weanling mice had a 20-30% reduction in the relative amount of mitochondria in liver; lower respiratory control ratios, and lower respiratory quotients than PQQ-supplemented mice (2 mg PQQ/kg diet).

Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets.

Growth, reproductive performance, and indices of collagen maturation and expression were investigated in Balb/c mice fed chemically defined, amino acid-based diets with or without the addition 6 micro Mpyrroloquinoline quinone (PQQ)/kg diet. The diets were fed to virgin mice for 8 weeks before breeding. At weaning, the pups from successful pregnancies were fed the same diet as their respective dams.