Relative efficacy of lasmiditan versus rimegepant and ubrogepant as acute treatments for migraine: network meta-analysis findings.

BACKGROUND: In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA). METHODS: Data included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II-IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings. RESULTS: Across 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9-45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant. CONCLUSIONS: The efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting. 350/350 words.

Identification and mapping of worldwide sources of generic real-world data.

PURPOSE: The demand for real-world data as supportive evidence to traditional clinical studies has increased in the past few years. The present study aimed to identify worldwide generic sources of real-world data and to assess completeness and suitability of selected real-world evidence (RWE) data sources to conduct prespecified research. METHODS: A systematic literature review was conducted to identify generic (non-disease specific) sources of real-world data in Medline and Embase from January 1, 2010 to September 8, 2015. Data sources used in observational studies were identified and summarized based on their geographical distribution and the type of data. In the next step, the selected data sources were critically evaluated for their completeness. RESULTS: A total of 10,069 identified publications were screened, leading to 2635 unique data sources across 102 countries. Europe had the maximum number of data sources (n = 1163) followed by United States (n = 578), and Asia, Middle East, and African Countries (n = 374). The most common type of identified data sources across all countries was structured data sources, ie, administrative databases and registries. Of the identified data sources, 300 were selected for further investigation. From the selected databases, ~50% had confirmed information on over 60% of the investigated variables, ~61% were suitable for epidemiological research, and 60% had possibility of linkage. CONCLUSIONS: The present study applied a systematic literature review approach and identified available generic sources of real-world data worldwide, in addition to the United States and Europe, which are suitable for conducting pre-defined researches and support future RWE studies.

Effect of anti-diabetic drugs on bone metabolism: Evidence from preclinical and clinical studies.

Diabetes mellitus is associated with abnormal bone health and an increased risk of fracture even though patients have normal or higher BMD. The mechanisms behind diabetes mellitus- induced various skeletal disorders remain unclear. Anti-diabetic drugs may have negative or positive impact on bone metabolism. For instance, thiazolidinediones increases the bone loss and risk of fracture possibly through PPARγ activation in bone marrow cells and hamper osteoblastogenesis via decreasing Runx2 transcription factor, IGF-1 and Wnt signalling pathways. In contrast, metformin and sulfonylureas have a neutral or positive effect on bone health and reduced risk of fracture. Results from the preclinical and clinical studies convey conflicting findings over insulin safety profile on bone health. Incretin-based therapy (GLP-1 receptor agonist and DPP-4 inhibitors) and SGLT2 inhibitors are currently marketed anti- diabetic drugs. While evidence from animal studies suggest that incretin-based therapy have anabolic effect on bone, limited clinical data of DPP-4 inhibitors and GLP-1 receptor agonist indicated a neutral effect on the bone health and risk of fracture. SGLT2 inhibitors may cause bone loss or increase fracture risk due to altered calcium, phosphate and sodium concentration. Therefore, safety concerns of anti-diabetic drugs are crucial for the management of diabetes mellitus. In this review, analysis of the available evidence for effect of anti-diabetic drugs on the bone metabolism and fracture risk in diabetes mellitus is described.