Incorporating Unstructured Patient Narratives and Health Insurance Claims Data in Pharmacovigilance: Natural Language Processing Analysis of Patient-Generated Texts About Systemic Lupus Erythematosus.

BACKGROUND: Gaining insights that cannot be obtained from health care databases from patients has become an important topic in pharmacovigilance. OBJECTIVE: Our objective was to demonstrate a use case, in which patient-generated data were incorporated in pharmacovigilance, to understand the epidemiology and burden of illness in Japanese patients with systemic lupus erythematosus. METHODS: We used data on systemic lupus erythematosus, an autoimmune disease that substantially impairs quality of life, from 2 independent data sets. To understand the disease's epidemiology, we analyzed a Japanese health insurance claims database. To understand the disease's burden, we analyzed text data collected from Japanese disease blogs (tobyoki) written by patients with systemic lupus erythematosus. Natural language processing was applied to these texts to identify frequent patient-level complaints, and term frequency-inverse document frequency was used to explore patient burden during treatment. We explored health-related quality of life based on patient descriptions. RESULTS: We analyzed data from 4694 and 635 patients with systemic lupus erythematosus in the health insurance claims database and tobyoki blogs, respectively. Based on health insurance claims data, the prevalence of systemic lupus erythematosus is 107.70 per 100,000 persons. Tobyoki text data analysis showed that pain-related words (eg, pain, severe pain, arthralgia) became more important after starting treatment. We also found an increase in patients' references to mobility and self-care over time, which indicated increased attention to physical disability due to disease progression. CONCLUSIONS: A classical medical database represents only a part of a patient's entire treatment experience, and analysis using solely such a database cannot represent patient-level symptoms or patient concerns about treatments. This study showed that analysis of tobyoki blogs can provide added information on patient-level details, advancing patient-centric pharmacovigilance.

Risk for cardiovascular disease in Japanese patients with rheumatoid arthritis: a large-scale epidemiological study using a healthcare database.

OBJECTIVES: To study risk for cardiovascular disease (CVD) in Japanese patients with rheumatoid arthritis (RA). METHODS: We used a Medical Data Vision database mainly composed of health insurance claim data and diagnosis-procedure combination data from Japan. Patients with RA diagnosed from April 2011 to March 2014 at 71 hospitals were identified with the International Classification of Diseases 10th revision (ICD-10) and history of anti-RA drug prescription. Hospitalizations for CVD including ischemic heart disease, heart failure, and stroke were identified by a combination of diagnosis (ICD-10) and diagnostic procedures. CVD incidence rate ratio (IRR) for RA versus osteoarthritis was calculated. Risk factors were analyzed using univariate and multivariate Cox proportional hazard models with baseline C-reactive protein (CRP) and traditional risk factors as covariates. RESULTS: We identified 8658 patients with RA. The age-sex adjusted IRR for RA versus osteoarthritis was high for total CVD [2.12; 95 % confidence interval (CI) 1.93-2.32], ischemic heart disease (2.16; 95 % CI 1.86-2.50), heart failure (2.34; 95 % CI 2.07-2.65), and stroke (1.68; 95 % CI 1.41-2.00). Risk factor analysis showed a tendency for cardiovascular risk to increase with higher baseline CRP, although the difference was not statistically significant (hazard ratio 1.43; 95 % CI 0.99-2.07). CONCLUSION: Our study indicates an increased risk for CVD and an association between systemic inflammation and CVD in Japanese RA patients.

Bias in spontaneous reporting of adverse drug reactions in Japan.

BACKGROUND: Attitudes of healthcare professionals regarding spontaneous reporting of adverse drug reactions (ADRs) in Japan are not well known, and Japan's unique system of surveillance, called early post-marketing phase vigilance (EPPV), may affect these reporting attitudes. Our objectives were to describe potential effects of EPPV and to test whether ADR seriousness, prominence, and frequency are related to changes in reporting over time. METHODS: A manufacturer's database of spontaneous ADR reports was used to extract data from individual case safety reports for 5 drugs subject to EPPV. The trend of reporting and the time lag between ADR onset and reporting to the manufacturer were examined. The following indices for ADRs occurring with each drug were calculated and analyzed to assess reporting trends: Serious:Non-serious ratio, High prominence:Low prominence ratio, and High frequency:Low frequency ratio. RESULTS: For all 5 drugs, the time lag between ADR onset and reporting to the manufacturer was shorter in the EPPV period than in the post-EPPV period. All drugs showed higher Serious:Non-serious ratios in the post-EPPV period. No specific patterns were observed for the High prominence:Low prominence ratio. The High frequency:Low frequency ratio for peginterferon alpha-2a and sevelamer hydrochloride decreased steadily throughout the study period. CONCLUSIONS: Healthcare professionals may be more likely to report serious ADRs than to report non-serious ADRs, but the effect of event prominence on reporting trends is still unclear. Factors associated with ADR reporting attitude in Japan might be different from those in other countries because of EPPV and the involvement of medical representatives in the spontaneous reporting process. Pharmacovigilance specialists should therefore be cautious when comparing data between different time periods or different countries. Further studies are needed to elucidate the underlying mechanism of spontaneous ADR reporting in Japan.

Orally active opioid µ/δ dual agonist MGM-16, a derivative of the indole alkaloid mitragynine, exhibits potent antiallodynic effect on neuropathic pain in mice.

(E)-Methyl 2-((2S,3S,7aS,12bS)-3-ethyl-7a-hydroxy-8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate (7-hydroxymitragynine), a main active constituent of the traditional herbal medicine Mitragyna speciosa, is an indole alkaloid that is structurally different from morphine. 7-Hydroxymitragynine induces a potent antinociceptive effect on mouse acute pain through µ-opioid receptors. In this study, we developed dual-acting µ- and δ-opioid agonists MGM-15 and MGM-16 from 7-hydroxymitragynine for the treatment of acute and chronic pain. MGM-16 showed a higher potency than that of 7-hydroxymitragynine and MGM-15 in in vitro and in vivo assays. MGM-16 exhibited a high affinity for µ- and δ-opioid receptors, with K(i) values of 2.1 and 7.0 nM, respectively. MGM-16 showed µ- and δ-opioid full agonistic effects in a guanosine 5'-O-(3-[(35)S]thiotriphosphate) binding assay and in a functional test using electrically elicited guinea pig ileum and mouse vas deferens contractions. Systemic administration of MGM-16 produced antinociceptive effects in a mouse acute pain model and antiallodynic effects in a chronic pain model. The antinociceptive effect of MGM-16 was approximately 240 times more potent than that of morphine in a mouse tail-flick test, and its antiallodynic effect was approximately 100 times more potent than that of gabapentin in partial sciatic nerve-ligated mice, especially with oral administration. The antinociceptive effect of MGM-16 was completely and partially blocked by the µ-selective antagonist ß-funaltrexamine hydrochloride (ß-FNA) and by the δ-selective antagonist naltrindole, respectively, in a tail-flick test. The antiallodynic effect of MGM-16 was completely blocked by ß-FNA and naltrindole in a neuropathic pain model. These findings suggest that MGM-16 could become a class of a compound with potential therapeutic utility for treating neuropathic pain.