Data mining differential clinical outcomes associated with drug regimens using adverse event reporting data

Sarangdhar, Mayur; Tabar, Scott; Schmidt, Charles W.; Kushwaha, Akash; Shah, Krish; Dahlquist, Jeanine E; Jegga, Anil G.; Aronow, Bruce J.

doi:10.1038/nbt.3623

Cited by 61 publications

(55 citation statements)

References 29 publications

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“…15 Within the FAERS, SGLT2 inhibitors appear to be disproportionally associated with GUTIs, with a very robust PRR of~4. 5 alone, suggesting that this finding is specific to DPP-4 inhibitors.…”

Section: Discussionmentioning

confidence: 76%

“…The FAERS collects AE reports filed to the US Food and Drug Administration (FDA) from all over the world: each report contains a unique identifier, demographic patient characteristics, type(s) and date of AE, suspect or concomitant drugs with indication(s) for use, outcome of the AE, reporting source and country, although not all reports are complete. We used software (AERSMine) spanning publicly available FAERS files from January 1, 2014 to December 31, 2016 . We retrieved number of cases, and calculated rates and proportional reporting ratios (PRRs), as previously described .…”

Section: Methodsmentioning

confidence: 99%

“…We used software (AERSMine) spanning publicly available FAERS files from January 1, 2014 to December 31, 2016. 5 We retrieved number of cases, and calculated rates and proportional reporting ratios (PRRs), as previously described. 6 We searched GUTI reports in patients on SGLT2 inhibitor therapy alone (without a DPP-4 inhibitor) and in patients on SGLT2 inhibitor with concomitant DPP-4 inhibitor therapy.…”

mentioning

confidence: 99%

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Dipeptidyl peptidase‐4 inhibitors moderate the risk of genitourinary tract infections associated with sodium‐glucose co‐transporter‐2 inhibitors

Fadini

Bonora

Sarangdhar

et al. 2017

Diabetes Obesity Metabolism

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Genitourinary tract infections (GUTIs) are the most common adverse event (AE) occurring during therapy with sodium-glucose co-transporter-2 (SGLT2) inhibitors. We evaluated whether dipeptidyl peptidase-4 inhibitors moderate the risk of GUTI during SGLT2 inhibitor therapy, using two approaches. First, we screened the literature for randomized controlled trials (RCTs) directly comparing the frequency of GUTIs in patients receiving DPP-4 inhibitor/SGLT2 inhibitor combination therapy vs those receiving an SGLT2 inhibitor only. In the five trials we retrieved, the pooled risk ratio for genital tract infections (GTIs) in patients on DPP-4 inhibitor/SGLT2 inhibitor combination therapy vs those on SGLT2 inhibitors alone was 0.51 (95% confidence interval [CI] 0.28-0.92). Second, we found that within the Food and Drug Administration AE Reporting System, the frequency of GUTIs among reports listing both SGLT2 and DPP-4 inhibitors as suspect or concomitant drugs was significantly lower than among reports listing SGLT2 inhibitors without DPP-4 inhibitors, with a proportional reporting ratio of 0.74 (95% CI 0.61-0.90). In conclusion, in RCTs and in a large pharmacovigilance database, combination therapy with a DPP-4 inhibitor appears to reduce the frequency of G(U)TIs associated with SGLT2 inhibitors.

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Section: Discussionmentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Dipeptidyl peptidase‐4 inhibitors moderate the risk of genitourinary tract infections associated with sodium‐glucose co‐transporter‐2 inhibitors

Fadini

Bonora

Sarangdhar

et al. 2017

Diabetes Obesity Metabolism

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“…FAERS files are made publicly available on a quarterly basis and are accessible using methods for orthogonal database searches. AERSMine, an open-access web-based data mining tool, is the most comprehensive software to analyse the FAERS up to 2016 Q3 [8].…”

Section: Methodsmentioning

confidence: 99%

SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System

2017

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Aims/hypothesis Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods We first analysed the entire public FAERS up to September (third quarter [Q3]) 2016 to extract the number of reports, background indications and concomitant medications, and to calculate proportional reporting ratios (PRRs) and safety signals. We then mined single FAERS files from the first quarter (Q1) of 2014 to 2016 Q3 to obtain detailed information on DKA reports. Results The FAERS database contains >2500 DKA reports in which SGLT2i are listed as suspect or concomitant drugs. The PRR of DKA in reports including vs those not including an SGLT2i and having a diabetes indication was 7.9 (95% CI 7.5, 8.4) and was higher for type 1 diabetes. Several concomitant conditions were less prevalent in DKA reports with SGLT2i vs DKA reports filed for other drugs. A detailed analysis of 2397 DKA reports for SGLT2i from 2014 Q1 to 2016 Q3 revealed a predominance of women, an extremely wide range of age and body weight, and a highly variable duration of SGLT2i treatment before onset of DKA. In 37 individuals (1.54%), DKA was fatal. Conclusions/interpretation Based on the profile of these reports, SGLT2i-associated DKA may not be limited to any particular demographic or comorbid subpopulation and can occur at any duration of SGLT2i use.

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“…A broad search term for thrombocytopenia was used and subsequent listings of adverse events were reviewed for inclusion. To evaluate adverse events reports for thrombocytopenia with linezolid before tedizolid was approved, we used AERSMine with a restricted time period of January 2004 through June 2014 (9). Using a case-non-case design, reporting odds ratios (ROR) and proportional reporting ratios (PRR), and corresponding 95% confidence intervals (CI) were calculated with OpenEpi (10-12).…”

Section: Methodsmentioning

confidence: 99%

Thrombocytopenia with Tedizolid and Linezolid

Lee

Caffrey

2018

Antimicrob Agents Chemother

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Word Count: 222Manuscript Word Count: 1,433 AbstractObjective: Though thrombocytopenia is a known adverse effect with linezolid, the first-in class oxazolidinone antibiotic, some have suggested a lower risk of thrombocytopenia with tedizolid, the second-in-class oxazolidinone antibiotic. We sought to evaluate adverse event reports for thrombocytopenia with tedizolid and linezolid from the Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: To assess the period since tedizolid approval, we included initial FAERS reports from ) and PRR was 11.1 (95% CI 10.38-11.87).Conclusion: We observed a significantly increased risk of thrombocytopenia of similar magnitude with both linezolid and tedizolid. Thrombocytopenia with tedizolid should be assessed with real-world comparative safety studies as more patients are treated with tedizolid.

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Data mining differential clinical outcomes associated with drug regimens using adverse event reporting data

Cited by 61 publications

References 29 publications

Dipeptidyl peptidase‐4 inhibitors moderate the risk of genitourinary tract infections associated with sodium‐glucose co‐transporter‐2 inhibitors

Dipeptidyl peptidase‐4 inhibitors moderate the risk of genitourinary tract infections associated with sodium‐glucose co‐transporter‐2 inhibitors

SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System

Thrombocytopenia with Tedizolid and Linezolid

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