Collateral damage: the conundrum of drug safety

Gale, E. A. M.

doi:10.1007/s00125-009-1491-8

Cited by 23 publications

(24 citation statements)

References 21 publications

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“…Limitations of the FDA AERS database, including incomplete data and reporting biases, are well-known. 29 However, AERS has proven effective in similar earlier evaluations at detecting unintended drug side effects. 30–32 This analysis was undertaken notwithstanding these limitations, given the paucity of safety data available for this class of drugs, which is gaining a rapid increase in usage for a common disease.…”

Section: Discussionmentioning

confidence: 99%

Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1–Based Therapies

et al. 2011

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BACKGROUND & AIMS Glucagon-like peptide-1–based therapy is gaining widespread use for type 2 diabetes, although there are concerns about risks for pancreatitis and pancreatic and thyroid cancers. There are also concerns that dipeptidyl peptidase-4 inhibitors could cause cancer, given their effects on immune function. METHODS We examined the US Food and Drug Administration’s database of reported adverse events for those associated with the dipeptidyl peptidase–4 inhibitor sitagliptin and the glucagon-like peptide-1 mimetic exenatide, from 2004–2009; data on adverse events associated with 4 other medications were compared as controls. The primary outcomes measures were rates of reported pancreatitis, pancreatic and thyroid cancer, and all cancers associated with sitagliptin or exenatide, compared with other therapies. RESULTS Use of sitagliptin or exenatide increased the odds ratio for reported pancreatitis 6-fold as compared with other therapies (P < 2 × 10−16). Pancreatic cancer was more commonly reported among patients who took sitagliptin or exenatide as compared with other therapies (P < .008, P < 9 × 10−5). All other cancers occurred similarly among patients who took sitagliptin compared with other therapies (P =.20). CONCLUSIONS These data are consistent with case reports and animal studies indicating an increased risk for pancreatitis with glucagon-like peptide-1–based therapy. The findings also raise caution about the potential long-term actions of these drugs to promote pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1–Based Therapies

et al. 2011

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“…Although no clear explanation has emerged, interest in the diabetes-cancer relationship was recently heightened by some epidemiologic analyses linking insulin in general and basal insulin glargine in particular to incident cancers (2), linking sulfonylureas to the development of cancers, and linking metformin to protection from cancers (3). Other epidemiologic findings have suggested that n-3 polyunsaturated fatty acid intake may reduce the risk of colorectal, prostate, breast, or other cancers (4,5).…”

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confidence: 99%

The Association of Basal Insulin Glargine and/or n-3 Fatty Acids With Incident Cancers in Patients With Dysglycemia

Bordeleau

Yakubovich

Dagenais³

et al. 2014

Diabetes Care

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OBJECTIVEEpidemiologic studies linking insulin glargine and glucose-lowering therapies to cancers and n-3 fatty acids to cancer prevention have not been confirmed. We aimed to assess the effect of insulin glargine and n-3 fatty acids on incident cancers within the context of the ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial. RESEARCH DESIGN AND METHODSThe ORIGIN trial is an international, long-term, randomized two-by-two factorial study comparing insulin glargine with standard care and n-3 fatty acids with placebo (double blind) in people with dysglycemia at high risk for cardiovascular events. The primary outcome measure (cancer substudy) was the occurrence of any new or recurrent adjudicated cancer. Cancer mortality and cancer subtypes were also analyzed. RESULTSAmong 12,537 people (mean age 63.5 years, SD 7.8; 4,388 females), 953 developed a cancer event during the median follow-up of 6.2 years. In the glargine and standard care groups, the incidence of cancers was 1.32 and 1.32 per 100 person-years, respectively (P = 0.97), and in the n-3 fatty acid and placebo groups, it was 1.28 and 1.36 per 100 person-years, respectively (P = 0.39). No difference in the effect of either intervention was noted within predefined subgroups (P for all interactions ‡0.17). Cancer-related mortality and cancer-specific outcomes also did not differ between groups. Postrandomization HbA 1c levels, glucose-lowering therapies (including metformin), and BMI did not affect cancer outcomes. CONCLUSIONSInsulin glargine and n-3 fatty acids have a neutral association with overall and cancer-specific outcomes, including cancer-specific mortality. Exposure to glucoselowering therapies, including metformin, and HbA 1c level during the study did not alter cancer risk.Both type 2 diabetes mellitus (hereafter referred to as diabetes) and cancer are common diseases that are rising in incidence and prevalence throughout the world. Moreover, epidemiologic data suggest that diabetes is associated with an increased risk of several different cancers (1). Reasons for this association may include metabolic features typical of diabetes such as hyperglycemia, insulin resistance, and/or

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“…These cases are spontaneously reported by consumers, healthcare professionals, and lawyers, and are thus susceptible to such reporter bias [25]. We have attempted to compensate for misdiagnoses and report duplications by reviewing the fulllength reports.…”

Section: Discussionmentioning

confidence: 99%

Assessing the likelihood of new-onset inflammatory bowel disease following tumor necrosis factor-alpha inhibitor therapy for rheumatoid arthritis and juvenile rheumatoid arthritis

2014

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The association between inhibition of tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and the onset of inflammatory bowel disease (IBD) is unclear. We sought to evaluate this association by analyzing adverse events (AEs) reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) with a standardized scoring tool for drug-induced AEs. A search of the FAERS for RA or JRA (January 2003-December 2011) reported with adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab was performed. This dataset was then queried for cases indicating IBD. Full-length reports were accessed using the Freedom of Information Act and organized by age, sex, concomitant medications, co-morbidities, type of TNF-α inhibitor used, and diagnosis/treatment details. The Naranjo score was used to determine whether the drug-induced AEs were definite, probable, possible, or doubtful. There were 158 cases of IBD after TNF-α inhibitor exposure in RA or JRA patients. Use of the Naranjo score revealed that, in a majority of the cases (71.5 %), TNF-α inhibitor exposure was considered a 'possible' cause. A majority of the 'probable cases' in JRA were reported with etanercept (40 patients, 90.91 %). There were no 'definite' cases of anti-TNF-induced IBD. After applying the Naranjo scale, a weak association between new-onset IBD and TNF-α inhibitor therapy in RA patients and a moderately strong association especially with etanercept exposure in JRA patients was observed. However, causality cannot be determined due to limitations of the FAERS and the Naranjo score.

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Collateral damage: the conundrum of drug safety

Cited by 23 publications

References 21 publications

Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1–Based Therapies

Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1–Based Therapies

The Association of Basal Insulin Glargine and/or n-3 Fatty Acids With Incident Cancers in Patients With Dysglycemia

Assessing the likelihood of new-onset inflammatory bowel disease following tumor necrosis factor-alpha inhibitor therapy for rheumatoid arthritis and juvenile rheumatoid arthritis

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