Comprehensive study of vaccine safety concludes that vaccines are ‘remarkably safe’

Below please find summaries of new articles that will be published in the next issue of

Annals of Internal Medicine

. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.

1. Comprehensive study of vaccine safety concludes that vaccines are ‘remarkably safe’

Findings confirm the robustness of the vaccine approval system and postmarketing surveillance

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A comprehensive review of vaccine data over a 20-year period finds that vaccines are remarkably safe.

A large proportion of safety issues were identified through existing postmarketing surveillance programs and were of limited clinical significance. Findings from a cohort study are published in

Annals of Internal Medicine

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Vaccines are considered one of the greatest achievements of modern public health, saving countless lives and all but eliminating once prevalent diseases such as mumps, measles and poliomyelitis. The current COVID-19 pandemic is a reminder of life with contagious infectious diseases without an effective vaccine. However, vaccination hesitancy has reduced vaccination rates in recent years and outbreaks linked to intentional unvaccination have been reported.

Researchers from Tel Aviv Sourasky Medical Center studied initial and subsequent labels of 57 vaccines that were FDA-approved between January 1996 and December 2015 to explore postmarketing safety modifications in U.S. Food and Drug Administration (FDA)-approved vaccine labels. The researchers aggregated hundreds of thousands of reports from the FDA’s Vaccine Adverse Event Reporting System (VAERS) following hundreds of millions of administered vaccines for their study. They found 58 postapproval, safety-related label modifications associated with 25 vaccines. The most common safety issue triggering label modifications was restriction of vaccination for specific populations, such as immunocompromised patients or pre-term infants, followed by allergies. Most new safety data were identified through VAERS, underlining the quality of the FDAs postmarketing surveillance of vaccine side effects. According to the researchers, these findings do not support vaccine hesitancy; but rather, show that vaccines are safe and that public vaccination should remain as a major public health strategy.

Media contacts: For an embargoed PDF please contact Lauren Evans at

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. The lead author, Daniel Shepshelovich, MD, can be reached through Avi Shushan at

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2. Poor adherence to denosumab dosing associated with increased risk for vertebral fracture

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Delayed administration of subsequent denosumab doses by more than 16 weeks is associated with increased risk for vertebral fracture compared with on-time dosing. Evidence was insufficient to conclude that fracture risk was increased at other anatomical sites with delayed dosing. Findings from a population-based cohort study are published in

Annals of Internal Medicine

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Denosumab is an effective treatment for osteoporosis when doses are administered regularly and on time. However, delayed dosing is common in clinical practice. Almost 50 percent of patients have at least one delay of more than 4 months, which is associated with reduced improvement in BMD. Its effect on fracture risk has not previously been studied.

Researchers from Brigham and Women’s Hospital studied health records for nearly 2,600 patients initiating denosumab therapy for osteoporosis to estimate the risk for fracture among users of denosumab who delayed subsequent doses compared with users who received doses on time. The data showed that patients who delayed subsequent denosumab doses by more than 16 weeks had increased risk for vertebral fracture compared with those who adhered to the recommended dosing schedule. There was not enough evidence to draw conclusions about fracture risk at other sites of the body. According to the researchers, these finding suggest that strategies to improve timely administration of denosumab in routine clinical settings are needed.

Media contacts: For an embargoed PDF please contact Lauren Evans at

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. The lead author, Daniel H. Solomon, MD, MPH, please contact Haley Bridger at

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3. Tofacitinib induces remission in celiac patient, despite gluten-containing diet

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Tofacitinib, a Janus kinase inhibitor approved to treat rheumatoid arthritis and bowel diseases, may allow patients with celiac disease to eat gluten without experiencing intestinal and extraintestinal symptoms. A case report published in

Annals of Internal Medicine

found tofacitinib to be effective for inducing remission in a patient with celiac disease, despite eating a gluten-containing diet.

Celiac disease, or gluten intolerance, requires a lifelong gluten-free diet, as no other non-dietary treatments have established efficacy. Dietary adherence is crucial for mucosal healing and prevention of long-term complications, but complete avoidance of gluten is difficult for even the most committed patients.

Researchers from University Hospitals Leuven, Leuven, Belgium describe the case of a male patient with celiac disease and alopecia. After achieving some remission following a gluten-free diet, the patient resumed eating gluten and had symptoms on and off, still suffering from alopecia. After discussing the risks and benefits, the patient decided on watchful waiting. He did not return to a gluten-free diet, but started off-label use of tofacitinib, 5 mg twice daily, for alopecia. Follow-up investigations unexpectedly showed complete histologic and serologic remission of celiac disease while he was still on a gluten-containing diet. The patient continued tofacitinib use, with regular blood tests showing normal complete blood count, lipid levels, and creatine kinase levels. While these results are encouraging for patients with celiac disease, the authors caution that potential side effects limit the use of tofacitinib to refractory disease only.

Media contacts: For an embargoed PDF please contact Lauren Evans at

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. To speak with the lead author, Lucas Wauters, MD, please contact him directly at

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4. SGLT-2 inhibitors associated with 3-fold increased risk for diabetic ketoacidosis

Study findings suggest a class effect with these drugs

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M20-0289

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Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are associated with an almost 3-fold increased risk for diabetic ketoacidosis (DKA). Molecule-specific analyses suggest a class effect with these drugs. As such, caution is advised when prescribing SGLT-2 inhibitors for type 2 diabetes. Findings from a multi-center cohort study are published in

Annals of Internal Medicine

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SGLT-2 inhibitors are a newer class of diabetes medication. Randomized controlled trials have demonstrated that they reduce the risk for myocardial infarction, heart failure, renal failure, cardiovascular mortality, and potentially all-cause mortality in patients with type 2 diabetes at high cardiovascular risk. However, there are several important safety concerns related to their use, including a possible increased risk for DKA.

The Canadian Network for Observational Drug Effect Studies (CNODES) Investigators studied electronic health care databases from seven Canadian provinces and the United Kingdom to assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes. They found robust evidence that SGLT-2 inhibitors are associated with an increased risk for DKA. Of note, increased risks were observed in all molecule-specific analyses. Because the beneficial effects of SGLT-2 inhibitors in the prevention of cardiovascular and renal disease will probably increase their uptake in the following years, the authors caution that physicians should be aware of DKA as a potential adverse effect.

Media contacts: For an embargoed PDF please contact Lauren Evans at

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. The lead author, Kristian B. Filion, PhD, can be reached through Tod Hoffman at

[email protected]

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Also in this issue:

Thirty Years After Passage of the Americans With Disabilities Act: Has the Medical Community Done Enough?

Tom Harkin, and Lyndi Buckingham-Schutt, PhD, RDN, LD

Ideas and Opinions

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M20-4554