Silencing the FDA’s Voice on Drug Information

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T Watson, C Robertson. NEJM 2023; 389; 25: 2312-2314. Silencing the FDA’s Voice — Drug Information on Trial

Recently (9/1/23), “a panel of the Fifth Circuit Court of Appeals allowed a case to proceed against the Food and Drug Administration (FDA) concerning its public statements on the use of ivermectin for treating Covid-19.1“ Even though a district court had dismissed the suit due to “sovereign immunity,” the Fifth Court stated the FDA had exceeded its authority.

Some excerpts from this commentary:

Between August 2021 and April 2022, however, the agency released several public messages about ivermectin and Covid-19 — including an informal consumer update titled “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19”…

Three physicians who prescribed and promoted ivermectin for Covid-19 treatment sued the FDA, alleging that its statements interfered with their ability to practice medicine and harmed their professional reputations, even though they hadn’t been named by the FDA. One doctor claimed the agency’s statements had caused him to be referred to his state medical board; the others claimed to have lost admitting privileges at a hospital and a role at a medical school.

According to the Fifth Circuit, the FDA “has authority to inform, announce, and apprise — but not to endorse, denounce, or advise”….

The Fifth Circuit panel’s opinion is puzzling in light of the FDA’s long-standing and generally unquestioned role as a public health educator. The agency routinely releases consumer-directed information; for example, its website instructs consumers about the appropriate use of antibiotics and includes related clinical information. The opinion suggests the FDA may need to reevaluate each of these communications — an impractical proposition.

The opinion is also in tension with a long-standing constitutional principle known as the government speech doctrine, according to which the government can itself be a speaker, like any person or corporation, and isn’t required to be neutral when it expresses an opinion..

The Fifth Circuit’s holding reflects suspicion of agency influence, even in matters in which the agency is an expert speaking directly about products it regulates. The court’s interpretation of the FDA’s proper role may permit only narrow forms of expression...

Subsequent courts could use the Fifth Circuit’s logic to disempower other agencies with health-related missions, such as the Centers for Disease Control and Prevention and the Environmental Protection Agency… Meanwhile, “junk science” pervades social media and harms public health.2

My take: It is hard to believe that the justification for this challenge comes from three physicians prescribing ivermectin. It turns out the FDA’s advice was spot on and that these physicians were offering an ineffective therapy. This is a worrisome trend in which the judicial branch seeks

  1. To limit government agencies without explicit line-by-line authorization by a dysfunctional congress
  2. And to substitute its judgement over matters in which it has little expertise over governmental agencies tasked with protecting our country (eg. FDA, CDC, EPA, and others)

Here is a link to one of the FDA’s communications on Ivermectin –good advice (12/10/21): Why You Should Not Use Ivermectin to Treat or Prevent COVID-19

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Eosinophilic Esophagitis -Increasing Incidence and Emergence of Biologic Treatments

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1st article: JW Hahn et al. Clin Gastroenterol Hepatol 2023; 21: 3270-3284. Open Access! Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976–2022: A Systematic Review and Meta-analysis

This research utilized 40 studies which met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents.

Key findings:

  • The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years and 40.04 cases per 100,000 inhabitant-years, respectively.
  • The pooled prevalence and incidence of EoE were higher in high-income countries, males, and North America.
  • The pooled prevalence and incidence of EoE have increased from 1976 to 2022.
Time trends of incidence (A) and prevalence (B) of EoE, 1976 to 2022. Pooled estimates, cases per 100,000 inhabitant-years.

2nd Article: DL Snyder, ES Dellon. Clin Gastroenterol Hepatol 2023; 21: 3230-3233. Biologics in the Treatment of Eosinophilic Esophagitis: Ready for Use?

“This review summarizes the data leading to FDA approval for dupilumab and provides a practical approach for clinical use of dupilumab.” Dupilumab, a humanized monoclonal antibody that blocks interleukin (IL)-4 receptor alpha, is currently the only FDA-approved medication for EoE. It is noted that in the trials leading to FDA approval, all patients were PPI refractory and ~70% had received topical steroids (with about half either intolerant or nonresponsive).

Dosing: 300 mg weekly injection with a single-dose prefilled autoinjector pen or a syringe with a needle shield. It is recommended that refrigerated medicine is brought to room temperature for at least 45 minutes prior to injection. It “can remain unrefrigerated up to 14 days.”

In Figure 1, the articles details positioning of use of dupilumab in EoE management algorithm:

  • New diagnosis, patient preference
  • Additional atopic condition with approved dupilumab use (strong indication)
  • Lack of response to current treatment (diet, PPI, swallowed steroids) or adverse effects from current treatment (strong indications)
  • “It is reasonable to repeat endoscopy with biopsy 24 weeks after initiation of dupilumab in many patients…However, endoscopy may be completer earlier” in selected patients.

At least 5 other biologics are in phase 2 or phase 3 studies (listed in Table 1).

My take: EoE is increasing in prevalence and new therapies (often expensive) are emerging.

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Also, there is a fairly good patient education 7-page pamphlet from the makers of Dupixent encouraging patients with symptoms suggestive of EoE to speak with their physicians.

Link: This is EoE

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Does Nonerosive Reflux Increase the Risk of Esophageal Cancer?

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From Gastroenterology and Endoscopy News (12/20/23): Nonerosive GERD Did Not Increase Esophageal Ca Risk in Nordic Nations

An excerpt:

Patients diagnosed with nonerosive gastroesophageal reflux disease did not have a higher incidence of esophageal adenocarcinoma than the general population in a new study published in the BMJ.

This extensive population-based cohort study leveraged data spanning over three decades from national healthcare registries in Denmark, Finland and Sweden, known for their broad scope and high quality…

The incidence rate of EAC [esophageal adenocarcinoma] among 285,811 patients with nonerosive GERD (no esophagitis, Barrett’s esophagus or other esophageal condition), was 11.0 per 100,000 person-years, similar to that of the general population (BMJ 2023;382:e076017). Moreover, the rate remained stable regardless of the length of follow-up…

Harish K. Gagneja, MD, FACG, AGAF, FASGE, who was not involved in the research, commented that “patients with nonerosive GERD don’t require additional follow-up endoscopies unless they have alarm symptoms such as dysphagia, weight loss or anemia, etc.”…

The findings will need to be confirmed in well-designed studies from other countries. But the large sample size, population-based design, substantial duration of follow-up and inclusion of a contrasting erosive GERD cohort for validation are just some of the study’s strengths, supporting the validity of its findings.

My take: This study indicates that nonerosive reflux was not associated with an increased risk of esophageal adenocarcinoma.

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Rock Art (need to keep my day job)     

Bad Advice for COVID, Then and Now

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  1. Hydroxychloroquine (HCQ) was used off-label for COVID-19 during the first wave despite the absence of evidence documenting its clinical benefits. A recent study has estimated that it resulted in an increase death rate of 11%. ”The number of hydroxychloroquine related deaths in hospitalized patients is estimated at 16,990 in six countries.” Ref: Open Access! A Pradelle et al. Biomedicine & Pharmacotherapy 2024; 171: 116055. Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate
  2. NY Times 1/3/24: Citing Misinformation, Florida Health Official Calls for Halt to Covid Vaccines

An excerpt:

Florida’s surgeon general on Wednesday called for a halt to the use of Covid vaccines, citing widely debunked concerns that contaminants in the vaccine can permanently integrate into human DNA.

Dr. Ladapo’s latest contention is “very irresponsible,” said John Wherry, a vaccine expert and director of the Institute for Immunology at the University of Pennsylvania. “He has, however, demonstrated a tenuous grasp of science and medicine in general over the course of the pandemic so this is not surprising,” Dr. Wherry said….

For Dr. Ladapo’s claim to be true, humans would need to have an enzyme that can incorporate foreign DNA into their genomes. “We don’t have one,” said Dr. Eric Rubin, a member of the F.D.A.’s vaccine advisory committee and the editor in chief of the New England Journal of Medicine.

My take: The first article estimates the number of deaths due to the bad advice of using hydroxychloroquine. Perhaps in a few years, researchers will be able to calculate the number of deaths and hospitalizations that occur due to the bad advice of Florida’s surgeon general.

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Is Thalidomide the Best Therapy for Angiodysplasia?

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Chen H, et al. NEJM 2023; 389: 1649-1659. Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia

In this multicenter, double-blind, randomized, placebo-controlled trial, 150 adult patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. Thalidomide has antiangiogenic activity, with inhibition of VEGF.  It also has many adverse effects of thalidomide including peripheral neuropathy, fatigue, and teratogenic effects.

Key finding:

  • The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively

Discussion points -(from the associated editorial by Loren Laine): The data for thalidomide for small-intestinal angiodysplasia is “of higher quality than evidence for any other therapy for this indication. In addition,….thalidomide may be disease-modifying, with efficacy persisting after discontinuation. However, many clinicians will still use somatostatin analogues first” due to convenience and safety.

My take: I am glad this is a rare problem in pediatrics. I am not at all excited about using thalidomide.

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Vedolizumab and Infliximab: Expected Dosing When Switching From IV to SC Routes

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Z Wang et al. Clin Gastroenterol Hepatol 2023; 3188-3190. Therapeutic Drug Monitoring Can Guide the Intravenous-to-Subcutaneous Switch of Infliximab and Vedolizumab: A Simulation Study

The authors performed population pharmacokinetic (popPK) simulations to determine optimal dosing recommendations.

Key points:

  • Infliximab: “The Q2W SC dosing regimen of infliximab has been selected with the purpose of exceeding a C,trough,ss of 5 mg/L.” This tends to align with 5 mg/kg Q8W IV dosing.
  • Infliximab: “Patients on Q6W or Q8W IV infliximab can safely switch to Q2W SC infliximab…only patients on Q4W IV infliximab need Q1W SC dosing”
  • Vedolizumab: “Only patients on Q4W IV vedolizumab should switch to Q1W SC dosing”
  • Both agents: “Switching 4 instead of 8 weeks after the last IV dose can hit SS[steady state] faster, thereby avoiding the risk of temporary underexposure.”

My take: It is still important to see how switching from IV to SC route affects clinical outcomes in real-world cohorts. This study, though, does provide a good starting point when trying to provide the right dose frequency to achieve good therapeutic troughs.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Eradicating Hepatitis C Dependent on Congressional Action

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Francis Collins, NY Times 11/28/23: We Are Squandering One of the Most Important Medical Advances of the 21st Century

An excerpt:

Congress has an opportunity to turn this ongoing human tragedy into a public health advancement, by providing support for a five-year project to eliminate hepatitis C in the United States...

Each year, about 15,000 Americans die from hepatitis C, many in their 40s and 50s. Given the safe and effective cure available for the last nine years, the correct number of deaths in 2023 should be zero...

In March, President Biden came out in favor of a five-year program to put the United States on track to eliminate hepatitis C…The plan includes an innovative approach to provide broad access to curative medications, modeled on a successful effort in Louisiana. Under this approach, sometimes known as the “Netflix model,” a drug company or companies agree to provide full access to medications for a population in need in exchange for a set lump sum payment. In the current proposal, the populations who would have access to free hepatitis C drugs are Medicaid enrollees, the uninsured, Native Americans, and those in the prison and jail systems. If structured correctly, many more people can get lifesaving care and the cost per cure drops significantly…the plan also includes training, technical support and resources for primary care offices, federally qualified health centers, drug treatment centers, and jails and prisons…

An expert group has estimated that a national initiative to end hepatitis would save society more than $18 billion in health care costs over the next decade, with $13.3 billion of that savings accruing to the federal government.

My take: The advent of safe and effective hepatitis C medications has helped many. Particularly with the challenge of more infections due to intravenous drug use, it will take a concerted effort to eliminate this infection.

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Nutramigen Recall 12/30/23

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12/30/23 FDA: Reckitt/Mead Johnson Nutrition Voluntarily Recalls Select Batches of Nutramigen Hypoallergenic Infant Formula Powder Because of Possible Health Risk

An excerpt:

PARSIPPANY, N.J.–(BUSINESS WIRE)–Reckitt/Mead Johnson Nutrition (MJN), a producer of nutrition products, announced today that it has voluntarily chosen to recall from the U.S. market select batches of Nutramigen Powder, a specialty infant formula for the dietary management of Cows Milk Allergy (CMA) in 12.6 and 19.8 oz cans, due to a possibility of contamination with Cronobacter sakazakii in product sampled outside the U.S. All product in question went through extensive testing by MJN and tested negative for the bacteria...


The following recalled product batch codes and can size associated with each batch were distributed in the U.S.:

  • ZL3FHG (12.6 oz cans);
  • ZL3FMH (12.6 oz cans);
  • ZL3FPE (12.6 oz cans);
  • ZL3FQD (12.6 oz cans);
  • ZL3FRW (19.8 oz cans); and
  • ZL3FXJ (12.6 oz cans).

The products have a UPC Code of 300871239418 or 300871239456 and “Use By Date” of “1 Jan 2025”.

No other U.S. distributed Nutramigen batches or other Reckitt products are impacted...

What Consumers Should Do if They Purchased This Product

Consumers who purchased Nutramigen should check the bottom of the can to identify whether the batch number is affected. Product with the batch codes listed above should be disposed of, or contact us for a total refund. Please contact us at 866-534-9986 or by email at consumer.relations@rb.com and we will help verify if this product was impacted. If you have any concerns, contact your health care provider. For more information, please visit us at www.enfamil.com

Most Popular Posts 2023

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