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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Some related links:

Favorite Posts 2023

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Thanks to all of you who provided articles, suggestions and encouragement to make this blog better this past year. This has been the 12th year for this blog and it has continued to gain more views each year. Here are links to many of my favorite posts from 2023 along with a few pictures:

GI:

Eosinophilic Esophagitis:

Endoscopy:

IBD:

Liver:

Personal:

Humor:

General Health/Health Economics:

New IBD Medication: Guselkumab for UC (QUASAR study)

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Previous work has established Guselkumab, a IL-23p19 subunit antagonist for Crohn’s disease (Guselkumab: Expanding the GALAXI of Treatments for Crohn’s Disease).

Peyrin-Biroulet et al now provide data showing its efficacy for ulcerative colitis (UC): Gastroenterol 2023; 165: 1443-1457. Open access! Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study

Background/Methods: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. In this double-blind, placebo-controlled, dose-ranging, induction study, adult patients (n=313), with median disease duration of 7.5 years, were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8.

Key findings:

  • Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). (Patients received IV induction at 0,4, and 8 weeks)
  • Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12
  • Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24 (after another dose of guselkumab (2nd dose SC). Thus, by week 24, 80.2% (81/101) of patients in the 200 mg IV induction and 78.5% *84/107) in the 400 mg IV induction had a clinical response.
  • Clinical response was noted as early as 2 weeks (first timepoint assessed)
  • Safety was similar among guselkumab and placebo groups.

My take: This is an era with rapidly expanding medical treatments for inflammatory bowel disease; it should help reduce the problem of individuals who are refractory to available treatments.

Unionization of Physicians, Pharmacists and Health Care Workers

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NY Times 12/3/23: Why Doctors and Pharmacists Are in Revolt

The reasons for the recent labor actions appear straightforward. Doctors, nurses and pharmacists said they were being asked to do more as staffing dwindles, leading to exhaustion and anxiety about putting patients at risk…the explanation runs deeper: A longer-term consolidation of health care companies has left workers feeling powerless in big bureaucracies. They say the trend has left them with little room to exercise their professional judgment…

Professionals in a variety of fields have protested similar developments in recent years. Schoolteachers, college instructors and journalists have gone on strike or unionized amid declining budgets and the rise of performance metrics that they feel are more suited to sales representatives than to guardians of certain norms and best practices.

But the trend is particularly pronounced in health care…Over time, however, consolidation and the rise of ever-larger health care corporations left workers with less influence…

Many health systems had increased tensions with doctors and nurses by failing to involve them more in developing and putting in place the system of metrics on which they are judged…

The breaking point came when the height of the pandemic passed, but conditions barely improved, according to many workers…

During an interview in October, while Dr. Smith [a pharmacist] and his colleagues were still awaiting the company’s response, he made clear that his patience had run out. “I’ve been asking and asking and asking for improvements for years,” he said. “Now we’re not asking any more — we’re demanding it.”

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Delayed Diagnosis of Cystic Fibrosis and Long-Term Impact

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In pediatrics, there is often a prevailing view that kids can overcome a lot due to their resiliency. However, just like a a track event, if you trip or fall back in a race, you may never catch up. With many medical conditions, it is unclear whether a delay in diagnosis results in long-term deficits. Recent data have found that a ~1 month delay in the treatment of cystic fibrosis is associated with poorer nutritional/growth outcomes, even 5 years later.

SL Martiniano et al. J Pediatr 2023; 262: 113595. Late Diagnosis in the Era of Universal Newborn Screening Negatively Affects Short- and Long-Term Growth and Health Outcomes in Infants with Cystic Fibrosis

Using the U.S. Cystic Fibrosis Foundation patient registry (CFFPR), the authors examined children born between 2010-2018 who were diagnosed based on newborn screening (NBS). Age at first event (AFE) serves as a proxy for when CF care was likely initiated. Patients were divided into 3 cohorts based on AFE: <14 days (early cohort), 14 days to <33 days, and 33 days or more (late cohort).

Key findings:

  • Infants in the late cohort were more likely to have a sweat test as their first CF event.
  • Pulmonary exacerbations were reported as the reason for hospitalization in in 59.1% of late cohort compared with 4.8% of early cohort with hospitalization as their first CF event.
  • Height-for-age z-scores were consistently lower in the late cohort. At 1 yr and 5 yrs, median z-scores were -0.6 (vs. -0.42) and -0.26 (vs. -0.12 in early group) respectively

The authors note that the early and late groups had differences in parental education attainment which “may be evidence that the late cohort had lower socioeconomic status that could have resulted in barriers to timely evaluation.”

The discussion notes that the introduction of highly effective modulator therapy does not overcome early stunting; which indicates that even with newer therapy, institution of nutritional treatments remains critical.

The study confirms that

  1. NBS/early identification has clear benefits.
  2. There is a need to quickly get suspected patients seen by CF centers.

My take: There was persistently (through at least 5 yrs) reduced height-for-age z-scores in patients with CF who presented just 27 days later.

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How to Improve the Gift of Life

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MS Cattral et al. Gastroenterol 2023; 165: 1315-1317. Open access (PDF)! Anonymous Living Donor Liver Transplantation: The Altruistic Strangers

This commentary, from Toronto General Hospital practitioners, discusses the increasing use of anonymous living liver donation (ALLD) in North America and donor altruism which is a term coined and popularized by the French philosopher Auguste Comte in the 1800s. Altruism is the principle and moral practice of concern for the welfare or happiness of others.

Key points:

  • Living-donor liver transplantation (LDLT) … in Toronto currently makes up 30% of adult and 80% of pediatric liver transplants.
  • Over the past 4 years, ALLD activity has doubled and now accounts for 15% of our yearly LDLT activity (80–85/year). Similar rates of growth in ALLD have occurred in the USA, whereas it remains rare outside of North America
  • The Canadian system provides several important advantages for anonymous donors: publicly funded health care that covers the cost of the donor assessment, surgery, and
    postoperative care; supportive employers and social programs that minimize financial losses; and a provincially funded program (Prelod) that reimburses incidental costs related to travel, accommodation, and meals up to $6000.
  • Important steps toward supporting living donation have been taken in the USA, such as the development of the National Living Donor Assistance Center as well as the Patient Protection and Affordable Care Act, which makes it illegal for insurance companies to deny
    health coverage to living donors…
  • Donors in the USA, however, still face significant obstacles to obtaining life insurance, long term care insurance, and disability insurance. Notably, the National Living Donor Protection act, which aims to rectify this problem (https://www.congress.gov/bill/117th-congress/
    house-bill/1255/text    ) has yet to move through Congress despite pressure from the transplant community

My take: It is definitely a good idea to promote living donors by removing insurance obstacles/discrimination

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