Dr. Kathleen Toomey, Commissioner and State Health Officer at Georgia, in an AJC report (Jan 21, 2023):
“We are going to see an increase in maternal mortality during the time of COVID,” Toomey said. “It’s sad but not unexpected.“
Toomey spoke during budget hearings at the state Capitol, saying her agency is pivoting away from an all-hands-on-deck pandemic focus. She said her department would use some of its available bandwidth now to focus on the maternal mortality issue.
For the years 2018-2020, DPH posted pregnancy-related deaths for white women at 22.7 deaths per 100,000 births, and pregnancy-related deaths for Black women at 48.6 deaths per 100,000 births. It did not post overall figures for those years.
In another study (see below) on maternal mortality, it is noted that the mortality rate was 62% higher in states with restrictive abortion policies, likely related to poor availability of health care.
However, I take exception to this one line (hence this post’s title): “Now, premedication with H2 antagonists often is used to enhance tracer uptake into gastric tissue, and a Meckel scan has high sensitivity and specificity, both approaching 100%.3“
My take: A Meckel’s scan is very helpful when it is abnormal due to its high specificity. However, its sensitivity is suboptimal and many children need surgery for a Meckel’s diverticulum even with a negative scan.
Yesterday’s post reviewed the landmark study leading to dupilumab’s FDA approval. Today’s case report shows that we have a lot we need to learn about its use.
The authors present a case report of a patient with eosinophilic esophagitis (EoE) who had ongoing active EoE while receiving topical steroids (TS) and PPI (and previously dietary elimination therapy). He achieved remission after the addition of dupilumab. “When his TS were weaned after achieving remission, his disease relapsed with worsening of his dysphagia and a peak eosinophilic count (PEC) of 55 eosinophils per high power field (eos/hpf). Upon restarting TS to his ongoing dupilumab, symptoms fully resolved, and he achieved histologic remission (PEC 10 eos/hpf).”
My take: This study indicates that there are some patients need dupilumab and topical steroids in combination, rather than monotherapy. Reliable biomarkers to more easily determine response and/or to predict optimal therapy are clearly needed.
This study was pivotal for receiving FDA approval of dupilumab (dupixent) for the treatment of EoE (the only FDA approved therapy). Background: “Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis..Standard-of-care treatments for eosinophilic esophagitis include food elimination diets, proton-pump inhibitors (PPIs), swallowed topical glucocorticoids (applied to the esophagus by swallowing), and, in the case of strictures, esophageal dilation.11,12 However, the rates of response are variable (30 to 40% of patients may not have a response to first-line treatments).”
Key findings from three-part study (see images below):
Part A: Histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo
Part B: Histologic remission occurred in 47 of 80 patients (59%) with weekly dupilumab, in 49 of 81 patients (60%) with dupilumab every 2 weeks, and in 5 of 79 patients (6%) with placebo
Dysphagia Symptom Questionnaire (DSQ) scores: the scores improved with weekly dupilumab as compared with placebo, with differences of –12.32 (95% CI, –19.11 to –5.54) in Part A and –9.92 (95% CI, –14.81 to –5.02) in Part B (both P<0.001) but not with dupilumab every 2 weeks (difference in Part B, –0.51; 95% CI, –5.42 to 4.41)
The most common adverse effect was injection site reactions. There were 10 serious adverse events; none of these “were considered by the trial investigators to be related to the trial regimen.”
In the associated commentary, (pg 2379-2380), Dr. Alex Straumann notes that since EoE is localized to the esophagus, whether a patients should be treated with a systemically acting medication, “particularly in light of the fact that topical glucocorticoids have been shown to be as efficacious as systemically acting prednisone.”
My take (borrowed in part from editorial): It remains unclear whether dupilumab “is better than the good old topical glucocorticoids in improving disease outcomes, particularly in light of considerable costs associated with this treatment.” Due to its cost (see below), dupillumab is likely best situated as a 2nd line treatment at this time for most patients.
Food recipes -type ingredients you have at home, and ask it for a recipe
Explain complicated topics at age-appropriate levels
Travel itinerary (can specify if active vacation, with kids, specific goals)
Recommendation letters
Resumes
Lesson plans
Solve complex math problems in step-by-step fashion
Provide scientific/journal references
Write music in almost any genre
Write essays and develop ideas for novels
Provide personal advice
Create content in multiple languages
Medication appeal letters
Write or fix computer coding/software
Develop questions for speaker question and answers
Prep for interview
My take: Only George Santos can claim more accomplishments than ChatGPT (AI). It is important to verify the information that ChatGPT provides –it is sometimes wrong.
Between 1995 and 2016, the incidence rate (95% confidence interval) per 100,000 person-years rose from 9.1 (8.3–10.0) to 17.8 (16.8–19.0) for CD, and from 21.0 (19.8–22.3) to 28.4 (27.0–29.8) for UC.
The highest increase in CD and UC incidence rates occurred in children and young adults, respectively.
The prevalence of IBD doubled from 1995 to 2016; the greatest increase (2.5-fold) was in UC prevalence among individuals aged >40 years. During this period, the median age of the IBD population increased by 6 to 7 years.
In this retrospective study (n=130), therapeutic drug levels in the postoperative period were associated with improved outcomes for anti-TNF agents (infliximab (IFX) or adalimumab (ADA) but NOT for ustekinumab (UST):
In patients with IFX ≥3 µg/mL, higher rates of deep remission (39% vs 0%; P = .02) existed compared with those with IFX less than 3 µg/mL. This was true for clinical remission (44% vs 9%; P = .04) and objective (83% vs 62%; P = .1) remission.
In patients with ADA ≥7.5 µg/mL, rates of deep (42% vs 0%; P = .02), clinical (42% vs 0%; P = .02), and objective (88% vs 40%; P = .007) remission were higher than patients with lower concentrations.
For UST, rates of deep (28% vs 17%; P = 1.0), clinical (33% vs 33%; P = 1.0), and objective (70% vs 67%; P = 1.0) remission were similar between patients regardless of drug concentration.
In this retrospective study (n=147), a fecal calprotectin >800 mcg/g independently predicted the need for inpatient medical rescue therapy (odds ratio, 2.61; 95% CI, 1.12-6.12). An admission calprotectin >800 mcg/g independently predicted surgery within 3 months (odds ratio, 2.88; 95% CI, 1.01-8.17). My take: This is the least surprising study I’ve read this past month —those with more severe colitis, based on calprotectin values, were more likely to need more intensive treatments.
In this retrospective pediatric study (n=171), the authors found that a generic oral supplement (Fortsip) was as effective as a specialized formula (Modulen IBD) for enteral nutrition. “No difference was demonstrated in remission rate (Fortisip n = 67 of 106 [63%] vs Modulen IBD n = 41 of 64 [64%], P = .89), nonadherence rate (Fortisip n = 7 of 106 [7%] vs Modulen IBD 3 of 64 [5%], P = .57) or method of administration.” The main difference in outcome was a lower expense in the group receiving the generic formula. My take: This study is in agreement with previous studies.
Amjevita (adalimumab-atto) will be available in prefilled autoinjector pens (40 mg) and prefilled syringes (20 mg, 40 mg). Amjevita products will come in low-concentration forms, but they will be citrate-free. It’s expected to launch on January 31, 2023.
2. Cyltezo
Cyltezo (adalimumab-adbm) became the first biosimilar to be designated as interchangeable with Humira. Interchangeable biosimilars go through additional studies to determine whether you can switch back and forth between the biosimilar and the original product without issues. Biosimilars without this designation haven’t gone through these same studies.
Cyltezo will only be available in a prefilled syringe and will come in two doses: 20 mg and 40 mg. Both are low-concentration forms and citrate-free. Cyltezo is expected to launch in the U.S. as early as July 1, 2023.
3. Hyrimoz
Hyrimoz (adalimumab-adaz): a 40 mg dose will be available in both a pen and a syringe. A 10 mg syringe will also be available. Both are low-concentration forms. These products contain citric acid, which is closely related to citrate. Citric acid can also make injections more painful. A citrate-free high-concentration form of Hyrimoz is currently under FDA review. Hyrimoz is expected to launch in the U.S. on September 30, 2023.
4. Hadlima
Hadlima (adalimumab-bwwd) will be available in both an autoinjector and a syringe in a 40 mg dose. And it will come in both low- and high-concentration forms. The high-concentration form will be citrate-free. Hadlima is expected to launch in the U.S. on or after July 1, 2023.
5. Abrilada
Abrilada (adalimumab-afzb) will be available in a prefilled pen (40 mg) and in a syringe (10 mg, 20 mg, 40 mg). All Abrilada products will be low-concentration forms and citrate-free. Abrilada’s manufacturer has applied for interchangeable status with Humira. Abrilada is expected to launch in the U.S. as early as July 1, 2023.
6. Hulio
Hulio (adalimumab-fkjp) will be available in a prefilled pen (40 mg) and in a syringe (20 mg and 40 mg). All forms are low-concentration and citrate-free. Hulio is expected to launch in the U.S. on or after July 1, 2023.
7. Yusimry
Yusimry (adalimumab-aqvh) will only be available in a 40 mg prefilled syringe. It will be in a low-concentration form and citrate-free. Yusimry is expected to launch in the U.S. on or after July 1, 2023.
8. Idacio
Idacio (adalimumab-aacf) will be available in a 40 mg dose in both a pen and a syringe. Both forms will be low-concentration and citrate-free. Idacio is expected to launch in the U.S. as early as July 1, 2023.
My take: In high school, one of math teachers used to call me Hochman sub-1 and my twin brother Hochman sub-2. Perhaps, we can start designating biosimilars in a similar fashion?
“Gaming” U.S. Patent System by Big PharmaHumira, a rheumatoid arthritis drug from the Chicago-based biotech firm AbbVie, generated $17.3 billion in annual sales in 2021. There are 311 patent applications for the drug, 94% of which were sought after FDA approval. AbbVie’s original patent on the drug expired in 2016, but it won’t face competition until 2023
Two other important studies I wanted to cite -both studies have Benjamin Gold, one of my better-known partners, as one of the authors:
KA Chien, C Thomas, V Cooley, T Weinstein, KF Murray, L Muir, C Hayes, BD Gold, LM Gerber, CG Sauer, G Tomer. JPGN 2023; 76: 25-32. Physician Burnout in Pediatric Gastroenterology In this survey with 408 responses (23% response rate), the authors found 29% reported high risk for emotional exhaustion, 18% reported high risk for depersonalization, and 33% reported overall burnout.
VC Cohran, BD Gold, DJ Spencer, CR Cole. JPGN 2022; 75: 689-691. Health Care Disparities in Gastroenterology: The Pediatric Gastroenterology Perspective This commentary reviewed survey results highlighting healthcare disparities which have been identified in IBD, NALFD, and liver transplantation. The authors outline some of the steps that NASPGHAN has taken as well as some of the work that is needed.
In total, 6723 patients completed new patient gastroenterology visits for a primary diagnosis of constipation between 2013 and 2019. Of these, 993 (14.8%) patients had abdominal radiographs taken within 24 hours of their initial visit. Over the 7 years of this project, a mean frequency of abdominal radiograph use decreased from 24% to less than 11%.
No increases in subsequent emergency department visits or hospitalization for constipation within 30 days of patients’ initial visits were seen.
One of the keys to improvement was providing data to individual providers
The authors note that routine radiographs are NOT recommended by expert guidelines in patients presenting with functional constipation.
My take: The trend of using radiographs less frequently shows that a QI project can help avoid low value testing though more than 10% is still too high.
In this retrospective study from Israel with nearly 600,000 children, key findings:
The incidence rate of acid-suppressant medication use increased by 2.8-fold from 18.2 per 1000 in 2005 to 51.0 per 1000 in 2020
Primary care providers accounted for 74.8% of prescribing physicians in 2005 vs 96.1% in 2020, whereas the prevalence of prescribing gastroenterologists decreased from 18.8% to 2.8%
Other factors associated with increased use: first born child, male sex, multiple births and greater socioeconomic status; this latter group is more likely driven by health-seeking tendency rather than financial disparity due to national health insurance
Comments: This high use of acid suppression medications in infancy has been reported in multiple other studies despite the lack of efficacy in prior studies. Pediatricians, more than pediatric gastroenterologists, may be less familiar with the GERD guidelines and potential adverse effects of acid suppression (including association with an increase food allergies).
My take: This Israeli study shows that pediatric gastroenterologists are using acid blockers less in infants while pediatricians are using them more often. It is interesting that after the first child, parents are less likely to seek medical attention & are more tolerant of reflux symptoms.
27 patients with moderate to severe ulcerative colitis (UC) completed followup in this single-center, prospective, longitudinal cohort study. Key findings:
Bowel wall thickness (BWT) correlated with endoscopic Mayo score. “The most accurate cutoff for BWT was 2.8 mm for endoscopic remission, 3.9 mm for improvement, and a decrease of 32% for response.”
The associated editorial (C Palmela, C Maaster.Gastroenterol 2022; 163: 1485-1487. Open Access! The Use of Intestinal Ultrasound in Ulcerative Colitis-More Than a Mucosal Disease?) details other studies showing the utility of intestinal ultrasound, including the TRUST%UC study which enrolled 253 patients with UC. “. At baseline, 88.5% of patients had increased bowel wall thickness (BWT). Response to therapy could be detected as early as 2 weeks after initiation of therapy, as shown by reduction of abnormal BWT.” In anothre study with severe UC, “BWT reduction of >20% being an excellent predictor of response to intravenous steroids at 48 hours, as shown recently by Ivemark et al.10“
The editorial notes that intestinal ultrasound “is often thought as being operator dependent. Nonetheless, several studies have shown an excellent inter-observer agreement in IUS, especially for the assessment of BWT,7,12 as was also found in this [De Voogd] study.” An additional finding in the De Voogd study was that the “the submucosa was the most thickened layer, and after 8 weeks of therapy it was also the most responsive layer;” thus, UC is not simply a mucosal disease.
My take: This study shows that with more widespread adoption, many UC patients could be followed non-invasively with intestinal ultrasound (and calprotectin).
gutsandgrowth 