Rising Prescription Drug Denials by Health Insurers

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S Kliff, NY Times, 7/18/25: Health Insurers Are Denying More Drug Claims, Data Shows

An excerpt:

Prescription drug denials by private insurers in the United States jumped 25 percent from 2016 to 2023, according to a new analysis of more than four billion claims… compiled for The New York Times by the medical data company Komodo Health, shows that denial rates rose from 18.3 percent to 22.9 percent….

Experts who have studied denials said the skyrocketing costs of popular new weight loss medications and greater automation of the claims process with artificial intelligence may have contributed to the rising rejection rates…

Prior authorization was responsible for about 10 percent of denied claims in the Komodo data. The analysis found that the most common reason for a drug claim to be rejected was that a refill had been requested “too soon,” before the patient was eligible for more medication…

Pricey new GLP-1 weight loss drugs like Ozempic, and other blockbuster medications, may have led insurers to increase restrictions on other drugs as they grappled with ways to offset those growing costs.

My take: Insurance companies and their pharmacy benefit managers are increasing their denials of medications. Presumably, much of this increase is driven by the pursuit of higher profits rather than the pursuit of better patient outcomes.

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Enhanced Placebo Effect For Irritable Bowel Syndrome and Functional Abdominal Pain in Adolescents

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R Rexwinkel, NK Vermeijeden et al. Gastroenterol 2025; 169: 94-103. Open Access! Mebeverine and the Influence of Labeling in Adolescents With Irritable Bowel Syndrome or Functional Abdominal Pain Not Otherwise Specified: A 2 × 2 Randomized, Placebo-Controlled Trial

Methods:  This was a randomized trial with 12-17 yr olds with irritable bowel syndrome or functional abdominal pain who received mebeverine (200 mg twice daily) or placebo for 8 weeks. Treatment was labeled as “mebeverine or placebo” (blinded trial label) or “mebeverine” (mebeverine label), creating the following 4 groups: (1) mebeverine-blinded trial label, (2) mebeverine-mebeverine label, (3) placebo-blinded trial label, and (4) placebo-mebeverine label. Randomization (1:1:1:1) was masked to physicians, except for drug labeling. Primary end point was treatment success (>50% reduction of abdominal pain intensity and frequency) after 8 weeks. The key secondary end point was adequate relief of symptoms.

Key findings:

  • Blinded Trial Label: Treatment success was similar between those receiving mebeverine (groups 1 and 2) (n = 31 [23.4%]) and placebo (groups 3 and 4) (n = 30 [22.0%]; odds ratio [OR], 1.08
  • Effect of Being Informed of Treatment with Active Medication: Treatment success was higher in groups with the mebeverine label (groups 2 and 4) (n = 42 [31.6%]) compared with the blinded trial label (groups 1 and 3) (n = 19 [14.1%]; OR, 2.84

Discussion Points:

  • “This is the first study evaluating the impact of positive labeling on pain in a pediatric population. Our findings of a doubled treatment effect rate (32.9% vs 15.1%) when children were told they were receiving the active drug, are in line with adult studies showing higher pain reduction with positive labeling..14,19 It underscores the importance of positive expectations in pain management, which operates via multiple mechanisms.”
  • “Results of previous research has shown that children with IBS can also report symptom relief when they know that they are receiving an inert compound, known as an ‘“’open-label placebo.’22“
  • “Ethical norms state that ‘“’the use of a placebo without the patient’s knowledge may undermine trust, compromise patient–physician relationship, and result in medical harm to the patient.’26“

My take: This is a fascinating study showing how expectations for treatment can enhance the placebo effect. While the authors and the associated editorial mull over the ethical issues regarding deception of giving placebo without the family’s knowledge, in clinical practice many of the current drugs (eg. antispasmotics, neuromodulators, probiotics) have uncertain benefit and can be given without concern for deception.

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“You Can’t Outrun a Bad Diet”

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It has been recognized for quite some time that physical exercise, while important for health, does NOT play a big role in weight loss (see: Challenging the Obesity Myths, NEJM 2013; 368: 446-54. “Physical education, as typically provided, has not been shown to reduce or prevent obesity”). This article and the associated commentary from NPR provide further evidence of this.

Methods:  The authors examined energy expenditure and two measures of obesity (body fat percentage and body mass index, BMI) for 4,213 adults from 34 populations across six continents and a wide range of lifestyles and economies, including hunter-gatherer, pastoralist, farming, and industrialized populations

Key findings:

  • “Economic development was positively associated with greater body mass, BMI, and body fat, but also with greater total, basal, and activity energy expenditure. Absolute measures of TEE (total energy expenditure) and AEE (activity energy expenditure) are greater in more economically developed populations (Fig. 2), consistent with their larger body size. Body size–adjusted TEE decreased marginally with greater development”
  • “Estimated energy intake was greater in economically developed populations, and in populations with available data (n = 25), the percentage of ultraprocessed food in the diet was associated with body fat percentage, suggesting that dietary intake plays a far greater role than reduced energy expenditure in obesity related to economic development.”

Commentary from NPR:

“Back in the 1800s, obesity was almost nonexistent in the United States. Over the last century, it’s become common here and in other industrialized nations…One common explanation is that as societies have developed, they’ve also become more sedentary, and people have gotten less active….But in a major new study published in the journal PNAS, Pontzer and an international team of collaborators found that’s not the case…the total calories burned per day is really similar across these populations, even though the lifestyle and the activity levels are really different…it does mean we can’t outrun a bad diet. Pontzer says if we want to tackle obesity, the public health message should focus on changing what’s on our plates.”

My take: This article further supports the idea that a healthy diet is the crucial factor with regard to weight gain. However, numerous studies have shown that physical activity is important for good health, regardless of one’s weight.

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Boats for punting at the Magdalen Bridge/River Cherwell. Oxford, UK

Improving Ultrasound Examination to Identify Biliary Atresia

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A Upton et al. J Pediatr Gastroenterol Nutr. 2025;81:204–211. An ultrasound approach to visualize the “duct at the hilum” in infants undergoing evaluation for biliary atresia

Methods: Ultrasound exams were reviewed from infants undergoing evaluation for biliary atresia at Texas Children’s Hospital during two periods. First, exams performed before 2021 were reviewed to develop a systematic approach to visualize the duct at the hilum (DaH). Second, exams performed during a subsequent 26-month period were reviewed to assess the approach’s diagnostic performance in 64 infants (mean age 25 days).

Key findings:

  • The approach identified all 12 patients with biliary atresia and excluded 49 out of 52 infants without biliary atresia, for a sensitivity of 1.00 and specificity of 0.94.
  • There were three false-positive studies (i.e., the DaH was absent, but diagnosis was not BA) in infants with choledochal cyst, Trisomy 18, and an aberrant main portal vein (which interfered with the US examination),
  • The approach could be performed in feeding infants and often in <5 min.

Discussion:

  • “First, the DaH was easier to identify when infants were allowed to feed. In some cases, a DaH could be seen in fasting images but was longer and more prominent in subsequent non-fasting images”
  • “Tthe approach had high sensitivity and could efficiently rule out infants who did not have biliary atresia”
  • “We have not determined the precise segment of the extrahepatic biliary tree visualized by our approach; however, in contrast to previous reports, we do not think the approach is imaging the “common bile duct.” Rather, the DaH is a segment closer to the liver and could be the common hepatic duct.”
  • “Larger, multisite studies are needed…we may have overestimated sensitivity because the 12 infants with biliary atresia were all categorized as Japanese Biliary Atresia Society classification Type II or III…Similarly, we may have overestimated specificity because all ultrasound exams were performed by 1 sonographer with 10+ years of experience.”
  • Link to instructional video on this technique: jpn370081-sup-0001-Duct_at_the_Hilum_v_001_241127.mp4 985.2 MB

My take: It does seem that the presence of biliary atresia should be identifiable with ultrasound. However, this likely relies on the skills of the ultrasonographer, especially given the small size of these patients. Thus far, in clinical practice, an ultrasound has been mainly helpful at excluding choledochal cysts/anatomic malformations. A tiny or contracted gallbladder (with fasting) does increase the likelihood of biliary atresia. In my experience, other ultrasound findings like the ‘triangular cord’ sign are less helpful than serum matrix metalloproteinase 7 (MMP-7) tests.

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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

JAKne: JAK inhibitor–induced acne

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S Honap et al. Clinical Gastroenterology and Hepatology 2025 (EPUB). Open Access! Janus Kinase (JAK) Inhibitor-Induced Acne in Inflammatory Bowel Disease: An International, Multicenter, Retrospective Cohort Study

Mehtods: This international, multicenter, retrospective cohort study consecutively enrolled JAK-inhibitor-treated patients with IBD who subsequently developed acne (aka JAKne).

Key findings:

  • Among 2183 JAK inhibitor–treated patients with IBD, 272 developed acne
  • 70% of acne cases occurred within the first 3 months of treatment initiation
  • The crude prevalence rates of acne were 15.9% for upadacitinib, 4.3% for tofacitinib, and 1.9% for filgotinib, with dose-dependent relationships observed for upadacitinib and tofacitinib
  • Most cases were mild-moderate in severity. Mild (<10% of body surface area) was noted in 68%, Moderate (10-30% of BSA) was noted in 24%, and Severe (>30% of BSA) was note in 8%
  • Among those who developed acne, areas that were affected included the face in 89%, the back in 33%, the chest in 27% and the scalp in 1%
  • 40% received pharmacologic intervention
  • 18% of patients who developed acne had JAK inhibitor dose reduction or discontinuation

My take: JAKne is a common adverse effect.  Early identification, proactive counseling, and timely interventions, such as dose reduction, acne therapies or referral to dermatology, are crucial in managing this side effect.

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St James’s Park, London

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.

Chronic Nonbacterial Osteomyelitis (CNO): What a GI Doctor Should Know

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L Lim et al. The Journal of Pediatrics, Volume 283, 114636. Open Access! Chronic Nonbacterial Osteomyelitis: A Noninfectious Autoinflammatory Disorder of Bone

Prior to this review, I was familiar with the term chronic recurrent multifocal osteomyelitis (CRMO) but not CNO. CRMO is a severe form of CNO, usually characterized by symmetrical inflammatory bone lesions (DY Zhao et al. J Transl Autoimmun 2021; 4:100095. Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO)).

In this useful review, it is noted that IBD was associated with ~9% of cases of chronic nonbacterial osteomyelitis (CNO).

    Key points:

    • “IBD identified before, during, or after CNO diagnosis, has been well-reported as an associated condition.34-37 A review of cases of CNO with IBD showed that the diagnosis of CNO preceded the diagnosis of IBD in over half of the reported cases.38“
    • “Children with CNO frequently experience a high burden of pain and impaired physical function. CNO can cause permanent deformities in any bone, but especially if there is spinal involvement and diagnosis and treatment are delayed”
    • “Bone biopsies should be performed if there is clinical suspicion of infection or malignancy, although tissue usually is not needed for diagnosis unless the clinical presentation is atypical”
    • “MRI is now the standard imaging test that usually starts with targeted examination of the affected area…A whole-body MRI (WB-MRI) should be considered for all patients with CNO at diagnosis when possible, as it may help support a diagnosis of CNO by detecting additional sites of bone inflammation that may be clinically inapparent, particularly vertebral lesions”
    • “Non-steroidal anti-inflammatory drugs (NSAIDs) are usually first-line treatment for children with CNO, except for those with vertebral lesions, who require systemic treatment… over half of children treated with NSAIDs experience a disease flare within the first 2 years,14 requiring either retreatment with NSAIDs or another systemic medication”
    • “In the presence of vertebral CNO lesions, or after failing NSAID monotherapy, three categories of systemic treatments are recommended by the Childhood Arthritis and Rheumatology Research Alliance (CARRA)56: 1) synthetic DMARDs, 2) bisphosphonates, or 3) tumor necrosis factor-inhibitor (TNFi) biologic agents with or without methotrexate (to prevent the development of antibodies to the drug)”
    • “In practice, TNFi tends to be used more if children also have comorbid conditions for which TNFi already is indicated such as inflammatory arthritis and sacroiliitis,7 IBD,4,72 and psoriasis.4,14,24 “

    My take: Being familiar with CNO is important for GI physicians as it can occur (rarely) in our patients with IBD. Another important caveat, which is not discussed in this review, is that CNO can occur paradoxically due to the use of TNFi treatment.

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    The London Eye. This view makes it look a lot like a bicycle wheel.

    Ten-Year Trends in Pediatric Pharmacology for Gastroesophageal Reflux and Pediatric Feeding Disorders

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    S Hirsch et al. J Pediatr 2025;283:114628. Ten-Year Trends in Pharmacologic Management of Gastroesophageal Reflux Disease and Pediatric Feeding Disorders in Young Children

    Methods: Single-center, retrospective cohort study of children less than 2 years (49,483) diagnosed with GERD or PFD (pediatric feeding disorder) between January 2014 and December 2023. Prescriptions were searched for proton pump inhibitors (PPI), H2-receptor antagonists (H2RA), cyproheptadine, erythromycin, metoclopramide, or prucalopride, and procedures were searched for intrapyloric botulinum injections.

    Key findings:

    • There was an increasing number of patients seen annually (6516 in 2014 vs 9109 in 2023)
    • The percent of patients receiving any prescription for GERD or PFD declined by almost 50%, from 36.5% in 2014 to 18.7% in 2023 (P < .001)
    • There was a particular decline in PPI prescriptions, with 25.3% of patients receiving PPI in 2014 and 7.1% receiving PPI in 2023 (P < .001)
    • There was also a decline in H2RA prescriptions, with 17.0% of patients receiving H2RA in 2014 and 11.1% receiving H2RA in 2023 (P < .0001).
    • In their discussion, the authors note that: “in contrast to the current findings, prior studies typically have shown increasing PPI prescriptions, with some of these studies demonstrating declining H2RA prescriptions (9-17)…. However, it is notable that 3 more recent international studies did demonstrate declining PPI prescriptions specifically in the final years of the study (18-20).”
    • “Multiple studies have failed to demonstrate efficacy of acid suppression in infants with nonspecific gastroesophageal reflux symptoms, and there is no evidence that acid suppression affects feeding behaviors.(21-23)”
    • “In addition, there has been growing concern about PPI side effects, which include increased infections, decreased bone density, and increased allergy development
      including eosinophilic esophagitis, with numerous recent studies on these risks.(24-26)”

    My take: I’ve been a big fan of the aerodigestive research from the pediatric GI group in Boston. This is another useful study showing less use of acid suppression, especially PPIs in young children and infants. This likely indicates better alignment of clinical practice with consensus recommendations that advise against acid suppression as first-line management in this population.

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    Medications and the Risk of Microscopic Colitis

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    H Khalili et al. Annals of Internal Medicine 2025; https://doi.org/10.7326/ANNALS-25-0026. Medications and Risk for Microscopic Colitis: A Nationwide Study of Older Adults in Sweden

    Methods: The authors used Total Population Register, which includes information on the age and sex of all residents in Sweden. Then the cohort of older adults in Sweden was linked to the ESPRESSO study), which contains data on GI-related biopsies from all 28 pathology departments in Sweden from January 1965 until April 2017.

    Key findings:

    • Estimated 12-month risk differences were close to null under angiotensin-converting enzyme versus calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker versus CCB initiation, nonsteroidal anti-inflammatory drug initiation versus noninitiation, proton-pump inhibitor initiation versus noninitiation, and statin initiation versus noninitiation. 
    • There was a slight increase risk of microscopic colitis in patients receiving SSRIs compared to mirtazapine. The estimated 12-month risk difference was 0.04% (95% CI, 0.03% to 0.05%) for selective serotonin receptor inhibitors (SSRIs) versus mirtazapine.
    • Several medications were also associated with increased risk for receiving a colonoscopy with a normal colorectal mucosa biopsy result.

    My take: Microscopic colitis is a very infrequent problem in the pediatric population. With the exception of SSRIs, this study in older adults did not find a significant relationship between purported “trigger” medications and the development of microscopic colitis. In addition, the low persistent associations with SSRI initiation may be due to surveillance bias.