Vedolizumab -Not Likely to Help Primary Sclerosing Cholangitis

A recent retrospective study (TJ Laborda et al. JPGN 2020; 71: 459-464 Vedolizumab Therapy in Children With Primary Sclerosing Cholangitis: Data From the Pediatric Primary Sclerosing Cholangitis Consortium) indicates that vedolizumab (VDZ) is unlikely to be helpful for primary sclerosing cholangits (PSC).

VDZ was initiated at median age of 16 years [IQR 15–18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis.

Key findings:

  • Overall, there was a mild increase in median GGT after initiation of VDZ. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response (defined as GGT <50 or at least a 75% decline) after 9 to 12 months
  • For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response

In the discussion, the authors note that their findings are in agreement with three retrospective studies in adults which have shown that VDZ is not effective for PSC in patients with IBD.

My take: This study indicates that VDZ is not likely to help with PSC, though 62% of IBD patients had improvement in their GI disease.

From The Onion

Cholangitis After Kasai Procedure for Biliary Atresia

K Cheng et al. JPGN 2020; 71: 452-458. Cholangitis in Patients With Biliary Atresia Receiving Hepatoportoenterostomy: A National Database Study

This study, which relied on data from a pediatric database (PHIS) with 48 pediatric centers, identified 1112 subjects with biliary atresia (2004-2013).

Key findings:

  • Median age at time of Kasai (hepatoportoenterostomy) procedure: 63 days
  • Median number of admissions for cholangitis within 2 years was 2 episodes. The presence of portal hypertension (OR 2.24) and black race (OR 1.51) were associated with higher risk of cholangitis
  • When Kasai was performed at >90 days, this lowered the likelihood of cholangitis (OR 0.46)
  • With regards to those with 5 or more bouts of cholangitis, risk factors included Asian ethnicity (OR 2.66), public insurance (OR 1.72), and portal hypertension (OR 2.88)
  • 56% of patients had portal hypertension and 15.6% had esophageal varices
  • Neither steroids nor ursodeoxycholic acid were found to affect patient outcome
  • Limitations: lack of clear definition for cholangitis diagnosis and episodes of cholangitis may not have been captured if patients received care outside the participating centers

My take: Cholangitis is a common problem following hepatoportoenterostomy. Earlier diagnosis of biliary atresia provides the best opportunity for improving long-term outcomes.

Related blog posts:

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.

AAP Behind the Scenes (Fall 2020)

This Georgia AAP (virtual) board meeting started with a brief review from Dr. Kathleen Tomey (Department of Health)

Some slides:

This data should be interpreted based on limited testing in this age group

AAP Update from Dr. Scornik:

Toolkit available at Georgia AAP Website
Full link: Race, Postoperative Complications, and Death in Apparently Healthy Children
Link to register: Fall AAP Meeting

Safe sleep initiatives briefly discussed by Dr. Sarah Lazarus which aligns with Strong4Life campaign:

From Dr. Evan Anderson’s presentation to AAP Board Meeting
Dr. Anderson notes that COVID-19 mortality and morbidity IN CHILDREN exceeding other conditions with vaccines like Varicella and Influenza.
Letter from AAP President to FDA (Dr. Hahn) and HHS (Alex Azar)

Other information:

Update on E-Cigarettes Webinar*+: Wednesday, October 28 at 12:30 pm
Please note new date! Here’s a chance to still register.
First in a series of three webinars offered to Georgia Pediatricians on the growing epidemic of youth e-cigarette use
Faculty: Alice Little Caldwell, MD, FAAP
https://register.gotowebinar.com/register/8457518617359610381

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

Stelara (Ustekinumab) Safety

F Poizeau et al. JAMA Dermatol. Published online September 9, 2020. doi:10.1001/jamadermatol.2020.2977. Association Between Early Severe Cardiovascular Events and the Initiation of Treatment With the Anti–Interleukin 12/23p40 Antibody Ustekinumab

Methods: “This case-time-control study used data from the French national health insurance database, covering 66 million individuals, on all patients exposed to ustekinumab between April 1, 2010, and December 31, 2016, classified according to their cardiovascular risk level (high- and low-risk strata). The risk period was the 6 months before the SCE, defined as acute coronary syndrome or stroke, and the reference period was the 6 months before the risk period. Statistical analysis was performed from September 20, 2017, to July 6, 2018.”

Key findings:

  • Of the 9290 patients exposed to ustekinumab (4847 men [52%]; mean [SD] age, 43 [14] years), 179 experienced SCEs (65 cases of acute coronary syndrome, 68 cases of unstable angina, and 46 cases of stroke).
  • Among patients with a high cardiovascular risk, a statisically significant association between initiaton of ustekinumab treatment and SCE occurrence was identified (odds ratio, 4.17; 95% CI, 1.19-14.59).
  • Conversely, no statistically significant association was found among patients with a low cardiovascular risk (odds ratio, 0.30; 95% CI, 0.03-3.13).

My take: This study suggests that the initiation of ustekinumab treatment may trigger SCEs among patients at high cardiovascular risk; however, the study conclusions are limited as this was an observational study (not a randomized trial).

Be Kind & the 21st Century Cures Act

I remember when I was first taught to dictate consultations. I was a resident doing a genetics rotation. My mentor, Peter Dignan, made several suggestions. One was to try to always include something nice about the patient. Many of my current colleagues are amused how many of my patients are ‘delightful.’ While there are a lot reasons for putting some kind information in the medical record, Dr. Dignan emphasized that patients and families can get hold of their records and undoubtedly they would appreciate a friendly word. Now with the 21st Century Cures Act Final Rule, access to records and notes will expand considerably and Dr. Dignan’s advice is probably even more important.

A good source of information on this new law, which is in effect Nov 2nd, 2020, is from the 33charts blogCures Act Final Rule – How It Will Change Medicine: “The ONC Cures Act Final Rule (Cures Rule) is the biggest health care law you’ve never heard of. But it’s a law that’s going to fundamentally shift the way we see patients and their information. It will change how physicians talk to patients about information. It will shift the way health professionals connect patients to their information.” This blog post details how this change is going to affect both healthcare providers and families. The two key changes are

  • Access to clinical notes (ie, ‘open notes’)
  • Immediate release of tests and studies.

The key point: “The Cures Rule will force health systems to be better stewards of information on behalf of our patients. I think this is going to force health professionals to help patients think about information and what they do with it. It will force patients to recognize the difference between information and knowledge and wisdom. I suspect that the most critical ultimate change will be transparent conversations and more timely physician follow-up on high stakes studies.”

Another take on the 21st Century Cures Act: C Blease et al. Annals of Internal Medicine; 2020: https://doi.org/10.7326/M20-5370. New U.S. Law Mandates Access to Clinical Notes: Implications for Patients and Clinicians

Some additional information (from EPIC training) — there are limited exceptions for note sharing:

Another reference:

My take: When this rolls out, a lot of physicians (myself included) will need to make some adjustments; since it is the law, don’t expect to avoid these changes. I expect early on this will generate a lot of additional questions and phone calls. In the long run, this is likely to improve communication, transparency, and availability of patient information. For example, it is more likely that needed lab results from referring physicians will be more available after this law is in effect.

PPD (TB Skin Test) or Interferon-Gamma Release Assay (TB Blood Test)?

A recent editorial (JG Hashash et al. Inflamm Bowel Dis 2020; 26: 1315-1318Approach to Latent Tuberculosis Infection Screening Before Biologic Therapy in IBD Patients: PPD or IGRA?) provides some guidance on screening for tuberculosis prior to biologic therapy as well as background on how these tests work.

Key points:

  • The authors state that both a PPD or TB Blood Test (aka Quantiferon-TB Gold) are reasonable for most individuals, though they have a preference for the TB Blood Test.
  • For those with history of BCG vaccination, the TB Blood Test is recommended
  • Steroids are associated with negative PPD and indeterminate TB Blood Test.
  • The authors advocate baseline testing prior to biologic therapy for everyone.
  • Annual testing: For  those in high TB endemic areas, “we propose yearly chest x-ray in addition to IGRA [TB Blood Test]…in low endemic areas…we do not perform yearly chest x-rays nor do we check yearly IGRA unless mandated by a patient’s insurance.”

My take: TB blood testing is more convenient but more costly.  The authors indicate that  for patients from low endemic areas, yearly TB testing is mainly to check boxes mandated by insurance companies rather than improving care.

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

Use of Famotidine for COVID-19

A recent study (DE Freedberg et al. Gastroenterol 2020; DOI:https://doi.org/10.1053/j.gastro.2020.05.053Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study, highlighted on AGA blog, indicates that famotidine may improve outcomes in those with COVID-19.

Methods: Freedberg et al collected data from 1620 patients who tested positive for SARS-CoV-2 no more than 72 hours following admission; 84 of the patients (5.1%) had received famotidine (any dose, form of administration, or duration; median dose of 136 mg) within 24 hours of hospital admission.

Key finding: After the authors adjusted for baseline patient characteristics, use of famotidine was independently associated with risk for death or intubation (adjusted hazard ratio 0.42, 95% CI, 0.21–0.85). This did not change after propensity score matching to balance covariables (hazard ratio 0.43, 95% CI 0.21–0.88).

My take: While these results indicate that famotidine may improve outcomes with COVID-19, a randomized controlled trial is needed to confirm these findings (currently one is underway to determine whether famotidine can improve clinical outcomes in hospitalized patients with COVID-19 (NCT04370262)).

AGA Blog Summary: Use of Famotidine Associated With Improved Outcomes of Hospitalized COVID-19 Patients

Related blog posts:

Gluten-Free Diet Can Be Unhealthy

In some patients with celiac disease, institution of a gluten-free diet may be detrimental without good dietary counseling as a highly-processed diet can increase the risk of adverse cardiovascular events.

A recent study (J Runde et al. JPGN 2020; 71: 533-535. A Narrow Window: Booming Gluten-free Market and Fostering Healthy Dietary Habits in Children With Celiac Disease) assessed dietary patterns of children with celiac disease and indicates that early counseling is crucial.

In total dietary surveys were completed for 100 children with celiac disease. Key findings:

  • 77% consumed processed gluten-free (GF) foods multiple times per day
  • 20% ate exclusively processed GF foods
  • The main reasons for processed GF foods were convenience and taste
  • Patients and families interest in dietary counseling diminished with time. In children <1 year from diagnosis, 35% were interested in dietary feedback, compared to 18% 2-3 years after diagnosis, 15% 4-6 years after diagnosis, and 11% at 7+ years from diagnosis

The authors speculate that highly-processed foods are leading to obesity which is increasingly reported in pediatric celiac disease.

My take:

  • The greatest opportunity for dietary counseling is at the time of the diagnosis.
  • Children with celiac disease commonly consume an unhealthy diet and are at risk for the same types of outcomes as children without celiac disease who also frequently consume an unhealthy diet

Related blog posts:

 

It looks like the COVID-19 epidemic is going to get worse -while there is more testing, there is also a trend of more hospitalizations that is not likely explained by more testing.

How Much Infliximab Can You Give to Young Children?

A recent case series (A Assa et al. JPGN 2020; 71: 516-520. Therapeutic Drug Monitoring-guided High-dose Infliximab for Infantile-onset Inflammatory Bowel Disease: A Case Series) describes four infants (2 mo-12 mo) with infantile-onset IBD who received high doses of infliximab.

Treatments regimens utilized infliximab dosing of 10-22 mg/kg/dose with initial three doses over 2-4 weeks. Other prior treatments in these patients included antibiotics (eg. vancomycin/gentamicin) and corticosteroids. Sulfasalazine was administered in two of the patients.

Other Key Points:

  • The authors noted that patients gradually transitioned to every 4 week therapy whild seeking to maintain trough concentrations >10 mcg/mL.
  • Infants have several risk factors for inadequate serum infliximab levels. Infliximab clearance is not linearly weight-related and infants are “most susceptible for under-dosing.”
  • Infliximab distribution in infants & children differs from adults with more peripheral compartment distribution, leading to lower trough levels.
  • Severity of disease impacts infliximab levels and can cause a ‘sink’ effect

The authors note that higher doses may increase adverse events, including infections

My take: This study shows that highly-selected patients may need both accelerated and higher doses of infliximab to enable response. It adds to the literature that children, in general, are at high risk of under-dosing with ‘standard’ infliximab dosing.

Related blog posts: