Adalimumab Biosimilars on the Horizon (Finally) Plus Two Studies

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GoodRx Health (Jan 3, 2023): Humira Biosimilar Boom: 8 Meds Launching in 2023 There are more than 17 billion reasons why there are 8 new adalimumab (Humira) biosimilars coming to the market.

Excerpts:

1. Amjevita

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?

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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.

Quality Improvement: Fewer Xrays for Constipation

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ME McSweeney et al. J Pediatr 2022; 251: 127-133. A Quality Improvement Initiative to Reduce Abdominal X-ray use in Pediatric Patients Presenting with Constipation

Key findings:

  • 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.

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Unfavorable Trends in Reflux Management of Infants & Update on USNWR Rankings

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T Achler et al. J Pediatr 2023; 252: 141-145. Trends and Correlates of Early-Life Exposure to Acid-Suppressant Therapy in Israel (2005-2020)

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.

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Siesta Key, FL –what are the qualifications for driving a vehicle in FL?

Related blog post: U.S. News & World Report’s Flawed Rankings Plus One

Coming to a GI Clinic Near You? Intestinal Ultrasound for Ulcerative Colitis

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F De Voogd, et al. Gastroenterol 2022; 163: 1569-1581. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study

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).

Related blog post:

Brief Updates: H pylori Resistance Rates, VEDOKIDS, Increasing Bariatric Surgery in Kids

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F Megraud et al. AJG 2022; doi: 10.14309/ajg.0000000000002045 Open Access: Rates of Antimicrobial Resistance in Helicobacter pylori Isolates From Clinical Trial Patients Across the US and Europe. Resistance rates were established in isolates from 907 participants. Overall, 22.2% were resistant to clarithromycin, 1.2% to amoxicillin, and 69.2% to metronidazole.

O Atia et al. Lancet Gastroenterol Hepatol 2022; DOI:https://doi.org/10.1016/S2468-1253(22)00307-7. Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study

Methods: VEDOKIDS was a paediatric, multicentre, prospective cohort study done in 17 centres in six countries. We report the 14-week outcomes as the first analyses of the planned 3-year follow-up of the VEDOKIDS cohort

Key findings:

  • 32 (42%) of 77 children with ulcerative colitis and 21 (32%) of 65 children with Crohn’s disease were in steroid-free and exclusive enteral nutrition-free remission at 14 weeks.
  •  In children who weighed less than 30 kg, the optimal drug concentration associated with steroid-free and exclusive enteral nutrition-free clinical remission was 7 μg/mL at week 14, corresponding to a dose of 200 mg/m2 body surface area or 10 mg/kg

USAToday 11/14/22: More teens are getting weight loss surgery but some experts think more needs to be done

And of course, an important story from The Onion: Arsonist Worried He Forgot To Turn Stove On Before Leaving House

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.

Coding Correctly in 2023

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The following information was provided by our coding advisor, Mary Suhr.

Key points:

  1. Time codes (when used) for inpatient visits have changed (see below). In 2023, when you share a service with an APP, you may bill on patient medical decision making or time spent.  You can add the time together and whoever spends more total time on that date of service (including face to face and non-face to-face) gets to be the service provider for that charge. 
  2. Extra time code: 99418 for every 15 minutes increments above average inpatient code.
  3. Observation codes are obsolete.
  4. Specific requirements for documentation of History and Physical exam are NOT needed for coding. Good documentation is still important part of medical practice and for liability; patient still needs to be examined.
  5. ALL outpatient and inpatient E/M visits will be leveled using the same methodology.
  6. Coding is based on medical decision making or time code (whichever has higher complexity). When selecting a level of service for Medical Decision Making, there is still the concept of having three components/tables and the requirement that two of the three components are met.  Tables 1, 2, and 3 outline the requirements.
  7. CPT 99251 (Straightforward Inpatient Consult) and CPT 99241 (Straightforward Outpatient Consult) are going away because the history and exam requirements for consults no longer apply and history/exam was the only difference between level 1 and level 2 consultation codes.
  8. For consultations, you still need a requesting provider, a reason for the consult and a report back to the provider.  CMS was explicit this year that assuming care of the problem is not considered a consult.
  9. Consultations cannot be shared between two providers (e.g. physicians and APPs).  If a consultation is shared between an APP and a MD, our advisor recommends the use admission codes for those.  This is true for inpatient consultations as well as office-based consultations.

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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.

FDA Approves Pharmaceutical Fecal Transplant Product

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FDA News Release (11/30/22): FDA Approves First Fecal Microbiota Product

“Rebyota is approved for the prevention of recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older. It is for use after an individual has completed antibiotic treatment for recurrent CDI.”

“Rebyota is administered rectally as a single dose [150 mL]. Rebyota is prepared from stool donated by qualified individuals….The effectiveness of Rebyota was evaluated in an analysis of data from a randomized, double-blind, placebo-controlled, multicenter study….the overall estimated rate of success in preventing recurrent CDI through 8 weeks was significantly higher in the Rebyota group (70.6%) than in the placebo group (57.5%).”

My take: As pharmaceutical companies gain approval for fecal transplant products, I would anticipate a significant increase in costs. This product seemed to have a fairly low success rate compared to placebo.

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White Sands National Park. New Mexico.

Vancomycin for Chronic Pouchitis & ASPEN Infant Formula Resources

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G Lupu et al. Inflamm Bowel Dis 2022; 28: 1610-1613. Vancomycin Is Effective in the Treatment of Chronic Inflammatory Conditions of the Pouch

In this retrospective study of 41 adults with history of ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), the authors evaluated the clinical response (subjective judgement of provider) to chronic vancomycin therapy (125 mg twice a day).

Key findings:

  • At 4 weeks, 21 (51%) of patients had a clinical response. 16 of these patients maintained a clinical response at 3 and 6 months (remained on treatment).
  • 6 additional patients demonstrated a later response. In total 22 (54%) were considered clinical responders at 3 and 6 months.
  • The mean number of antibiotics utilized prior to vancomycin was 4, including ciprofloxacin, metronidazole, levofloxacin, rifaximin, sulamethoxazole-trimetoprim, amoxicillin, and amoxicillin-clavulanic acid

My take: Since vancomycin has poor enteral absorption, it’s side effect profile is very favorable. More prospective and objective data is needed; however, vancomycin’s high cost will likely limit frequent use.

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Link: ASPEN Formula Resource Practice Tool (sponsored by ByHeart)

Improving Reflux While You Sleep

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JM Schuitenmaker et al. Clin Gastroenterol Hepatol 2022; 20: 2753-2762. Open Access! Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial

Methods: This was a double-blind, randomized, sham-controlled trial in patients (n=100) with nocturnal symptoms of gastroesophageal reflux. Patients were advised to sleep in the left lateral decubitus position and were assigned randomly (1:1) to an electronic sleep positional therapy wearable device (applied with an adhesive sticker), programmed to either produce a vibration when in the right lateral position (intervention) or only during the first 20 minutes (sham).

Key findings:

  • In the intention-to-treat analysis, the rate of treatment success (defined as a 50% or more reduction in the nocturnal reflux score) was 44% in the intervention group (22 of 50) vs 24% in the sham group (12 of 50) 
  • There was increased time sleeping in the left lateral decubitus position (intervention 60.9% vs sham 38.5%)

My take: In those with nocturnal heartburn, this appears to be a helpful nonpharmacological tool.

Website for the company (side sleep technologies) that makes the device: The Left ” Your body will be conditioned to sleep at least 80% on your left within a week.” (I do not have any financial relationship with this company).

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.

Short Bowel Syndrome is a Full Time Job

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C Belza et al. J Pediatr 2022; 250: 75-82. Carrying the Burden: Informal Care Requirements by Caregivers of Children with Intestinal Failure Receiving Home Parenteral Nutrition

This was a cross-sectional study of caregivers of children (n=34) with intestinal failure receiving long-term parenteral nutrition. 97% of caregivers were the child’s mother and median duration of providing care among respondents was 3.4 years.

Key findings:

  • Caregivers reported a median of 29.2 hours per week (IQR, 20.8-45.7 hours per week) of direct medical care. 6.1 hours was spent on providing PN and care of the central venous catheter. 6.3 hours was spent on enteral nutrition and enteral tube care.

In the associated editorial (pgs 10-12 by S Mauskar, JG Berry. Open Access! “Failing to Support Families’ Burden of Care for Children with Intestinal Failure“), the authors note that in the U.S. there has been a growing population of children at home with greater medical complexity and reliance on medical technology and that the need for home nursing support “greatly exceeds the supply, leaving many families on their own to care for their children.”

They also note that the medical literature (over the last 25 years) on caregiver burden for children notes it is associated with “marital discord, loss of employment, and financial struggle…In the U.S. a substantial portion of children with medical complexity assisted with technology live in single-parent households, in poverty, and are exposed to adverse childhood events…very vulnerable to the effects of high caregiving burden.”

My take: This study shows that while we have an effective treatment for intestinal failure, the burden of this treatment is very high even with care coordination and social worker help. Understanding this burden could help medical providers be more empathetic for the family who is struggling with home medical care (eg. child with recurrent admissions for central line infections).

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Island Ford National Recreational Area. Sandy Springs, GA