Adalimumab Biosimilars on the Horizon (Finally) Plus Two Studies

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 HumiraInterchangeable 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?

Related blog posts:

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.

What is the Difference Between Burnout and Depression?

S Sen. NEJM 2022; 387: 1629-1630. Is It Burnout or Depression? Expanding Efforts to Improve Physician Well-Being

Key points:

  • “This growing attention has helped to reduce the stigma associated with burnout, highlighting the health care system, rather than the individual, as the primary driver of the problem.”
  • What is burnout? “One review identified 142 different definitions of physician burnout in 182 studies.3 …the most commonly used is the Maslach Burnout Inventory, which assesses continuous scores for three domains: emotional exhaustion, depersonalization, and reduced sense of personal accomplishment.”
  • There is a lot of overlap with depression especially with emotional exhaustion. However, depression is still stigmatized as due to individual weakness. “Work-related stress is the primary driver of depression among physicians. A stark illustration of this dynamic is the fact that the prevalence of depression among training physicians before they enter residency is similar to that among young adults in the general population, but depression rates quintuple immediately after residency begins.”
  • “Whether burnout is meaningfully distinguishable from depression, the argument that depression and burnout are caused by fundamentally different precipitants is unsupported by the evidence to date”

My take (borrowed from the author): “Crucially, identification and treatment of depression can help reduce the risk of suicide among physicians. Unfortunately, when we encourage clinicians to consider themselves burned out rather than depressed, they tend not to seek or receive the individual-level interventions that can improve well-being.”

Related NPR Story (11/11/22): Study: Mindfulness-based stress reduction works as well as a popular anxiety drug. This report is based on the following reference:

Briefly Noted: Avoid Food Sensitivity Testing, Physician Burnout Worsening and Apple Medication Tracker

NY Times (9/13/22): Is Food Sensitivity Testing a Scam?

Key points:

  • According to Dr. David Stukus, director of the Food Allergy Treatment Center at Nationwide Children’s Hospital in Columbus, Ohio, the term food sensitivity is used more in marketing than in medicine. “There really is no consensus definition of what a food sensitivity is,”…A food intolerance or sensitivity is different from a food allergy, Dr. Stukus said, which is an immune reaction to certain foods that can cause more severe symptoms like vomiting, hives, shortness of breath or even life-threatening anaphylaxis, usually within minutes of eating even a small amount. There are also more chronic immune reactions to foods, like those from celiac disease, a serious autoimmune condition triggered by gluten.
  • Aside from the breath tests that gastroenterologists sometimes use to diagnose certain intolerances, like those to lactose or fructose, there aren’t validated tests for food intolerances or sensitivities… The only way to figure out if you are sensitive to certain foods or ingredients is to see how your symptoms change after eliminating them from your diet, ideally with the help of a registered dietitian or physician
  • Medical organizations, including those in the United StatesEurope and Canada, have recommended against using food sensitivity or intolerance tests because there is no good evidence that they work.

Related blog posts:

NY Times (9/29/22): Physician Burnout Has Reached Distressing Levels, New Research Finds This article reports on a survey from the Mayo Clinic Proceedings. The research is limited by a low response rate by mass email and likely selection bias.

Related blog posts:

WSJ (9/10/22) (Behind Pay Wall) Apple’s Medications Reminder Is Coming in iOS 16. Here’s How to Use It. And from 9to5Mac (9/20/22): Track medications and supplements on iPhone: How the new iOS 16 feature works (lots of pictures on this website)

Track medications on iPhone: iOS 16 guide

  1. Running iOS 16 on iPhone, open the Health app
  2. Choose the Browse tab in the bottom right corner
  3. Tap Medications, then choose Add a Medication
  4. Use your camera to scan your medication or type it in manually (Apple says scanning will be limited to US users for now)
  5. Follow the prompts to set reminders and more
  6. Head back to the Health app > Browse tab > Medications any time to log what you’ve taken and more

Why Physician Burnout Is Happening & How to Fix It

A recent commentary (P Hartzband, J Groopman. NEJM 2020; 382: 2485-87) provides critical insights into the issue of physician burnout.

Full Text: Physician Burnout, Interrupted

Some excerpts (bold =my highlights):

Initially, the prevailing attitude was that burnout is a physician problem and that those who can’t adapt to the new environment need to get with the program or leave….The unintended consequences of radical alterations in the health care system that were supposed to make physicians more efficient and productive, and thus more satisfied, have made them profoundly alienated and disillusioned…

Solutions have largely targeted the doctor, proposing exercise classes and relaxation techniques, snacks and social hours for decompressing, greater access to child care, hobbies to enrich free time, and ways to increase efficiency and maximize productivity. There is scant evidence that any of these measures have had a meaningful impact…

Medicine is in many ways unique. Doctors, nurses, and other health care professionals have traditionally viewed their work as a calling. They tend to enter their field with a high level of altruism coupled with a strong interest in human biology, focused on caring for the ill. These traits and goals lead to considerable intrinsic motivation. In a misguided attempt to improve the medical system, health care reformers put into place various positive and negative extrinsic motivators, without realizing that they would actually erode and destroy intrinsic motivation, eventually leading to “amotivation” — in other words, burnout...

Gagné and Deci posit that there are three pillars that support professionals’ intrinsic motivation and psychological well-being: autonomy, competence, and relatedness.3 All three have been stripped away as a direct result of the restructuring of the health care system.1  …

Evidence from the meta-analysis of controlled interventions supports the restoration of autonomy; giving doctors flexibility in their schedule to allow for individual styles of practice … The EHR … must be reconfigured to work for physicians rather than forcing physicians to work for it….

Competency can be restored by purging the system of meaningless metric…Relatedness should be authentic, aligning the system’s values with those of physicians, nurses, and other health care professionals

My take: Flexibility in scheduling is a crucial element for satisfaction.  Competency, which in my view equates to high quality care, is the other crucial element.

Audio Interview Link (11 minutes):  Audio Interview with Dr. Pamela Hartzband

Related blog posts:

Discrimination, Abuse, and Harassment in Medical Training

A recent study (Y-Y Hu et al. NEJM 2019; 381: 1741-52) reported high rates of discrimination, abuse, and harassment based on a cross-sectional survey of general surgical residents (n=7409) in 2018.

Key findings:

  • 31.9% reported gender discrimination and 16.6% reported racial discrimination–with main source being patients/families
  • 30.3% reported verbal or physical abuse and 10.3% reported sexual harassment -with attending surgeons being the most frequent sources
  • Residents who experienced discrimination, abuse or harassment were more likely to have symptoms of burnout (OR 2.94) and suicidal thoughts (OR 3.07).  Overall, weekly burnout symptoms were noted in 38.5% of residents and 4.5% reported suicidal thoughts in previous year

The authors note that there were substantial numbers of programs with very low rates of mistreatment which indicates that improvement in training environment is feasible.

My take: This is a black eye for the entire healthcare field.  It is important to address these pervasive problems and to determine the rate of these issues in other areas of medicine.

Botanical Gardens, Chicago

What Doctors Could Do Together (Organized)

A recent commentary (recommended by one of my sons) by Eric Topol discusses how doctors could be organized to advance the practice of medicine, address the deterioration in doctor-patient relationships, and focus on the needs of patients, whereas current medical organizations are mainly focused on the business interests of medical practice.

An excerpt from Why Doctors Should Organize:

“It’s possible to imagine a new organization of doctors that has nothing to do with the business of medicine and everything to do with promoting the health of patients and adroitly confronting the transformational challenges that lie ahead for the medical profession. Such an organization wouldn’t be a trade guild protecting the interests of doctors. It would be a doctors’ organization devoted to patients. Its top priority might be restoring the human factor—the essence of medicine—which has slipped away, taking with it the patient-doctor relationship. It might oppose anti-vaxxers; challenge drug pricing and direct-to-consumer advertisements; denounce predatory, unregulated stem-cell clinics; promote awareness of the health hazards of climate change; and call out the false health claims for products advocated by celebrities such as Gwyneth Paltrow and Mehmet Oz. This partial list provides a sense of how many momentous matters have been left unaddressed by the medical profession as a whole…

Because of the unique technological moment at which we live, we may not see an opportunity like this one for generations to come. We have a chance to affect the future of medicine; to advocate for patient interests; to restore the time doctors need to think, to listen, to establish trust, and build bonds, one encounter at a time. For these purposes, and in these times, an organization of all doctors is necessary. Rebuilding our relationships with our patients: that is our lane.

“Pistol Butt” Pine. Tree takes on this shape due to heavy snowfall leaning on tree at early stage. Crater Lake, Oregon.

Briefly Noted: Costs of Physician Burnout

NPR coverage of story: What’s Doctor Burnout Costing America?

An excerpt:

The study authors calculate that for health care organizations, the cost of burnout comes out to $7,600 per physician per year. The study notes that their cost estimate is conservative, only taking into account lost work hours and physician turnover. But other research shows burned out doctors are also more likely to make medical mistakes, have less satisfied patients, and get sued for malpractice, all of which have indirect costs.

Related blog posts:

Mental Health of Medical Students

It is well-recognized that there is a high rate of burnout and even suicides among physicians.  The concern regarding mental health extends to medical students.  According to a recent commentary (JF Karp, AS Levine. NEJM 2018; 1196-8), “despite entering medical school with relatively good mental health, medical students become depressed, burned out, and suicidal at alarming rates.”  This is thought to be due to “demanding schedules, cost, and stigma” to obtain mental health services.

The editorial advocates for medical students: “Working closely with the physician-services divisions of large hospital systems may help schools and hospitals leverage resources and provide shared opportunities to improve the care of students, trainees, and faculty and staff physicians.”

Related blog posts on burnout:

Frpm NEJM twitter feed

EMR Learning Curve -Long-term Benefits & Burnout Narrative

  1. Electronic Health Records Associated With Lower Hospital Mortality After Systems Have Time To Mature
  2. Beyond Burnout Moving narrative on the issue of burnout (JAMA link from 33mail -Bryan Vartabedian)

Related blog posts on EMRs:

Related blog posts on burnout:

Physician Burnout -“Hidden Health Care Crisis”

A really good review on the topic of physician burnout: BE Lacy, JL Chan. Clin Gastroenterol Hepatol 2018; 16: 311-17.

This topic has been discussed on this blog and multiple other sites.  This reference covers a lot of ground and provides a lot of useful information.  Also, some esoteric piece of information: “The term burnout first was used in the psychology literature in 1974 by Herbert Freudenberg during his work with drug addicts. He observed that many of his patients would stare blankly at their cigarettes until they burned out.”

Three key components to burnout: emotional exhaustion, depersonalization, and decrease sense of personal accomplishment

Physicians at greatest risk: perfectionists, personal qualities of idealism, and “intense sense of responsibility”

Root causes -work stress (in all its forms)

Prevention of burnout: take care of yourself, exercise, good sleep habits, “learn to say no,” use your vacation time/disconnect

Keys to treating physician burnout:

  • “learn to balance personal and professional goals”
  • “shape your career and identify stressors”
  • “nuture wellness strategies”
  • Try to become engaged in your job
  • Work on resilence

Related blog posts: