By Henry Ehrlich
We have covered this breakthrough drug for years from before FDA approval when a presentation by Dr. Emma Guttman-Yassky at a New York Allergy & Asthma Society dinner treated the audience to “before” pictures of atopic dermatitis that made patients’ legs look like rotisserie lamb and “after” pictures that looked normal. At that time, Dr. Guttman-Yassky heralded an approaching “golden era for atopic dermatitis.” Now following a couple of years on the market, we are starting to see what a blockbuster looks like in the real world.
Dr. Peter Lio wrote about dupilumab—now Dupixent—for us in December 2016. He said, “The dream of patients and providers alike–aside from preventing it in the first place or a total cure, of course!–is a medication that would work quickly to calm the itch and inflammation, to truly allow the skin to truly heal. It would do so safely, without toxic side effects to the liver or kidneys and without an increased risk of cancer and infection. It would be easy to use instead of greasy creams or cumbersome wraps. Finally, it would not simply suppress the inflammation, but would help block the escalating itch-scratch cycle and not result in a rebound flare up when stopped.”
He described the drug and its action in this way: “It is composed of monoclonal antibody–proteins that are part of our immune system normally– and, as such, is sometimes referred to as a ‘biologic’. It is specifically designed to bind to (and thus inhibit or block) two important chemical messengers in the body: interleukin-4 (IL-4) and interleukin-13 (IL-13). These messengers, called cytokines, are very important in that they seem to be overproduced in eczema. Their message, in large part, seems to be: ‘Make more inflammation and itch! Make an allergic reaction!. Thus, it follows that by very carefully quieting them down, the resulting eczema quiets down. Perhaps most importantly, it does so WITHOUT shutting down the entire immune system or poisoning the body.”
Dr. Lio has recently published two journal articles that point to problems that arise in the real world of a drug post introduction. The first is an editorial from JAMA Dermatology, published online in December of last year entitled “Considerations in Weaning or Withdrawing Dupilumab Therapy—Nothing is Forever”. It seems strange that having waited their whole lives for relief from their eczema, patients should be anxious to find an exit strategy, but that is the case, for two primary reasons. One is that they must get the shots every two weeks. Based on a description by a friend of her child’s routine on shot day, it’s not a quick in-out. The other consideration is the astonishing cost, which is north of $30,000 annually.
Delineating the line between research and real world, Dr. Lio writes, “Dupilumab was studied for 52 weeks at continuous dosing every 2 weeks to establish its safety and efficacy, but inevitably for patients who are doing well while receiving treatment (and even for those who are not), the question arises, ‘Do I have to take this medicine forever?’” Dr. Lio describes atopic dermatitis as a “waxing and waning disease. The waning cycle leads people to wonder if they are cured or if at least may require less frequent dosing for maintenance.
Given experience with biologics for other diseases, the portents are not good. Patients tend not to do as well after stopping and restarting, and they may develop antibodies to the medicine. With dupilumab specifically, researchers “found that continuing treatment with the original dosage (300 mg weekly or every 2 weeks) resulted in a better maintenance of response than a less frequent dosage and significantly better than placebo for all end points. Moreover, the less frequent dosage regimens produced some dose-dependent reduction in efficacy but no previously unreported safety events…The authors* thus concluded that continued treatment with dupilumab using the more frequent treatment regimens (ie, every 2 weeks) ensures the most consistent maintenance of treatment effect and appears to confer no greater risk than (and likely fewer risks) than less frequent administration.”
Dr. Lio’s second article, published online in Dermatology in April 2019, was co-written with two colleagues from the University of Arizona, is called “Dupilumab and Alopecia: Causative or Therapeutic.” This one had particular resonance for me because I had recently spoken to someone who experienced hair loss with Dupixent as she was trying to cope with topical steroid withdrawal and red skin syndrome. She felt the mild relief wasn’t worth the added indignity.
According to Dr. Lio and his co-authors, the door swings both ways on this. “Our literature review yielded 6 recent case reports on ‘dupilumab’ and ‘alopecia, with four describing alopecia developing after initiation of dupilumab and two reporting resolution of pre-existing alopecia.” The hair loss seems to constitute a drug reaction.
Clearly, this drug is just getting started.
Peter A. Lio, MD is an Assistant Professor of Clinical Dermatology & Pediatrics at the Northwestern University Feinberg School of Medicine, and a Diplomate of the American Board of Dermatology. Dr. Lio received his medical degree from Harvard Medical School, completed his internship at Boston Children’s Hospital and his dermatology training at Harvard. He served as a full-time faculty at Harvard (Beth Israel & Children’s Hospital Boston) from 2005-2008 before returning home to his native Chicago to join Northwestern and Children’s Memorial Hospital. He is also a trained acupuncturist and a leader in the Chicago integrative health care community.
Dr. Lio will be speaking at the 6th East-West Integrative Medical Symposium for Immunology & Wellness at the New York Medical College in Valhalla, NY on June 20, 2020.
*Worm M, Simpson EL, Thaçi D, et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial [published online December 26, 2019].JAMA Dermatol. doi:10. 1001/jamadermatol.2019.3617 7.