Systemic Immunomodulators Before and After Dupilumab Approval in Atopic Dermatitis

In this feature interview, The Dermatologist met with Dr Maria Schneeweiss to discuss her recent study¹ on the patterns when using systemic immunomodulators in the United States before and after dupilumab approval when treating adults with atopic dermatitis (AD).

Maria Schneeweiss, MD, is an instructor of medicine in the department of medicine, Division of Pharmacoepidemiology at Brigham and Women's Hospital in Boston, MA.

Why did your team choose to conduct this study?

We've had these great clinical trials for these new medications and, aside from looking at dupilumab, there’s still a real need to see how these medications have played out in the real world, how they’ve permeated into everyday care, and how they’ve changed the care paradigm in terms of conventional medications that we may have had beforehand. We were also very interested in adherence to medications, so we wanted to see treatment persistence at 3-month intervals for a 1-year period after starting a first systemic medication and how that might be different across the different medications.

Why did patients starting systemic treatment increase from 319 before dupilumab approval to 1358 after?

There seems to be several things contributing to this. One is that the systemic medications that were available for AD beforehand were all off label. There were no systemic treatments approved for AD specifically. This means you have no safety or efficacy data for these medications in AD, and you have to extrapolate from other rheumatologic conditions for which they may be approved. Usually, it's only a handful of patients and providers who feel comfortable using these off-label medications. Sometimes, you wait until the patient's very sick and really needs it. These can sometimes be special use cases, which is what we're seeing with the 319.

The other aspect is, as we get new systemic drugs approved for AD, it makes systemic therapy for AD more regular. It makes systemic therapy a more normal part of the AD treatment paradigm. If there's nothing there, then treatment ends at topicals and phototherapy. But now, and especially in 2019 when not just dupilumab approved but other systemic JAK inhibitors and anticytokine inhibitors are in clinical trials, AD is treated with systemic treatments, which adds to the treatment paradigm and makes it more normalized.

Another smaller aspect is that there's now better documentation of ICD codes for AD due to insurance approval. Because the other medications were off label, the coding was often not as rigorous. For example, rash, dermatitis, eczema NOS (not otherwise specified). Insurance requires a recorded ICD code for AD, so now that it's tied to treatment, physicians are using the AD code more.

Why are patients aged 60 years and younger (and those who used steroid-sparing topical treatments) more likely to receive dupilumab?

For patients 60 years and older, they typically don't qualify for clinical trials where usually the cutoff is age 65. This means we don’t have that safety and efficacy data that you have for the younger population.

With older age often comes more comorbidities and polypharmacy that can further complicate starting a new systemic medication. For the steroid-sparing agents, it may partially relate to insurance. Typically for dupilumab approval, it's required to have failed 2 topical agents. So, 1 could be a topical corticosteroid, and the other is a topical steroid-sparing agent. This could explain that 6-month period before they start the medication that we're looking at and may have contributed to this being a predictor for dupilumab use.

Are there any other insights you would like to share with your colleagues regarding the use patterns of systemic immunomodulators before and after dupilumab?

It's amazing how quickly dupilumab was adopted. In the 2017 to 2018 utilization plot, the year of dupilumab approval, you can really see the early adopters, and that dermatologists worked quickly to switch their patients from off-label systemics to dupilumab even very early on. This is a brand-new medication, and the first systemic medication for AD, so the fast uptake is impressive.

For the 2019 to 2020 plot, when dupilumab has been on the market for a couple years now, you see that second wave of physicians who wanted to wait a couple years after approval to see the safety and efficacy outcomes. This is also a time when more data on new medications for AD were being released and the adolescent trials for dupilumab had come out. So, now we are more reassured of its safety and efficacy in children or at least adolescents, which can provide another level of comfort.

From a methods perspective, this fast uptake of dupilumab is interesting, in that, what should researchers choose as a comparator when they’re looking at head-to-head studies for safety of dupilumab, especially because there really aren’t any other comparator? The only other comparators in the US would be off-label medications, which, as we can see from the utilization plots, have been overtaken by dupilumab. New comparator agents will start coming now that other new medications have been approved for AD at the end of 2021 and 2022.

This reflects an incredible time in dermatology right now where we have so many medications coming to market for these conditions, especially for these diseases that are very burdensome to patients. For AD, we went from only off-label systemic medications to now having 4 systemic medications within the span of 4 years.

Reference
1. Anand P, Schneeweiss S, Mostaghimi A, Schneeweiss MC. Use patterns of systemic immunomodulators in the United States before and after dupilumab approval in adults with atopic dermatitis. Pharmacoepidemiol Drug Saf. Published online ahead of print December 17, 2022. doi:10.1002/pds.5586