Systemic Treatments for Special Populations in Dermatology

Managing moderate to severe atopic dermatitis in special populations—such as pregnant women, older adults, or patients with complex comorbidities—presents unique clinical challenges. In this wide-ranging discussion, Dr Katrina Abuabara offers expert guidance on shared decision-making, individualized monitoring protocols, treatment transitions, and assessing real-world evidence in the absence of comprehensive clinical trial data.

From evaluating the evolving safety profiles of biologics and JAK inhibitors to counseling patients on fetal exposure timelines and polypharmacy considerations, Dr Abuabara highlights both the opportunities and the limitations that dermatologists must weigh when treating vulnerable or underrepresented patient groups.

Katrina Abuabara, MD, MA, MSCE, is a researcher and dermatologist at the University of California in San Francisco, CA.

• Patient-Centered Shared Decision-Making:

  • Align treatment plans with patient priorities: skin clearance, itch control, sleep improvement, medication burden, and visit frequency.

  • In special populations (e.g., pregnant, elderly, comorbid), individualized goal-setting is critical for selecting appropriate systemic therapy.

• Systemic Therapy and Pregnancy Considerations:

  • Avoid: Methotrexate and JAK inhibitors due to teratogenicity risks.

  • Cautious Use: Cyclosporine—despite nephrotoxicity and hypertension risks, has historical use during pregnancy in transplant populations with close monitoring.

  • Promising but Limited Data: Biologics (e.g., dupilumab) have reassuring preclinical data and >100 reported pregnancy exposures with no major signals, though human data remains limited.

  • Counseling Tip: Most IgG transfer to fetus occurs after first trimester; this can inform timing decisions around biologic initiation or discontinuation.

• Treatment Transitions and Comorbidity-Based Decisions:

  • For patients developing new contraindications to current systemic therapies (e.g., renal insufficiency on cyclosporine), consider switching or discontinuing.

  • Phototherapy (narrowband UVB) is a safe alternative if logistics allow (2–3 sessions/week or supervised home units).

  • Monitoring burden (e.g., frequent labs for JAK inhibitors) must be weighed against the patient’s capacity and comorbid conditions.

• Drug Class Safety Profiles by Population:

  • Biologics: Generally well-tolerated across most populations; real-world and pooled clinical trial data (e.g., dupilumab, tralokinumab) in older adults (n≈70–75 per trial) suggest similar efficacy and safety to younger cohorts, though trials not powered for this subgroup.

  • JAK Inhibitors: Greater caution warranted in elderly or polypharmacy patients due to elevated risks of malignancy, thromboembolism, and cardiovascular events; consider dose reduction in these populations.

• Polypharmacy and Drug Interaction Considerations:

  • For older adults on multiple medications, risk of adverse events increases with JAK inhibitors. Biologics are generally safer in these patients.

  • Phototherapy remains a non-pharmacologic and systemically safer option when feasible.

• Data Limitations and Research Needs:

  • Key Gap: Special populations (pregnant, elderly, comorbid) are systematically excluded from phase 3 trials.

  • Need for Inclusive Trials: More generalizable trial populations are essential to guide treatment decisions across risk groups.

  • Real-World and Post-Marketing Data: Critical to understand:

    • Reactivation risks of latent infections

    • Impact of systemic treatments on vaccine response

    • Safety during pregnancy and in immunocompromised states

  • Clinicians are encouraged to publish observational data to strengthen the evidence base.

The Dermatologist: What strategies help you navigate shared decision-making with special populations who may have higher treatment risks?

Dr Abuabara: I really think it's important to understand the patient's goals. Are they most interested in clearing their skin? Is it the itch? Is their sleep? Do they want fewer medications or to minimize the number of doctor's visits they have? Those are all really important considerations when thinking about a treatment strategy for any patient. But especially for a patient who we call a special population, they may have other existing conditions that require special consideration.

The Dermatologist: What monitoring protocols do you follow when starting systemic therapy in patients with pre-existing conditions?

Dr Abuabara: Great question. It depends on which population we're talking about, and unfortunately, there aren't guidelines or protocols set out that make it very easy. You really have to approach each patient as an individual. There's some guidance from different bodies. For example, on pregnant or lactating women. There's some clear cut recommendations. For example, never use methotrexate. We know it's a teratogen. Similarly, we urge great caution with the new JAK inhibitors in pregnant and lactating women because preclinical studies suggest they could be teratogenic. On the other hand, some of the new biologics, for example, the preclinical studies are promising for all of the new licensed biologics in the US for atopic dermatitis, but there's very limited data from humans. People have now written up reviews of case reports. They're over a hundred with dupilumab, for example, a hundred women who have been exposed during pregnancy, and the results thus far are reassuring. But for some patients, they prefer to go with something with more data. So some of the physician papers out there recommend the use of an older drug like Cyclosporine that has known risk for, again, any patient, but especially pregnant women that require really close monitoring of both blood pressure and kidney function. But there's a lot of experience, especially from patients who use cyclosporine for solid organ transplants during pregnancy and lactation. So again, it depends a little bit on the population. I've given some examples from the pregnant and lactating women.

The Dermatologist: In patients with complex medical histories, how do you decide when to switch systemic therapies, and how do you manage that transition?

Dr Abuabara: Again, I think it really depends on the population we're thinking about. So if a patient is already on a systemic therapy and it's not working, or they have a reason that they need to move to a different one, then we have to think about all the same considerations. So for example, for any patient, if they develop a new condition that makes you concerned about the systemic treatment a patient is already on, it's always good to think about phototherapy. UVV Phototherapy is generally safe for most patients. The main consideration is the logistical one. Can patients come in 2 to 3 times a week to have it done, or could you get them a home phototherapy unit and reasonably supervise its use? That's always a good consideration.

Other things to think about are the frequency of monitoring. So if you have a patient on a JAK inhibitor, for example, they need to come in more frequently for monitoring. That may be difficult with their other condition. Things like cyclosporine, for example. If you had a patient who was on cyclosporine and developed any kind of renal insufficiency, you'd want to think very quickly about changing that.

For most conditions, the biologics seem to be fairly safe. However, again, they're limited data because special populations are purposely excluded from phase 3 clinical trials, which focus on generally healthy adults, not over the age of 65. So for these older adult populations or patients with comorbidities, histories of infection, renal disease, other considerations, we really have to go off real world data and that can be somewhat limited. So we don't know all the risks and benefits as of yet.

The Dermatologist: How has your real-world experience with newer biologics and JAK inhibitors shaped your approach to treating special populations?

Dr Abuabara: I think it's given us a lot more options. We have a bigger armamentarium now, which is wonderful. It used to be that for systemic treatment, you were really limited to phototherapy or what we call traditional systemics - drugs like methotrexate and cyclosporine, azathioprine that are broad-based immunosuppressives and have some downside. The newer drugs, the newer systemic drugs, the biologics and the JAK inhibitors tend to be both more effective, but also come with less information. So again, because patients who have comorbidities or who are older are often not included in the clinical trials, we have to go off limited data. When we make recommendations to patients and talk about the safety, the data may come from other populations. For example, there's more information on the use of JAK inhibitors in patients with other indications like rheumatoid arthritis, which may not always be completely relevant to our patient population. Those other patients may have other comorbidities. So it's important to talk to patients about what we know from other indications, what we know from the dermatology world, and how there may be limitations to each of those sources of information.

The Dermatologist: How do you assess and manage potential drug interactions when treating older adults or polypharmacy patients?

Dr Abuabara: Being older patients or patients who are on multiple medications is always a challenge. Again, phototherapy is a great option if it works for that patient. Certainly with older patients, it can be more challenging for a number of logistical reasons. There's also an increasing amount of data on the biologics. That category as a whole tends to have positive indications thus far in the data. When we've looked back at the data from randomized trials of dupilumab and tralokinumab, there were only about 70, 75 patients in each of the phase 3 pool data that were over the age of 65. And the analysis, the studies were not powered to look at safety nor efficacy in that population. But given those limited data, the efficacy and safety profile looks quite similar. Also based on real world experience to date, the safety profile of the new biologics looks fairly promising. The opposite is true of JAK inhibitors where we do see some concern for their use in older adults given the risks of cancer, thrombosis, cardiovascular disease in older patients. So we urge caution using those in older patients or patients who are under other medications and to often think about dose reduction if you are going to use it in an older patient.

The Dermatologist: What gaps in research or clinical guidance would help improve treatment decisions for these special populations?

Dr Abuabara: I think that we need more data from trials when possible. The more inclusive trials can be, the more generalizable there will be to these populations. And then importantly, really rigorous post-marketing data. As we have more real world experience in these populations that may have a history of infection or require vaccinations, we get to learn more about whether we see any reactivation of potential viruses. If patients are treated while they're on the medication, the efficacy of vaccinations while they're on the medication, the safety in older adults, the safety in pregnant women. These are all very important considerations that we're not going to receive from standard phase 3 trials. So again, the post-marketing studies, the more inclusive they can be and also the real world data. I encourage people to collect that in a rigorous way and publish it because it'll help us to manage our patients best.

The Dermatologist: Are there any tips or insights you would like to share with your dermatology colleagues regarding systemic treatments in special population of adults with atopic dermatitis?

Dr Abuabara: So this is rather specific, but when thinking about pregnant women, for example, one thing that I tell them when considering the different systemic treatment options is that the most of the IgG transfer occurs after the first trimester. So oftentimes, patients are thinking about conception or had conceived and are concerned about being on a biologic. There's a whole host of risks and benefits to talk about, but the amount of fetal exposure increases after the second and third trimester. So that's an important point of counseling that might help you and your patient think about timing of starting or stopping a treatment.