Apremilast as an Oral Treatment Option for Pediatric Moderate-to-Severe Plaque Psoriasis: Efficacy, Safety, and Clinical Considerations
Loretta Fiorillo, MD, FRCPC, Director of Pediatrics and Dermatology at the University of Alberta, discusses findings from a study on apremilast for pediatric psoriasis. The study highlights apremilast as the first oral systemic treatment for children aged 12 to 17, offering a needle-free alternative to biologics and immunosuppressants. Dr. Fiorillo underscores its efficacy, tolerability, and long-term safety, emphasizing its role in expanding treatment options for moderate to severe pediatric psoriasis.
Additional Resource:
- Fiorillo L, Becker E, de Lucas R, et al. Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial. J Am Acad Dermatol. 2024;90(6):1232-1239. doi:10.1016/j.jaad.2023.11.068
TRANSCRIPTION
Loretta Fiorillo, MD, FRCPC: Well, hello, good morning. I'm Loreta Fiorillo. I am the director of Pediatrics and Dermatology at University of Alberta. And I'm the first author on the study of apremilast for treatment in children with psoriasis age 12 to 17.
Consultant360: Could you explain the significance of apremilast’s efficacy in pediatric patients with moderate to severe plaque psoriasis, particularly in achieving a ≥75% reduction in PASI scores? How does this compare to existing treatment options?
Dr Fiorillo: In terms of the significance, it is highly significant for children because this is a oral medication. And as we consider other equally effective options, they are all intramuscular or subcutaneous or by infusion, and therefore all involve needles, which children, especially the younger ones, don't like injecting children regularly, like it happens with other drugs, approved for psoriasis, such as ENBREL, which is a subcutaneous injection twice a week causes significant pain, anxiety, and psychological, general psychological distress in children, which can then even evolve into mistrust of adults, mistrust of institutions, of the medical system, etc.
So the fact that we now have an oral option is fantastic for children. They don't have to have injections. They just need to take a pill. And this particular drug, apremilast does not require routine blood work either. And in this way is also different from another oral option, which is methotrexate, which is a common drug that is commonly used in the severe psoriasis in both children and adults, but methotrexate requires blood work every month for the first 3 months and every 3 months thereafter, while with apremilast we don't need to do routine blood work.
C360: Safety is always a key concern in pediatric populations. Were there any specific adverse events or tolerability issues observed during the trial, and how do these align with the known safety profile of apremilast?
Dr Fiorillo: It was actually quite similar to the safety profile that was seen in adults. The most common side effects we noted was nausea, stomach pain, some looser bowel movements, not completely diarrhea, but loser bowel movements. These GI side effects were noted in our children as well. And in some children, we noticed that a slight decrease in the dose seemed to help. We had an occasional child who ended up taking it just in the morning and not in the evening, and that really did the trick, helped her. Most children eventually settled. For most children, the initial stomach upset resolved after the first couple of weeks of treatment, and then they were able to continue. We really did not have any children in our group that discontinued due to the side effects.
C360: What insights can you share about the potential for sustained benefits or long-term safety concerns for this population?
Dr Fiorillo: We have now published a long-term extension study that shows sustained efficacy and no new side effects in the long-term study, which is really good, so that these patients appear to have had no other problems.
The apremilast study is now concluding and we have published publishable data to 52 weeks with no new signal in the in this longer term.
C360: Beyond efficacy and safety, what other factors should clinicians weigh when deciding on systemic treatments for this population?
Dr Fiorillo: Well first of all is the severity of the psoriasis. You would not consider systemic treatment for children who have mild psoriasis that can be treated with the topical products, and there are many topical products available mostly topical corticosteroids. So systemic treatment of psoriasis is indicated if the child has a large body surface area, if the areas involved are a special site, such as the face, the genitals, they can be more bothersome, hands and feet, or if it is involving the scalp.
Other considerations are the possibility of other systemic conditions associated with psoriasis, such as psoriatic arthritis, which is not that common in children, but can follow severe psoriasis or more rarely can precede the onset of skin psoriasis. And systemic treatment often helps both the skin psoriasis and the psoriatic arthritis. So these are all considerations we make when we decide to go to a systemic treatment.
C360: Based on the results of this study, how might apremilast address unmet needs in treating pediatric patients with moderate to severe plaque psoriasis, particularly for those who are inadequately controlled by topical therapies?
Dr Fiorillo: Exactly, apremilast is the only systemic treatment for psoriasis that does not belong to traditional immunosuppressants. So traditional immunosuppressants used for severe psoriasis in children include methotrexate and cyclosporine.
Both of them are immunosuppressants, cyclosporine more than methotrexate, and therefore are associated with increased risk of infections in children and potentially in the long run, increased risk of malignancies.
Apremilast, it's not a traditional immunosuppressant and it does not suppress the immune system like methotrexate or cyclosporine and it is oral. So for these reasons is preferred to the previous two immunosuppressants. And because it is oral and not injectable, it's preferred over the injectable biologics for children who are afraid of needles or who are anxious about needles.
There are always newer drugs coming up in the market for psoriasis. And there are other oral medications coming up in the market, such as JAG inhibitors. They may become also approved eventually for psoriasis in children. For now, apremilast is the only oral approved medication apart from the immunosuppressants.