Biologics vs Nonbiologics for Treating Psoriasis: Choosing the Right Agent
Biologic agents have become an important part of the treatment regimen for psoriasis and psoriatic arthritis. Biologic agents differ from traditional systemic agents in that they only target parts of the immune system. They treat psoriatic disease by inhibiting T cells, tumor necrosis factor α (TNF-α), or IL- 17A, IL-12, or IL-23.1,2 Systemic agents work throughout the body and are indicated for patients with psoriasis or psoriatic arthritis who have failed other forms of therapy.3
“I think it’s important for dermatologists to know that patients with psoriasis are undertreated and that it is ok to treat with systemic or biologic agents. I have seen patients covered in psoriasis plaques, and all they have been given is a jar of triamcinolone,” said Sylvia Hsu, MD. Dr Hsu is a professor and the chair of the department of dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania.
“That is what I did 30 years ago when I was a resident, because we had nothing else. I hated treating patients with psoriasis 30 years ago; nobody got better, and it was not satisfying. But now, it’s so easy to treat psoriasis. We have so many good options.”
The first biologic for treating psoriasis was approved by the US Food and Drug Administration (FDA) in 2003. In 2022, more than 10 biologics are available for treating psoriasis, with more in development.2
Current Guidelines and Recommendations
The American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) have published joint guidelines for the treatment of psoriasis.4 The guidelines outline recommendations for biologics, comorbidities, phototherapy, systemic nonbiologic agents, and topic therapies, as well as treatment for the pediatric population.4
“We have different classes of biologics, and for people who have certain comorbidities, we try to choose a biologic that is most appropriate for them,” Dr Hsu explained. “For example, if somebody has congestive heart disease or multiple sclerosis, a TNF-α inhibitor would not be your first choice. If they have inflammatory bowel disease, an IL-17 inhibitor would not be your first choice.”
When choosing a biologic that is appropriate for your patient, consider the patient’s disease severity, comorbid conditions, and treatment history.5 The extent of affected body surface area is one way to assess a patient’s disease severity, and an extensive history-taking process will help you understand the patient’s comorbidities and treatment history.6
Benefits of Biologics
In addition to targeting specific immune pathways, biologics are also beneficial because they can improve symptom control for patients who have failed other treatments. Moreover, if patients need to skip a dose, they will likely not experience a flare in the short-term.7
“The good thing about these biologics is if you miss a dose, nothing bad is going to happen,” Dr Hsu explained. “The patient is not going to flare. It’s not like one of the biologics we had more than a decade ago, in which the psoriasis would rebound if the patient stopped taking the biologic suddenly. With the biologics that we have now, if you skip some doses, typically you don’t flare. It takes a little while for psoriasis to come back.”
This is also good news for patients who need to pause treatment for surgery. Although disease flares occur depending on how long a patient stops taking the biologic, there is no increased risk of postsurgical complications.8
“In terms of skipping a dose for surgery, the guidelines depend on which society guidelines you’re reading, but there are no studies that show there’s an increase in infection if you don’t hold biologics,” Dr Hsu said. “A lot of it is based on expert opinion, so some people say skip a dose, some people say hold for 5 half-lives before the surgery.”
In addition, patients taking biologics can still receive COVID-19 vaccines.10 “I get this question every week. I tell patients to get their vaccine. The COVID-19 vaccine is not a live vaccine, so it is safe for patients taking biologics,” Dr Hsu said.
When to Prescribe Systemic Agents
The AAD/NPF guidelines specifically outline the recommended use of the 4 most common systemic agents available for treating psoriasis: methotrexate, cyclosporine, acitretin, and apremilast.10
Methotrexate is recommended for adults with moderate to severe psoriasis but is not recommended for patients with obesity, since these patients are at higher risk of nonalcoholic fatty liver disease and methotrexate has a higher risk of hepatotoxicity.
“Some dermatologists still use methotrexate a lot, but I don’t,” Dr Hsu said. “The Comprehensive Dermatologic Drug Therapy, by Wolverton and colleagues,11 says that it’s not prudent to use methotrexate in anybody with obesity. The definition of obesity includes anybody with a body mass index of 30 kg/m2 or higher. Where I practice, that’s like half the population.”
Regular monitoring is recommended for infections and hepatotoxicity, and Dr Hsu said that she does not recommend methotrexate to patients who fear needles. “Some people are on methotrexate because they’re scared of needles. When patients bring that up, I tell them that, if they do start methotrexate, they’re going to get a lot more blood draws for treatment monitoring. That means more needles, and those needles go deeper—the vein for blood draws vs fat for the biologic.”
Cyclosporine is recommended for adults with intractable severe psoriasis, generalized pustular psoriasis, and/or palmoplantar psoriasis. It is not recommended for long-term use but has a role in treating acute flares and erythroderma.10 It can also act as a bridge to biologic treatment as a quick fix before the biologic is approved by the insurance company.
“Cyclosporine is not a long-term solution,” Dr Hsu said. “When I start cyclosporine with my patients, I already have a plan on how I am going to get them off cyclosporin; the FDA says you shouldn’t be using cyclosporine longer than 12 months. I try to not prescribe it longer than 12 weeks, so I use it as a transition to, say, a biologic.”
Acitretin, a non-immunosuppressive agent, is relatively slow- acting and is less beneficial than other systemic agents for plaque-type psoriasis.10 It is more efficacious for pustular psoriasis than plaque-type psoriasis. For plaque-type psoriasis, acitretin decreases scale but does not reduce the affected body surface area. Acitretin is beneficial for patients with immunocompro- mising comorbidities, like HIV.
There is also a strong contraindication against use in pregnant women: “If this drug is taken with alcohol, it converts to etretinate, which stays in the fat for 3 years,” Dr Hsu said. “So, if a woman of childbearing age takes it, she can’t get pregnant for 3 years, because etretinate is a teratogen; it causes birth defects. So, I personally do not prescribe acitretin for any woman of childbearing age.”
Apremilast is recommended for adults with psoriasis, regardless of severity. As far as efficacy, though, it is not as efficacious as other systemic agents: “In the original studies, the PASI 75 at week 16 for apremilast was about 35%; so basically 35% of people reached PASI 75 at 4 months,” Dr Hsu explained. “Therefore, the drug is not as efficacious as any biologic we have.”12
“For more than 5 and a half years, we didn’t have any new biologics. I had a lot of patients who had been on all the biologics that we had at the time, and they worked for a while, but the efficacy was going down. So, I had to prescribe some patients combination biologic plus methotrexate. Then, when apremilast came out, I had patients on combination biologic plus apremilast. But it’s the biologic that was doing the heavy lifting,” Dr Hsu concluded.
1. Biologics. National Psoriasis Foundation. Updated October 1, 2020. Accessed January 24, 2022. https://www.psoriasis.org/biologics
2. Psoriasis treatment: biologics. American Academy of Dermatology Association. Accessed January 24, 2022. https://www.aad.org/public/diseases/psoriasis/treatment/ medications/biologics
3. Systemics. National Psoriasis Foundation. Accessed January 24, 2022. https://www. psoriasis.org/systemics/
4. Psoriasis guidelines. National Psoriasis Foundation. Accessed January 24, 2022. https://www.psoriasis.org/psoriasis-guidelines
5. Martin G, Young M, Aldredge L. Recommendations for initiating systemic therapy in patients with psoriasis. J Clin Aesthet Dermatol. 2019;12(4):13-26. https://www.ncbi.nlm. nih.gov/pmc/articles/PMC6508485/
6. Measuring body surface area. National Psoriasis Foundation. Published August 24, 2020. Accessed January 24, 2022. https://www.psoriasis.org/watch-and-listen/measur- ing-body-surface-area/
7. Umezawa Y, Torisu-Itakura H, Morisaki Y, et al; Japanese Ixekizumab Study Group. Long-term efficacy and safety results from an open-label phase III study (UNCOVER-J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab. J Eur Acad Dermatol Venereol. 2019;33(3):568-576. doi:10.1111/jdv.15292
8. Bakkour W, Purssell H, Chinoy H, Griffiths CE, Warren RB. The risk of post-operative complications in psoriasis and psoriatic arthritis patients on biologic therapy undergoing surgical procedures. J Eur Acad Dermatol Venereol. 2016;30(1):86-91. doi:10.1111/ jdv.12997
9. Wack S, Patton T, Ferris LK. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: Review of available evidence. J Am Acad Dermatol. 2021;85(5):1274-1284. doi:10.1016/j.jaad.2021.07.054
10. Psoriasis clinical guideline. American Academy of Dermatology Association. Accessed January 24, 2022. https://www.aad.org/member/clinical-quality/guidelines/pso- riasis
11. Wolverton S, Wu J. Comprehensive Dermatologic Drug Therapy. 4th ed. Elsevier; 2019.
12. Abrouk M, Nakamura M, Zhu TH, Farahnik B, Koo J, Bhutani T. The impact of PASI 75 and PASI 90 on quality of life in moderate to severe psoriasis patients. J Dermatolog Treat. 2017;28(6):488-491. doi:10.1080/09546634.2016.1278198
