Dangers, Benefits of Biologics Must Be Carefully Weighed

Biologic therapy in dermatology has transformed the treatment of various systemic and cutaneous diseases. However, immunosuppression and immunomodulatory therapies can be challenging in patients with chronic infectious diseases, and clinicians must practice caution when contemplating treatment in this patient population, said Kieron Leslie, MD, in a presentation at the American Academy of Dermatology 2021 Virtual Meeting Experience (AAD VMX) in April.¹

“Particularly in patients with chronic infectious diseases such as viral hepatitis, tuberculosis (TB), HIV, and now COVID-19 infections, finding the appropriate treatment can be difficult,” said Leslie, dermatologist in the Dermatology Clinic at Mount Zion and professor of dermatology at the University of California, San Francisco School of Medicine, both located in San Francisco, California. 

“As systemic immunosuppressive therapies are precluded in this patient population, physicians need to be clear on what they can prescribe and what to avoid.”

Biologics

Managing immunosuppressive therapy in patients and determining how best to oversee the vaccination of those patients against COVID-19 is a key issue for dermatologists. According to Leslie, the current evidence in the dermatological and rheumatological literature indicates that, in general, immunosuppressives are not a significant risk factor for COVID-19 infection. However, high-dose steroid use does appear to have an increased infection risk of the virus.

The AAD recently released guidelines regarding the appropriate administration of immunosuppressives in the COVID-19 pandemic era.² This guidance recommends that immunosuppressive agents be continued in patients who have not tested positive for COVID-19 or exhibited signs or symptoms of COVID-19 but should be discontinued in patients who are infected with COVID-19. The agents can be restarted when a patient has recovered from the virus. Also, clinicians should consider the risks, benefits, and balances with comorbidities such as obesity, diabetes, and hypertension in patients who may require the start of new medications.

“The AAD guidelines regarding the restart of medications, however, are not clearly defined, as they could mean restart 7 to 14 days after symptoms subside or after polymerase chain reaction [PCR] testing becomes negative,” Leslie said. As such, the decision has been left up to the clinician’s discretion and judgment.”

Clinicians have several immunosuppressive therapies to choose from in the dermatologic armamentarium. Options include high-dose corticosteroids, etanercept, guselkumab (Tremfya; Janssen Biotech) and methotrexate (MTX). Leslie advised avoiding high-dose corticosteroids when possible. No other agents have been implicated yet in an increased risk of COVID-19 infection.

The AAD has not issued guidelines regarding how to vaccinate patients on immunosuppression, however, the American College of Rheumatology (ACR) has. It shares many of the same medications used in dermatology.³ 

Based on the ACR guidelines, Leslie noted that there are no modifications to therapy or vaccination timing with regard to immunosuppressives, apart from MTX and JAK inhibitors such as tofacitinib.

Patients taking certain JAK inhibitors should be placed on a drug holiday 1 week after each vaccination dose. For rituximab, the vaccine series should be initiated approximately 4 weeks prior to the next scheduled rituximab cycle. The administration of infliximab does not require modifications to the timing of COVID-19 vaccination.

HIV

Individuals with HIV are more susceptible to a whole host of inflammatory skin diseases, particularly psoriasis and eczema, and often have extremely severe disease, especially when their HIV is not controlled well. According to Leslie, antiretroviral therapy is effective for these patients and can quickly improve their psoriasis symptoms.

“Psoriasis is very common in [individuals] living with HIV, almost double the incidence of patients without HIV, and is particularly severe when the CD4+ count is low,” Leslie said. “The first line therapy here is antiretrovirals together with concomitant skin-directed therapies including topical corticosteroids, phototherapy, and retinoids.”

There is no evidence on whether immunosuppressive agents can be used safely in HIV-positive patients who fail these treatment measures because all patients with HIV are typically excluded from these clinical studies, Leslie said. National Psoriasis Foundation guidelines issued in 2010 suggest optimizing antiretroviral therapy, using topical medications, and, as a second line, using systemic acitretin.⁴ 

“This approach does not work for everyone and...there have been many case reports of various agents being used in [HIV-positive] patients with psoriasis, including cyclosporine, MTX, apremilast, and IL-17 blockers such as secukinumab and guselkumab, essentially most of the agents that are FDA approved,” Leslie said.

The greatest body of evidence from case series and case reports are tumor necrosis factor α blockers, which, according to Leslie, likely reflect the clinicians’ familiarity with these agents, followed by the IL-12 and IL-23 blockers, such as ustekinumab, and the IL-17 blockers.

“It’s fair to say that the biologics are preferred to conventional disease modifying drugs such as cyclosporine or MTX, as these do seem to [lead to] a higher rate of infection,” Leslie said. 

Various types of eczema and prurigo also are very common in individuals with HIV infection. Recently, there have been a number of case series using dupilumab in patients with HIV without any reported adverse events. Leslie noted that the safety profile reported thus far with dupilumab is encouraging.

When contemplating immunosuppression treatment in dermatology patients with HIV, Leslie suggested a 4-step approach:

1. Try to optimize antiretroviral therapy by suppressing the patient’s viral load and raising CD4 count.

2. Consider other nonimmunosuppressive alternatives such as phototherapy, other topicals, and apremilast (Otezla; Amgen). 

3. Consult with the patient’s HIV/ID provider if immunosuppressants are deemed necessary.

4. Monitor patients carefully once treatment is initiated, including viral load and CD4 count. 

According to the National Psoriasis Foundation, Leslie said, acitretin is the only medication that can be safely used in HIV-positive patients, as the retinoids are considered a second-line agent in this patient population.

Leslie also sees broader issues evolving. Chronic infectious diseases such as viral hepatitis, TB, HIV, and COVID-19 disproportionally affect minority populations and individuals immigrating to the United States who may not have health coverage. Bringing appropriate therapy to these patient subsets can be challenging and should be addressed, Leslie said.

Disclosure:

Leslie reported no relevant or financial disclosures.

References:

1. Leslie K. Danger and defense in the age of biologics. American Academy of Dermatology 2021 Virtual Meeting Experience (AAD VMX); April 23-25, 2021; virtual. Accessed April 30, 2021.

2. Guidance on the use of immunosuppressive agents. American Academy of Dermatology. Updated October 15, 2020. Accessed May 4, 2020. https://www.aad.org/member/practice/coronavirus/clinical-guidance/biologics

3. COVID-19 vaccine clinical guidance summary for patients with rheumatic and musculoskeletal diseases. American College of Rheumatology. Updated March 4, 2021. Accessed May 6, 2021. https://www.rheumatology.org/Portals/0/Files/COVID-19-Vaccine-Clinical-Guidance-Rheumatic-Diseases-Summary.pdf

4. Menon K, Van Voorhees AS, Bebo BF Jr, et al. Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62(2):291-299. doi:10.1016/j.jaad.2009.03.047