Review Highlights Benefits, Drawbacks of Dual Biologic Therapy in Dermatology

Dual biologic therapy may be effective and generally well-tolerated in treating refractory inflammatory skin conditions such as psoriasis, new findings suggest, although it carries a moderate risk of infection.1

This finding and others were the conclusions that resulted from a recent systematic review on dual biologic therapy use in skin disease. These data were authored by such investigators as Eric McMullen, MD, of the University of Toronto Department of Medicine’s Division of Dermatology.

McMullen and his coauthors highlighted that dual biologic therapy, a process involving the concurrent use of biologic treatments, is an approach for refractory cases of inflammatory skin diseases individuals living with comorbid inflammatory conditions who are in need of additional therapies.

“This systematic review aims to document, synthesize and critically appraise the current literature on dual biologic therapy in inflammatory skin diseases,” McMullen and colleagues wrote.1

Design and Findings

The trial investigators used 5 databases—including Embase, MEDLINE, CENTRAL, Scopus, and Web of Science—for their comprehensive literature search, conducted across these databases' inceptions through March 2024. The team used a search strategy that involved both subject headings and keywords related to various types of biologic agents, inflammatory dermatologic conditions, and combination (dual) biologic use.

The review adhered to PRISMA 2020 guidelines and was registered with PROSPERO.2 McMullen et al maintained a set of criteria for inclusion, looking only at studies assessing the safety and effectiveness of dual biologic therapy in skin diseases that were also written in English. 40 studies were found to have met these criteria, encompassing data from 106 total patients, 59.4% of whom were labeled as female.

Among these trial subjects, the investigators noted the mean age across the cohort as 47.1 years, with ages ranging from 10 - 79 years. Before initiating dual biologic therapy, patients assessed in these studies had failed an average of 1.3 topical drugs, 2.4 non-biologic systemic drugs, and 2.1 biologic monotherapies.

The most frequently reported biologic pairing was found by the investigative team to be omalizumab alongside rituximab, which accounted for 25.7% of cases. This was mostly observed in those showing treatment-resistant bullous pemphigoid. The next most common biologic combination was omalizumab and secukinumab, among 16.5%, which is implemented for refractory chronic spontaneous urticaria (CSU) and psoriasis.

All 106 of these individuals showed demonstrated clinical response to the dual biologic agent regimens. The most prevalent conditions treated among these subjects included bullous pemphigoid among 28.3%, CSU among 35.8%, psoriasis among 23.6%, and atopic dermatitis among 9.4%. It was noted that 30.2% of patients initiated dual therapy after being prompted by an inadequate response to single-agent biologic treatment, while others required combination biologics as a result of coexisting inflammatory diseases. These were both dermatologic (35.8%) and non-dermatologic (34.0%).

McMullen and coauthors noted that the mean follow-up period of 14.7 months saw 78.3% of patients report no adverse events. Among those who did, the most frequent were non-severe infections (10.4%). Loss of therapeutic response took place in 4 of the study subjects. Serious adverse outcomes included a single case of respiratory failure and 1 fatality in a patient with multiple comorbid conditions—acute lymphoblastic leukemia, bullous pemphigoid, renal failure, sepsis, and graft-versus-host disease. 9 patients had infections, with a notable link to therapies involving ustekinumab or TNF inhibitors being observed by the investigative team.

A notable therapeutic approach for resistant CSU and psoriasis involved co-administration of anti-IgE and anti-IL-17 agents. Such biologics act on separate yet potentially synergistic immunological pathways. IL-17A, a cytokine elevated in psoriasis, can promote IgE class switching and IgE-secreting cell differentiation when stimulated via anti-CD40 and anti-IL-4 pathways. Given that IL-17A may contribute both to psoriatic inflammation and to IgE-driven allergic responses, dual iIL-17A and IgE pathway inhibition could allow for enhanced clinical efficacy.

This systematic review underscores dual biologic therapy's potential in helping achieve clinical responses with an acceptable safety profile in individuals living with inflammatory diseases impacting the skin. However, a 10.4% infection rate was noted by the investigators as raising questions about increased susceptibility due to compounded immunosuppression and impaired immune surveillance.

“Distinct and complementary mechanisms such as IL-17 and anti-IgE in psoriasis and CSU highlight these promising findings, yet current evidence is limited by small sample sizes and likely publication bias,” they concluded.1 “Future studies should prioritize larger studies, extended follow-up periods and refined patient selection criteria to better assess the efficacy and safety of dual biologic therapy.”

References

1. McMullen E, Croitoru D, Piguet V, et al. Efficacy and safety of dual biologic therapy in inflammatory skin diseases: A systematic review. J Eur Acad Dermatol Venereol. https://doi.org/10.1111/jdv.20839.

2. Page MJ, McKenzie JE, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71.