Biologics are used to treat a number of atopic and inflammatory conditions, including bronchial asthma, urticaria, atopic dermatitis, chronic rhinosinusitis with nasal polyps (CRSwNP), hereditary angioedema, atopic dermatitis (AD), as well as rheumatoid arthritis and psoriatic arthritis.
The authors, from German medical centers and universities, focused much of their review on omalizumab, which was first approved by EU regulators in 2005 as an add-on therapy for patients 12 years of age and older with severe persistent asthma. It was first approved in the United States in 2003 for allergic asthma; it is also approved for chronic urticaria and in December 2020 was approved by the FDA to treat CRSwNP.
Omalizumab has been shown to reduce the frequency of exacerbations and improve symptoms, quality of life, and lung function in patients with bronchial or severe allergic asthma. Compared with placebo, it has also demonstrated effectiveness in reducing nasal polyp scores, nasal obstruction and other symptoms of CRSwNP.
Other biologics for asthma include mepolizumab and reslizumab, which block interleukin 5 (IL-5); the IL-5 receptor benralizumab; and dupilumab, which inhibits the signaling of interleukin-4 and interleukin-13, 2 proteins that play a central role in type 2 inflammation.
Dupilumab is the only approved biologic for AD; it is approved for CRSwNP as well. The authors noted that it is considered a game-changer in AD as it is the only systemic therapy and that guidelines recommend limited use of corticosteroids.
The review also looked athereditary angioedema (HAE), a rare genetic condition that causes recurrent edema of the skin and mucous membranes occurs; its affects about 1 in 50,000 individuals. One biologic, lanadelumab, is available for long-term prevention of HAE in several markets, including Australia, Canada, those of the EU, Switzerland and the United States. It inhibits the activity of plasma kallikrein, an enzyme which is uncontrolled in HAE.
In CRSwNP, other biologics are in or have recently finished clinical trials could join omalizumab. They include mepolizumab, reslizumab, and benralizumab.
Administration and adverse events
Omalizumab, mepolizumab, benralizumab, and dupilumab are approved for self-administration in the European Union and in the United States. Even if home administration is available, the researchers recommend seeing a physician for administration for at least 4 to 12 months to ensure that the patient doesn’t have any adverse reactions.
The authors noted that anaphylactic reactions to biologics can occur even after months of use, and all biologics run the risk of cytokine release reactions, or type alpha reactions, as a result of an overstimulated immune response that are tied to the substance and dose. They are more frequent than unpredictable anaphylactic reactions and typically decrease if therapy continues.
Opportunities for research
The authors also briefly discussed what is known and unknown about biologic therapy in certain populations, namely, during pregnancy and in patients with unknown SARS-CoV-2 infection status.
In pregnancy, knowledge stems from what is known from the use of biologics in rheumatoid arthritis, lupus erythematosus, or psoriasis vulgaris. Older biologics, such as the use of anti-tumor necrosis factors infliximab, adalimumab, and etanercept, are recommended in pregnancy up to week 20. A newer biologic, certolizumab, has been shown to be safe for the entire pregnancy.
Guidelines are silent on omalizumab, although it was studied in a trial of pregnant women and was not shown to cause birth defects, the authors said.
Other biologics either lack data or are not recommended; the authors suggested the use of register-based data or case-control studies for this population.
For the population of patients on biologic treatment concerned about infection with SARS-CoV-2, the authors cited a German position statement that therapy should continue, adding, “the therapy should be decided on individually together with the patient after a risk-benefit analysis in case of justified suspicion or proof of an infection with SARS-CoV-2.”
Jappe U, Beckert H, Bergmann KC, et al. Biologics for atopic diseases: Indication, side effect management, and new developments. Allergol Select. Published online January 5, 2021. doi: 10.5414/ALX02197E