Biologics have significantly improved the treatment of dermatological diseases. Their use in the treatment of melanoma and atopic dermatitis was discussed during the virtual EADV Congress on 31 October 2020.
Immune checkpoint inhibitors have revolutionized the treatment of malignant dermatological diseases, says Simone Ribero (Dermatological Clinic of the University of Turin, Italy). Ipilimumab, pembrolizumab, and nivolumab are approved on their own and in combination for the treatment of advanced melanoma. Nivolumab and pembrolizumab have shown to be superior to ipilimumab in terms of their effect on overall survival while being better tolerated.
Immune checkpoint inhibitors have also shown to be effective in the adjuvant setting. They are currently being tested in a neoadjuvant setting. According to Ribero, the initial results of an Italian study indicate that this therapeutic approach could be successful. The melanoma patients had received 4 cycles of ipilimumab/nivolumab neoadjuvant and were treated with 6 cycles of nivolumab after surgery.
Further studies are looking at combinations of immune checkpoint blockers with various other substances, such as the combination with the PD1 inhibitor spartalizumab, the CD-122 IL-2 pathway agonist bempegaldesleukin (development code NKTR-214), the LAG3 antibody relatlimab, the IDO1 inhibitor epacadostat, or the tyrosine kinase inhibitor (TKI) lenvatinib.
Atopic dermatitis severely affects the quality of life of those affected and their families, according to Richard Langley (Department of Dermatology at Dalhousie University, Halifax, Nova Scotia, Canada). Atopic dermatitis is a complex disease with a disruption of the immune system.
There is still a great need for substances for the acute and long-term control of the disease. Biologics that may be considered for treatment are the IL4-/IL-13 antagonist dupilumab, the IL-13 antagonist tralokinumab, and the IL-13 antagonist lebrikizumab.
Dupilumab is approved for the parenteral treatment of moderate to severe atopic dermatitis in adults and adolescents aged 12 years and older who are eligible for systemic therapy. In the pivotal SOLO-1, SOLO-2, CHRONOS, and CAFÉ phase-3 trials, dupilumab, alone or in combination with topical glucocorticoids, has been shown to be more effective than placebo or topical glucocorticoids in people over 18 years of age with moderate to severe atopic dermatitis. The AD-1526 study confirmed its efficacy in adolescents.
The most common adverse effects were nasopharyngitis, upper respiratory tract infections, conjunctivitis, and injection site reactions.
Tralokinumab has been studied in the ECZTRA (ECZema TRAlokinumab) 1, 2, and 3 phase 3 trials compared to placebo with and without topical glucocorticoid treatment. All three trials demonstrate the efficacy of tralokinumab 300mg in moderate to severe atopic dermatitis. The most common adverse effects were upper respiratory tract infections. Rare were conjunctivitis and reactions at the injection site.
There are results from a phase 2b dose-finding study of lebrikizumab in 280 adults with moderate to severe atopic dermatitis. Langley also said the results of this study were very encouraging. During the 16-week treatment, clinical manifestations of atopic dermatitis improved rapidly and dose-dependently. Side effects included injection site reactions, herpes virus infection, and conjunctivitis. If these findings can be confirmed in phase 3 trials, lebrikizumab should become a valuable treatment alternative.
Source:
Symposium "Biologics in dermatology: Present and future". 29th Congress EADV Virtual, 29 to 31 October 2020, Session ID D3T01.4.