The safety and efficacy of dual biological therapy: Dupilumab and fremanezumab

Prescription of biological disease-modifying agents for inflammatory cutaneous disease has become increasingly popular given their favourable safety profile and high rates of efficacy. Patients with multiple medical comorbidities may require the use of simultaneous biological therapies to manage coexistent conditions. There is a paucity of literature regarding patient safety and outcomes of those receiving dual biological therapies for their skin disease or concomitant medical condition. Dupilumab is an interleukin-4/-13 (IL-4/-13) receptor alpha antagonist indicated for the treatment of moderate-to-severe atopic dermatitis (AD), asthma, eosinophilic oesophagitis and severe chronic rhinosinusitis with nasal polyposis. In Australia, dupilumab has been approved for the use of moderate-to-severe AD. Fremanezumab is a humanised IgG2a monoclonal antibody approved for the use in chronic migraine. Fremanezumab selectively targets calcitonin gene-related peptide (CGRP), a neuropeptide involved in the pathophysiological pathway of migraine. Fremanezumab prevents CGRP from binding to its receptor on blood vessels and the subsequent vasodilatation responsible for headaches. Common adverse events associated with fremanezumab include localised injection site reactions and nasopharyngitis.1, 2 Beyond migraine neurobiology, CGRP has been shown to dampen the body's inflammatory response by influencing the differentiation of CD4 T cells away from Th1 and TH17 pathways. It can be posturised that those being treated with CGRP monoclonal antibodies may potentially develop inflammatory complications. Reported cutaneous complications include psoriasis flares and the development of urticarial dermatitis. No AD associations have been reported.2 We describe the case of a 40-year-old female with a lifelong history of moderate-to-severe AD. She also had intractable migraines requiring multiple hospital admissions, treatment resistant to topiramate, chlorpromazine and amitriptyline. Her AD had previously been managed with the Janus kinase (JAK) inhibitor abrocitinib with good effect; however, this was ceased due to an adverse event. Four weeks later, fremanezumab was started with a reduction in migraine days, and 6 weeks later, dupilumab was commenced. She has now been on dual monoclonal antibody biological therapy for over 6 months. Her AD is well controlled, with a reduction in Eczema Activity Severity Index (EASI; 23.8 to 0.1) and Physician's Global Assessment (PGA; 4 to 1). The improvement in migraine days remains unchanged after starting dupilumab. There were no adverse events related to the combination of two monoclonal antibodies. Considering the extensive current and future availability of targeted biological therapies, it is vital for clinicians to be aware of any potential pharmacological interactions. A review of the literature of cobiologic therapy with dupilumab is limited to small case series (see Table 1). Reported examples include combination with other monoclonal antibodies such as guselkumab, secukinumab, omalizumab, benralizumab, adalimumab, evolucumab, cetuximab and abatacept for concomitant disorders.3 The observational data available show modest evidence for safety and efficacy, none of which have investigated the use of dupilumab and fremanezumab specifically.3-5 1 Here, we have found dupilumab and fremanezumab to be effective combination therapy with no adverse interactions over a 6-month period, although longer follow-up is required. This adds to the literature suggesting that dual biological therapy may not increase risk or impair the patient's clinical response. Continued discussion and debate combined with more robust data of the use of dual biological therapies will provide greater opportunities for future patient care. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians. The authors declare that they have no financial or other conflicts of interest in relation to this article.