Dupixent and Multiple Sclerosis

​Question: Can you look at case studies for dupixent in MS and comment on them?

Answer:
Dupilumab (Brand name Dupixent) was approved for the treatment of atopic dermatitis (i.e. eczema)  refractory to topical therapies (i.e. applied to the skin) in 2017 and for adjunctive treatment of asthma in 2018. It is also indicated for treatment of chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis and prurigo nodularis (another skin condition). Dupilumab is a monoclonal antibody therapy that inhibits signaling of 2 cytokines (IL-4 and IL-13) known to be associated with these aforementioned conditions. According to recent posts by the manufacturer (Regeneron) there are over 800,000 people treated with Dupixent worldwide. The current FDA package insert does NOT include any warnings regarding the use of Dupixent in people with multiple sclerosis. 

A review of the literature in PubMed reveals 5 case reports (3 in a single publication) since 2021 of the use of Dupixent in people with MS.

Case report 1 (Laageide L et al. JAAD Case Reports 2021 Sep; 15: 33–35) describes a 34-year-old woman with undiagnosed multiple sclerosis for a year who began Dupixent 2 months before an MS relapse and 4 months before her Multiple Sclerosis Diagnosis. She was not on a disease modifying therapy until after her diagnosis with MS . Dupixent was stopped and her MS was controlled with ocrelizumab.
Case report 2 (Gelato F et al. Dermatol Ther 2022 Oct;35(10):e15740)doi: 10.1111/dth.15740)) describes a 21-year-old with severe atopic dermatitis started on Dupilumab in January 2019 with excellent results. However, after 1 ½ years on Dupilumab treatment he began to experience symptoms of multiple sclerosis (onset July 2020) which was diagnosed in September 2020. Treatment with dupilumab was stopped and his multiple sclerosis was controlled with natalizumab (Tysabri)
Case report 3 (Esposito M, et al. JAAD Case Reports 2022 Nov 5:31:1-5. 
doi: 10.1016/j.jdcr.2022.10.031) describes three people with well-established MS, ages 47, 53 and 60, who received Dupixent for atopic dermatitis while receiving teriflunomide (brand name Aubagio) to treat their Multiple Sclerosis. None of the patients experienced a relapse or worsening of MS symptoms on Dupixent and their MRI scans remained stable. 

The authors of case reports 1 and 2 advised caution when using Dupilumab in people with MS. They hypothesized that inhibition of Th2 responses through inhibition of IL-4 signaling in susceptible individuals may aggravate Th17 mediated immune responses commonly associated with certain forms of autoimmunity including MS. It is important to note that both case reports 1 and 2 describe young, undiagnosed people with MS who started dupilumab before starting a disease modifying therapy for MS. In contrast Case report 3 described no significant adverse consequences of prescribing dupilumab in three older MS patients already on a DMT treatment. 
What conclusions can we draw from these case reports?

1. We need more information before jumping to any conclusions. If you know of anyone with MS who has experienced a worsening of their MS on dupilumab, this should be reported to the FDA through your physician or the manufacturer.
2. I agree with using caution when prescribing dupilumab in untreated, multiple sclerosis patients, particularly young relapsing MS cases. However, we should use caution when we treat people with MS with ANY therapies that can modulate immune responses. Remember, there are many medical conditions associated with different forms of inflammation treated with immune modulators, usually monoclonal antibodies. For instance, we know that TNF inhibitors used to treat rheumatoid arthritis and other rheumatologic conditions are associated with worsening of multiple sclerosis and the FDA has indicated this warning in their labels for all TNF inhibitors.Please note that the conditions treated by dupilumab are all associated with significant morbidity and impairment of quality of life. Unless there is more information available, it would not be rationale to deny this treatment outright to people with MS. 

Revere P (Rip) Kinkel, MD
Professor of Neurosciences
Director of the Multiple Sclerosis Program
University of California San Diego
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#Dupixent #multiplesclerosis