D2.333 - Glatiramer acetate: when immunomodulation is not enough

Introduction: Glatiramer acetate is an immunomodulatory drug that is widely prescribed for the treatment of multiple sclerosis. It is frequently associated with local injection site reactions and generalized urticaria, in approximately 10% of patients it is also associated with immediate post-injection systemic reactions. Case report: We describe the case of a sclerosis multiple affected 28-year-old man who developed generalized urticaria/angioedema 20 minutes to one hour after glatiramer acetate sc administration; systemic reactions developed starting from 7 months after the first drug injection and required anti-reactve therapy. In vivo diagnostic tests, in particular glatiramer acetate percutaneous and intradermal skin tests, were performed with glatiramer acetate. The immediate reaction was red after 15 minutes. Skin prick tests (SPTs) were performed at 1:1000 (0.02 mg/mL) and resulted negative; subsequent dilutions were not performed for irritative reaction risk. Intradermal tests (IDTs) were performed at 1:10.000 dilution (0.002 mg/mL) and 1:1000 dilution (0.02 mg/mL), a wheal and flare reaction (10 mm) appeared at immediate lecture at 0.02 mg/mL, Fig. 1.Basophils activation test (BAT) has been performed as in vitro test and confirmed cells activation after drug exposure. Serum triptase was 4.7ug/L. Patient's consent has been obtained for case publication. Discussion: The immunomodulatory action of glatiramer acetate, mediated by regulatory T cells induction, favours anti-glatiramer acetate IgG4 without specific anti-IgE antibodies production in the most of treated patients. We have described a case of IgE-immediate systemic reaction to glatiramer acetate. The absence of story of anaphylaxis permitted us to perform in vivo tests, seeing positive results and concluding for a lgE-mediated sensitization, due to the immediate nature of reaction, that is a risk factor for anaphylaxis. A review of data from the FDA Adverse Event Reporting System and published case reports identified 82 cases of anaphylaxis associated with use of glatiramer acetate that occurred between December 1996 and May 2024, including 51 requiring hospitalization and 6 that were fatal. Although most cases occurred within 12 months after starting treatment with glatiramer acetate, about 25% of the cases occurred >12 months after the drug was started. In 2025 the FDA has required a new boxed warning in the label of the subcutaneously injected immunomodulatory drug glatiramer acetate about a risk of anaphylaxis. Patients receving glatiramer acetate should be counseled about the risk of anaphylaxis and cautioned that symptoms of anaphylaxis can overlap with those of more typical injection-related reactions which typically occur within minutes after injection and are generally self-limited.