Successful Rapid Desensitization to Glatiramer Acetate in a Patient With Multiple Sclerosis.

Glatiramer acetate (GA; Copaxone, Τeva Pharmaceuticals) is an injectable peptide mixture with immunomodulatory properties. It is approved by the FDA as a first-line treatment for reducing the frequency of relapse and slowing the progression of disability in the relapsing-remitting form of multiple sclerosis (MS) [1]. A considerable amount of research conducted over the last decade has demonstrated that GA is a clinically effective and well-tolerated drug with a more favorable adverse effect profile than other diseasemodifying therapies for MS [1]. However, local skin reactions to subcutaneous injection of GA may occur in approximately 20% to 60% of patients, while up to 10% of patients may develop immediate postinjection systemic reactions, which are mainly characterized by flushing, chest pain, palpitations, dyspnea, throat constriction, and urticaria [2]. To the best of our knowledge, there is only 1 previous study reporting successful desensitization to GA in a small series (6 cases) of patients with MS and GA-associated local or systemic reactions [2]. Herein, we report an additional case of successful rapid desensitization to GA in a patient with MS. A 51-year-old woman with MS had been treated with daily subcutaneous administration of GA for the previous 4 years without adverse reactions. Four weeks before presenting to us she developed injection site redness and swelling followed by generalized urticaria which was resistant to antihistamines (high dose of levocetirizine 5 mg×4/24h) and corticosteroid therapy (methylprednisolone 60 mg/24h). The patient discontinued GA, as advised by her neurologist, and her urticaria resolved. She was referred to our department for further evaluation. Skin prick tests (SPTs) and intradermal (ID) skin testing to GA and mannitol (an inactive ingredient of Copaxone with allergenic potential) were performed 4 weeks after the initial hypersensitivity reaction to minimize the risk of false-negative results; a positive reaction was defined as the presence of a wheal with a diameter of at least 3 mm larger than that produced by a negative control (diluent) 20 minutes later. Histamine (10 mg/mL) was used as a positive control. For the SPT, a drop was applied to the volar surface of the forearm. For ID injections, 0.03 mL was injected. In the case of GA, the patient was tested with concentrations of 1:100 (0.2 mg/mL), 1:10 (2 mg/mL), and 1:1 (20 mg/mL) for the SPTs and of 1:1 000 000 (0.00002 mg/mL), 1:100 000 (0.0002 mg/mL, and1:10 000 (0.002 mg/mL) for the ID tests. Mannitol was tested at a concentration of 100 mg/mL for the SPT and 10 mg/mL for the ID test. SPT showed a borderline reaction to GA (wheal diameter, 3 mm) at a concentration of 20 mg/mL, while ID testing produced a positive reaction at a concentration of 0.002 mg/mL (1:10 000). SPT and ID skin testing with mannitol produced negative results. After obtaining the patient’s informed consent, subcutaneous desensitization to GA was carried out in an outpatient setting under close medical supervision. Increasing doses of GA were administered subcutaneously every 15 minutes, with a starting dose of 0.000002 mg followed by gradual dose escalation up to 11 mg (the exact protocol used is shown in the Table). The entire desensitization procedure lasted 3 hours and 15 minutes and was well tolerated, with no immediate or delayed adverse events. The patient was able to resume daily administration of GA with no recurrence of urticaria or any other hypersensitivity reactions during a follow-up period of 3 months. The development of postinjection systemic reactions is a well-recognized adverse effect of treatment with GA.