Incidence of Lipoatrophy Associated with Autoinjection Versus Manual SQ Injection of Glatiramer Acetate

Background: The incidence of lipoatrophy occurring as a consequence of subcutaneous injection (SQ) of glatiramer acetate (GA) has been reported as 2% in the GA package label. The prevalence and severity of lipoatrophy with long-term GA therapy for multiple sclerosis (MS) is largely unknown. The exact cause of lipoatrophy is speculative, but it is thought to be the consequences of some adverse immunologic side effect of the culprit injection. It has also been proposed that local elevated production of tumor necrosis factor-alpha leads to the dedifferentiation of adipocytes in the SQ tissue.

Objectives: Compare the incidence of lipoatrophy associated with long-term use of autoinjection versus manual SQ injection of GA in a clinical practice population of MS patients. 

Methods: Seventy-three MS patients maintained on GA (mean 36 months) had been given the option of use of autoject 2 versus manual SQ injection.  Forty patients (54.8%) employed the autoinjection and the remaining 33 patients (45.2%) opted for manual SQ injections.  Both groups were followed with clinical examinations and serial photographic analysis every three months. All patients were counseled on proper injection site rotation and methods on each visit. (Autoject 2 apparatus was provided through Shared Solutions.)

Results: A total of 46 patients (63%) taking GA developed lipoatrophy over a 3-year interval.  Of this number, the overwhelming majority, 35 patients (76%) occurred with the use of autoject 2.  Lipoatrophy occurred predominantly in women and was noted at multiple injection sites in the same patient. In some patients, lipoatrophy developed within the first 3 months of injection initiation and was severe enough to necessitate switching to another MS disease modifying therapy (DMT).  Upon GA treatment discontinuation, lipoatrophy remained permanent. Serial photographs of individual patient lipoatrophy will be presented.

Conclusions: Of the side effects of SQ GA, lipoatrophy is the most disfiguring and is invariably permanent. Our clinical experience with GA showed that 63% of patients developed lipoatrophy.  This occurrence (greatest in the autoinjection group) was substantially higher than previously reported and was often the solitary factor in prompting patients to switch to another MS DMT. Our data is also suggestive that a heightened risk of lipoatrophy is an inherent autoimmune problem and may not necessarily be mitigated by vigilant injection site rotation irrespective of the methodology of GA administration.