Copaxone lipoatrophy far more common than reported

DALLAS – The risk of lipoatrophy with glatiramer acetate is greater than 60%, according to a review of 73 multiple sclerosis patients at one clinic.

The risk is "substantially higher than previously reported and [is] often the sole factor prompting patients to switch to another MS [disease-modifying therapy]. Our data also suggest that a heightened risk of lipoatrophy is an inherent autoimmune problem and is not necessarily mitigated by vigilant injection-site rotation. The psychological consequences may be significant," said investigator Dr. Ronald Bailey, director of the MS clinic at the Riverside (Calif.) Medical Clinic.

A total of 46 glatiramer acetate (GA, Copaxone) patients (63%) developed lipoatrophy, an injection-site indentation that can be deep and disfiguring; 35 (76%) of them used an autoinjector. Once noted, the dents didn’t improve during a 3-year observation period, which included photographic documentation and instructions on how to inject the drug every 3 months.

In some patients, lipoatrophy developed within the first 3 months of starting the shots and was noted at multiple injection sites, which prompted the team to suspect that an autoimmune reaction was at work. "Upon GA treatment discontinuation, lipoatrophy remained permanent," he noted.

Lipoatrophy "appears to progress, even when you stop the injections. It’s a pretty impressive disfiguration. It’s important to emphasize [with patients] that this isn’t necessarily going to be remedied with plastic surgery. [However,] if patients were stable, most of them thought that this was a small price to pay to be in remission," Dr. Bailey said at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

GA labeling reports the risk of lipoatrophy to be 2% with the 20-mg/mL daily formulation, which has been on the market for almost 2 decades, and 0.5% with the 40-mg/mL three times weekly option, which was approved by the Food and Drug Administration in 2014. Lipoatrophy "is thought to be permanent. There is no known therapy. To assist in possibly minimizing these events, the patient should be advised to follow proper injection technique and to rotate injection sites with each injection," according to the GA label, which is in contrast with the Riverside finding that site rotation wasn’t much help.

Most of the patients at the clinic were women, in keeping with MS epidemiology, and 40 (55%) opted for the autoinjector, specifically the Autoject 2; the device’s labeling notes that the autoinjector can "help with hard-to-reach areas on your body." Perhaps, by helping patients reach those difficult areas, the autoinjector makes it easier to miss the proper subcutaneous fat layer. That might have something to do with the problem, Dr. Bailey said, but the team simply reported their observations and didn’t report any statistical analysis of the findings, so it’s impossible to discern causes, he noted.

The findings aren’t new for some. The "prevalence of lipoatrophy [is] much higher than expected," one team noted several years ago (Can. J. Neurol. Sci. 2004;31:58-63).

No one knows why GA seems to cause lipoatrophy. Maybe "an elevation in tumor necrosis factor–alpha ... causes a dedifferentiation of adipocytes in [subcutaneous] tissue," Dr. Bailey said.

He is a paid spokesman for Genzyme, Biogen, and Teva, the maker of GA. There was no outside funding for the project.

[email protected]

DALLAS – The risk of lipoatrophy with glatiramer acetate is greater than 60%, according to a review of 73 multiple sclerosis patients at one clinic.

The risk is "substantially higher than previously reported and [is] often the sole factor prompting patients to switch to another MS [disease-modifying therapy]. Our data also suggest that a heightened risk of lipoatrophy is an inherent autoimmune problem and is not necessarily mitigated by vigilant injection-site rotation. The psychological consequences may be significant," said investigator Dr. Ronald Bailey, director of the MS clinic at the Riverside (Calif.) Medical Clinic.

A total of 46 glatiramer acetate (GA, Copaxone) patients (63%) developed lipoatrophy, an injection-site indentation that can be deep and disfiguring; 35 (76%) of them used an autoinjector. Once noted, the dents didn’t improve during a 3-year observation period, which included photographic documentation and instructions on how to inject the drug every 3 months.

In some patients, lipoatrophy developed within the first 3 months of starting the shots and was noted at multiple injection sites, which prompted the team to suspect that an autoimmune reaction was at work. "Upon GA treatment discontinuation, lipoatrophy remained permanent," he noted.

Lipoatrophy "appears to progress, even when you stop the injections. It’s a pretty impressive disfiguration. It’s important to emphasize [with patients] that this isn’t necessarily going to be remedied with plastic surgery. [However,] if patients were stable, most of them thought that this was a small price to pay to be in remission," Dr. Bailey said at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

GA labeling reports the risk of lipoatrophy to be 2% with the 20-mg/mL daily formulation, which has been on the market for almost 2 decades, and 0.5% with the 40-mg/mL three times weekly option, which was approved by the Food and Drug Administration in 2014. Lipoatrophy "is thought to be permanent. There is no known therapy. To assist in possibly minimizing these events, the patient should be advised to follow proper injection technique and to rotate injection sites with each injection," according to the GA label, which is in contrast with the Riverside finding that site rotation wasn’t much help.

Most of the patients at the clinic were women, in keeping with MS epidemiology, and 40 (55%) opted for the autoinjector, specifically the Autoject 2; the device’s labeling notes that the autoinjector can "help with hard-to-reach areas on your body." Perhaps, by helping patients reach those difficult areas, the autoinjector makes it easier to miss the proper subcutaneous fat layer. That might have something to do with the problem, Dr. Bailey said, but the team simply reported their observations and didn’t report any statistical analysis of the findings, so it’s impossible to discern causes, he noted.

The findings aren’t new for some. The "prevalence of lipoatrophy [is] much higher than expected," one team noted several years ago (Can. J. Neurol. Sci. 2004;31:58-63).

No one knows why GA seems to cause lipoatrophy. Maybe "an elevation in tumor necrosis factor–alpha ... causes a dedifferentiation of adipocytes in [subcutaneous] tissue," Dr. Bailey said.

He is a paid spokesman for Genzyme, Biogen, and Teva, the maker of GA. There was no outside funding for the project.

[email protected]

DALLAS – The risk of lipoatrophy with glatiramer acetate is greater than 60%, according to a review of 73 multiple sclerosis patients at one clinic.

The risk is "substantially higher than previously reported and [is] often the sole factor prompting patients to switch to another MS [disease-modifying therapy]. Our data also suggest that a heightened risk of lipoatrophy is an inherent autoimmune problem and is not necessarily mitigated by vigilant injection-site rotation. The psychological consequences may be significant," said investigator Dr. Ronald Bailey, director of the MS clinic at the Riverside (Calif.) Medical Clinic.

A total of 46 glatiramer acetate (GA, Copaxone) patients (63%) developed lipoatrophy, an injection-site indentation that can be deep and disfiguring; 35 (76%) of them used an autoinjector. Once noted, the dents didn’t improve during a 3-year observation period, which included photographic documentation and instructions on how to inject the drug every 3 months.

In some patients, lipoatrophy developed within the first 3 months of starting the shots and was noted at multiple injection sites, which prompted the team to suspect that an autoimmune reaction was at work. "Upon GA treatment discontinuation, lipoatrophy remained permanent," he noted.

Lipoatrophy "appears to progress, even when you stop the injections. It’s a pretty impressive disfiguration. It’s important to emphasize [with patients] that this isn’t necessarily going to be remedied with plastic surgery. [However,] if patients were stable, most of them thought that this was a small price to pay to be in remission," Dr. Bailey said at a meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

GA labeling reports the risk of lipoatrophy to be 2% with the 20-mg/mL daily formulation, which has been on the market for almost 2 decades, and 0.5% with the 40-mg/mL three times weekly option, which was approved by the Food and Drug Administration in 2014. Lipoatrophy "is thought to be permanent. There is no known therapy. To assist in possibly minimizing these events, the patient should be advised to follow proper injection technique and to rotate injection sites with each injection," according to the GA label, which is in contrast with the Riverside finding that site rotation wasn’t much help.

Most of the patients at the clinic were women, in keeping with MS epidemiology, and 40 (55%) opted for the autoinjector, specifically the Autoject 2; the device’s labeling notes that the autoinjector can "help with hard-to-reach areas on your body." Perhaps, by helping patients reach those difficult areas, the autoinjector makes it easier to miss the proper subcutaneous fat layer. That might have something to do with the problem, Dr. Bailey said, but the team simply reported their observations and didn’t report any statistical analysis of the findings, so it’s impossible to discern causes, he noted.

The findings aren’t new for some. The "prevalence of lipoatrophy [is] much higher than expected," one team noted several years ago (Can. J. Neurol. Sci. 2004;31:58-63).

No one knows why GA seems to cause lipoatrophy. Maybe "an elevation in tumor necrosis factor–alpha ... causes a dedifferentiation of adipocytes in [subcutaneous] tissue," Dr. Bailey said.

He is a paid spokesman for Genzyme, Biogen, and Teva, the maker of GA. There was no outside funding for the project.

[email protected]