The extension study experience confirms that daily glatiramer acetate injections are well tolerated. Injection site reactions rarely led to early termina- tion of dosing, and the self-limited, transient sys- temic reactions were rare and did not lead to permanent or life-threatening sequelae. There were no laboratory abnormalities considered to be associ- ated with glatiramer acetate, a finding previously reported in trials of glatiramer a ~ e t a t eT. ~he adverse events profile for glatiramer acetate is distinctly bet- ter than the experience observed with the beta inter- ferons when used in similar patient ~opulations.'~J~
The role of neutralizing antibodies in limiting the effectiveness of long-term therapies used to modify MS is still unclear. There is preliminary evidence that the beta interferons lose effectiveness once neu- tralizing antibodies to them develop16; however, these finding are still being investigated.
Patients chronically injected with glatiramer ace- tate commonly develop binding antibodies that peak at 3 to 6 months and then decline. However, inde- pendent studies have failed to demonstrate that an- tibodies neutralize either experimental or clinical effects of the drug treatment.17-19The continued clin- ical benefit, observed in regard to both the MS re- lapse rate and on neurologic disability when this study was extended, suggests that the modifying ef- fect of glatiramer acetate on MS was not compro- mised by appearance of neutralizing antibodies. Because levels of antibody specific for glatiramer ac- etate have not been determined beyond the 24- month point, no direct information is available on this issue.
The comprehensive care of the patient with RR MS requires attention to four management areas: medications to reduce the frequency of relapses, treatment of serious relapses with corticosteroids, modification of symptoms with appropriate drugs, and attention to the patient's quality of life. Glati- ramer acetate, with its significant effect on MS re- lapses and disability and its excellent history of patient tolerance, should be considered as a first-line drug for the prevention of relapses and as replace- ment treatment for patients who fail therapy with the beta interferons or are unable to tolerate their side effects.
Appendix
"he Copolymer 1 Multiple Sclerosis Study Group, in addi- tion to the authors, comprises the following investigative teams: Hospital of the University of Pennsylvania, Fran- cisco Gonzalez-Scarano, MD; Shawn J. Bird, MD; Chris- tian Constantinescu, MD; Dennis L. Kolson, MD, PhD; Daniel Brennan, RN; Dorothea Hohl, RN. University of New Mexico School of Medicine, Raul N. Mandler, MD; Gary A. Rosenberg, MD; Carol Jeffrey, RN. Wayne State University School of Medicine, Geoffrey R. Barger, MD; Balbir Gandhi, MD; Patricia M. Moore, MD; Lisa R. Rog-