OBJECTIVES: To evaluate the impact of product enhancements such as a new autoinjector (Rebiject II) and finer needles upon adherence to therapy for patients receiving subcutaneous (sc) Interferon-beta-1a (IFNB-1a) 44 mcg tiw. Injection site reactions (ISRs) are a common cause of treatment discontinuation in patients with multiple sclerosis (MS). Support organizations such as the MS LifeLines program may help patients manage ISRs, however, simplification of the injection process via autoinjectors and finer gauge needles may also help to decrease ISRs. METHODS: Data were gathered by the MS LifeLines program between August 2003 and November 2004 (before product enhancements) and again between December 2004 and March 2006 (after product enhancements). Patients were contacted by nurse educators at regular intervals and asked a series of questions to determine whether they were adherent to therapy or had discontinued, and, if they had discontinued, why they had done so. Reasons for discontinuation were recorded and divided into 3 categories: ISRs, pain and/or burning at the injection site, or other reasons. RESULTS: Between August 2003 and November 2004, 11,783 total patients received subcutaneous (sc) IFNB-1a 44 mcg tiw. Of the 2079 patients who discontinued therapy 190 (9.1%) were due to ISRs and 175 (8.4%) were due to pain and/or burning at the injection site. Between December 2004 and March 2006, when Rebiject II and finer gauge needles were incorporated, 12,968 total patients received sc IFNB-1a 44 mcg tiw. Of the 1780 (13.7%) who discontinued therapy 99 (5.6%) were due to ISRs and 33 (1.9%) were due to pain and/or burning at the injection site. CONCLUSION: These results demonstrate that product enhancements have dramatically decreased discontinuation of therapy due to overall ISRs and injection pain or burning in patients administering (sc) IFNB-1a 44 mcg tiw. The decreased discontinuation to therapy may potentially improve long-term outcomes.