PMID- 18640466 OWN - NLM STAT- MEDLINE DCOM- 20081216 LR - 20151119 IS - 0149-2918 (Print) IS - 0149-2918 (Linking) VI - 30 IP - 6 DP - 2008 Jun TI - Tolerability and safety profile of 12- to 28-week treatment with interferon beta-1b 250 and 500 microg QOD in patients with relapsing-remitting multiple sclerosis: a multicenter, randomized, double-blind, parallel-group pilot study. PG - 1102-12 LID - 10.1016/j.clinthera.2008.06.013 [doi] AB - BACKGROUND: It is not known whether the currently available treatment regimen of interferon beta-1b (IFNbeta-1b) 250 microg provides the maximum benefit possible in the treatment of relapsing-remitting multiple sclerosis (RRMS), or whether higher doses of IFNbeta-1b will prove to be more beneficial. OBJECTIVE: The objective of the present study was to evaluate the tolerability and safety profile of IFNbeta-1b 500 microg compared with the currently approved 250-microg dose. METHODS: A multicenter, randomized, double-blind, parallel-group pilot study was carried out to compare IFNbeta-1b 250 microg with IFNbeta-1b 500 microg, both self-administered SC QOD for >or=12 weeks in patients with RRMS. Patients in both groups started with 25% (0.25 mL) of their final dose and were scheduled to increase the dose by 0.25 mL every 2 weeks, so that the full dose (1.0 mL, 250 microg or 500 microg) would be reached by week 7. The primary outcome measure was the percentage of patients experiencing each of the following adverse events (AEs): influenza-like symptoms (general term used to code the presence of >1 symptom typical of influenza), fever, myalgia, asthenia, headache, injection-site reactions, injection-site pain, or liver or hematologic abnormalities. All patients underwent a priori magnetic resonance imaging (MRI) with 0.1 mmol/kg gadolinium (Gd)-diethylenetriaminepentaacetic acid as contrast medium at screening and at week 12. MRI evaluation was included as a safety measure to monitor for excessive new disease not visible through clinical symptoms. RESULTS: Seventy-seven patients were assessed for inclusion in the study. Of these, 6 patients were screening failures and the remaining 71 were randomized to treatment (38-250 and 33-500 microg IFNbeta-1b). The uneven numbers in the groups were a consequence of the randomization process. Two patients in the 250-microg group (withdrawal of consent) and 1 in the 500-microg group (not completing follow-up visit) prematurely discontinued medication. The demographic characteristics were not significantly different between the 250-microg (n=38; mean [SD] age, 37.9 [8.3] years; weight, 83.5 [19.0] kg; height, 168.4 [9.3] cm) and 500-microg (n=33; mean [SD] age, 37.8 [7.7] years; weight, 82.3 [19.5] kg; height, 169.9 [10.5] cm) treatment groups. The patients in both groups were mostly white (87% and 73%, respectively). Baseline Expanded Disability Status Scale scores also were not significantly different between the 2 groups (mean [SD] score, 2.8 [1.4] vs 2.0 [1.4], respectively). In the IFN(2)-1b 250-microg group, 97% of the patients titrated to the full dose at some point during the course of the study, compared with 91% of the 500-microg group (P=NS). A dose-response effect was observed in some of the more frequent AEs (no. [%]) that included influenza-like syndrome (250-microg group, 13 [34] vs 500-microg group, 16 [48]), asthenia (13 [34] vs 16 [48], respectively), headache (12 [32] vs 12 [36]), myalgia (10 [26] vs 13 [39]), hypesthesia (10 [26] vs 11 [33]), nausea (6 [16] vs 8 [24]), paresthesia (6 [16] vs 8 [24]), myasthenia (4 [11] vs 8 [24]), chills (3 [8] vs 6 [18]), depression (3 [8] vs 5 [15]), back pain (2 [5] vs 5 [15]), increased liver enzymes (4 [11] vs 6 [18]), lymphopenia (4 [11] vs 3 [9]), fever (2 [5] vs 4 [12]), and pain in extremities (1 [3] vs 4 [12]). The between-group incidence of injection-site reactions was not significantly different. No new or unexpected AEs were recorded. Changes in MRI parameters between screening and 12 weeks were not significantly different between dose groups; these included median T2 lesion volume, median Gd-enhanced lesion volume, median Gd-enhanced lesion number, and mean number of newly active lesions. CONCLUSIONS: IFNbeta-1b 500 microg administered SC QOD was generally well tolerated in these patients with RRMS. Large, randomized controlled studies are needed to determine if there are significant differences in MRI end points between the 250- and 500-microg doses. FAU - Hurwitz, Barrie J AU - Hurwitz BJ AD - Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. hurwi003@mc.duke.edu FAU - Jeffery, Douglas AU - Jeffery D FAU - Arnason, Barry AU - Arnason B FAU - Bigley, Kim AU - Bigley K FAU - Coyle, Patricia AU - Coyle P FAU - Goodin, Douglas AU - Goodin D FAU - Kaba, Samer AU - Kaba S FAU - Kirzinger, Stephen AU - Kirzinger S FAU - Lynch, Sharon AU - Lynch S FAU - Mandler, Raul AU - Mandler R FAU - Mikol, Daniel AU - Mikol D FAU - Rammohan, Kottil AU - Rammohan K FAU - Sater, Richard AU - Sater R FAU - Sriram, Subramaniam AU - Sriram S FAU - Thrower, Ben AU - Thrower B FAU - Boateng, Francis AU - Boateng F FAU - Jakobs, Peter AU - Jakobs P FAU - Wash, Mary Beth AU - Wash MB FAU - Bogumil, Timon AU - Bogumil T LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Adjuvants, Immunologic) RN - 0 (Recombinant Proteins) RN - 145155-23-3 (Interferon beta-1b) RN - 77238-31-4 (Interferon-beta) SB - IM MH - Adjuvants, Immunologic/*administration & dosage MH - Adult MH - Disability Evaluation MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Follow-Up Studies MH - Humans MH - Interferon beta-1b MH - Interferon-beta/*administration & dosage MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged MH - Multiple Sclerosis, Relapsing-Remitting/diagnosis/*drug therapy/rehabilitation MH - Pilot Projects MH - Recombinant Proteins MH - Retrospective Studies MH - Time Factors MH - Treatment Outcome MH - Young Adult EDAT- 2008/07/22 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/07/22 09:00 PHST- 2008/03/19 00:00 [received] PHST- 2008/07/22 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/07/22 09:00 [entrez] AID - S0149-2918(08)00214-2 [pii] AID - 10.1016/j.clinthera.2008.06.013 [doi] PST - ppublish SO - Clin Ther. 2008 Jun;30(6):1102-12. doi: 10.1016/j.clinthera.2008.06.013.