Rituxan results from ECTRIMS
Posted: Sat Oct 13, 2007 8:14 am
Looks like rituxan is pretty good at reducing lesions, but then so is high-dose interferon, but it's effect on relapses isn't quite as impressive. I guess I'm more hopeful about rituxan as a treatment for PPMS anyway, so relapses won't matter in that trial.
Safety and efficacy of rituximab in adults with relapsing-remitting multiple sclerosis: results of a phase II placebo-controlled, multicentre trial through 48 weeks
E. Waubant, S. Hauser, D.L. Arnold, T. Vollmer, J.P. Antel, R. Fox, A. Bar-Or, M. Panzara, N. Sarkar, S. Agarwal, A. Langer-Gould, C. Smith (San Francisco, USA; Montreal, CAN; Phoenix, USA; Cleveland, USA; Cambridge, South San Francisco, USA)
Objective: To investigate the safety and efficacy of rituximab (RTX) in treating relapsing remitting MS (RRMS).
Background: Evidence exists for a pathogenic role of antibodies and B cells in MS, identifying B cells as a potential therapeutic target. RTX, an antibody selectively depleting CD20+ B cells, offers a unique opportunity to evaluate this hypothesis.
Design/Methods: In a double-blind, controlled trial, 104 patients (Pts) with RRMS were randomized to 1000 mg intravenous RTX (n=69) or Plc (n=35) on days 1 and 15 and followed for 48 weeks (Wks). The primary endpoint was the total number of gadolinium (Gd)-enhancing lesions at Wks 12, 16, 20, and 24. Secondary MRI and clinical endpoints were total number of new Gd lesions, change in T2 lesion volume, and proportion of Pts relapsing at various timepoints through 48 Wks.
Results: The primary endpoint was met with RTX, with a significant (p<0.0001) mean reduction in total Gd-enhancing lesion counts at Wks 12, 16, 20, and 24 vs. Plc (mean 0.5 RTX vs. 5.5 Plc, 91% relative reduction). Over the same period, RTX significantly (p<0.0001) reduced the number of new Gd-enhancing lesions vs. Plc (mean 0.16 RTX vs. 4.5 Plc). Mean reduction in T2 lesion volume from baseline to Wks 24 and 36 was significantly greater in RTX vs. Plc (p=0.0077 and p=0.0041, respectively). The proportion of Pts with relapses was significantly reduced in RTX vs. Plc at Wk 24 (34.3% vs. 14.5%, p=0.0238) and Wk 48 (40% vs. 20.3%, p=0.037), a relative reduction of 58% and 49%, respectively. Adjusted annualized relapse rate during 48 Wks was the same as at 24 Wks with RTX (0.37) although no longer statistically significant compared with Plc (0.72, p=0.086). Excepting infusion-associated adverse events (AEs), infection-associated AEs and serious AEs were comparable between groups through 48 Wks. While a greater proportion of RTX (78.3%) vs. Plc (40.0%) Pts experienced infusion-associated AEs within 24 hours of the first infusion, with the second infusion, AEs were comparable with RTX (20.9%) vs. Plc (40.0%).
Conclusions/Relevance: In Pts with RRMS, a single course of RTX was generally safe and well tolerated through 48 Wks and led to significantly fewer Gd-enhancing lesions, T2 lesion volume, and relapses through 24 Wks. The effects on Gd lesions and relapses appeared durable through 48 Wks. These results provide evidence of B cell involvement in the pathophysiology of MS. We continue to monitor long-term safety of RTX in this population.
ECTRIMS link
Safety and efficacy of rituximab in adults with relapsing-remitting multiple sclerosis: results of a phase II placebo-controlled, multicentre trial through 48 weeks
E. Waubant, S. Hauser, D.L. Arnold, T. Vollmer, J.P. Antel, R. Fox, A. Bar-Or, M. Panzara, N. Sarkar, S. Agarwal, A. Langer-Gould, C. Smith (San Francisco, USA; Montreal, CAN; Phoenix, USA; Cleveland, USA; Cambridge, South San Francisco, USA)
Objective: To investigate the safety and efficacy of rituximab (RTX) in treating relapsing remitting MS (RRMS).
Background: Evidence exists for a pathogenic role of antibodies and B cells in MS, identifying B cells as a potential therapeutic target. RTX, an antibody selectively depleting CD20+ B cells, offers a unique opportunity to evaluate this hypothesis.
Design/Methods: In a double-blind, controlled trial, 104 patients (Pts) with RRMS were randomized to 1000 mg intravenous RTX (n=69) or Plc (n=35) on days 1 and 15 and followed for 48 weeks (Wks). The primary endpoint was the total number of gadolinium (Gd)-enhancing lesions at Wks 12, 16, 20, and 24. Secondary MRI and clinical endpoints were total number of new Gd lesions, change in T2 lesion volume, and proportion of Pts relapsing at various timepoints through 48 Wks.
Results: The primary endpoint was met with RTX, with a significant (p<0.0001) mean reduction in total Gd-enhancing lesion counts at Wks 12, 16, 20, and 24 vs. Plc (mean 0.5 RTX vs. 5.5 Plc, 91% relative reduction). Over the same period, RTX significantly (p<0.0001) reduced the number of new Gd-enhancing lesions vs. Plc (mean 0.16 RTX vs. 4.5 Plc). Mean reduction in T2 lesion volume from baseline to Wks 24 and 36 was significantly greater in RTX vs. Plc (p=0.0077 and p=0.0041, respectively). The proportion of Pts with relapses was significantly reduced in RTX vs. Plc at Wk 24 (34.3% vs. 14.5%, p=0.0238) and Wk 48 (40% vs. 20.3%, p=0.037), a relative reduction of 58% and 49%, respectively. Adjusted annualized relapse rate during 48 Wks was the same as at 24 Wks with RTX (0.37) although no longer statistically significant compared with Plc (0.72, p=0.086). Excepting infusion-associated adverse events (AEs), infection-associated AEs and serious AEs were comparable between groups through 48 Wks. While a greater proportion of RTX (78.3%) vs. Plc (40.0%) Pts experienced infusion-associated AEs within 24 hours of the first infusion, with the second infusion, AEs were comparable with RTX (20.9%) vs. Plc (40.0%).
Conclusions/Relevance: In Pts with RRMS, a single course of RTX was generally safe and well tolerated through 48 Wks and led to significantly fewer Gd-enhancing lesions, T2 lesion volume, and relapses through 24 Wks. The effects on Gd lesions and relapses appeared durable through 48 Wks. These results provide evidence of B cell involvement in the pathophysiology of MS. We continue to monitor long-term safety of RTX in this population.
ECTRIMS link