Tuesday, 11 June 2013

ENS 2013: DMF or BG12 works in early MS

BG12 or Demethyl fumarate works as well if not better in newly diagnosed MSers. #MSBlog #MSResearch

Gold et al. Effect of BG-12 (dimethyl fumarate) in newly diagnosed patients with relapsing-remitting multiple sclerosis from the DEFINE and CONFIRM studies. Multiple Sclerosis III: Other

Objectives: In Phase 3 clinical trials, BG-12 (dimethyl fumarate) demonstrated consistent clinical and radiological efficacy across a broad range of RRMSer. Here we evaluate the impact of BG-12 on the clinical efficacy in the newly diagnosed RRMS population from the DEFINE and CONFIRM trials. 

Methods: MSers included in these post-hoc analyses were diagnosed with RRMS within one year of entry onto DEFINE or CONFIRM and were naive to treatment with a disease-modifying therapy. Treatment efficacy was assessed by annualized relapse rate (ARR) and time to first relapse over 2 years. Annualized relapse rate was analyzed using a negative binomial model, and time to first relapse was analyzed using a Cox proportional hazards model. Both ARR and time to first relapse were adjusted for the number of relapse(s) one year prior to study entry, baseline age (<40, >=40 years), EDSS score (<=2.0, >2.0), and region. 

Results: A total of 678 MSers were treated with placebo (N=223), BG-12 twice daily (BID) (N=221), or BG-12 three times daily (TID) (N=234), with similar baseline demographic and clinical characteristics across treatment groups. A mean (standard deviation) of 4.3 (5.27), 4.3 (5.81), and 3.8 (4.13) years had elapsed since first MS symptoms, and 0.50 (0.50) years had elapsed since diagnosis in each of the placebo, BG-12 BID, and BG-12 TID groups. Over two years, ARR in the newly diagnosed population was 0.38 (95% CI 0.30-0.50) in the placebo group compared with 0.17 (0.12-0.23) in the BG-12 BID group and 0.15 (0.11-0.21) in the BG-12 TID group. BG-12 BID and BG-12 TID reduced ARR versus placebo at 2 years by 56% (hazard ratio 0.44 [95% CI 0.30.-0.65]; p<0.0001) and by 60% (0.40 [0.27-0.58]; p<0.0001), respectively. The proportion of subjects relapsed over two years was 42.2% in the placebo group compared with 21.3% in the BG-12 BID group and 20.5% in the BG-12 TID group using the Kaplan-Meier method. Compared with placebo, the risk of relapse at two years was reduced by 54% (0.46 [0.32-0.67]; p<0.0001) and 57% (0.43 [0.30- 0.62]; p<0.0001) in the BG-12 BID and BG-12 TID groups, respectively.

Conclusion: BG-12 demonstrated strong treatment effect on ARR and time to first relapse in the newly diagnosed MS population. Together with an acceptable safety profile, this analysis further supports the potential for BG-12 to become a valuable oral treatment option for newly diagnosed RRMS.

"These results are not surprising given the effectiveness of the phase 3 studies"

CoI: multiple

1 comment:

  1. "These results are not surprising given the effectiveness of the phase 3 studies"

    In the phase III studies, efficacy was superior for women and below 40yo patients. It was also much higher for patients suffering from flushing (table 41 in the FDA medical review). First relapses and early EDSS change are mainly based upon subjective criteria. So, it is really not surprising that results in early MS look better.
    It would be interesting to check if patients with flushing had better MRI response too just to check if unblinding can impact MRI response too


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