Emerging therapies in MS AAN 2012 Mark Freedman

Random Notes

 

1.  Tereflunomide- blocks de novo synthesis of pyrimidine synthesis

 

"Nobody has a clue how these things really work"

 

2. TEMSO  2 doses used 7 and 14 mg decreased RR, time to attack, and EDSS progression at 2 years and disease activity free measure increased by 60 percent  with higher dose, decreased Gd+ lesions

 

3. Minor safety issues minor GI , hair thinning (reversible) ; decreased pain (???)

 

4.  TENERE  -- primary point not efficacy but effectiveness which comparator Rebif.  looked at time to treatment failure due to relapse or AE's leading to stop drug.  RR similar except low dose, but effectiveness was better with tereflunomide.LFT's only thing seen reliably.

 

5.  Add on therapy to IFN or GA, patients doing well, added on TFN, did not need attack, just stable dose of drug or placebo, added TFN.  Patients doing well, followed with monthly MRI's, half patients had a Gd+ lesions (.57) decreased 80 % when TFN added.  patients doing well were not doing so well, even without relapses.  Keracles is a phase 3 study of combined.  IFN + TFN > GA + IFN

 

6.  BG 12 blocks NF pathway.  - no effect of BG 12 until got to dose of 240 bid.  bid v tid (240 mg) improved RR , EDSS 9by 30-40 %).  Curves for rr split at 6 months, why ph 2 study (6 month trial) failed, but effect persists and sustains. 

 

7.  Confirm:  beats GA for RR and MRI. 

 

8. DEFINE -- 30 % dropout, mostly flushing and nausea.  Used in Germany for years

 

9.  Laquinomid-- Allegro and Bravo.  23 % reduction RR overall, 36 % reduction risk to progression, modest effect on MRI, well tolerated.  Rare LFT elevations.Did not beat avonex for rr.  EDSS progression "barely significant " for laquinomid.

 

10. alemtuzumab. 

 

Care MS I (naive patients).less than 5 years into disease, EDSS < 3. 

.39 RR, much better with alemtuzumab, EDSS progression, only 11 % progressed in IFN arm, not powered to see .  MRI affected positively at 2 years.  AE's: minor infections, infusion reactions. AI disease; Graves, mild to moderate, usually managed effectively with tapazole.  ITP picked up in 4 patients.  May be a biomarkers to predict ITP.

 

Care MS 2- breakthrough patients with activity. EDSS < 5, years of disease < 10.  2+ attacks in 24 months before entry. 1+ attack during therapy with IFN.  Was 49 % reduction in RR, 42 % risk reduction of sustained disability.

 

1. Daclizumab-- anti CD 25 effect-

 

RR

 

Average duration of disease in initial trials was seven years, so there is a huge difference in timing of treatment