1. Onderzoek met geneesmiddelen

2. Fases onderzoek Fase I: veiligheid Fase II: Doeltreffendheid
Fase III: I en II op grote schaal
Fase IV: Opvolging van het geneesmiddel

3. overview of Tofacitinib UC Clinical development program

4. Tofacitinib UC Phase 3 Program
OCTAVE Induction 1
Randomization
Assessment
10 mg BID
Nonresponders
Placebo
OCTAVE Sustain
OCTAVE Open
Responders†
8 weeks*
N=598 (4:1)
Re-randomization
Assessment
Enrollment
Assessment
10 mg BID
5 mg BID‡
Completers
& Treatment Failures
5 mg BID
10 mg BID‡
OCTAVE Induction 2
Placebo
Randomization
Assessment
52 weeks*
N=593 (1:1:1)
Responders†
10 mg BID
Up to 1st approval
Estimated N=944
Placebo
8 weeks*
N=541 (4:1)
Nonresponders
* Final complete efficacy assessment at Week 8/52. Treatment continued up to Week 9/53. † “Responders” refers to subjects who achieved clinical response during OCTAVE Induction 1 or 2. ‡ Subjects in remission at Week 52 of OCTAVE Sustain were assigned to tofacitinib 5 mg BID; subjects who completed 8 weeks of treatment in OCTAVE Induction 1 or 2 and were classified as nonresponders, and subjects who completed OCTAVE Sustain but did not meet remission criteria or who withdrew from the study early due to treatment failure, were assigned to tofacitinib 10 mg BID.
BID=twice daily; UC=ulcerative colitis.
1. Clinicaltrials.gov. NCT Clinicaltrials.gov. NCT Clinical trials.gov. NCT Clinicaltrials.gov. NCT
5. Pfizer data on file.

5. Key Inclusion and Exclusion Criteria
Inclusion Criteria
Exclusion Criteria
≥18 years old with diagnosis of UC ≥4 months prior to screening
Moderate to severe active UC defined by baseline total Mayo score ≥6, with rectal bleeding subscore ≥1, and endoscopic subscore ≥2
Based on central endoscopy reading
History of failure or intolerance to ≥1 of the following therapies:
Oral or intravenous corticosteroids
Azathioprine or 6-MP
TNF inhibitors
Patients permitted to use the following medications for UC:
Oral 5-ASA or sulfasalazine with stable dose ≥4 weeks prior to baseline
Oral corticosteroids (prednisone up to 25 mg/day; budesonide up to 9 mg/day) with stable dose ≥2 weeks prior to baseline
Chronic treatment with antibiotics with stable dose ≥2 weeks prior to baseline
Indeterminate, microscopic, ischemic, or infectious colitis; or clinical findings suggestive of Crohn’s disease
Disease limited to distal 15 cm
No previous treatment for UC (ie, treatment naive)
Signs of fulminant colitis or toxic megacolon
Inadequate washout for the following medications prior to baseline:
Azathioprine, 6-MP, MTX within 2 weeks
TNF inhibitors or interferon therapy within 8 weeks
Cyclosporine, mycophenolate mofetil/mycophenolic acid, or tacrolimus within 4 weeks
Intravenous corticosteroids within 2 weeks
Rectally administered corticosteroid or 5-ASA within 2 weeks
Anti-adhesion molecule therapy within 1 year
5-ASA=5-aminosalicylic acid; 6-MP=6-mercaptopurine; MTX=methotrexate; TNF=tumor necrosis factor; UC=ulcerative colitis.
A and A Final Protocols.

6. 178 ziekenhuizen in 23 landen: 2011-2015
Dubbel blind placebogecontroleerde RCT

8. Eindpunten Primaire eindpunt: Major secondaire eindpunt:
Klinische respons na week 6: afname 100 ptn CDAI score / CDAI <150
Major secondaire eindpunt:
Klinische remissie na week 8 (CDAI <150)
Klinische respons na week 8
Afname van baseline CDAI van ≥ 70 ptn op week 3 en 6

9. Studies in LUMC Stamcellen bij proctitis
Poeptransplantatie (later in 2018)
Dosis verlaging adalimumab
Monitoren bijwerkingen diverse medicamenten
…….