PMID- 22924949
OWN - NLM
STAT- MEDLINE
DCOM- 20130115
LR  - 20220330
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 167
IP  - 3
DP  - 2012 Sep
TI  - Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the 
      treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging 
      study.
PG  - 668-77
LID - 10.1111/j.1365-2133.2012.11168.x [doi]
AB  - BACKGROUND: Tofacitinib is a novel, oral Janus kinase inhibitor under 
      investigation as a potential treatment for plaque psoriasis. OBJECTIVES: This 
      Phase 2b, 12-week, dose-ranging study (A3921047, NCT00678210) aimed to 
      characterize the exposure-response, efficacy and safety of tofacitinib vs. 
      placebo in patients with moderate-to-severe chronic plaque psoriasis. METHODS: 
      One hundred and ninety-seven patients were randomized. The primary endpoint was 
      the proportion of patients achieving a >/= 75% reduction in the Psoriasis Area and 
      Severity Index (PASI 75) score at week 12. RESULTS: At week 12, PASI 75 response 
      rates were significantly higher for all tofacitinib twice-daily groups: 25.0% 
      (2 mg; P < 0.001), 40.8% (5 mg; P < 0.0001) and 66.7% (15 mg; P < 0.0001), 
      compared with placebo (2.0%). Significant increases in the proportion of PASI 75 
      responses were seen by week 4 and were maintained at week 12. Exposure-response 
      over the 0-15 mg tofacitinib twice-daily dose range was successfully 
      characterized. PASI 50, PASI 90 and Physician's Global Assessment response rates 
      were also higher for tofacitinib vs. placebo. The most frequently reported 
      adverse events (AEs) were infections and infestations: 22.4% (2 mg twice daily), 
      20.4% (5 mg twice daily), 36.7% (15 mg twice daily) and 32.0% (placebo). 
      Discontinuations due to AEs were 6.0%, 2.0%, 4.1% and 6.1% of patients in the 
      placebo, and 2, 5 and 15 mg twice-daily tofacitinib groups, respectively. 
      Dose-dependent increases from baseline in mean serum high-density lipoprotein, 
      low-density lipoprotein and total cholesterol, and decreases in haemoglobin and 
      neutrophils were observed. CONCLUSION: Short-term treatment with oral tofacitinib 
      results in significant clinical improvement in patients with moderate-to-severe 
      plaque psoriasis and is generally well tolerated.
CI  - (c) 2012 The Authors. BJD (c) 2012 British Association of Dermatologists.
FAU - Papp, K A
AU  - Papp KA
AD  - Probity Medical Research, 135 Union Street East, Waterloo, ON N2J 1C4, Canada. 
      kapapp@probitymedical.com
FAU - Menter, A
AU  - Menter A
FAU - Strober, B
AU  - Strober B
FAU - Langley, R G
AU  - Langley RG
FAU - Buonanno, M
AU  - Buonanno M
FAU - Wolk, R
AU  - Wolk R
FAU - Gupta, P
AU  - Gupta P
FAU - Krishnaswami, S
AU  - Krishnaswami S
FAU - Tan, H
AU  - Tan H
FAU - Harness, J A
AU  - Harness JA
LA  - eng
SI  - ClinicalTrials.gov/NCT00678210
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Dermatologic Agents)
RN  - 0 (Piperidines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 87LA6FU830 (tofacitinib)
RN  - EC 2.7.10.2 (Janus Kinase 3)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Chronic Disease
MH  - Dermatologic Agents/*administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Janus Kinase 3/*antagonists & inhibitors
MH  - Male
MH  - Piperidines
MH  - Psoriasis/*drug therapy
MH  - Pyrimidines/*administration & dosage/adverse effects
MH  - Pyrroles/*administration & dosage/adverse effects
MH  - Treatment Outcome
EDAT- 2012/08/29 06:00
MHDA- 2013/01/16 06:00
CRDT- 2012/08/29 06:00
PHST- 2012/08/29 06:00 [entrez]
PHST- 2012/08/29 06:00 [pubmed]
PHST- 2013/01/16 06:00 [medline]
AID - 10.1111/j.1365-2133.2012.11168.x [doi]
PST - ppublish
SO  - Br J Dermatol. 2012 Sep;167(3):668-77. doi: 10.1111/j.1365-2133.2012.11168.x.