Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, on Clinical Signs of Moderate-to-Severe Plaque Psoriasis in Different Body Regions
March 2014 | Volume 13 | Issue 3 | Original Article | 252 | Copyright © March 2014
Alan Menter MD,a Kim A. Papp MD PhD FRCPC,b Huaming Tan PhD,c Steve Tyring MD PhD,dRobert Wolk MD PhD DSc,c and Marjorie Buonanno MSN RNc
aBaylor Research Institute, Dallas, TX bProbity Medical Research and K. Papp Clinical Research Inc, Waterloo, Ontario, Canada cPfizer Inc, Groton, CT dDepartment of Dermatology, The University of Texas Medical School at Houston, Houston TX
INTRODUCTION: Tofacitinib is a novel, oral Janus kinase inhibitor currently under investigation for plaque psoriasis.
METHODS: This exploratory analysis of a Phase IIb, 12-week, dose-ranging study (clinicaltrials.gov identifier: NCT00678210) evaluated tofacitinib efficacy in four body regions of patients with moderate-to-severe chronic plaque psoriasis. Patients (n=197) were randomized to tofacitinib 2, 5, or 15 mg, or placebo, twice daily (BID). Psoriasis Area and Severity Index (PASI) score, body surface area values and change from baseline to week 12 were measured according to body region (head/neck, upper limbs, trunk and lower limbs). Change in Target Plaque Severity Score (TPSS) from baseline to week 12 was measured according to typically responsive as well as non-responsive treatment areas.
RESULTS: At week 12, mean improvements in PASI and body surface area values were significantly greater with tofacitinib doses vs placebo across all four body regions measured (P
<0.0001). TPSS in responsive areas decreased (improved) with tofacitinib 2, 5, and 15 mg BID vs placebo: -4.35, -4.79 and -6.32, vs -2.06, respectively (P
<0.0001). In non-responsive areas, TPSS decreased with tofacitinib 2, 5, and 15 mg BID vs placebo: -3.74, -4.60 and -6.15, vs -2.23, respectively (P
CONCLUSION: Short-term (12-week) treatment with oral tofacitinib produced clinical improvement across all body regions assessed in patients with moderate-to-severe plaque psoriasis, including areas typically non-responsive to treatment. J Drugs Dermatol.
Psoriasis is a common, lifelong, immune-mediated genetic disease, resulting in a substantial physical and emotional burden. In psoriasis, an activated cytokine network stimulates a cycle of ongoing inflammation and cellular proliferation, ultimately leading to classic lesion development.1 The Janus kinase signaling pathway plays an important role in psoriasis pathogenesis.2
Several novel systemic and biologic agents have been evaluated and approved for the treatment of moderate-to-severe psoriasis, which affects up to 25% of the psoriasis population.3,4 However, difficulties with administration routes, immunogenicity, side effects and potential loss of efficacy over time may limit the use of these agents.5,6
Psoriasis responds differently to treatment in various areas of the body.7 In particular, head and neck psoriasis, primarily the scalp, is frequently resistant to traditional topical and systemic therapies.8,9 Thus, being able to predict a positive response in this difficult to treat region would be beneficial to patients and physicians alike.
Tofacitinib is a novel oral Janus kinase inhibitor under investigation for psoriasis. A Phase IIb, 12-week, randomized, placebo-controlled, dose-ranging study (A3921047; clinicaltrials.gov identifier: NCT00678210) evaluated efficacy and safety of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis.10 The primary endpoint was the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI) 75 score from baseline after 12 weeks’ treatment. A significantly higher proportion of patients treated with tofacitinib achieved PASI75 vs placebo during the 12 weeks’ treatment.10 A dose response was observed for PASI75, with the magnitude of response increasing over time.10 Here we report an exploratory analysis of this Phase IIb study where we evaluated tofacitinib efficacy across all four different body regions utilized in the PASI assessment.