AMSTERDAM – Oral tofacitinib for psoriasis proved as effective as – and in certain domains better than – subcutaneous etanercept in improving patient-reported quality of life endpoints in a phase III clinical trial.
The double-blind study included 1,101 patients with moderate to severe chronic plaque psoriasis who were randomized to 12 weeks of the oral Janus kinase inhibitor tofacitinib at 5 mg twice daily, 10 mg twice daily, subcutaneous etanercept (Enbrel) at 50 mg twice weekly, or placebo. The findings were presented by Dr. Fernando Valenzuela at the annual congress of the European Academy of Dermatology and Venereology.
Courtesy of the Centers for Disease Control and Prevention (CDC)
Improvement in itch in patients randomized to tofacitinib at 10 mg twice daily was greater than with etanercept, and occurred faster.
Earlier in 2014, at the annual meeting of the American Academy of Dermatology in Denver, Dr. Valenzuela presented the phase III study’s primary results, in which the oral small molecule proved noninferior to the tumor necrosis factor inhibitor in improving PASI scores. At the EADV Congress in Amsterdam, he focused on the secondary outcomes, which arguably matter more to patients than do changes in PASI scores, namely, measures of quality of life and itchiness.
From a baseline Itch Severity Item score of 5, indicative of moderate to severe itching, week 12 scores fell by a mean of 3.2, 4.0, 3.5, and 0.4 points, respectively, in patients on low- or high-dose tofacitinib, etanercept, and placebo. The improvement in itch in patients randomized to tofacitinib at 10 mg twice daily was not only greater than with etanercept, it occurred faster as well, with significant reduction in itch scores documented on day 2 of therapy, reported Dr. Valenzuela, a dermatologist at the University of Chile in Santiago.
The median baseline Dermatology Life Quality Index (DLQI) score was 12. Significant improvement was seen from week 4 in all three active treatment study arms. By week 12, DLQI scores had dropped by an average of 7.3 points in patients on tofacitinib at 5 mg twice daily, 9.7 points in those on 10 mg twice daily, 9.0 points in etanercept-treated patients, and 1.9 points with placebo. Seventy-eight percent of patients on tofacitinib at 10 mg twice daily experienced a 5-point or larger drop in the DLQI by week 12, as did 75% of those on etanercept, 66% of those on low-dose tofacitinib, and 32% of those on placebo.
At baseline, 30% of patients rated their psoriasis as moderate and 70% rated their psoriasis as severe based on Patient Global Assessment. By week 12, more than 50% of patients on tofacitinib at 10 mg twice daily or etanercept rated their skin as clear or almost clear.
More than 70% of patients in all three active treatment arms indicated at week 12 that they were satisfied with their medication. Satisfaction scores were highest, and equally so, in those on high-dose tofacitinib and etanercept.
“Patients using tofacitinib at the low dose had not that good an improvement. It was better improvement than with placebo, but it doesn’t look like etanercept,” Dr. Valenzuela concluded.
Tofacitinib is approved as Xeljanz for the treatment of rheumatoid arthritis, but remains investigational for psoriasis. According to a company statement, Pfizer intends to submit a supplemental New Drug Application (sNDA) to the Food and Drug Administration by early 2015.
The study was funded by Pfizer. Dr. Valenzuela is an adviser to Pfizer, AbbVie, Eli Lilly, Janssen, Merck, and Novartis.