Tofacitinib Improves Pruritus Severity

New Orleans—A 12-week, double-blind, placebo-controlled, phase 2b study found that patients with psoriasis who took tofacitinib had sustained clinically meaningful improvement in pruritus severity. Carla Mamolo, PhD, associate director of outcomes research at Pfizer Inc and the trial’s lead author, presented the results during a poster presentation at the AAD meeting. The poster was titled An Evaluation of the Effect of Tofacitinib (CP-690, 550), an Oral Janus Kinase Inhibitor, on Pruritus in Patients with Plaque Psoriasis. Pruritus is typically found in patients with psoriasis, a common chronic immune-mediated disease. Dr. Mamolo cited studies that have shown pruritus occurs in >80% of psoriasis patients, is unresponsive to many antipruritics, and has a significant impact on health-related quality of life. Tofacitinib, a novel oral selective Janus kinase inhibitor, is being investigated to use in renal transplant studies and to treat patients with autoimmune diseases such as psoriasis and rheumatoid arthritis. The authors evaluated 3 regimens of tofacitinib administered 2 times per day compared with placebo to determine the product’s safety and effectiveness in patients with moderate-to-severe chronic plaque psoriasis. The 197 patients in the study had psoriasis affecting ≥15% body surface area and a Psoriasis Area and Severity Index score ≥13. There were 50 patients in the placebo group, while 49 patients took 2 mg of tofacitinib twice daily, 49 patients took 5 mg of tofacitinib twice daily, and 49 patients took 15 mg of tofacitinib twice daily. To measure pruritus, the authors used the Itch Severity Item (ISI) outcome data. The ISI scale ranged from 0 (indicating no itching) to 10 (indicating worst possible itching) and evaluated recall from the previous 24 hours. The patients recorded their self-assessed ISI scores in a diary on a daily basis during the first 2 weeks and then at each clinic visit. The authors used a repeated-measures longitudinal model containing all data from the study’s first 16 weeks to estimate the relationship between ISI and the patient-reported Patient Global Assessment (PtGA) score. The PtGA scale ranged from 0 (clear/no psoriasis) to 4 (severe). They also calculated effect sizes (ES) of the treatment effects, and defined the ES as trivial (ES>0.20), small (ES≥0.20 and <0.50), moderate (ES≥0.50 and <0.80), and large (ES≥0.80). At baseline, the average ISI measurement for the placebo group was 6.78 compared with 7.04 for the 2-mg tofacitinib group, 6.98 for the 5-mg tofacitinib group, and 6.96 for the 15-mg tofacitinib group. The authors indicated all 3 tofacitinib groups had a significant decrease in ISI score as early as day 3 and a statistically significant improvement in mean ISI score by day 6, which continued to week 12. At week 12, the mean difference in ISI score was −4.70, −4.59, and −5.98 for the 2-mg, 5-mg, and 15-mg tofacitinib groups, respectively, while the placebo group had a mean difference of −0.84. Using PtGA as a continuous anchor, the authors estimated that the ISI clinically important difference was 1.64 (95% confidence interval [CI], 1.50-1.78) and found that by day 6 all tofacitinib groups had a mean ISI score change >1.64, indicating the differences were clinically relevant. They also said there was a significant treatment effect in each tofacitinib group. In addition, the authors defined a clinically important responder as a 29.8% change (95% CI, 23.3%-36.4%) in ISI score. At week 2, there were between 68.8% and 77.8% clinically important responders in the tofacitinib groups compared with 34.0% in the placebo group (P<.0001). At week 12, there were between 87.2% and 100% clinically important responders in the tofacitinib groups compared with 29.4% in the placebo group (P<.0001).