Tofacitinib reached musculoskeletal safety endpoints in PsA

MADRID — Two different dosing levels of tofacitinib bested placebo in response rate and safety parameters for patients with psoriatic arthritis, according to findings presented at the EULAR Annual Congress.

“This is the first report of a clinical trial restricted to patients with [psoriatic arthritis] PsA and an inadequate response to a [tumor necrosis factor] TNF inhibitor,” Dafna D. Gladman, MD, of the Department of Medicine at the University of Toronto and Toronto Western Hospital in Canada, said. “The primary endpoint was achieved. Efficacy was maintained through 6 months. Tofacitinib may represent one of the potential novel treatments for PsA patients who have failed TNF inhibitors.”

The study included 131 patients treated with tofacitinib (Xeljanz, Pfizer) at 5 mg twice daily, 132 patients treated with tofacitinib at 10 mg twice daily, 66 patients treated with placebo who ultimately shifted to the 5-mg tofacitinib dose and 65 patients treated with placebo who shifted to the 10-mg dose.

ACR20 served as the primary outcome measure. The investigators also looked at psoriasis area and severity index (PASI75) score, health assessment questionnaire disability index (HAQ-DI) and safety parameters.

Results indicated a 50% ACR20 response rate in the 5-mg group, 47% for the 10-mg group and 24% for the combined placebo populations. Change in HAQ-DI was -0.39 among patients treated with 5 mg tofacitinib, -0.35 for 10 mg and -0.14 for placebo.

Regarding the time course, Gladman noted that response occurred as early as 2 weeks. “It reached a plateau at 1 month and remained that way through 3 months,” she said. “Up to 6 months, the response was maintained. For the placebo patients, once they got the drug, they responded in a similar manner.”

She added that a similar pattern was observed for HAQ-DI response.

For ACR50, the response was seen at around 3 months and was maintained through 6 months. For the PASI75 score, Gladman reported that only the 10-mg dose demonstrated a response, with 43% of patients responding at 3 months.

“The dactylitis severity score improved in both doses of tofacitinib,” she added.

The overall adverse event rate was about 60%, with serious events occurring in 6.1% of patients treated with 10 mg of the study drug and 3.8% of those treated with 5 mg. Serious infections occurred in four patients treated with tofacitinib, while herpes zoster occurred in three. There were two cardiovascular events in the tofacitinib group.

“At month 3, there were some changes in hemoglobin levels and lymphocyte counts,” Gladman said. — by Rob Volansky

Reference:

Gladman DD, et al. Abstract #OP0202. Presented at: EULAR Annual Congress; June 14-17, 2017; Madrid.

Disclosure: Gladman reports receiving grant or research support from Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer Inc, Novartis and UCB; consulting for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer and UCB; and being on the speakers bureau for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer and UCB. She also reported that the study was funded by Pfizer.