麻豆果冻传媒影音

Secukinumab (Cosentyx) showed promise as a steroid-sparing agent in giant cell arteritis, a researcher reported here.

In a phase II trial that enrolled 52 patients, 70.1% (95% CI 51.6-84.9) of those who were randomized to secukinumab were in sustained remission at week 28 compared with 20.3% (95% CI 12.4-30) of those given placebo, according to Jens Thiel, MD, of the University of Freiburg in Germany.

On that primary endpoint, which was met, the median odds ratio for being in sustained remission at week 28 was 9.3 (95% CI 3.5-26.3), he reported in a presentation at the American College of Rheumatology virtual meeting.

Moreover, the proportion of patients who remained in sustained remission at week 52 was 59.3% (95% CI 38.8-77.6) in the secukinumab group compared with only 8% (95% CI 1-26) of those in the placebo group.

Giant cell arteritis is a chronic inflammatory disease affecting medium and large-sized arteries, especially branches of the proximal aorta.

Secukinumab inhibits interleukin (IL)-17A, and has shown significant benefits in conditions mediated by this cytokine such as plaque psoriasis, psoriatic arthritis, and axial spondyloarthritis.

"There also are experimental and preclinical data that point towards a role for IL-17A in the pathogenesis of giant cell arteritis, and therefore IL-17A inhibition by blocking vascular inflammation is potentially a new therapeutic target," he said.

This study, known as TitAIN, is the first multicenter randomized trial to investigate the potential efficacy and safety of secukinumab in giant cell arteritis.

Participants were ages 50 and older with either new onset or relapsing giant cell arteritis, which is characterized by headache and potentially, loss of vision. Traditional treatment has involved high-dose glucocorticoids.

The patients, who were biologic-naive, were given subcutaneous secukinumab, 300 mg, or placebo weekly for five doses and every 4 weeks thereafter through week 48. They also received prednisolone, at initial doses of 25 to 60 mg/day tapered to zero mg/day over 26 weeks.

Participants' mean age was 73, and two-thirds were women. The disease was new onset in 80%.

Median time to flare among patients in the placebo group was 197 days (95% CI 101-280); the median time to flare in the secukinumab group was not reached because there were very few flare events through week 52 in that group, he said.

Cumulative prednisolone doses were similar in the two groups at week 28, being 2,689 mg in the secukinumab group and 2,693 mg in the placebo group. But by week 52, the cumulative dose was higher in the placebo group (3,375 mg vs 2,841 mg).

The most common adverse events through week 52 were hypertension, occurring in six patients in the secukinumab group and in eight patients in the placebo group, and nasopharyngitis in five patients in each group.

Serious adverse events were reported in 22.2% of patients in the secukinumab group and in 44% of those in the placebo group. Two patients in each group experienced adverse events leading to drug discontinuation, and one in each group died. The deaths were not considered treatment related.

There were no cases of malignancy or inflammatory bowel disease among patients receiving secukinumab.

No new safety signals were reported, and the overall safety profile was similar to what has been seen with secukinumab in other studies.

"The TitAIN proof-of-concept phase II study supports further development of secukinumab as a treatment option for giant cell arteritis. And I'm very happy to let you know that a phase III study has just started enrolling patients," Thiel said.

Comment