番茄社区

SAN DIEGO -- Radiographic progression of structural joint damage was inhibited in patients with psoriatic arthritis (PsA) who were treated with secukinumab (Cosentyx), especially in those treated with a loading dose, compared with placebo, researchers reported here.

In the FUTURE 5 study, a significantly higher proportion of patients randomized to the interleukin (IL)-17a inhibitor showed no worsening of structural joint damage at 24 weeks than those randomized to placebo, said Philip Mease, MD, of the University of Washington in Seattle, and colleagues in a presentation at the American College of Rheumatology (ACR) annual meeting.

Secukinumab is the second agent in its class to demonstrate inhibition of radiographic progression of PsA. In the study, ixekizumab (Taltz) was superior to both placebo and adalimumab (Humira) on measures of structural damage progression in patients with PsA, who were not previously treated with biologic agents.

FUTURE 5 included both patients who were naïve to tumor necrosis factor (TNF) inhibitors and those with inadequate response to a TNF inhibitor. The efficacy of secukinumab across all endpoints in FUTURE 5 was greater in the anti-TNF-naïve group than in who had previously received TNF inhibitors.

"We have two drugs in the IL-17 inhibitor class that have shown [response]," Mease told 番茄社区. "So it's kind of confidence building. Over the long haul, we can expect to have some inhibition of radiographic progression."

In FUTURE 5, 996 adults with active PsA were randomized to one of the following groups:

• Secukinumab: 300 mg with a 300-mg loading dose
• Secukinumab: 150 mg with or without a 150-mg loading dose
• Placebo

All groups received secukinumab or placebo at baseline and then at 1, 2, 3 and 4 weeks, and then every 4 weeks thereafter.

About 30% of the study cohort received prior TNF inhibitor therapy, while 50% were taking concomitant methotrexate at randomization, and 17% were receiving a systemic glucocorticoid.

A total of 66 of the 996 (6.9%) discontinued the study by week 24, with the greatest number (n=37) from the placebo group.

A ≥20% improvement from baseline in the ACR response criteria at week 16, the primary endpoint, was achieved by 62.6% of the arm receiving 300 mg of secukinumab with a loading dose, which was significantly greater than the 27.4% in the placebo arm (P<0.0001). Some 55.5% of patients receiving 150 mg of secukinumab with a loading dose and 59.5% of those receiving 150 mg of secukinumab without a loading dose achieved an ACR20 response (P<0.0001 for both secukinumab 150-mg groups).

Radiographic structural progression, as determined by the change from baseline in the mean van der Heijde-modified Total Sharp score (vdH-mTSS), was inhibited significantly at week 24 in all secukinumab groups compared with placebo.

The authors also reported that 88% of the arm assigned to 300 mg of secukinumab had no radiographic progression, compared with 80% of the patients assigned to 150 mg of secukinumab with a loading dose, 84% assigned to 150 mg of secukinumab without a loading dose, and 74% of patients assigned to placebo.

Mean changes in the vdH-mTSS at week 24 in the overall population were 0.5 in the placebo arm and 0.08 in those randomized to 300 mg of secukinumab (P<0.01); 0.17 in those randomized to 150 mg of secukinumab with no loading dose (P<0.05 vs placebo); and -0.09 in those randomized to 150 mg of secukinumab with a loading dose (P<0.01 vs placebo).

In the patients naïve to a TNF inhibitor, the changes in the vdH-mTSS were 0.48 in the placebo arm, 0.01 in the secukinumab 300-mg arm (P<0.001), 0.12 in the secukinumab 150 mg with a loading dose arm (P<0.05 vs placebo) and -0.25 in the arm that received secukinumab 150 mg without a loading dose (P<0.05 vs placebo).

"A lot of times it's the swollen joints that have brought patients in, but they have all these aches and pains that they've had for a while but haven't attributed to the disease. After taking the drug, their rib cage pain or subtle back pain or the knee cap pain they've had has improved," Mease said.

Resolution of enthesitis at week 24 was experienced by 61.4% of the secukinumab 300-mg group, which was significantly better than the 34.4% in the placebo group (P<0.0001). Secukinumab 150 mg with (P<0.05) and without a loading dose (P<0.001) were also significantly better than placebo on this endpoint. Also, complete resolution of dactylitis was significantly more common in all secukinumab dose groups compared with placebo (P<0.0001 for all secukinumab arms vs placebo).

"The data tell me that you need to use, ideally, 300 mg and you need the load; five injections at the beginning followed by monthly dosing," Mease stated. "In the United States, it's the same cost for the 150- or 300-mg dose."

The safety profile of secukinumab was consistent with that previously reported, with no new safety signals.

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