番茄社区

Inhibition of interleukin (IL)-17 was an effective and safe option for the treatment of ankylosing spondylitis in a meta-analysis of six randomized clinical trials.

The primary endpoint of a 20% improvement on the criteria of the Assessment of Spondyloarthritis International Society (ASAS20) at week 16 was met by 57.6% of patients receiving secukinumab (Cosentyx) or ixekizumab (Taltz) compared with 35.3% of those given placebo, for a risk ratio of 1.63 (95% CI 1.45-1.84, P<0.001), according to Yufeng Yin, MD, of Soochow University in Jiangsu, China, and colleagues.

The active treatment was, however, associated with more non-severe infections (27.4% vs 15%, RR 1.82, 95% CI 1.40-2.37, P<0.001), mostly mild or moderate upper respiratory tract infections and nasopharyngitis, they reported online in .

First-line treatment for ankylosing spondylitis, which is characterized by structural damage to the sacroiliac and spinal joints, remains nonsteroidal anti-inflammatory drugs, with biologic agents being recommended for nonresponders. The biologics most often used have been the tumor necrosis factor (TNF) inhibitors, but some 30% to 40% of patients have persistent disease with these treatments.

IL-17 is a proinflammatory cytokine involved in the pathogenesis of various inflammatory disorders including ankylosing spondylitis. Secukinumab is a monoclonal antibody that directly targets IL-17A and was the first IL-17 inhibitor licensed for use in ankylosing spondylitis.

Ixekizumab also targets IL-17A and has been approved for use in plaque psoriasis and psoriatic arthritis, and have also shown benefits in ankylosing spondylitis.

Another IL-17 receptor A inhibitor, brodalumab, has been used for psoriasis and psoriatic arthritis but have occurred, and are currently evaluating other IL-17 inhibitors such as bimekizumab and netakimab for use in ankylosing spondylitis.

To provide a current summary of the efficacy and safety of secukinumab and ixekizumab for ankylosing spondylitis, the researchers conducted a systematic literature review and meta-analysis that included 1,733 patients enrolled in phase III trials. In the four trials of secukinumab, 777 patients received the active treatment and 389 were given placebo, while in the two studies of ixekizumab, 376 received the active treatment and 191 were given placebo.

Dosages varied in the different studies. Secukinumab was given as 75 mg, 150 mg, or 300 mg every 4 weeks, with or without loading doses, and ixekizumab was given as 80 mg every 2 or 4 weeks.

Patients were mostly in their 40s, and the majority were men.

As with the primary endpoint, subgroup analyses of the two drugs separately found superiority compared with placebo. With secukinumab, ASAS20 was achieved at week 16 by 58.4% of the active treatment group compared with 35.7% of the placebo patients (RR 1.64, 95% CI 1.41-1.89, P<0.001), and for ixekizumab, the numbers were 55.9% versus 34.6% (RR 1.63, 95% CI 1.31-2.01, P<0.001). Only mild heterogeneity was observed among the studies, the researchers noted.

Similar differences were seen on the secondary endpoint of ASAS40:

• Both IL-17A inhibitors: 37.1% vs 17.6%, RR 2.12 (95% CI 1.75-2.56, P<0.001)
• Secukinumab: 36.9% vs 18.8%, RR 1.97 (95% CI 1.57-2.47, P<0.001)
• Ixekizumab: 37.5% vs 15.2%, RR 2.49 (95% CI 1.75-3.57, P<0.001)

Patients who had not previously been treated with a TNF inhibitor had higher ASAS20 responses than patients with previous anti-TNF exposure (61.7% vs 47.7%, RR 1.27, 95% CI 1.06-1.52, P=0.01), but significant differences were not seen on ASAS40 responses.

Overall adverse events (AEs) were more common with the active treatment (57.2% vs 51.4%, RR 1.11, 95% CI 1.01-1.22, P=0.03).

There were no differences between the IL-17 inhibitors and placebo in serious AEs such as bacterial sepsis (2.3% vs 3.1%, RR 0.74, 95% CI 0.42-1.33, P=0.32), discontinuation because of AEs (2.5% vs 2.1%, RR 1.18, 95% CI 0.62-2.26, P=0.62), or deaths (0.17% vs 0.17%, RR 0.70, 95% CI 0.14-3.52, P=0.86).

Two deaths occurred among patients receiving an IL-17 inhibitor: one was a myocardial infarction in a patient receiving the 75-mg dose of secukinumab and the other was suicide in a patient on ixekizumab with a year-long history of depression. This was not considered treatment-related.

The safety findings "were consistent with those from studies of IL-17 inhibitors in psoriasis, psoriatic arthritis, and rheumatoid arthritis," the researchers observed.

"IL-17 inhibitors can be considered a favorable option for patients with active ankylosing spondylitis," they concluded.

A limitation of this analysis was the inclusion of different dosage patterns among the studies.

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