IL-17 Inhibitors Can Ease Symptoms But Raise Infection Risk, Review Shows

Treatments blocking interleukin (IL)-17A, the so-called IL-17 inhibitors, can effectively ease symptoms in people with ankylosing spondylitis (AS), but also increase the risk of mild to moderate infections, a review study reports.

The data show that IL-17 inhibitors — such as Novartis’ Cosentyx (secukinumab) and Eli Lilly’s Taltz (ixekizumab) — are favorable therapeutic options for AS patients, including those who previously experienced inadequate responses or intolerance to tumor necrosis factor (TNF) inhibitors.

The study, “Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis,” was published in the journal Arthritis Research & Therapy.

Treatment of AS typically includes first-line non-steroidal anti-inflammatory drugs (NSAIDs), followed by second-line biological disease modifying anti-rheumatic drugs (bDMARDs) such as TNF inhibitors. These medicines act by blocking TNF, a key inflammatory mediator.

However, approximately 30% to 40% of AS patients do not respond to NSAIDs and/or TNF inhibitors, and the use of IL-17 blockers, another type of bDMARDs, is recommended in such cases.

By suppressing the activity of IL-17A — a pro-inflammatory protein associated with several inflammatory conditions — this type of therapy has the potential to lower inflammation and halt disease progression in AS patients. Notably, similar to TNF-inhibitors, IL-17 inhibitors are associated with an increased risk of infection.

To date, Cosentyx and Taltz are the only IL-17 inhibitors approved in the U.S. for the treatment of AS, but others (such as bimekizumab by UCB and netakimab by Biocad) are currently in clinical trials.

Researchers in China set out to assess the safety and effectiveness of IL-17 inhibitors in AS patients by reviewing published data from clinical trials up to November 2019.

The studies had to include AS patients with active disease and compare the effectiveness of IL-17 inhibitors to a placebo using the ankylosing spondylitis assessment score (ASAS) response criteria after at least 16 weeks of treatment.

ASAS20 is defined as an improvement of at least 20% and ASAS40 of at least 40% in at least three of four categories: global assessment of disease, pain, function, and inflammation.

From a total of 87 studies assessed for eligibility, five met the intended criteria and were included in the pooled analysis, covering six Phase 3 clinical trials and a total of 1,733 AS patients.

Three studies reported data from four trials of Cosentyx (777 patients treated with Cosentyx vs. 389 patients on a placebo), while two studies concerned two trials of Taltz — 376 patients treated with Taltz vs. 191 patients on a placebo.

In these six trials, participants’ mean age ranged from 40.1 to 47.4, while the proportion of male participants ranged from 52% to 83.7%.

Results at week 16 showed that a significantly higher proportion of people treated with any dose and type of IL-17 inhibitor achieved an ASAS20 response, compared with those treated with a placebo (57.6% vs. 35.3%).

The ASAS40 response rate was also significantly higher in patients on IL-17 blockers (37.1%) than in people receiving a placebo (17.6%). An analysis of the effectiveness of each IL-17 inhibitor showed that Cosentyx and Taltz were both superior to a placebo.

Further subgroup analysis revealed superior ASAS20 response rate at week 16 among patients not previously treated with TNF inhibitors than in those who had a previous inadequate response or intolerance to such therapies. However, no such difference was seen in the ASAS40 analysis.

Pooled safety data up to week 16 showed that treatment with IL-17 inhibitors was associated with a significantly higher risk for adverse events and non-severe infections than the placebo.

Most infections were mild to moderate, with upper respiratory tract infections and common colds as the most frequent. No patient discontinued treatment due to a non-severe infection.

The team also found no significant differences between IL-17 inhibitors and a placebo in the rates of severe adverse events, treatment discontinuation due to adverse events, or death.

Overall, the findings suggest that “IL-17 inhibitors can be considered a favorable option for patients with active ankylosing spondylitis,” the researchers wrote, adding that their use is, however, associated with a higher occurrence of mild to moderate infections.