乌鸦传媒

Short-term improvements in axial spondyloarthritis (axSpA) symptoms seen with the interleukin-17A blocker ixekizumab (Taltz) persisted and even increased further among clinical trial participants who continued on the drug for 3 years, without any new safety signals.

The proportion of patients achieving "clinically important improvement" in Ankylosing Spondylitis Disease Activity Score (ASDAS) values in three of ixekizumab's pivotal trials reached 70-80% by year 3, up from about 60-70% after 1 year, according to Atul Deodhar, MD, of Oregon Health & Science University in Portland, and colleagues.

Rates of ASDAS scores lower than 2.1, indicating low disease activity, also increased during the extension, the researchers . Depending on participants' diagnosis (radiographic vs non-radiographic axSpA), previous treatment experience (i.e., biologic-naive vs biologic treatment failure), and dosing regimen (80 mg every 2 vs 4 weeks), ASDAS <2.1 was achieved by approximately 35-75% of patients by year 3.

"There were no new or unexpected safety concerns through 3 years" in this group of patients, Deodhar and colleagues wrote. "[Adverse events] leading to discontinuation were low, in line with what has been reported previously for all pooled patients treated with [ixekizumab] through 2 years of exposure." Fungal infections with Candida, major cardiovascular events, and malignancies also remained rare, the group added.

These results are consistent with other analyses of ixekizumab, which first came on the market in 2016 for treating plaque psoriasis, in long-term use. (It has since gained approvals for inflammatory non-radiographic axSpA, ankylosing spondylitis, and psoriatic arthritis.) Although there had been no major worries about the drug's safety, analyses "from multiple studies and long-term extension studies" remain vital as a continuing check, the researchers noted.

Their new analysis covered participants in ixekizumab's so-called COAST program in axSpA, which comprised three separate trials: COAST-X, which enrolled biologic-naive patients with non-radiographic disease; COAST-W, enrolling patients with radiographic disease who had failed on tumor necrosis inhibitors; and COAST-V, for patients with radiographic disease and no previous biologic therapy.

The primary analyses were conducted at week 16, after which patients originally assigned to the control group (placebo in one study, adalimumab [Humira] in two studies) were switched to ixekizumab, initially at 80 mg every 4 weeks with the possibility of escalation to 2-week dosing. For the extension study, patients who had received ixekizumab and achieved remission were then re-randomized to continue ixekizumab or withdrawal to placebo; the new placebo group with a total of 53 patients was excluded from the current analysis.

Not counting the patients switched from ixekizumab to placebo, 932 participated in the extension, of whom 68% stayed on the drug for the full 3 years.

A majority experienced at least one treatment-emergent adverse event (TEAE) at some point. Among all 932 participants, 30% had TEAEs rated as mild, 45% had moderate events, and 11% experienced severe TEAEs. Events leading to discontinuation occurred in 7% of participants, and three died. Most patients who left the study without completing year 3 had either declined to participate in the extension or quit for no specified reason.

The most common type of adverse event was infection, seen in 58% of participants, although only 23 cases were considered serious. Nineteen cases of candidiasis were seen along with 12 episodes of herpes zoster. Nine patients developed new-onset cancers and six suffered major cardiovascular events. Seventeen were newly diagnosed with ulcerative colitis or Crohn's disease.

One complication to the study was that clinicians dissatisfied with patients' clinical response at week 116 could raise the dosing frequency from 4 weeks to 2 weeks. Such patients were then classified as "nonresponders" according to the prespecified protocol and their subsequent observed data were excluded from the ASDAS efficacy analysis.

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