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Tadekinig potentially beneficial for Still's disease

Audrey Abella
11 Apr 2018

Interleukin (IL)-18 inhibition using the recombinant human IL-18 binding protein tadekinig alfa demonstrated early signs of efficacy and a favourable safety profile in patients with adult-onset Still’s disease (AOSD), a rare inflammatory disease of unknown aetiology, a phase II study shows.

Twenty-three patients with active AOSD with inadequate response to prednisone and/or synthetic DMARDs* received subcutaneous injections of tadekinig alfa at a dose of 80 or 160 mg (n=10 and 13, respectively) thrice weekly for 12 weeks. After 3 weeks, six participants who had inadequate response to the 80-mg dose were uptitrated to 160 mg for another 12 weeks. [Ann Rheum Dis 2018;doi:10.1136/annrheumdis-2017-212608]

Half of the population achieved adequate clinical response** at week 3 (five and six patients receiving 80 and 160 mg, respectively) and week 12 (two and eight, respectively, including those who were uptitrated).

“[Fifty-percent] response rates [were achieved] irrespective of the … dosage in this heterogeneous population of difficult-to-treat patients,” said the researchers. The lack of difference in response between treatment arms suggests that the 80-mg dose already demonstrated a clinically meaningful effect, they added.

Most adverse events (AEs) were mild and resolved after drug discontinuation, with the most frequent being injection site reactions, upper airway infections, and arthralgia. A total of 155 treatment-emergent AEs were recorded, 47 of which were considered study drug-related. Three serious AEs were reported, with one possibly related to treatment (toxic optic neuropathy).

However, the Data Safety Monitoring Board (DSMB) indicated other potential explanations for the toxic optic neuropathy that may not have been ruled out. “[The DSMB suggested that there could have been] insufficient information to draw any firm conclusion [that this could be drug-related] since there had been insufficient exploration to discard the diagnosis of ophthalmic vein thrombosis,” the researchers pointed out.

Compared with baseline, there was improvement in skin rash (six vs 13; p=0.02) and significant decrease in inflammatory biomarker levels (ferritin; p=0.003, IL-6; p=0.007, neutrophils; p=0.02, S100A8/9; p=0.01, and S100A12; p=0.01) in the overall population at 12 weeks.

The increase in serum levels of free IL-18 in AOSD suggests the potential role of IL-18 in the pathogenesis of AOSD and has been correlated with clinical and biological markers of disease activity. [Int J Inflam 2012;doi:10.1155/2012/879020; Rheumatology 2016;55:2237-2247]

Although previous studies demonstrated the efficacy of anticytokine therapy in systemic-onset juvenile idiopathic arthritis, there are insufficient data showing its efficacy in AOSD. [N Engl J Med 2012;367:2396-2406; Front Pharmacol 2017;8:369; Best Pract Res Clin Rheumatol 2016;30:222-238]

The findings show the potential of tadekinig alfa as a therapeutic option in AOSD and provide important results regarding the safety of IL-18 blockade despite the open-label design and lack of a control group, highlighted the researchers. “[T]he clinical response in … patients with chronic disease despite the use of DMARDs and inclusion of objective measures such as biomarkers of inflammatory responses provide supportive data for treatment efficacy.”

“Our results show that IL-18 inhibition offers another possibility of therapy within the scope of anticytokine treatment for the management of AOSD,” concluded the researchers, who called for further evaluation to validate the safety and efficacy of tadekinig alfa in this setting.

 

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Most Read Articles
4 days ago
Chocolate consumption is not associated with risk of coronary heart disease (CHD), stroke or both combined in postmenopausal women free of pre-existing major chronic disease, a study suggests.
Pearl Toh, 5 days ago
More intensive lowering of LDL-C levels was associated with a progressively greater survival benefit than less intensive approach, when the baseline LDL-C levels were ≥100 mg/dL, reveals a meta-analysis of 34 randomized trials.
4 days ago
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2 days ago
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