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Pearl Toh, 3 days ago
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Pearl Toh, 07 Dec 2018
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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
Pearl Toh, 3 days ago
First-line therapy with the BTK* inhibitor ibrutinib plus the anti-CD20 immunotherapy rituximab confers significant survival advantage over the current gold-standard regimen of fludarabine, cyclophosphamide, and rituximab (FCR) for young, fit patients with treatment-naïve chronic lymphocytic leukaemia (CLL), according to the E1912 trial, a large cooperative group study supported by the US National Cancer Institute.
6 days ago
Percutaneous coronary intervention (PCI) displays comparable rates of mortality and serious composite outcomes but a higher rate of target-vessel revascularization at 10 years relative to coronary artery bypass grafting (CABG) in patients with significant left main coronary artery (LMCA) disease, reports a study. On the other hand, CABG delivers lower mortality and serious composite outcome rates compared with PCI with drug-eluting stents after 5 years.
Pearl Toh, 07 Dec 2018
Apixaban slashes the risk of recurrent venous thromboembolism (VTE) by 90 percent in cancer patients compared with the low-molecular-weight heparin (LMWH) dalteparin, with no increase in major bleeding risk, according to the ADAM VTE study presented at ASH 2018.
2 days ago
Rates of major bleeding events are similar across cancer patients taking direct oral anticoagulants (DOAC), low-molecular-weight heparin (LMWH) or vitamin K antagonist (VKA), with gastrointestinal bleeding being the most frequent event, a recent study has shown. In addition, DOAC and LMWH recorded higher rates of venous thromboembolism than earlier studies.