Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis

Abstract

Objectives: To systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis. Methods: A systematic review of the literature was performed for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. Meta-analyses were used to determine the efficacy and safety of the IL-17 inhibitors in the treatment of these patients. The primary endpoint was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary endpoint was defined as ASAS40 at week 16. Results: Six phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR = 1.63, 95% CI 1.45 to 1.84, p = 0.00) and the secondary endpoint ASAS40 response rate (RR = 2.12, 95% CI 1.75 to 2.56, p = 0.00) versus those for the placebo. With respect to the safety profile, more treatmentemergent adverse events (RR = 1.11, 95% CI 1.01 to 1.22, p = 0.03) and non-severe infections (RR = 1.82, 95% CI 1.40 to 2.37, p < 0.001) were described after treatment with IL-17 inhibitors than after treatment with placebo, while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including death, discontinuation due to adverse events, or serious adverse events. Conclusions: IL-17 inhibitors produced favorable response rates but an increased risk of non-severe infections in the treatment of active ankylosing spondylitis.

Depression and Obesity in Patients With Psoriasis and Psoriatic Arthritis: Is IL-17-Mediated Immune Dysregulation the Connecting Link?

“…We and others have shown that is IL-17 per se, as well as IL-17 axis, is pivotal for the development and progression of Ps and PsA ( 12 , 13 , 22 – 27 ). More recently, the imperative role of Il-17 in the induction and maintenance of ankylosing spondylitis and other spondylarthropathies has been revealed ( 28 ).…”

IL-17 Biological Effects and Signaling Mechanisms in Human Leukemia U937 Cells

“…Activation of PKC by IL-17 is associated with enhanced PKC ability to regulate cell cycle progression in leukemia cells [130]. As indicated earlier, IL-17 is profoundly implicated in many human diseases [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74], thus supporting the suggestion that design and production of anti-IL-17 drugs could lead to better strategies for development of new therapies for those diseases [88][89][90]. Although the recent reports implicating IL-17 in the mechanism of the "cytokine storm" event in COVID-19 infection is far from conclusion, there are calls for development of anti-IL-17 drugs as adjunct therapy for diseases in which IL-17 plays an active role [87,131].…”

“…Hence, there is strong interests in understanding IL-17's biology and it roles in COVID-19 patients [85][86][87]. It is not surprising that IL-17's role in these diseases , have prompted experts in pharmaceutical industries to develop anti-IL-17 type therapies for diseases in which IL-17 is implicated [88][89][90].…”

New Frontiers in Psoriatic Disease Research, Part II: Comorbidities and Targeted Therapies

“…In terms of therapeutic safety, TNF-a inhibitors have been associated with serious infections, reactivation of tuberculosis, reactivation of hepatitis B infection, demyelinating disorders, malignancy, congestive heart failure, and paradoxical psoriasis. Although meta-analyses do not show an increased risk of serious infection in IL-17 inhibitors (Li D Yan et al et al, 2020;Yin et al, 2020;Yiu et al, 2016), they are associated with a higher incidence of mucocutaneous candidiasis (Blauvelt, 2016). IL-17 inhibitors are also uniquely associated with both new onset and exacerbation of pre-existing inflammatory bowel disease, and in the case of brodalumab, they have been associated with suicide (Lebwohl et al, 2018b).…”