Th17 Inhibitors in Active Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Abstract

tool was used for assessing quality. The pooled relative risk (RR) was derived from random effects models. Results: Seven randomized controlled trials were included which randomized 1,718 patients to Th17 inhibitors and 840 to placebo. Patients treated with Th17 inhibitors had an RR of 2.04 (95% CI: 1.79-2.33; p < 0.001) for achieving an ACR20 response at week 12 (I 2 = 0%; p = 0.89) compared to placebotreated patients. There was no evidence of publication bias. The result was consistent for study phase and outcome (ACR50/70), mechanism of action and TNF-α naivety. RR of infections was 1.06 (0.91-1.23), that of candida infections was 3. 35 (0.75-14.95), that of serious adverse events was 0.82 (0.42-1.59) and that of discontinuation of treatment was 0.54 (0.31-0.93) among treated versus placebo subjects. No incident cases of tuberculosis were reported. Conclusion: In patients with active PsA, biologics targeting the Th17 axis produce a clinically significant improvement in joint disease activity with acceptable safety and tolerability for short-term treatment compared to placebo. © 2017 S. Karger AG, BaselKeywords Meta-analysis · Biological therapy · Active psoriatic arthritis · Systematic review · Th17 pathway inhibitors Abstract Background: Several biologics targeting the Th17 pathway have been developed for the treatment of psoriatic arthritis (PsA), a disabling disease with moderate response and an increased incidence of serious infections to first-line biologics (TNF-α antagonists). Th17 inhibitors could replace TNF-α antagonists as first-line biologic agents. We determined the overall treatment effect of Th17 pathway inhibitors compared to placebo or active control on American College of Rheumatology (ACR) 20 response at week 12 (primary objective), risk of infections, discontinuation of treatment due to adverse events, and serious adverse events during the placebo-controlled period (12-24 weeks) in adults with active PsA in published randomized controlled trials. Methods: The SCOPUS database was searched. The Cochrane risk of bias

Efficacy and safety of biologics in psoriatic arthritis: a systematic literature review and network meta-analysis

“…Our SLR identified 50 randomised controlled trials for possible inclusion in the NMA that evaluated the efficacy and/or safety of bDMARDs and/or targeted synthetic DMARDs in patients with PsA. This NMA is in line with other reviews and indirect comparisons conducted over the past 2 years,10–14 27–30 and it is one of the most comprehensive NMAs to date, including a broad range of comparators relevant for healthcare decision-making as well as the commonly investigated outcomes in PsA, such as ACR, PsARC and PASI response rates. It was also comprehensive in terms of safety outcomes, including TEAEs, SAEs, DAEs and all-cause discontinuation, and the variety of interventions included.…”

“…Various safety end points were also evaluated, including treatment-emergent adverse events (TEAEs), serious/severe adverse events (SAEs), discontinuation due to adverse events and all-cause discontinuation. Although recent NMAs have been conducted comparing bDMARDs in PsA,10–14 few include ixekizumab, a recently approved high-affinity monoclonal antibody that selectively targets IL-17A 15. In addition, publication and dissemination of NMA results are essential activities to support international health technology assessments of ixekizumab in PsA.…”

Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases

“…The interleukin-17 (IL-17) family is a group of pro-inflammatory cytokines with a key role in defense against fungi and bacteria. Elevated IL-17 levels have been associated with the development of chronic inflammatory immune-mediated diseases [ 5 , 6 , 7 ] and several therapeutic strategies targeting IL-17 are approved for the treatment of psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) [ 8 ], pointing to the role of this cytokine in the pathogenesis of these autoimmune diseases [ 9 , 10 , 11 ]. The role of IL-17 on RA has been extensively studied [ 7 , 12 , 13 ]; therefore, this review will focus on the role of IL-17 in the pathogenesis of other systemic rheumatic diseases, mainly SLE, SS and SSc, as well as the potential therapeutic intervention on these diseases.…”

A Case of Psoriasis Vulgaris Treated with Brodalumab in a Hemodialysis Patient with End-Stage Renal Disease due to Diabetic Nephropathy

“…During anti-IL-17 therapy, the incidence of Candida infection increases only marginally, but no basis for an increased incidence of tuberculosis is found. A meta-analysis showed that there was no significant difference in the incidence of serious adverse events among patients treated with 17 inhibitors versus placebo [13]. Respiratory diseases to be differentiated when using biologics are bacterial pneumonia, mycobacterial infection, pneumocystis pneumonia, and drug-induced interstitial pneumonia.…”