A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab and tildrakizumab for the treatment of moderate to severe plaque psoriasis

Bilal, Jawad; Berlinberg, Adam; Bhattacharjee, Sandipan; Trost, Jaren R.; Riaz, Irbaz Bin; Kurtzman, Drew J.B.

doi:10.1080/09546634.2017.1422591

Cited by 110 publications

(114 citation statements)

References 46 publications

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“…Systematic reviews suggest that agents targeting IL-17 may be more effective than those targeting IL-23 in patients with moderate to severe plaque psoriasis and that ixekizumab ranks among the most effective of the anti-IL antibodies. [4][5][6][7] Reviewing similar evidence based on clinical trials, NICE concluded that ixekizumab was more clinically effective than adalimumab and ustekinumab, and agreed it was likely that ixekizumab was comparable with secukinumab and infliximab, in terms of the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75 response) after 12 weeks' treatment. 2 Direct comparative trials with ustekinumab (n=302) 8 and etanercept (two studies involving a total of 2570 patients, though not all received the licensed dose) 9 in patients with moderate to severe psoriasis have been published.…”

Section: Efficacymentioning

confidence: 99%

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Sbidian

Chaimani

García‐Doval

et al. 2017

Cochrane Database of Systematic Reviews

267

309

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Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.

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Section: Efficacymentioning

confidence: 99%

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Sbidian

Chaimani

García‐Doval

et al. 2017

Cochrane Database of Systematic Reviews

267

309

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“…Further studies comparing treatments are ongoing or awaiting publication, including guselkumab vs. secukinumab (phase 2, NCT03553823; phase 3, NCT03090100) and vs. ixekizumab (phase 4, NCT03573323) and risankizumab vs. secukinumab (phase 3, NCT03478787). In addition, three recent meta‐analyses have assessed the safety of IL‐23p19 inhibitors compared with other classes of biologic agents used for the treatment of psoriasis . To avoid risk of confounding, these meta‐analyses exclusively used data from the placebo‐controlled treatment periods of randomized controlled trials (typically 12–16 weeks).…”

Section: Other Safety Datamentioning

confidence: 99%

“…The second meta‐analysis assessed the efficacy and safety of IL‐23p19, IL‐12/23p40 and IL‐17 inhibitors in moderate to severe plaque psoriasis and included data from 24 trials involving 15 388 patients . Safety outcomes included the number of patients with at least one AE, with at least one SAE and withdrawing from therapy because of an AE at 12–16 weeks.…”

Section: Other Safety Datamentioning

confidence: 99%

“…In addition, three recent meta-analyses have assessed the safety of IL-23p19 inhibitors compared with other classes of biologic agents used for the treatment of psoriasis. [50][51][52] To avoid risk of confounding, these meta-analyses exclusively used data from the placebo-controlled treatment periods of randomized controlled trials (typically 12-16 weeks). Sbidian and colleagues 50 conducted a network meta-analysis of 109 studies to compare the efficacy and safety of conventional systemic agents, small molecules and biologic agents in 39 882 patients with moderate to severe psoriasis.…”

Section: Other Safety Datamentioning

confidence: 99%

“…50 The second meta-analysis assessed the efficacy and safety of IL-23p19, IL-12/23p40 and IL-17 inhibitors in moderate to Table 3 Incidence of AEs of special interest from long-term follow-up studies, pooled analyses and patient registries. Data are presented as rates per 100 PY 11,12,24,48,49 51 Safety outcomes included the number of patients with at least one AE, with at least one SAE and withdrawing from therapy because of an AE at 12-16 weeks. No differences in any safety outcomes were reported for tildrakizumab 100 mg or 200 mg compared with placebo.…”

Section: Other Safety Datamentioning

confidence: 99%

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Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Crowley

Warren

Cather³

2019

Acad Dermatol Venereol

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Psoriasis is a chronic disease that requires long‐term treatment. Consequently, understanding the safety and tolerability of any potential treatment over time is critical to effective prescribing. The biologic agents currently available for the treatment of psoriasis target a number of different inflammatory cytokines involved in psoriasis disease pathogenesis. The monoclonal antibodies tildrakizumab, guselkumab and risankizumab target the p19 subunit that is specific to interleukin (IL)‐23. This article reviews published data on the safety of these IL‐23p19 inhibitors in patients with psoriasis compared with other currently available biologic therapies. Data from randomized, placebo‐ and active‐controlled phase 3 clinical trials show tildrakizumab, guselkumab and risankizumab to have a favourable risk–benefit profile in patients with moderate to severe psoriasis. No significant safety concerns have been observed for any of these IL‐23p19 inhibitors in the data published to date. The most commonly reported adverse events (AEs) associated with these agents in phase 3 studies were upper respiratory tract infections. No increase was seen in rates of serious infections, malignancies or major adverse cardiovascular events, with no signals suggestive of an elevated risk of opportunistic infections, active tuberculosis or reactivation of latent tuberculosis infection, mucocutaneous Candida infections, triggering or worsening of inflammatory bowel disease, demyelinating disorders or suicidal ideation. Selectively targeting IL‐23p19 may help avoid AEs that have been associated with biologic agents with other mechanisms of action. Data from long‐term extension studies and patient registries will further establish the safety profile of IL‐23p19 inhibitors for the treatment of moderate to severe psoriasis in routine practice.

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Serious adverse events associated with systemic treatments for psoriasis: a network meta-analysis of observational studies and randomized controlled trials

Guelimi,

Chaimani,

Parisi

et al. 2024

Cochrane Database of Systematic Reviews

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A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab and tildrakizumab for the treatment of moderate to severe plaque psoriasis

Abstract: Ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab were highly efficacious and generally well-tolerated when used as treatments for moderate to severe plaque psoriasis.

Cited by 110 publications

References 46 publications

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Serious adverse events associated with systemic treatments for psoriasis: a network meta-analysis of observational studies and randomized controlled trials

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