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

Abstract

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.

Systemic immunomodulatory treatments for atopic dermatitis: protocol for a systematic review with network meta-analysis

“…Using psoriasis as an example, most new systemic agents are only compared with placebo and, sometimes, a single active comparator. Recent NMAs for psoriasis have provided a solution, giving patients, clinicians and other stakeholders a means of comparing relevant therapeutic options 41 42. NMA does have limitations in the setting of systemic therapies for AD, particularly differences in clinical trial design across included studies.…”

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

“…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).…”

“…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 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. They found no significant differences between tildrakizumab, guselkumab, ustekinumab, etanercept, infliximab, adalimumab and certolizumab verses placebo in terms of the risk of SAEs, serious infections, malignancies or MACE …”

Trends in hospitalization rates for psoriasis flares since the introduction of biologics: a time series in France between 2005 and 2015

“…Up until the mid‐2000s, the available systemic treatments, that is methotrexate, cyclosporine, acitretin, fumaric acid esters, phototherapy, were only moderately effective in cases of moderate‐to‐severe psoriasis. Indeed, in randomized controlled trials of these conventional treatments, the risk difference between the active treatment and placebo groups for achieving a 75% improvement in the initial Psoriasis Area Severity Index (PASI 75) at weeks 12 to 16 varied from 30% to 50% . In the mid‐2000s, the introduction of biologics targeting key inflammatory cytokines (TNF‐α, IL‐12, IL‐17 and IL‐23) improved the short‐term outcomes of patients with moderate‐to‐severe psoriasis.…”

“…In the mid‐2000s, the introduction of biologics targeting key inflammatory cytokines (TNF‐α, IL‐12, IL‐17 and IL‐23) improved the short‐term outcomes of patients with moderate‐to‐severe psoriasis. Indeed, the risk difference for achieving PASI 75 at week 12 to 16 ranges from 50% to 85% with these new biologics . This efficacy seemed to persist over time, as evidenced by high drug survival rates in national cohorts .…”