Psoriasis is a common immune-mediated skin disease.
The prevalence of psoriasis in adults ranges between 0.91 and 8.5%
worldwide and the incidence of psoriasis is higher in adults than
in children (1). Psoriasis is
characterized by symptoms of plaque, pustular and other skin
lesions. Chronic plaque psoriasis accounts for 90% of all psoriasis
cases (2,3).
A number of biological therapies are used to treat
moderate to severe psoriasis, including etanercept, briakinumab,
ustekinumab, adalimumab and infliximab (4–8).
Etanercept, adalimumab and infliximab are monoclonal antibodies
against tumor necrosis factor (TNF), which function by neutralizing
the biological activity of TNF for treating the TNF-mediated
inflammation (5,9). By contrast, ustekinumab and briakinumab
are human monoclonal antibodies against interleukin (IL)-12/23p40
(8). These biological therapies are
used to treat psoriasis and improved clinical outcomes have been
observed. However, the efficacy of these therapies has been not
systematically reviewed.
In the present study, a network meta-analysis was
performed to review and compare the efficacy of these
aforementioned biological therapies of psoriasis. The Psoriasis
Area and Severity Index (PASI) response (10) was used as an indicator for assessing
the effect of treatment on the severity of psoriasis. PASI 50, PASI
75 and PASI 90 responses for the therapies were systematically
assessed. The pooled results provide further information on
selecting the most suitable treatments for moderate to severe
psoriasis.
Studies with the following characteristics were
included in the current meta-analysis: i) Randomized controlled
trials (RCTs) reporting the treatment of moderate to severe
psoriasis with the aforementioned drugs. Moderate to severe
psoriasis is defined as body surface area >10 or psoriasis area
and severity index >10 and dermatology life quality index >10
(11); ii) studies including the
adults as participants; and iii) studies reporting the PASI
response rate (50, 75 and 90%). Any reviews, case reports and
letters were excluded from the meta-analysis. Any studies
investigating patients with mild psoriasis and those written in a
language other than English were also excluded.
Two reviewers independently extracted the following
data: The name of the first author, publication year, sample size,
intervention, demographic characteristics of the included patients
and PASI response rate. The controversies were discussed with a
third reviewer to reach consensus. The methodological quality of
the included studies was evaluated by the Cochrane Collaboration
Risk of Bias Tool (12).
All analyses were performed using the ADDIS software
version 1.16.5 (Drug Information and Monitoring Systems, Groningen,
The Netherlands). Odds ratios (ORs) and their 95% confidence
intervals (CIs) were pooled. The network analysis performed was
based on the Bayesian framework. Data were evaluated by Markov
chain Monte Carlo methods and all analyses were performed using the
random effects model. The consistency of the RCTs was assessed by
Node-splitting analysis, and the consistency model was used if
P>0.05. Otherwise, the inconsistency model was used to pool the
odd ratios (13).
In the present study, a network meta-analysis was
performed to systematically review and compare the efficacy of
seven drugs used at different doses for treating moderate to severe
psoriasis. Based on the results of the network analysis, infliximab
(5 mg) may be an appropriate option to treat moderate to severe
psoriasis.
Psoriasis has been reported to be associated with a
high concentration of TNF-α (41)
and infliximab treatment can neutralize the biological activity of
TNF-α (42). However, the role of
the TNF-α in the pathogenesis of psoriasis remains unclear.
Previous studies have reported that TNF-α may serve an important
role in the upstream of the inflammatory responses of psoriasis
(43,44). An in vitro study determined
that infliximab was able to inhibit the activation of skin-homing T
cells and impair the antigen-presenting capacity of immature
dendritic cells in psoriasis patients (43). However, another TNF-α inhibitor,
etanercept, has been found to be effective in the treatment of
psoriasis by reducing the Th17 cell products, as well as the
production of IL-17, IL-22, IL-23 and inducible NO synthase from
dendritic cells (44). Thus, it has
been suggested that the infliximab may serve a different role with
other treatments on moderate to severe psoriasis.
Although the present meta-analysis indicated that
infliximab treatment had a high PASI score, a higher percentage of
adverse events were observed in infliximab-treated patients
compared with those in the placebo group (18), indicating that infliximab treatment
induces adverse effects. In addition, infliximab treatment
increases the incidence of infusion reactions (45). However, these outcomes were not
considered to be important due to the small sample size of each
study or the fact that the data were unavailable. Thus, the
therapeutic effect of the infliximab should be systematically
assessed in further studies. Besides, the dosage and treatment
duration of infliximab should be optimized according to the disease
severity of psoriasis.
In the present study, briakinumab and ustekinumab
(90 mg) treatments were superior to other treatments for PASI 90
response. Thus, anti-IL-12/23 monoclonal antibodies appear to be
more appropriate compared with anti-TNF-α treatment for treating
moderate to severe psoriasis. However, briakinumab and ustekinumab
showed no significantly improved therapeutic effect in PASI 75 and
PASI 50 responses when compared with the anti-TNF-α treatments. In
addition, the long-term safety profile, including severe infections
and cardiac disorders, should be evaluated in further studies with
large sample sizes and strict study design.
To the best of our knowledge, the present study is
the first network meta-analysis for evaluating the efficacy of
various treatments for moderate to severe psoriasis. The current
results may provide information for clinician and patients on the
selection of the suitable treatment for moderate to severe
psoriasis. However, there were also several limitations in the
present meta-analysis. Firstly, due to unavailable data in certain
included studies, confounding variables could not be adjusted and
subgroup analysis was not performed to reduce the effect of the
confounding variables. Secondly, due to unknown bias, the network
analyses of PASI 75 and PASI 50 responses were performed using an
inconsistency model. Finally, the results of the network
meta-analysis should be pooled only by a random effects model.
Thus, the pooled results may be conservative and certain borderline
significant effects may have been ignored (46).
In conclusion, the present meta-analysis results
suggested that infliximab (5 mg) may be a superior option compared
with other drugs for treating moderate to severe psoriasis due to
the relatively high PASI scores of patients. However, despite the
high PASI 90 responses, the efficacy of ustekinumab (90 mg) and
briakinumab were also high and therefore should be investigated in
further studies.
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