DISCUSSION
This network meta-analysis
synthesized efficacy, safety and tolerability data from 24 RCTs
comparing traditional and new topical medicines in adults with plaque
psoriasis. The findings of our review suggest that Cal/BD are more
effective than some new topical drugs,such as tofacitinib, tapinarof and
benvitimod. More improtantly We
provide new evidence that Cal/BD aerosol foam formulation had the
highest efficacy than other formulations. Furthermore, we considered
both efficacy safety and tolerability outcomes together in hierarchical
cluster analyses,suggesting that Cal/BD, roflumilast and betamethasone
demonstrate higher short-term efficacy,safety and
tolerability.These results have
potential clinical implications for clinicians to consider when choosing
treatment options.
Topical agents is the preferred therapy for patients with mild and
moderate psoriasis,however,patients can benefit from topical
treatments,regardless of disease severity.5 Extensive
forms of psoriasis may require a combination of systemic and topical
treatments to achieve complete regression of skin
lesions.37Plaque psoriasis usually requires a long
course of treatment,adherence to treatment is associated with better
efficacy,which is affected by frequency of application, and the
properties of the formulation and vehicle.38,39Most
frequently topical treatment is a fixed dose combination of
calcipotriene and betamethasone
dipropionate(Cal/BD) and various clinical trials have demonstrated the
efficacy and safety of Cal/BD.40 Halobetasol
propionate 0.01% and tazarotene 0.045% lotion(HP/TAZ) has been shown
to be more effective than tazarotene alone, and was consistently
effective in reducing the psoriasis symptoms of erythema, plaque
hypertrophy and scaling.31However,it also have some
concerns and limitations,for instance, betamethasone has been associated
with skin atrophy,telangiectasia and striae that limit the long-term
use, particularly sensitive areas like face and intertriginous
areas.Thus,due to these unmet needs for topical treatment of
psoriasis,new therapeutic durgs are emerging.
Some new topical treatments for psoriasis,such as tapinarof,has
completed a phase III study and showed good efficacy results and the
most common adverse reactions are folliculitis, contact dermatitis, and
headache ,but the most adverse reactions are
mild-to-moderate.19Benvitimod needs two daily
applications,it has the same active ingredients as
tapinarof
containing different escipients,and it can be used alternately and
sequentially with other topical drugs.Topical roflumilast,one of the
phosphodiesterase type 4 (PDE‑4) inhibitors,showed high efficacy,safety
and tolerability in our conclusions,.A 24-week extention study is
currently underway to assess its long-term safety.41Tofacitinib is a
small molecule Janus kinase (JAK) inhibitor and selectively JAK1 and
JAK3.42In our conclusion, tofacitinib is well
tolerated and has a high safety profile,consistent with the findings of
Ports WC,43but it showed only a modest improvement and
not significantly different from vehicle,some research on this drugs was
abandoned.44 Brepocitinib, a Tyrosine kinase 2 (TYK2)
/JAK 1 inhibitor, is the latest option in this class of drugs and also
undergoing a phase IIb clinical trial in patients with mild and moderate
psoriasis.45
Many topical corticosteroids used to treat psoriasis are available in
different formulations,development of new high-efficiency vehicle
formulations could improve patient compliance and efficacy of
treatment.46This systmetic review,we concluded that
Cal/BD aerosol foam, followed by PAD-cream,appears to be more efficacy
than the combination onitement,gel and topical suspension.
The purpose of this NMA was to compare the evidence of efficacy, safety
and tolerability of these topical therapies.
A previous NMA showed the
combination of potent corticosteroid and vitamin D analogue,
administered once daily in a single two-compound formulation or alone,
were the most effective interventions, with no significant difference
between them,10but some studies have shown that the
efficacy of Cal/BD is superior to
the monotherapy
components.4We performed a updated NMA,in order to
resolve controversial issues and incorporate recently topical
treatments.Our study suggested that compared with vehicle,the efficacy
and safety of Cal/BD was superior to the monotherapy components,and
there is significant difference between
them. In terms of new topical
drugs,the hierarchical cluster analyses demonstrated that topical AhR
inhibitors have have high efficacy
but lower safety and tolerability,
roflumilast has higher
efficacy,safety and
tolerability.However,tofacitinib has
poor efficacy but higher safety and tolerability.
This study had several limitations. First,because of short-term
observation,we cannot measure the difference in the long-term efficacy
and safety of these drugs. Second,in the included studies,the severity
of some patients psoriasis was recorded as moderate to severe and our
study did not involve a comparison of the frequency of drug
administration. Third, due to regional and racial differences, results
of NMA may not generalize to real-world patient populations.Fourth,
Other new drugs not included in some studies which results were not
reported. Therefore, the interpretation and implementation of the
results of this NMA should mainly consider short-term treatment and
require long-term follow-up treatment studies.