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.