Effectiveness And Safety Of Secukinumab In Chinese Patients With Psoriasis In A Real-world Setting

Background:Psoriasis is a chronic relapsing inflammatory skin disease mediated by immunologic disorder,and the T helper cell 17(Th17)and interleukin(IL)-23/IL-17 axis are recognized to have an essential role in the pathogenesis of psoriasis.Due to the ideal targeted therapeutic effect,biologic agents play an active and effective role in the treatment of the moderate to severe,refractory and special types of psoriasis.Secukinumab,the first biologic agent targeting IL-17A,has demonstrated significant efficacy and safety in patients with moderate to severe plaque psoriasis in many foreign studies.It was approved for marketing in China in March 2019 and its superior efficacy and tolerability were also shown in pre-marketing and post-marketing clinical studies with small sample size of Chinese moderate to severe plaque psoriasis patients.However,real-world evidence with large sample size in the Chinese patients is still needed to monitor its clinical efficacy and safety,especially for long-term application.Besides,secukinumab has been reported to be effective in treating specific types of psoriasis and psoriasis involving specific locations.Localized pustular psoriasis is a rare type of pustular psoriasis that poses a great challenge in clinical treatment.Some patients with localized pustular psoriasis have poor efficacy in using topical drugs,phototherapy,and traditional systemic treatment,or have difficulty in tolerating adverse drug reactions,and eventually become refractory patients.For this group of patients who lack effective treatment options,however,there are few reports on the application of secukinumab in China.In order to evaluate the effectiveness of secukinumab in the treatment of Chinese psoriasis patients,analyze the influencing factors of the efficacy,and observe the long-term safety,we conducted a prospective observational cohort study in the first part of this research and collected real-world clinical data.Additionally,to explore the clinical feasibility of secukinumab in localized pustular psoriasis treatment,we included patients with refractory localized pustular psoriasis who had poor efficacy or intolerance to previous standard treatments in the second part.Objectives:1.To assess the clinical efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis in a real-world environment,and search for factors that could have an influence on the response.2.To investigate the feasibility of secukinumab in the clinical application of refractory localized pustular psoriasis such as PPP and ACH who failed and/or were intolerant of traditional systemic treatment.Methods:A single-center,prospective,observational cohort study was conducted in the Department of Dermatology,Xijing Hospital,Air Force Medical University from September 2019 to May 2022.Patients with moderate-to-severe plaque psoriasis(PASI≥3,BSA≥3,or DLQI≥6 according to the 2018 complete edition of the Guideline for the diagnosis and treatment of psoriasis in China)and patients with refractory localized pustular psoriasis who failed traditional systemic treatment and/or phototherapy were included and treated with secukinumab.Secukinumab was administered in accordance with the package insert,namely s.c.administration at a dose of 300 mg subcutaneous once weekly for 5 weeks then once 4-week thereafter,and at a dose of 150 mg with the same regimen depending on bodyweight(<60Kg).To evaluate the efficacy and safety of secuchiumab,patients with moderate to severe plaque psoriasis and patients with localized pustular psoriasis were followed up for 52 weeks and 24 weeks,respectively.Results:Part 1 Secukinumab in the treatment of moderate-to-severe plaque psoriasis(1)Baseline characteristics:254 patients with moderate to severe plaque psoriasis were included.The majority were male(70.1%),with a mean age of 36.5±11.6 years.At baseline,mean Psoriasis Area and Severity Index(PASI)score and Body Surface Area(BSA)were 13.6±9.0 and 13.9%±12.3%,respectively.There were 205 and 49 patients treated in the secukinumab 300mg group and 150mg group,respectively.(2)Secukinumab demonstrated rapid onset of action and had shown long lasting efficacy in patients with moderate to severe plaque psoriasis.In the 300 mg secukinumab group,responders who had achieved PASI75,PASI90 and PASI100 response accounted for 91.7%,74.0%and 39.7%,respectively,at week 12,and 94.5%,74.5%and47.6%,respectively,at week 52.The efficacy of the 150mg group was similar to that of the 300mg group.(3)The effectiveness of secukinumab was associated with BMI and previous systemic therapy.The univariate and multivariate logistic regression analysis indicated that BMI,immune depressants treatment history,and biologic treatment history had negative influence on the responses of PASI improvement in the 300 mg secukinumab group.(4)The median time of maintenance of response after withdrawal in responsive patients was 16 weeks and correlated with BMI.Of the 50 patients with follow-up data after withdrawal,the median(first quartile,third quartile)time of maintenance of response was 16(12,20)weeks.Kaplan-Meier survival analysis and Log-rank test demonstrated that the duration of remission in patients with low BMI<25Kg/m~2 tended to be longer than that in patients with BMI≥25Kg/m~2(the median time:12 weeks and 20 weeks,respectively,P=0.015).(5)The drug survival rate at 52 weeks was low,and the main reason for discontinuation was due to disease remission combined with inconvenient follow-up.Out of these 186 patients who reached at least 52 weeks follow-up,44 patients discontinued treatment and the drug survival rate was 76.3%.61.3%(27/44)patients withdrew from treatment due to disease remission together with inconvenient follow-up during the COVID-2019 pandemic.(6)Secukinumab demonstrated a favorable safety profile over long-term treatment.Among all 254 patients,at least one adverse event occurred in 26.8%patients,with eczematous lesions being a common adverse reaction(10.2%).There was no case of reactivation of tuberculosis,hepatitis B or death reported during the follow-up period.Part 2 Secukinumab in the treatment of localized pustular psoriasis.(1)Secukinumab demonstrated efficacy in the treatment of PPP and ACH.Among 13 refractory localized pustular psoriasis patients included,6 patients were diagnosed as PPP,3 patients were diagnosed as ACH and 4 patients were diagnosed as PPP with ACH.10 patients were females,and the mean age of all 13 patients was33.2±14.6 years.After 24 weeks treatment,the percent of patients achieving a 50%,75%,and 90%reduction from the baseline of the Palmoplantar Pustulosis Area Severity Index(PPPASI)scores were 60%,40%,and 30%in ten patients with PPP form,respectively.In addition to Clinical Global Impression(CGI)score,6 of 7 subjects with ACH form attained‘very much improved’.(2)Secukinumab was safe for the treatment of PPP and ACH.No severe adverse drug reactions were reported during the follow-up.There were one case of follicular inflammatory papule and one case of eczema like skin lesions during treatment.After symptomatic treatment,both of them were relieved.Conclusion:1.Secukinumab demonstrates rapid onset of action and long lasting efficacy in Chinese patients with moderate to severe plaque psoriasis in real-world practice.BMI,immune depressants treatment history and biologic treatment history have negative influences on the effectiveness of secukinumab.The overall safety profile of secukinumab during the treatment is favourable,but the incidence of eczematous lesions is high.2.Secukinumab is effective and safe in the treatment of PPP and ACH,and can be used as a new treatment option for refractory pustular psoriasis localized on the extremities.