Secukinumab Research Articles

Secukinumab in United States Biologic-Naïve Patients With Psoriatic Arthritis: Results From the Randomized, Placebo-Controlled CHOICE Study.

To evaluate secukinumab (SEC) 300 mg and 150 mg vs placebo in a United States-only population of biologic-naïve patients with psoriatic arthritis (PsA). CHOICE was a double-blind, randomized controlled trial conducted in the US. Biologic-naïve patients with PsA and psoriasis (PsO) were randomized 2:2:1 to SEC 300 mg (n = 103), SEC 150 mg (n = 103), or placebo (n = 52). The primary objective was to show superiority of SEC 300 mg vs placebo in American College of Rheumatology 20% (ACR20) response at week 16. Additional objectives included the effect of SEC on dactylitis, enthesitis, PsO, and safety. ACR20 response rates at week 16 were higher with SEC 300 mg than with placebo (51.5% vs 23.1%; odds ratio 3.51 [95% CI 1.65-7.45]; P = 0.001). SEC 300 mg also led to greater ACR50/70 responses and improvements in other variables vs placebo. Responses were generally sustained over time. Patients with inadequate response to SEC 150 mg at weeks 16, 28, or 40 who received dose escalation to 300 mg experienced improved clinical response after uptitration. The most common adverse events were upper respiratory tract infections and diarrhea. No inflammatory bowel disease was reported or new safety signals observed. SEC 300 mg led to rapid and significant improvements over placebo in symptoms of PsA in this heavier population of US-only, biologic-naïve patients. Findings were consistent with previous studies and suggest that SEC 300 mg is a safe and efficacious first-line biologic treatment for patients with PsA. [ClinicalTrials.gov: NCT02798211].

Efficacy of targeted drugs for the treatment of adults with moderate-to-severe plaque psoriasis in the Russian Federation: a systematic literature review update

Background. A systematic literature review helps to identify the main treatment options, and evidence synthesis supports decision-making by comparing clinical efficacy of different treatments. Nowadays new drugs and clinical trials emerge rapidly, so previous network meta-analyses might need to be updated.Objective: to update the existing systematic review and network meta-analysis comparing efficacy of targeted drugs in adult patients with moderate-to-severe plaque psoriasis by adding randomized clinical trials (RCTs) on a new interleukin (IL) 23 inhibitor registered in the Russian Federation – risankizumab, and other RCTs published after 2019; to reassess the Psoriasis Area and Severity Index (PASI) 75/90 numbers of patients needed to treat to achieve clinical response to therapy and the costs per responder for 12–16 weeks and 1 year of therapy.Material and methods. We updated our systematic literature search in the PubMed/MEDLINE and Embase databases. Evidence synthesis included RCTs evaluating the efficacy of adalimumab (ADA), infliximab (INF), etanercept (ETN), certolizumab pegol (CZP), ixekizumab (IXE), netakimab (NTK), secukinumab (SEC), risankizumab (RIS), guselkumab (GUS), ustekinumab (UST), tofacitinib (TOFA), and apremilast (APR) after 12 weeks of therapy. The Bayesian meta-analyses with meta-regression models were performed in order to account for high heterogeneity in patient characteristics and significant differences in the placebo response rates. The considered drugs were ranked based on values of surface under the cumulative ranking curve (SUCRA). Additionally, drug class analyses were carried out.Results. Twenty three new RCTs were added to the network. IL-23 inhibitor RIS, recently approved in the Russian Federation, has joined the group of the most efficacious drugs, such as IL-17 inhibitors NTK and IXE, as well as IL-23 inhibitor GUS. In terms of PASI 75, RIS and IXE showed superiority compared to all tumor necrosis factor alpha (TNFα) inhibitors (INF, ADA, ETN), small molecules (TOFA and APR), and IL-12/23 inhibitor UST, while NTK and GUS were characterized by comparable efficacy with INF and outperformed the remaining drugs. There were no statistically significant differences in efficacy between all the TNFα inhibitors. GUS, IXE, INF, NTK, RIS and SEC demonstrated that no more than 2 patients need to be treated to achieve one PASI 75 response, and no more than 3 need to be treated for one PASI 90 response (according to the upper limit of 95% credible interval). Same as in the previously published study, NTK showed the lowest costs per responder for both 12-week and 1-year periods.Conclusion. The addition of head-to-head trials and increased statistical power of the network revealed previously unidentified significant differences between treatment options for moderate-to-severe plaque psoriasis.

Secukinumab in the treatment for patients with juvenile enthesitis related arthritis non-responsive to anti-TNF treatment according the Juvenile Spondyloarthritis Disease Activity Index.

To review the effectiveness of secukinumab (SEC) in patients with juvenile idiopathic enthesitis related arthritis (ERA), who had partial or no response on anti-TNF therapy. We conducted a retrospective monocentric chart review of patients with ERA, who were treated with SEC, until March 15th 2019. We used the JADAS10 and the Juvenile Spondyloarthritis Disease Activity Index (jspADA) to evaluate response. We analysed the onset of AE and SAE. We analysed 17 patients with ERA. The mean age at the start of the treatment was 19.5 years (SD 4.9, range 13-34 years, median 18.2). The mean disease duration was 6.3 years (SD 3.3, range 2-12 years). The patients received in average 1.9 (SD1.0) different anti-TNF'́s before switching to SEC. SEC was applied at the start of the treatment with 150 mg per dose (n=13, 76.5%) and 300 mg per dose (n=4, 23.5%). The dose of 150 mg was increased in 11 patients (85% of 13) after baseline. The mean follow-up of patients was 18.2 months (SD 7.2) accounting to 25.8 years under exposure to SEC. The jspADA (mean change of -1.3; p<0.001; 95%CI: -1.9 to -0.7) and JADAS10 (mean change of -2.4; p=0.021; 95%CI: -4.5 to -0.4) signi cantly improved between baseline and the 24-month follow-up. There was no serious adverse event observed. In our anti-TNF non-responder patients SEC showed good effectiveness. The 150 mg dose seems to be insufficient in anti-TNF non-responder patients and most patients had to be escalated to the 300 mg/dose.

Treatment adherence and persistence of seven commonly prescribed biologics for moderate to severe psoriasis and psoriatic arthritis in a U.S. commercially insured population

Background Adalimumab (ADA), certolizumab pegol (CER), etanercept (ETA), guselkumab (GUS), ixekizumab (IXE), secukinumab (SEC), and ustekinumab (UST) are biologics approved for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA). We examined adherence and persistence among PsO patients with comorbid PsA who initiated treatment with any of these biologics. Methods Adult patients with ≥1 pharmacy/medical claim for any of these seven biologics, and ≥1 diagnosis of both PsO and PsA were selected from the MarketScan Commercial database (July 2014–June 2019). Adherence and persistence rates were examined among the seven study cohorts during fixed follow-up periods (3, 6, 9, and 12 months). Results Among patients with ≥9 months of continuous enrollment, 3,251 initiated ADA, 418 CER, 1,563 ETA, 126 GUS, 422 IXE, 1,596 SEC, and 1,267 UST. During the 9-month follow-up period, the proportions of adherent patients were numerically highest among those treated with GUS (59.5%) and UST (57.0%), followed by SEC (47.9%), IXE (47.6%), ADA (46.8%), ETA (37.4%), and CER (22.0%); persistence rates were also numerically highest among those treated with GUS (65.9%) and UST (65.7%). Limitations Adjustment for potential confounders was not conducted. Conclusions Adherence and persistence rates were numerically highest among patients who initiated GUS and UST.

Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study.

Objectives:To evaluate, in a multicentric Italian cohort of axial spondyloarthritis (axSpA) patients on Secukinumab (SEC) followed for 24 months: (1) the long-term effectiveness and safety of SEC; (2) the drug retention rate and low disease activity (LDA) measured as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4/Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 and very low disease activity (VLDA) measured as BASDAI < 2/ASDAS < 1.3; (3) any differences in outcomes according to line of biological treatment (naïve/non-naïve), gender (male/female), subtype of axSpA [radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)].Methods:Consecutive axSpA patients treated with SEC were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical-values were recorded at baseline (T0), 6 (T6), 12 (T12), and 24 (T24) months. Effectiveness was evaluated over-time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug discontinuation and LDA at T6. Infections and adverse events were recorded.Results:A total 249 patients (47.8% male; median age 51) were enrolled; 40.9% had HLA-B27; 53.8% had r-axSpA, and 46.2% nr-axSpA. SEC was prescribed in 28.9% naïve and in 71.1% non-naïve patients. SEC effectiveness was shown as an improvement in several outcomes, such as ASDAS [T0 = 3.5 (2.9–4.4) versus T24 = 1.9 (1.2–2.4); p = 0.02] and BASDAI [T0 = 6.5 (5.0–7.5) versus T24 = 2.8 (1.8–4.0); p = 0.03]. At T24, naïve patients showed better physical functioning and lower disease activity than non-naïve. After 24 months of treatment, 90.7% of naïve and 75.3% of non-naïve patients achieved LDA (BASDAI < 4). Treatment was discontinued in 24.5% patients, mainly due to primary/secondary loss of effectiveness, and in 6.8% due to adverse events. Retention rate at T24 was 75% in the whole population, with some difference depending on gender (p = 0.002).Conclusion:In a real-life clinical setting, SEC proved to be safe and effective in axSpA, mainly in naïve-patients, with a notable drug retention rate. No differences were observed between r-axSpA and nr-axSpA.

Comparative efficacy of secukinumab against adalimumab and infliximab in patients with moderate-to-severe plaque psoriasis.

Background:Psoriasis is a common, chronic, immune-mediated inflammatory skin disease with increased epidermal proliferation. The objective of this review was to systematically identify the evidence and perform a network meta-analysis (NMA) to estimate the relative efficacy of secukinumab (SEC) against adalimumab (ADA) and infliximab (INF) for the treatment of moderate-to-severe plaque psoriasis.Methods:A systematic literature review (SLR) was conducted according to a pre-specified protocol to identify relevant studies. Initially, the databases were searched from database inception till June 2013, and the SLR was updated in April 2020. The eligibility criteria included adult patients (≥18 years old) with moderate-to-severe plaque psoriasis, and the SLR included randomized controlled trials (RCTs). The comparators of interest were SEC, ADA, INF, and placebo (PLA), while outcomes of interest were Psoriasis Area and Severity Index (PASI) (50, 75, and 90) at weeks 12, 16, and 24. A Bayesian NMA for PASI was utilized with a framework that evaluated the probability of PASI responses in different categories of PASI thresholds within a single model.Results:A total of 23 RCTs that assessed the efficacy of SEC, ADA, and INF in patients with moderate-to-severe plaque psoriasis were identified. At 12 weeks, SEC was associated with a significantly better response compared with PLA and ADA for PASI 75 and 90, while response results were comparable against INF. At 12 weeks, risk ratio (95% confidence interval) derived from NMA for SEC vs. ADA and INF for PASI 75 was 1.35 (1.19, 1.57) and 1.01 (0.90, 1.18), respectively. At the 16-week and 24-week time interval, SEC was significantly better than PLA, ADA, and INF for PASI 75 and 90.Conclusion:Efficacy of SEC in the treatment of patient populations with moderate-to-severe plaque psoriasis is well demonstrated through NMA.

New-onset inflammatory bowel diseases among IL-17 inhibitor-treated patients: results from the case-control MISSIL study.

To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life. A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease. Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD. The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.

Drug Adherence and Persistence of Patients with Moderate to Severe Psoriasis Treated with Biologic Medications in a US Commercially Insured Population

Background: Adalimumab (ADA), certolizumab pegol (CER), etanercept (ETA), guselkumab (GUS), ixekizumab (IXE), secukinumab (SEC), and ustekinumab (UST) are biologic medications approved in the USA for the treatment of moderate to severe psoriasis. We examined drug adherence and persistence of patients with moderate to severe psoriasis who initiated these seven biologic medications. Methods: Adult patients with ≥1 pharmacy/medical claim for any of the seven psoriasis medications and ≥1 diagnosis of psoriasis in the previous 6 months between July 1, 2014 and June 30, 2019 were selected from the IBM MarketScan® Commercial Claims and Encounters Database. The index date was defined as the date of the first prescription fill. Patients were required to have continuous health plan enrollment during the 6 months prior to their index date and ≥9 months after. Patients were grouped into seven study cohorts based upon their index biologic medication. Adherence was measured using the proportion of days covered (PDC) and defined by a PDC ≥80%. Adherence and persistence with index biologic medications were examined during fixed follow-up periods of 3, 6, and 9 months, with a subpopulation analysis carried out among patients with 12 months of follow-up. Results: Among psoriasis patients with ≥9 months of continuous enrollment included in the study population, the number of those who initiated each biologic medication was 10,324 for ADA, 431 for CER, 3,092 for ETA, 821 for GUS, 1,766 for IXE, 4,132 for SEC, and 5,441 for UST. The mean age at the time of initiating biologic treatment was 46.9 years. During the 9-month follow-up period, the proportions of adherent patients (i.e., PDC ≥80%) were numerically higher among those treated with UST (59.9%) and GUS (56.9%), followed by those treated with SEC (46.1%), IXE (45.5%), ADA (44.7%), ETA (33.9%), and CER (22.0%). The proportions of patients who were persistent with their index biologic medication during the 9-month follow-up period were numerically higher among those treated with UST (70.1%) and GUS (67.8%), followed by those treated with IXE (47.3%), SEC (46.9%), ADA (28.7%), CER (14.8%), and ETA (10.7%). Conclusions: In this large healthcare claims database analysis of psoriasis patients treated with seven different biologic medications, adherence was numerically higher among those treated with UST or GUS. UST and GUS were also associated with numerically greater persistence.

Comparison of Real-World Treatment Patterns Among Biologic-Experienced Patients with Psoriasis Treated with Ixekizumab or Secukinumab Over 18Months.

IntroductionReal-world data comparing effectiveness of ixekizumab (IXE) and secukinumab (SEC) among biologic-experienced patients are limited. This study compared treatment patterns over 18 months among biologic-experienced patients with psoriasis receiving IXE or SEC in the USA.MethodsA retrospective observational study using administrative claims data from IBM® Watson Health MarketScan® Research Databases included adult patients with ≥ 1 inpatient or ≥ 2 non-diagnostic (≥ 30 days apart) outpatient claim/s with diagnosis of psoriasis between March 1, 2015 and October 31, 2019, and ≥ 1 claim/s for index drugs, IXE or SEC, between March 1, 2016 and October 31, 2019. Patients had to have ≥ 1 claim/s for biologics indicated for psoriasis in the 6-month pre-period. During the 18-month follow-up, treatment adherence (proportion of days covered [PDC]), high adherence (PDC ≥ 80%), persistence, discontinuation, reinitiation, and switching were assessed. To address cohort imbalances, inverse probability of treatment weighting was employed. Logistic regression was used to estimate odds ratio for high adherence. Cox proportional hazard models were used to estimate hazard ratio for non-persistence, discontinuation, and switching.ResultsOverall, 411 IXE and 780 SEC users were included. After weighting, IXE users had significantly higher rate of high treatment adherence (42% vs. 35%, p = 0.019), higher persistence rate (44.9% vs. 36.9%, p = 0.007), lower discontinuation rate (48.4% vs. 56.0%, p = 0.012), and lower switching rate (26.6% vs. 34.0%, p = 0.009) compared with SEC users. After multivariable adjustment, compared with SEC, IXE use was associated with 36% higher odds of high treatment adherence (OR 1.36, 95% CI 1.05–1.74), 20% lower risk of treatment non-persistence (HR 0.80, 95% CI 0.68–0.93), 19% lower risk of discontinuation (HR 0.81, 95% CI 0.68–0.96), and 25% lower risk of switching (HR 0.75, 95% CI 0.60–0.93).ConclusionThis study suggests that IXE treatment is associated with significantly higher adherence rates and significantly lower non-persistence, discontinuation, and switching compared with SEC treatment.

Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain.

IntroductionThere is limited and conflicting evidence over the real-world drug survival of secukinumab (SEC) in patients with psoriasis, especially in the long term. Our objective was to analyze the short- and long-term survival of SEC (S-SEC) and its predictive factors for the treatment of psoriasis.Methods Patients clinically diagnosed with plaque psoriasis and under treatment with secukinumab (n = 384) in a daily practice setting were analyzed in a retrospective, multicenter study performed in a nationwide cohort and followed up for a period of 2 years. Kaplan–Meier curve was plotted to analyze drug survival time, and log-rank test was performed to compare several groups. Factors related to speed of treatment discontinuation were studied with a Cox regression model.ResultsThe overall cumulative secukinumab drug survival rates observed at 6, 12, 18, and 24 months were 97.1%, 89.0%, 81.1%, and 74.3%, respectively. Obesity [hazard ratio (HR), 1.809, CI 95% 1.114–2.962; p = 0.004] and previous experience with biological therapies, particularly those who had been treated with ≥ 2 biologicals with different mechanisms of action (HR 3.476, CI 95% 1.875–6.444; p = 0.017) were associated with an early discontinuation, whereas psoriatic arthritis was associated with delayed discontinuation, (HR 0.493, CI 95% 0.265–0.917; p = 0.025).ConclusionsIn our study, we found that cumulative secukinumab drug survival for psoriasis patients for the period 6–18 months was in the range of real-world evidence studies. Additionally, we observed a relatively high long-term survival rate at 24 months (74.3%).

26592 Characterization of response clusters identified by unsupervised machine learning: A post hoc analysis of the head-to-head ECLIPSE trial of guselkumab and secukinumab in patients with moderate-to-severe psoriasis

Introduction and Objectives: This post hoc analysis of ECLIPSE study data aimed to identify novel PASI response patterns in the guselkumab (GUS) and secukinumab (SEC) treatment arms, through unsupervised machine learning (ML).

26834 Secukinumab demonstrated sustained effectiveness in moderate-to-severe plaque psoriasis across weight categories: 36-month data from PURE

Introduction: Secukinumab (SEC), a fully human monoclonal antibody that selectively neutralizes interleukin-17A, showed sustained effectiveness and safety in psoriatic diseases (1-5). This abstract presents effectiveness and quality of life improvement data for patients treated with secukinumab across weight categories up to 36 months in the PURE registry.

Psoriasis treatment patterns and outcomes with ixekizumab in a real-world setting: results from a single US dermatology referral practice

Objective To assess treatment patterns of Ixekizumab (IXE) and evaluate the speed of onset and long-term clinical and quality-of-life outcomes among a subset of patients who switched from adalimumab (ADA) and secukinumab (SEC) to IXE in a real-world setting. Method A retrospective chart review study was conducted at a single US dermatology referral center. Result 153 patients were included in the study, 69.3% of patients were biologic-experienced. ADA was the most commonly used biologic prior to IXE initiation. 66.7% of patients remained on IXE at the study end. 47.7% of patients received concomitant methotrexate, and usage decreased consistently after 1 month. IXE treatment duration was longer among patients who were early responders (achieved sPGA (0,1) at 1 month) vs. non-early responders. 69.4% and 43.3% of patients who switched from ADA and SEC to IXE achieved sPGA (0,1) by week 4, respectively. Conclusion Patients who switched to IXE, specifically from ADA or SEC, had rapid treatment response as well as desirable long-term outcomes. IXE persistence was longer among early responders than non-early responders. Concomitant usage of methotrexate prior to switching to IXE and as a concomitant bridging treatment was reduced after IXE initiation while the proportion of patients achieving treatment targets remained high.

Treatment Dissecting Cellulitis of the Scalp With Secukinumab.

Treatment Dissecting Cellulitis of the Scalp With Secukinumab.

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Multicenter Study of Secukinumab Survival and Safety in Spondyloarthritis and Psoriatic Arthritis: SEcukinumab in Cantabria and ASTURias Study.

Objectives: We aimed to evaluate the drug retention rate and safety of secukinumab (SEC) in patients with axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) in a real clinical setting.Methods: This multicenter retrospective observational study included all AxSpA and PsA patients who received at least one dose of SEC. Adverse events (AE) and the drug retention rate were the main study outcomes. Drug survival was analyzed by Kaplan-Meier curves while predictive factors of discontinuation were evaluated using a Cox regression analysis. The weight of these associations was estimated by hazard ratio (HR) values.Results: We included 154 patients (59 PsA and 95 AxSpA). Mean disease duration was 6.5 years (IQR 2-8). Sixty-one percent of patients were treated with two or more biologics prior to SEC. The 1 and 2-year retention rates for SEC were 66 and 43%, respectively. The main causes of discontinuation were inefficacy (59%) and AE (36%). The factors associated with lower risk of discontinuation were male gender (HR 0.54, 95% CI 0.38-0.78 p = 0.001), obesity (HR 0.53, 95% CI 0.30-0.93 p = 0.027), hypertension (HR 0.55, 95% CI 0.30-0.93 p = 0.008), and diabetes (HR 0.42 95% CI 0.18-0.99 p = 0.047) while number of previous biologics and depression were predictors of discontinuation (HR 1.18, 95% CI 1.04-1.34 p = 0.011 and HR 2.53, 95% CI 1.61-3.96 p < 0.001).Conclusions: SEC showed a good retention rate in a population previously exposed to several biological therapies. As a novelty, cardiometabolic comorbidities were associated with better drug survival.

LB0004 EFFICACY AND SAFETY OF SECUKINUMAB IN ENTHESITIS-RELATED ARTHRITIS AND JUVENILE PSORIATIC ARTHRITIS: PRIMARY RESULTS FROM A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, TREATMENT WITHDRAWAL, PHASE 3 STUDY (JUNIPERA)

Background:Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are two ILAR categories of juvenile idiopathic arthritis (JIA) and represent paediatric correlates of axial spondyloarthritis (axSpA) and adult psoriatic arthritis (PsA), respectively.1,2 Secukinumab (SEC) has demonstrated efficacy and safety in adult patients (pts) with PsA, ankylosing spondylitis and non-radiographic axSpA.3-5Objectives:Evaluate efficacy and safety of SEC using a flare prevention design in pts with active ERA and JPsA.Methods:This 2-yr study consisted of an open-label (OL) s.c. SEC (75/150 mg in pts &lt;50/ ≥50 kg) at baseline (BL), and at Weeks (Wk) 1, 2, 3, 4, 8 and 12 in treatment-period (TP) 1. Responder pts who achieved at least JIA ACR 30 response at Wk 12 were randomised into the double-blinded TP2 to continue SEC or placebo (PBO) q4w until a disease flare, or up to Wk 100. Pts (aged 2 to &lt;18 yrs) classified as ERA or JPsA according to ILAR criteria of ≥6 months duration with active disease were included. Primary endpoint was time to flare in TP2 and key secondary endpoints were JIA ACR 30/50/70/90/100, inactive disease, JADAS, enthesitis count and safety. Analysis of time to flare in TP2 included proportion of disease flare, Kaplan-Meier (KM) estimate of median time to flare in days, hazard ratio (95% CI) from Cox model, and P-value for the Stratified log-rank test. KM estimates of the probability to disease flare by treatment groups in TP2 were plotted against days. Observed data were used in all analyses. Post-hoc analyses using non-responder imputation (NRI) were performed for JIA ACR 30/50/70/90/100 responses.Results:86/97 (89%) pts were enrolled in the OL period TP1 (mean age, 13.1 yrs; female, 33.7%; ERA, n=52; JPsA, n=34). At BL, mean JADAS-27 score was 15.1 and enthesitis count was 2.6. At the end of TP1, 90.4% (75/83) of pts achieved JIA ACR 30 and 69.9% (58/83) achieved JIA ACR 70. There were 21 and 10 flares in TP2, respectively in PBO and SEC treated pts with a significantly longer time to flare and 72% risk of flare reduction in SEC treatment vs PBO (HR: 0.28; 95% CI: 0.13–0.63; P&lt;0.001) (Figure 1). JIA ACR responses, disease activity and enthesitis count are reported in Table 1. NRI analyses showed that 87.2%, 83.7%, 67.4%, 38.4% and 24.4% of pts achieved JIA ACR 30/50/70/90/100, respectively. Rates of adverse events (AEs; 91.7% vs 92.1%) and serious AEs (14.6% vs 10.5%) in SEC and PBO groups were comparable in the entire TP. No new safety signals were observed.Table 1.Efficacy of secukinumab in Treatment Periods 1 and 2 (Key secondary endpoints)Efficacy Outcomes, %TP1TP2¥SEC (N=83)^SEC (N=37)PBO (N=37)P-valueJIA ACR 3090.489.264.90.014JIA ACR 5086.778.462.20.152JIA ACR 7069.967.643.20.042JIA ACR 9039.851.440.50.431JIA ACR 10025.343.237.80.745Inactive disease#36.147.237.80.500JADAS-27, mean (SD)15.1 (7.2)14.6 (8.1)13.3 (5.8)NAEnthesitis count, mean change from BL (SD)−1.8 (2.3)−2.1 (2.0)−1.9 (1.2)NAP-values: Cochran-Mantel-Haenszel test, adjusted for analysis factors: JIA category (ERA/ JPsA) and MTX use at BL¥The N numbers are values at the end of TP2^Efficacy outcomes (%) in TP1 calculated in patients with evaluable data at Wk 12 (N=83)#Inactive disease: Definition adapted from JIA ACR criteria of Wallace et al., 2011. N=36 for SEC at the end of TP2JADAS, Juvenile Arthritis Disease Activity Score; N, total number of patients in the treatment group; NA, data not availableFigure 1.Time to flare in Treatment Period 2 (Primary Endpoint)Conclusion:In children and adolescents with ERA and JPsA, efficacy of SEC was demonstrated with a significantly longer time to flare vs PBO with sustained improvement of signs and symptoms up to Wk 104 and a favourable safety profile.

POS1044 EFFECT OF SECUKINUMAB VERSUS ADALIMUMAB ON ACR CORE COMPONENTS AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM THE EXCEED STUDY

Background:EXCEED (NCT02745080) was the first fully blinded head-to-head trial to evaluate the efficacy and safety of secukinumab (SEC) versus (vs) adalimumab (ADA) monotherapy in patients with active psoriatic arthritis (PsA) with a primary endpoint of American College of Rheumatology (ACR) 20 at Week 52. Although SEC narrowly missed statistical significance for superiority vs ADA, numerically higher response for other musculoskeletal endpoints and composite indices were observed with SEC.1Objectives:To explore the effect of SEC and ADA on ACR core components, function and Health-related Quality of Life (HRQoL) outcomes.Methods:Patients were randomised 1:1 to receive SEC 300 mg (N=426) subcutaneous (s.c.) at baseline, Week 1-4, followed by every 4 weeks until Week 48 or ADA 40 mg (N=427) s.c. at baseline followed by same dosing every 2 weeks until Week 50. The primary, key secondary and some exploratory endpoints at Week 52 were previously reported.1 A supportive analysis for ACR50 response using logistic regression model and trimmed means model for Health Assessment Questionnaire-Disability Index (HAQ-DI) with gender and smoking status as factors was performed to adjust for imbalances in baseline characteristics. An exploratory analysis of ACR core components with SEC vs ADA at Week 52 was conducted using a mixed-effects repeated measures model that included tender and swollen joint counts, patient and physician global assessment, PsA pain (VAS) and erythrocyte sedimentation rate. HRQoL variables were also exploratory and assessed based on Short Form Health Survey Physical/Mental Component Summary (SF-36 PCS/MCS) scores and Dermatology Life Quality Index (DLQI).Results:The demographic and baseline disease characteristics were comparable across treatment groups, except for an imbalance in sex (females: 51.2% vs 46.4%) and smoking status (yes: 21.8% vs 17.8%) in SEC and ADA group, respectively. At Week 52, ACR50 responses were 49.0% and 44.8% (P=0.0929) and HAQ-DI mean change from baseline were −0.69 and −0.58 (P=0.0314) in SEC and ADA treatment groups, respectively after adjusting for gender and smoking status. No major difference across ACR core components was observed in both treatment groups at Week 52 (Table 1). At Week 52, SEC presented similar improvement in SF-36 PCS/MCS score and numerically higher improvement in DLQI compared to ADA (Figure 1).Conclusion:Secukinumab provided similar improvements in ACR core components and SF-36 based quality of life at Week 52 with adalimumab. Greater improvement in HAQ-DI response and DLQI was demonstrated with secukinumab compared to adalimumab.

POS0020 EFFICACY AND SAFETY OF SECUKINUMAB IN PATIENTS WITH ROTATOR CUFF TENDINOPATHY: A 24-WEEK, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE II PROOF-OF-CONCEPT TRIAL

Background:Rotator cuff tendinopathy (RC TP) is a multifactorial condition and one of the most common causes of musculoskeletal burden. Current standard of care (SoC) is limited to pain relief with NSAIDs and physiotherapy. Recent evidence indicates that IL-17A-expressing tendon-resident immune cells are present in human overuse tendinopathy, and IL-17A levels are increased in early human tendinopathic tissue samples [1, 2]. Secukinumab (SEC) is a fully human, monoclonal antibody that binds to and neutralises IL-17A.Objectives:To evaluate the efficacy and safety of SEC in patients with active overuse RC TP refractory to oral NSAIDs/acetaminophen, physiotherapy or corticosteroid injections.Methods:96 patients with symptomatic RC TP with no or &lt;50% rupture were randomly assigned to receive seven subcutaneous injections of SEC 300 mg or placebo (PBO) at baseline and Weeks 1, 2 and 3, followed by every 4 weeks starting at Week 4. The primary endpoint was change from baseline in the Western Ontario Rotator Cuff (WORC) index score at Week 14 for SEC vs PBO (two-sided p&lt;0.1). Secondary endpoints included, visual analogue scale (VAS) pain score, Disability of Arm, Shoulder and Hand Questionnaire (QuickDASH) score, American Shoulder and Elbow Surgeons Shoulder Evaluation Form (ASES), EQ-5D-5L score and patient global assessment (PGA) score. All endpoints were assessed through 24 weeks.Results:Clinically relevant improvement in both SEC and PBO groups on top of SoC treatment was observed, with no statistically significant difference demonstrated in the full study population on physical symptoms and function (Table 1). Similar results were observed in the secondary endpoints with marked improvement in both groups over time. Exploratory post-hoc analyses in a subpopulation of 39% of the study subjects with non-acute, moderate to severe disease, SEC provided significant and clinically relevant improvements vs PBO through Week 24 in total WORC score (overall treatment difference: 19.2, p &lt;0.01) and pain (VAS, overall treatment difference: 15, p = 0.02) with early effect observed after two weeks (Figure 1). A favourable treatment effect in the more severe subgroup was demonstrated in other patient-reported outcomes. No serious adverse events were reported.Conclusion:Although SEC did not demonstrate a significant benefit vs PBO in the overall patient population with active overuse RC TP, SEC did provide benefit in the subpopulation with non-acute, moderate to severe disease. Larger clinical trials of SEC in this area are warranted.