To evaluate the real-world effectiveness, treatment retention, and safety of secukinumab (SEC) uptitration to 300 mg in patients with axial spondyloarthritis (axSpA), including radiographic (r-axSpA) and nonradiographic (nr-axSpA) subtypes, with active disease despite receiving SEC 150 mg every 4 weeks. This multicenter, retrospective study included patients with axSpA who had received SEC 150 mg for ≥ 3 months and had active disease (Axial Spondyloarthritis Disease Activity Score [ASDAS] ≥ 2.1) at the time of dose escalation. Patients were followed for up to 24 months after escalation. Effectiveness was assessed through changes in ASDAS over time. Treatment retention was analyzed using Kaplan-Meier curves, with factors associated with discontinuation explored by Cox regression. Safety outcomes were reported as incidence of adverse events (AEs). Among 106 patients (77 r-axSpA, 29 nr-axSpA), ASDAS significantly declined within 6 months and was sustained through 24 months. Median ASDAS decreased from 4.1 to 2.0 in patients with r-axSpA and from 4.1 to 2.0 in those with nr-axSpA. Overall, 85.9% of patients achieved ASDAS ≤ 2.1 at least once after escalation. Retention of SEC 300 mg was 87.8% at 6 months and 59.1% at 24 months, with no significant difference between subtypes (log-rank P = 0.48). HLA-B27 positivity showed a nonsignificant trend toward higher discontinuation risk. AE incidence was 15.79 per 100 patient-years, and AEs were mostly mild infections and cutaneous reactions. No new safety signals were identified. SEC uptitration to 300 mg was associated with sustained improvements in disease activity and favorable retention and safety in axSpA patients with active disease after receiving SEC 150 mg, supporting dose escalation as a clinically effective and safe strategy.

ABSTRACTPsoriatic arthritis (PsA) is a chronic inflammatory disease, with prevalence among psoriasis patients ranging from 6% to 42% across populations. Although targeted therapies such as adalimumab (ADA), secukinumab (SEC), and upadacitinib (UPA) have demonstrated efficacy in randomized controlled trials, real‐world head‐to‐head comparisons remain limited. This study aimed to compare the real‐world effectiveness and safety of ADA, SEC, and UPA in PsA patients. We conducted a prospective cohort study using data from the PARWCH database. PsA patients treated with ADA, SEC, or UPA were included and followed at baseline, Week 4, Week 12, and Week 24. Skin responses were evaluated using PASI75/90. Joint outcomes—including peripheral and axial arthritis—were assessed with ACR, PsARC, and ASAS criteria. Patient‐reported pain, disease activity, and HAQ scores were also recorded. Adverse events (AEs) were monitored throughout treatment. MMRM and GLMM were used to analyze continuous and binary outcomes, respectively. A total of 187 PsA patients were included (SEC: 78; ADA: 66; UPA: 43). All three agents demonstrated comparable effectiveness in improving peripheral joint symptoms (ACR20: SEC vs. ADA, Coef = −0.29, p = 0.62; UPA vs. ADA, Coef = −0.29, p = 0.66) and axial involvement (ASAS20: SEC vs. ADA, Coef = −0.04, p = 0.81; UPA vs. ADA, Coef = −1.05, p = 0.23). UPA and SEC showed significantly greater effectiveness than ADA in improving skin lesions (PASI90: SEC vs. ADA, Coef = 1.84, p = 0.006; UPA vs. ADA, Coef = 1.53, p = 0.04). However, ADA was more effective in relieving pain compared to both UPA (Coef = 2.43, p < 0.001) and SEC (Coef = 1.21, p = 0.02). Over 24 weeks, 85 AEs were reported by 48 patients, with fatigue, rash, upper respiratory tract infection, and pruritus being the most common. No serious AEs occurred. In conclusion, UPA and SEC demonstrated balanced effectiveness across skin and joint domains, while ADA offered superior pain relief. These findings support personalized treatment strategies tailored to the clinical features of PsA patients.

Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory arthropathy presenting with multiple manifestations, including peripheral arthritis, enthesitis, and skin psoriasis (PSO). Immunosuppressive/immunomodulatory therapies, including biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD), are common effective treatments for PsA; however, discontinuation is reported and contributing factors remain unclear. To describe the probability of persistence and time to discontinuation (including switch) of b/tsDMARD therapy in both b/tsDMARD-naive and -experienced patients with PsA within 12 months following initiation of a new b/tsDMARD. Secondary objectives included (1) describing the factors associated with b/tsDMARD persistence or nonpersistence and (2) assessing maintenance dose changes among patients with PsA initiating the anti-IL17A agents secukinumab (SEC) or ixekizumab (IXE). SEC and IXE were of particular focus owing to the variability in their dosage recommendation guidelines at the time of this study. This observational cohort study used Merative MarketScan data and included patients initiating a new prescription of b/tsDMARD treatment for PsA, with a diagnosis of PsA between January 1, 2017, and June 30, 2021. The primary outcome was persistence, defined as days of b/tsDMARD therapy use from index date to 12 months of continuous index treatment, or first occurrence of b/tsDMARD discontinuation/switch. Associations between patient characteristics and outcomes were explored using Cox regressions, with descriptive dose analyses exploring proportions of patients with specific starting/maintenance b/tsDMARD doses. 7,037 adult patients with PsA were included: 26.7% with PsA only and 73.3% with PsA+PSO at baseline. The 12-month probability for persistence of b/tsDMARD treatment was 51.2% (95% CI, 49.5%-52.9%), with an 8.3-month mean length of persistence. Treatment persistence probability at 12 months was 52.7% (50.8%-57.7%) for patients with PsA+PSO and 47.0% (43.7%-50.3%) for patients with PsA only. Treatment persistence probability at 12 months was 51.4% (49.6%-53.2%) for the b/tsDMARD-naive subgroup and 49.8% (45.5%-54.1%) for the b/tsDMARD-experienced group. Female sex and a baseline codiagnosis of fatigue were associated with an increased probability of nonpersistence, whereas codiagnosis of PSO was associated with decreased probability of nonpersistence. In the dosing analysis, of the patients initiating SEC therapy included in the analysis, 60.4% were prescribed a starting maintenance dose of 300mg every 4 weeks (Q4W) and 34.1% were prescribed a starting maintenance dose of 150mg Q4W. Of patients initiating IXE therapy included in the analysis, 84.4% were prescribed an 80-mg Q4W starting maintenance dose and 10.4% were prescribed a 160-mg Q4W starting maintenance dose. The findings of this study provide relevant insights into tailoring b/tsDMARD therapy to maximize clinical benefit and potentially identify patients with the greatest unmet need.

Background: The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate Th17-mediated cytokine cascades, wherein IL-17 plays a critical role, as well as to explore the adjunctive anti-inflammatory effects of HONK on Th1 cytokine production, including IL-6, TNF-α, and Th2 cytokines. Methods: Mice were sensitized and challenged with ovalbumin (OVA) and lipopolysaccharide (LPS) was administrated to exacerbate pulmonary pathology, followed by administration of SECU, HONK (98% purity, C18H18O2), or their combination. Quantitative analyses incorporated OVA-specific IgE measurements, differential cell counts in bronchoalveolar lavage fluid (BALF), and extensive cytokine profiling in both BALF and lung tissue homogenates, utilizing precise immunoassays and histopathological scoring systems. Results: Both SECU and HONK, when used alone or in combination, display significant immunomodulatory effects in a murine model of allergic asthma concomitant with ALI. The combined therapy synergistically reduced pro-inflammatory mediators, notably Th1 cytokines, such as TNF-α and IL-6, as measured in both BALF and lung tissue homogenates. Conclusions: The combined therapy showed a synergistic attenuation of pro-inflammatory mediators, a reduction in goblet cell hyperplasia, and an overall improvement in lung histoarchitecture. While the data robustly support the merit of a combinatorial approach targeting multiple inflammatory mediators, the study acknowledges limitations in cytokine diffusion and the murine model's translational fidelity, thereby underscoring the need for further research to optimize clinical protocols for severe respiratory inflammatory disorders.

The Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional study investigating the comparative effectiveness and durability of biologic treatments for patients with moderate-to-severe psoriasis (PsO) over 36months. Patients were grouped into cohorts based on biologic class: anti-interleukin (IL)-17A/receptor A (anti-IL-17A), anti-IL-12/23, anti-IL-23 and anti-tumor necrosis factor (TNF)-α for the purpose of comparison. Additionally, the durability and effectiveness of individual biologic treatments were compared to ixekizumab (IXE). Effectiveness was assessed using Psoriasis Area and Severity Index (PASI) 90 and PASI100 response rates and durability, defined as achieving therapeutic response (PASI90/100) at week 12 and its maintenance at months 6, 12, 18 and 24. Statistical analysis included unadjusted descriptive summaries and model-based comparisons that accounted for baseline confounders using the frequentist model averaging (FMA) framework and marginal structural models (MSM) that accounted for both baseline and time-varying confounders. Results demonstrated that patients treated with anti-IL-17A biologics had significantly higher odds of achieving PASI100 and PASI90 compared to those treated with anti-IL-12/23 and anti-TNFα biologics. Specifically, at 24months, IXE showed greater PASI100 and PASI90 response rates compared to adalimumab (ADA) and ustekinumab (UST), with adjusted odds ratios of 1.9 and 2.3 for PASI100 and 2.0 and 2.5 for PASI90, respectively. IXE-treated patients also exhibited higher durability rates for PASI100 and PASI90 compared to ADA, UST, secukinumab (SEC), tildrakizumab (TILD) and guselkumab (GUS), with adjusted odds ratios (non-responder imputation [NRI]) between 1.7 and 4.3 (PASI100) and 1.6 and 4.2 (PASI90), while being similar to risankizumab (RIS). This study provides valuable real-world data on the long-term effectiveness and durability of biologic treatments for PsO, emphasizing the advantages of anti-IL-17A biologics, particularly IXE, in achieving and maintaining therapeutic responses. These findings support dermatologists in making informed decisions regarding PsO treatment strategies. The study was registered at the European Network of Centers for Pharmacoepidemiology and Pharmacovigilance (ENCEPP24207).

ObjectivesTreatment (tx) guidelines for psoriatic arthritis (PsA) recommend biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic (ts) DMARDs after inadequate response to conventional synthetic DMARDs (csDMARDs).[1] In clinical studies, ixekizumab (IXE) has shown efficacy in patients (pts) with PsA who were bDMARD-naïve,[2] tumor necrosis factor inhibitor (TNFi)-experienced,[3] and with and without concomitant csDMARDs. Data from real-world studies is limited. This interim analysis reports the effectiveness of IXE and other b/tsDMARDs in b/tsDMARD-naïve (naïve) and -experienced (exp) pts as well as in monotherapy (mono) and in combination (combo) with any csDMARD at 12 months (M) in real-world setting.MethodsIn the PRO-SPIRIT study, pts with PsA who initiated or switched to new b/tsDMARDs were evaluated in 5 European countries, and Canada. Pts were categorized by prior b/tsDMARD tx and concomitant csDMARD use at baseline (BL), respectively. Descriptive data for the analysis population at 12 M are presented. Mixed models for repeated measures (MMRM) were used to assess change from BL (CFB). Missing data was handled using multiple imputation.ResultsOf 1192* pts, TNF inhibitors (TNFi) (68.6%) and secukinumab (SEC) group (33.5%) had the highest proportion of naïve pts, whereas TNFi (53.5%) and JAKi (46.8%) had the highest proportion of combo pts (Table). At 12 M, similar mean CFB was observed in pts treated with IXE for clinical Disease Activity in Psoriatic Arthritis (cDAPSA) in the naïve (−13.6), exp (−12.1), mono (−12.3), and combo (−12.4) subgroups (subsequently reported in that order, herein); as well as for body surface area (BSA) (−5.0), (−3.6) (−4.4) and (−3.9). Similar trends were observed in tender joint counts and swollen joint counts. However, mean CFB in cDAPSA was lower in exp versus (vs) naïve pts treated with SEC (−8.9 vs −12.8), IL-12/23i (−7.4 vs −16.2) and IL-23i (−10.1 vs −17.2) and lower in mono vs combo in TNFi (−12.5 vs −15.2) and IL-23i (−11.0 vs −12.6). Mean CFB in BSA was lower in exp vs naïve pts treated with TNFi (−2.8 vs −5.4), and IL-23i (−2.0 vs −5.3).Table:BL characteristics for patients categorized by b/tsDMARD-naive, -experienced, monotherapy, and combination with csDMARDsConclusionIn real-world setting, IXE demonstrated similar effectiveness on joints and skin regardless of therapy line and concomitant csDMARDs, confirming findings from IXE clinical trials2,3. Other treatments showed less consistent results either in exp vs naïve pts (SEC, IL-12/23i, IL-23i) or in mono vs combo therapy (TNFi, IL-23i). [1.] Gossec L. Ann Rheum Dis 2020;79:700-12. [2.] Nash P. Lancet 2017;389:2317-27. [3.] Mease P. Ann Rheum Dis 2017;76:79-87.

To describe the access, effectiveness, survival, and adverse events (AEs) of secukinumab (SEC) in patients with axial spondyloarthritis (axSpA) and axial psoriatic arthritis (axPsA). In a multicenter, observational, retrospective cohort study, patients ≥ 18 years with axSpA or axPsA who had received ≥ 1 dose of SEC were included. The number of days between the request for the drug and the first application was calculated. Effectiveness was defined as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4 at 6 months. Drug survival was analyzed using Kaplan-Meier curves and Cox regression analysis. One hundred seventeen patients were included: 72 (61.5%) with axPsA and 45 (38.5%) with axSpA. Those having public health insurance presented a longer delay in receiving SEC (median 90 days [IQR 60-150]) vs those using the social security system (P = 0.01) and those with private health coverage (P = 0.009). Effectiveness of SEC after 6 months was achieved in 72/117 patients (61.5%): 44/72 patients with axial PsA (61.5%) and 28/45 patients with axSpA (62.2%; P = 0.91). The median SEC survival was 48 months (95% CI 32-63). The only factor associated with reduced survival was SEC as third-line treatment or higher (hazard ratio 3.43, 95% CI 1.11-11.10; P = 0.04). The incidence of AEs was 7.9 events/100 patients/year (95% CI 5-12). The delay in receiving SEC was longer in patients with public health insurance. Patients using SEC as third-line or higher therapy had 3.4 times less survival. AEs were mild and no AEs of interest were observed.

Many tools, such as the Psoriasis Area and Severity Index (PASI), are commonly used to evaluate treatment efficacy in clinical settings, but an optimal measure of treatment response may overlook the systemic response in psoriasis patients receiving treatment. This study aimed to assess and compare the co-benefits of adalimumab (ADA), ustekinumab (USTE), ixekizumab (IXE), secukinumab (SECU), and guselkumab (GUSE) during a 24-week follow-up period for the treatment of psoriasis in the Chinese population. We performed a prospective, randomized cohort study including patients receiving systemic biologic treatment for moderate to severe psoriasis. We conducted a follow-up of psoriatic patients treated with five biologics from January 2023 to June 2024 at four time points: baseline, week 4, week 12, and week 24. From baseline through every time point, we used the PASI, BSA (Body Surface Area), DLQI (Dermatology Life Quality Index), and metabolic and inflammatory screening for assessment and comparison of the clinical and systemic efficacy of biologics.This study included 385 participants treated with 5 different biologics. There was a dramatic clinical improvement from baseline to week 24, with a statistically significant difference (p < .001). Overall, 35 patients (9.09%), 145 (37.14%) and 335 (86.75%) achieved PASI 100 at week 4, week 12, and week 24 of the follow-up. Compared with other biologics, IXE (PASI 100 = 12.12% at week 4 vs. 87.27% at week 24) and SECU (PASI 100 = 7.79% at week 4 vs. 89.92% at week 24) were superior. At week 12, a high percentage with PASI 100 was observed for GUSE (38.71%) and SECU (40.28%). ADA and USTE continuously maintained a low percentage of the PASI 100. We observed quicker systemic improvements due to GUSE at time point 2 (p = .041, with low values of total cholesterol (TC) and non-HDL-C, p = .046) and week 24 for TNF-α (p = .024) than other biologics did. SECU and ADA had greater metabolic efficacy for GLU (p = .037 at week 12) and UA (p = .033 at week 24), respectively. This study confirmed the clinical efficacy of biologics and their ability to achieve complete skin clearance and further demonstrated that all biologics can continuously reduce systemic inflammation. We found that biologics have different effects on metabolic dysfunctions, such as SECU on glucose and GUSE on non-HDL.

Peptide-based hydrogel co-assembled with antibody-drug for enhanced retinal cell uptake and attenuated experimental autoimmune uveitis.

Evaluation of drug survival and predictive factors of alternative tumor necrosis factor inhibitor (TNFi) and secukinumab (SEC) use after TNFi therapy in patients with axial spondyloarthritis (axSpA). This was an observational retrospective study of axSpA patients who switched to second-line biological disease modifying antirheumatic drugs (bDMARD) between January 2018 and February 2023. Drug retention rate was evaluated using Kaplan-Meier analysis and log-rank test. Factors associated with drug survival of the second bDMARD were analyzed by multivariate regression analyses. A total of 201 axSpA patients (alternative TNFi: 143 patients, SEC: 58 patients) with a mean age 37.1 ± 8.6 years and consist of 58.2% male were included. Clinical characteristics and laboratory results at switching were comparable between groups. During a median follow-up period of 22.3 months, 80 (39.8%) of 201 patients discontinued bDMARD. Median follow-up period, drug discontinuation frequency, and drug retention rate were similar between groups. C-reactive protein (CRP) level (Hazard ratio (HR) = 0.98, 95% confidence interval (CI) = 0.95-0.99, p = 0.032) and primary failure (HR = 1.52, 95% CI = 1.03-2.27, p = 0.037) were significantly associated with the risk of TNFi discontinuation. Smoking (HR = 1.96, 95% CI = 1.05-3.69, p = 0.036) and Achilles enthesitis (HR = 1.93, 95% CI = 1.09-3.40, p = 0.024) were significantly associated with the risk of SEC discontinuation. In axSpA exposed to a TNFi, switching to a second TNFi has comparable effectiveness to switching to SEC. SEC may be a better option in patients who experienced primary failure of TNFi, whereas an alternative TNFi may be preferred in patients with higher CRP levels or Achilles enthesitis, or who are currently smoking.

Abstract Background/Aims Treatment (tx) guidelines for PsA recommend biologic DMARDs (bDMARDs) or targeted synthetic (ts) DMARDs after inadequate response to conventional synthetic DMARDs (csDMARDs). In clinical studies, ixekizumab (IXE) has shown efficacy in patients (pts) with PsA who were bDMARD-naive, TNFi-experienced, and with and without concomitant csDMARDs. Data from real-world studies are limited. This interim analysis reports the effectiveness of IXE and other b/tsDMARDs in b/tsDMARD-naive (naive) and -experienced (exp) pts as well as in monotherapy (mono) and in combination (comb) with any csDMARD at 12 months (M) in a real-world setting. Methods In PRO-SPIRIT, pts with PsA who initiated or switched to new b/tsDMARDs were evaluated in five European countries and Canada. Pts were categorised by prior b/tsDMARD tx and concomitant csDMARD use at baseline (BL), respectively. Descriptive data for the analysis population at 12 M are presented. Mixed models for repeated measures (MMRM) were used to assess change from BL (CFB). Missing data were handled using multiple imputation. Results Of 1192 pts, TNF inhibitors (TNFis) (68.6%) and secukinumab (SEC) group (33.5%) had the highest proportion of naive pts, whereas TNFi (53.5%) and JAKi (46.8%) had the highest proportion of comb pts. At 12 M, similar mean CFB was observed in pts treated with IXE for clinical Disease Activity in Psoriatic Arthritis (cDAPSA) in the naïve (-13.6), exp (-12.1), mono (-12.3), and comb (-12.4) subgroups (subsequently reported in that order, herein); as well as for body surface area (BSA) (-5.0), (-3.6) (-4.4) and (-3.9). Similar trends were observed in tender joint counts and swollen joint counts. However, mean CFB in cDAPSA was lower in exp versus (vs) naive pts treated with SEC ( -8.9 vs -12.8), IL-12/23i (-7.4 vs -16.2) and IL-23i (-10.1 vs -17.2) and lower in mono vs combo in TNFi (-12.5 vs -15.2) and IL-23i (-11.0 vs -12.6). Mean CFB in BSA was lower in exp vs naive pts treated with TNFi (-2.8 vs -5.4), and IL-23i (-2.0 vs -5.3). Conclusion In the real-world setting, IXE demonstrated similar effectiveness on joints and skin regardless of therapy line and concomitant csDMARDs, confirming findings from IXE clinical trials. Other treatments showed less consistent results either on exp pts (SEC, IL-12/23i, IL-23i) or in mono (TNFi, IL-23i). Disclosure P. Sewerin: Consultancies; AbbVie, Amgen, AXIOM Health, Celgene, Chugai, Deutscher Psoriasis-Bund, Eli Lilly and Company, Gilead Sciences, Hexal Pharma, Janssen, Johnson &amp; Johnson, Mediri GmbH, Novartis, Onkowissen GmbH, Pfizer, Pharma Marketing Ltd/Chugai Europe, Rheumazentrum Rhein-Ruhr, Roche, Sanofi-Genzyme, Spirit Medical Communication, Swedish Orphan Biovitrum, and UCB Pharma. Honoraria; AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead Sciences, Hexal Pharma, Janssen, Johnson &amp; Johnson, Novartis, Pfizer, Rheumazentrum Rhein-Ruhr, Roche, Sanofi-Genzyme, Swedish Orphan Biovitrum, and UCB Pharma. N. Gullick: Consultancies; AbbVie, Alphasigma, Janssen, Eli Lilly and Company, Novartis, and UCB Pharma. Grants/research support; AbbVie, Astra Zeneca, Galapagos NV, Janssen, Eli Lilly and Company, Novartis, and UCB Pharma. H. Russ: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. K. Ng: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. M. O’Neill: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. S. Moyano: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. F. Giurdanella: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. A. Gallego-Flores: None. F. Ciccia: Consultancies; AbbVie, Eli Lilly and Company, Galapagos, Janssen, Novartis, and UCB Pharma. Honoraria; AbbVie, Eli Lilly and Company, Galapagos, Janssen, Novartis, and UCB Pharma.

Introduction: The efficacy and real-world treatment persistence of guselkumab (GUS) has been shown to be superior to other advanced treatment options [1,2] for psoriasis (PsO); however, long-term real-world effectiveness vs. other biologic therapies warrants further study. Therefore, this study compared the real-world effectiveness of GUS with adalimumab (ADA), ixekizumab (IXE), secukinumab (SEC), and ustekinumab (UST) in PsO patients through 30 months of follow-up. Methods: An active comparator, new-user design was used to compare initiators of GUS to each comparator separately among adult patients with plaque PsO, an Investigator’s Global Assessment (IGA) score ≥2, and at least 30 months of follow-up prior to the data cutoff (June 2024) enrolled in the CorEvitas Psoriasis Registry in the US and Canada. Stabilized standardized mortality ratio (SMR) weights were used to balance baseline characteristics between GUS and each comparator. The primary outcome was achievement of IGA 0/1 at 30 months. Dermatology Life Quality Index (DLQI) 0/1 was assessed as a secondary outcome. Absolute differences were reported after incorporating the SMR weights. For all comparisons, P&lt;0.05 was considered statistically significant and Bonferroni-Holm adjustments were made for multiple testing. Results: After balancing on baseline characteristics, significantly greater proportions of GUS initiators achieved IGA 0/1 vs. those in each comparator group (GUS 50.7% (n=428) vs. ADA 24.0% (n=309): difference=26.7%, 95% CI: 13.6-39.7; p&lt;0.001; GUS 43.4% (n=587) vs. IXE 33.6% (n=580): difference=9.9%, 95% CI: 2.6-17.1; p=0.005; GUS 45.8% (n=546) vs. SEC 29.9% (n=614): difference=15.9%, 95% CI: 6.8-25.0; p&lt;0.001; GUS 45.9% (n=466) vs. UST 36.2% (n=224): difference=9.7%, 95% CI: 0.6-18.7; p=0.036). Similarly, greater proportions of GUS initiators achieved DLQI 0/1 vs. the comparators. Conclusion: Our findings suggest that GUS was superior to ADA, IXE, SEC, and UST in achieving both IGA 0/1 and DLQI 0/1 at 30 months. This is among the largest and longest real-world comparative effectiveness studies of GUS vs. ADA, IXE, SEC, and UST in PsO patients. Additional studies with longer follow-up and inclusion of emerging therapies could provide further data to inform clinical treatment considerations.

Sunitinib (SUN) is a chemotherapeutic agent showing renal toxicity that limits its clinical applications. The present research aimed to clarify the potential ameliorative effects of secukinumab (SEC) and dapagliflozin (DAPA) against SUN-induced renal toxicity and the underpinning molecular mechanisms. For this purpose, adult Wistar albino rats were received SUN (25 mg/kg 3 times/week, po) and co-treated with SEC (3 mg/kg/every 2 weeks, subcutaneously) or DAPA (10 mg/kg/day, po) for 4 weeks and compared with age-matched control group (CON). Markers of kidney functions were assessed in serum samples. Kidneys were harvested for biochemical and histological examination. Compared to CON group, SUN-treated rats displayed signs of kidney dysfunction along with renal histological changes that were ameliorated by SEC or DAPA. Both drugs significantly lowered the renal levels of IL-17, but SEC exerted more inhibitory effect than DAPA. Additionally, SUN-subjected rats showed significant increases in the renal expression of NLRP3 inflammasome and the other inflammatory mediators including IL-1β, END-1, and MCP-1. This was associated with marked decline of the renal levels of beclin-1. Co-treatment with SEC or DAPA significantly suppressed NLRP3-induced inflammation while enhanced beclin-1-mediated autophagy. The modulatory effect of DAPA on NLRP3 and beclin-1 was superior to that of SEC. Moreover, both drugs significantly and similarly attenuated the enhanced cleaved caspase-3 expression and interstitial fibrosis in renal tissue of SUN-subjected rats. Collectively, these findings may repurpose SEC and DAPA as candidate therapies to alleviate the renal toxicity of SUN and to rescue the renal functionality in SUN-treated cancer cases.

Interleukin-17A (IL-17A) has been implicated in the progression of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, the effect of the FDA-approved Secukinumab (SEC), an IL-17A inhibitor, on PD remains unclear. This study aimed to investigate the neuroprotective effect of SEC and its potential mechanisms in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Male C57BL/6J mice were mainly assigned to three groups: Sham, MPTP, and MPTP + SEC. Motor coordination was assessed using the climbing rod and rotarod tests. Dopaminergic neurons (TH +) and glial cells (Iba-1 + , GFAP +) in the substantia nigra were evaluated using immunohistochemistry and immunofluorescence. Flow cytometry was used to analyze immune cell populations in the brain and spleen. Inflammatory cytokines and chemokines were quantified using RT-PCR. SEC treatment significantly alleviated the loss of dopaminergic neurons and improved motor coordination in MPTP mice. It also reduced the infiltration of peripheral immune cells, including CD4 + T cells, NK cells, and monocyte-macrophages into the brain. SEC attenuated glial activation (Iba-1 + , GFAP +) and decreased the expression of pro-inflammatory cytokines and chemokines (CCL2, CXCL9), which recruit immune cells into the brain. These results suggest that Secukinumab protects dopaminergic neurons and attenuates neuroinflammation in MPTP-induced model. SEC treatment in PD might be an effective therapeutic approach for clinical application in the future. HIGHLIGHTS: • Secukinumab reduces the loss of dopaminergic neurons and axons in MPTP mice. • Secukinumab inhibits the infiltration of peripheral immune cells into the brain in MPTP mice. • Secukinumab inhibits the activation of glial cells and reduces neuroinflammation in MPTP mice.

In patients with axial spondyloarthritis (axSpA) initiating secukinumab (SEC), we aimed to identify baseline (treatment start) predictors of achieving low disease activity (LDA) after 6 months, as measured by the Axial Spondyloarthritis Disease Activity Score using C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), as well as treatment continuation after 12 months. From 11 European registries, patients with axSpA who initiated SEC treatment in routine care, with available data on 6-month ASDAS-CRP and BASDAI assessments were included. Logistic regression analyses on multiply imputed baseline data were performed; potential baseline predictors included demographic, diagnosis, lifestyle, clinical, and patient-reported variables. In a pooled cohort of 1174 patients with axSpA, 5 of 19 potential assessed variables were mutually predictive for achieving LDA by ASDAS-CRP and BASDAI: higher physician global assessment score, noncurrent smoking, lack of prior exposure to biologic/targeted synthetic disease-modifying antirheumatic drugs, and lower Health Assessment Questionnaire scores and BASDAI scores. Moreover, radiographic axSpA and CRP ≤ 10 mg/L were associated with achieving ASDAS-CRP LDA, and HLA-B27 positivity and history of psoriasis with achieving BASDAI LDA, whereas earlier time of secukinumab initiation (2015-2017) was associated with treatment continuation. In this European real-world study of patients with axSpA initiating SEC, predictors of achieving LDA by ASDAS-CRP and BASDAI at 6 months and remaining on treatment at 12 months included both clinical, patient-reported, and lifestyle factors, underscoring the complex mechanisms of real-world drug effectiveness.

Treatment of hidradenitis suppurativa (HS) remains a challenge in clinical practice for dermatologists. Although the effectiveness and safety of secukinumab (SEC) in the treatment of HS have been demonstrated in phase III studies, real-world data is limited. We conducted a retrospective multicenter study to evaluate the effectiveness and safety of SEC treatment in HS patients in real-world settings. Adult patients who were diagnosed with HS and used SEC for at least 3 months were included in the study. A total of 31 patients were included in the study; 14 of them (45.2%) were female. The mean age was 39.32 ± 10.26 years, and the mean disease duration was 11.77 ± 7.99 years. Nine (29%) patients were biologic-naive and 10 (32.3%) were adalimumab-naive. Disease severity was Hurley I in 7 patients (22.6%), Hurley II in 9 patients (29%), and Hurley III in 15 patients (48.4%). The Hidradenitis Suppurativa Clinical Response (HiSCR) was achieved in 20 patients (64.5%) in the third month of treatment. SEC treatment was discontinued due to primary ineffectiveness in 9 (29%) patients, secondary ineffectiveness in 1 (3.2%) patient, adverse effects in 1 (3.2%) patient, and loss of follow-up in 1 (3.2%) patient. Paradoxical pyoderma gangrenosum was observed as an adverse effect in 1 patient that resolved after discontinuing SEC and starting infliximab. SEC appears to be an effective and safe treatment option for HS, especially when used in the early and mild stages of the disease and in biologic-naive patients.

ABSTRACT Background Biologics are recommended for use in patients with psoriatic arthritis (PsA) after the failure of conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs). However, compared to csDMARDs, biologics are significantly more expensive. The aim of this study was to evaluate the cost-effectiveness of biologic treatments for active PsA patients who have failed treatment with csDMARDs, from the perspective of the Chinese healthcare system. Research design and methods A discrete event simulation model was constructed to estimate health and economic outcomes of patients. The seven biologics recommended by the Chinese psoriasis treatment guidelines were included in the evaluation. One-way and probabilistic sensitivity analysis were performed to ensure that our results were robust. Results Our results found that compared to the standard of care (SoC) and all other biologics strategies, secukinumab (SEC) had the highest quality-adjusted life years, and at a willingness-to-pay (WTP) threshold of US $38,161 per QALY, SEC was the most cost-effective option, with an incremental cost-effectiveness ratio of $14,968 per QALY. One-way sensitivity analysis and probabilistic sensitivity analysis confirmed the robust of this result. Conclusions From the perspective of the Chinese healthcare system, biologics are estimated to be cost-effective compared to SoC. Among these, SEC is the most cost-effective option.

Randomized clinical trials have demonstrated the efficacy of secukinumab (SECU) in reducing disease activity in psoriatic arthritis (PsA), while real-world studies prove a broader perspective on SECU's usefulness in everyday clinical practice. To assess the effectiveness of SECU by evaluating drug survival and identifying potential predictors of clinical response and treatment discontinuation in patients with moderate-to-severe PsA, using real-world data from the Italian Group for the Study of Early Arthritis (GISEA) registry. This longitudinal retrospective study included PsA patients treated with SECU, spanning from May 2016 to November 2023. Data from 1045 PsA patients, including 783 with peripheral-only PsA (perPsA) and 262 with peripheral and axial involvement (mixed PsA) were analyzed. Drug survival was estimated by Kaplan-Meier analysis. Clinical outcomes, including Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriasis Area Severity Index (PASI), Ankylosing Spondylitis Disease Activity Score (ASDAS, C-Reactive Protein (CRP)-based), and Visual Analogue Scale (VAS) measures, were evaluated at baseline and at 6, 12, and 24 months. Adjusted hazard ratios (aHRs) for discontinuing SECU were determined using multivariate Cox regression models. SECU survival at 24 months was 63.24%, significantly higher in mixed PsA compared to perPsA (p = 0.036). In the overall PsA population, DAPSA scores decreased significantly at 6 months, and further at 24 months (all p < 0.0001). In mixed PsA, ASDAS-CRP scores were significantly reduced at 6 months and remained stable through 24 months (all p < 0.0001). VAS pain scores also improved already at 6 months and continued to improve at 24 months (all p < 0.0001). Higher age (aHR = 0.98, 95% confidence interval (CI): 0.96-0.99, p = 0.007) and lower baseline DAPSA scores (aHR = 1.02, 95% CI: 1.01-1.03, p = 0.014) were associated with greater persistence of SECU treatment. SECU was well tolerated, with no serious adverse events. SECU showed sustained clinical improvements in both peripheral and axial involvement of PsA patients over 24 months, with higher persistence observed in mixed PsA patients. Our findings highlight the favorable clinical and safety profile of SECU in real world.

Evidence on the effectiveness, long-term safety and longevity of biologic therapies in pediatric psoriasis patients is sparse. This study aims to compares the efficacy, safety and drug survival (DS) rates of etanercept (ETA), adalimumab (ADA), infliximab (INF), ustekinumab (UST), secukinumab (SEC) and ixekizumab (IXE) in pediatric and adult psoriasis patients. 293 biologic treatment cycles of 198 patients (62 pediatric and 136 adult) from three academic psoriasis referral centres were analysed. The following were the Psoriasis Area and Severity Index 90 response scores of pediatric and adult psoriasis patients, respectively: ETA, 42.3% vs. 34.6%; ADA, 53.8% vs. 59.8%; INF, 33.3% vs. 33.3%; UST, 76.5% vs. 56.8%; SEC, 60% vs. 60%; and IXE, 50% vs. 87.5%. The differences of responses between the two groups were statistically insignificant (p>0.05). ETA had the longest mean DS time in the pediatric group but it was related to a significantly shorter DS in pediatric patients than in adults (pediatrics: 30.58 [18.64-42.52] months vs. adults: 72.34 [54.70-89.99] months; p=0.025). ADA had the longest mean DS time in the adult group with 101.28 [84.88-117.68] months. All treatments had favorable safety profiles. No specific severe adverse effects necessitating treatment discontinuation were observed in pediatric patients. Although responses to ETA and UST were numerically better among children, the difference was insignificant. The DS rates in each group were comparable, and no specific safety signals, limiting the long-term use of these agents, were detected in the pediatric group.

Doxorubicin (DOX) is used as a chemotherapeutic drug for treating cancer. Nevertheless, it causes damage to the heart by activating inflammatory pathways, resulting in cardiotoxicity. Imbalance in cytokine production is a crucial component that might trigger the initiation of inflammatory processes. Inflammatory cytokines could be targeted therapies against cardiovascular diseases (CVDs). Interleukin-17A (IL-17A) is a cytokine that promotes inflammation and stimulates harmful immunological reactions. The objective of the study was to determine the efficacy of secukinumab (SEC), a completely human monoclonal IgG1/κ antibody that targets IL-17A, in ameliorating DOX-induced cardiotoxicity (DIC). We administered 2.5 mg/kg of DOX intraperitoneally to male Wistar rats three times a week for 2 weeks and simultaneously administered 0.9 mg/kg of SEC along with 2.5 mg/kg of DOX injection three times a week for a duration of two weeks. The findings indicated that DOX induced damage to the heart tissue, resulting in a significant rise in indicators of cardiotoxicity (P < 0.001), as well as oxidative stress and inflammation. DIC may have arisen from DOX's activation of the Pyrin domain containing 3 (NLRP3) inflammasome and the nuclear factor kappa beta (NF-κB) pathway. The co-administration of SEC successfully reversed all DOX-induced abnormalities by restoring cardiac functions to their baseline levels, decreasing levels of inflammatory mediators such as IL-17A and interleukin-1β (IL-1β), and improving oxidative stress by reducing levels of malondialdehyde (MDA) and increasing levels of reduced glutathione (GSH). Furthermore, it mitigated the heightened activation of the NF-κB/NLRP3 pathway caused by DOX. This study shows that IL-17A neutralization can prevent DIC by regulating the NF-κB/NLRP3/Caspase-1/IL-1β pathway to be used as potential therapeutic target for CVDs.