Secukinumab Research Articles

Comparative early effectiveness across 14 PsA drugs and 5 classes of PsA treatment: 3-month results from the PRO-SPIRIT study

BackgroundThe psoriatic arthritis (PsA) Observational Study of Persistence of Treatment (PRO-SPIRIT) assesses effectiveness and persistence of real-world PsA treatments. Ixekizumab (IXE) is an interleukin (IL)-17A inhibitor (i) (IL-17Ai), approved for...

The Retention Rate and Safety of Secukinumab as a First-Line Biologic Agent in Axial Spondyloarthritis Compared to a First Tumor Necrosis Factor (TNF) Inhibitor: A Real-World, Longitudinal Study.

Background and objective Secukinumab (SECU)is a biologic disease-modifying antirheumatic drug (bDMARD)that has demonstrated effectiveness against axial spondyloarthritis (ax-SpA). However, in clinical practice, secukinumab is most commonly used as a second-line treatment after failure of or intolerance to tumor necrosis factorinhibitors (TNFi). In this study, we aimed to compare the two-yeardrug retention between secukinumab and TNFi in biologic-naïve patients with ax-SpA, to estimate the remission/low disease activity (LDA) rates in both groups and assess thesafety profiles. Methods This was a longitudinal observational study involving patients with ax-SpA who were biologic-naïve and were receiving SECU or TNFibetween December 2019 and December 2021. The two-year therapeutic retention rate in both groups was determined. Remission and LDA rates obtained at 24 months according to the Ankylosing Spondylitis Disease ActivityScorebased on C-reactive protein (ASDAS-CRP) scale, as well as the safety profile, were compared between the two groups. Results Seventy-five patients were included in the study. Of them, 34.6% received SECU, while 65.3% received TNFi; 85.3% were males. The mean age was 37.8 ±9 years, the mean disease duration was 10.2 ±6.1 years, and the initial ASDAS-CRP was 3.5 ±0.8. At 24 months; the therapeutic retention rate was 70% for SECU and 66% for TNFi. The reasons for discontinuation were inefficacy (SECU: 11.5%, TNFi: 20.4%, p=0.33), side effects (SECU: 0, TNFi: 4.1%, p=0.29), and socioeconomic conditions (SECU: 15.5%, TNFi: 10.2%, p=0.51). The rate of patients achieving remission and LDA was comparable between the two groups: (remission - SECU: 23.1%, TNFi: 24.5%, p=0.92; LDA - SECU: 73.1%, TNFi: 73.5%, p=0.16). There was no statistically significant difference in the safety profile. Conclusions Our findings suggestthat the effectiveness and safety of secukinumab for ax-SpA in biologic-naïvepatients are comparable to those of TNFi.

Secukinumab Ameliorates Oxidative Damage Induced by Subarachnoid Hemorrhage

This study aimed to investigate the histological and biochemical neuroprotective effects of secukinumab (SEC) on brain damage induced by subarachnoid hemorrhage (SAH) in male Wistar Albino rats. Forty male Wistar Albino rats were randomly divided into 4 groups of equal size: control, SEC, SAH, and SAH+SEC. SAH was induced the SAH and SAH+SEC groups by injecting autologous blood collected from the hearts of the rats into the subarachnoid space via the foramen magnum. SEC was administered intraperitoneally once a week to the SEC and SAH+SEC groups after the surgical procedure. On the 14th day of surgery, the rats were sacrificed and their cerebral tissues were collected for biochemical analysis and histopathological examination. SAH led to changes in oxidative stress parameters by increasing malondialdehyde levels and decreasing superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels. Histopathologically, cerebral tissues in the SAH groups showed alterations such as congestion and cell infiltration. Treatment with SEC significantly reduced malondialdehyde levels and increased superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels. SEC also decreased histopathological alterations in brain tissues. This study revealed that SEC (3mg/kg) therapeutically influenced oxidative and histopathological changes in blood parameters and brain tissues caused by experimental SAH. SEC helps reduce brain damage in rats with SAH and possesses antioxidant and neuroprotective properties. Further advanced studies are needed to prove its potential benefits for humans.

Psoriatic arthritis, biologic therapy experience, body mass index, and onset age of psoriasis were independent factors of secukinumab discontinuation in patients with psoriasis

ABSTRACT Introduction Despite the availability of several treatments for psoriasis (PsO), factors influencing the persistence of secukinumab (SEC) therapy remain inadequately understood. This study aimed to identify predictors of SEC persistence in PsO. Methods A retrospective analysis was conducted on 109 PsO patients who received SEC treatment at least 1 year. Patients were categorized based on continued or discontinued SEC therapy. Results Among the 109 patients, 64 continued SEC treatment while 45 discontinued. Univariate analysis demonstrated that PsA presence and previous biologic therapy use increased the risk of SEC discontinuation 3.56- and 2.33-fold (p = 0.001, %95 CI: 1.66–7.65 and p = 0.032, %95 CI: 1.08–5.04, respectively). Additionally, the risk of SEC discontinuation is 57% higher in patients with a body mass index (BMI) above 26.5 compared to those with a BMI below 26.5 (p = 0.016, %95 CI: 0.22–0.85). Additionally, patients with PsO onset age below 26.5 years were found to have a 2.93-times higher risk of discontinuing SEC compared to those with PsO onset age above 26.5 years (p = 0.004, %95 CI: 1.40–6.13). Conclusion PsA presence, previous biologic therapy experience, BMI, and PsO onset age were identified as independent predictors of SEC discontinuation. These findings underscore the importance of personalized treatment strategies for PsO patients receiving SEC therapy.

Experimental Insights on the Use of Secukinumab and Magnolol in Acute Respiratory Diseases in Mice.

This study investigates the combined treatment of secukinumab (SECU) and magnolol (MAGN) in a mouse model of LPS-induced ALI overlapped with allergic pulmonary inflammation, aiming to better understand the mechanism behind this pathology and to assess the therapeutic potential of this novel approach in addressing the severity of ALI. The combined treatment reveals intricate immunomodulatory effects. Both treatments inhibit IL-17 and promote M2 macrophage polarization, which enhances anti-inflammatory cytokine production such as IL-4, IL-5, IL-10, and IL-13, crucial for lung repair and inflammation resolution. However, the combination treatment exacerbates allergic responses and increases OVA-specific IgE, potentially worsening ALI outcomes. MAGN pretreatment alone demonstrates higher potency in reducing neutrophils and enhancing IFN-γ, suggesting its potential in mitigating severe asthma symptoms and modulating immune responses. The study highlights the need for careful consideration in therapeutic applications due to the combination treatment's inability to reduce IL-6 and its potential to exacerbate allergic inflammation. Elevated IL-6 levels correlate with worsened oxygenation and increased mortality in ALI patients, underscoring its critical role in disease severity. These findings offer valuable insights for the advancement of precision medicine within the realm of respiratory illnesses, emphasizing the importance of tailored therapeutic strategies.

A new mechanism in negative pressure wound therapy: interleukin-17 alters chromatin accessibility profiling.

Negative pressure wound therapy (NPWT) is extensively used in clinical settings to enhance the healing of wounds. Despite its widespread use, the molecular mechanisms driving the efficacy of NPWT have not been fully elucidated. In this study, skin wound-healing models were established, with administration of NPWT. Vimentin, collagen I, and MMP9 of skin tissues were detected by immunofluorescence (IF). Gene expression analysis of skin wound tissues was performed by RNA-sequencing (RNA-seq). Protein expression was assayed by a Western blotting or IF assay, and mRNA levels were quantified by quantitative PCR. Chromatin accessibility profiles of fibroblasts following NPWT or IL-17 exposure were analyzed by ATAC-seq. In rat wound-healing models, NPWT promoted wound repair by promoting reepithelialization, extracellular matrix (ECM) synthesis, and proliferation, which mainly occurred in the early stage of wound healing. These differentially expressed genes (DEGs) in NPWT wounds versus control wounds were enriched in the IL-17 signaling pathway. IL-17 was identified as an upregulated factor following NPWT in skin wounds. Moreover, the IL-17 inhibitor secukinumab (SEC) could abolish the promoting effect of NPWT on wound healing. Importantly, chromatin accessibility profiles were altered following NPWT and IL-17 stimulation in skin fibroblasts. Our findings suggest that NPWT upregulates IL-17 to promote wound healing by altering chromatin accessibility, which is a novel mechanism for NPWT's efficacy in wound healing.NEW & NOTEWORTHY To our knowledge, this is the first report of the efficacy of negative pressure wound therapy (NPWT) in promoting wound healing via IL-17. Moreover, NPWT and IL-17 can alter chromatin accessibility. Our study identifies a novel mechanism for NPWT's efficacy in wound healing.

E066 Baseline characteristics of patients initiating ixekizumab, secukinumab or a tumour necrosis factor inhibitor by country in the 24-month Prospective Psoriatic Arthritis Observational Study of Persistence of Treatment - PRO-SPIRIT

Abstract Background/Aims The Psoriatic Arthritis Observational Study of Persistence of Treatment (PRO-SPIRIT) is the first large-sample, multinational, prospective, observational study to provide real-world evidence for ixekizumab (IXE) in patients with psoriatic arthritis (PsA) who start a new biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), with a primary end point of persistence at 24 months. Aims: To describe baseline characteristics of PRO-SPIRIT patients initiating or switching to IXE, secukinumab (SEC) or a tumour necrosis factor inhibitor (TNFi) in Canada (CA), France (FR), Germany (DE), Italy (IT), Spain (ES) and the United Kingdom (UK). Methods PRO-SPIRIT enrolled adults diagnosed with PsA (≥6 months) between December 2019 and June 2022 to be initiated or switched to a new b/tsDMARD, locally approved for the management of PsA. Baseline characteristics, including patient demographics, therapy and disease activity measures, are described here by country for patients initiating IXE, SEC (both IL-17A inhibitors) or a TNFi (adalimumab, etanercept, infliximab or biosimilar) only. Results This analysis included 943 patients (Table 1). The overall proportion of patients with BMI ≥30 mg/kg2 was highest in CA (67.2%) and lowest in IT (24.5%); across countries, higher proportions of patients initiating an IL-17A vs a TNFi had BMI ≥30 mg/kg2 (except IXE groups in IT, ES and UK). Higher proportions of patients initiating an IL-17A vs a TNFi were diagnosed with PsA ≥3 years before baseline (except SEC groups in DE and ES). The highest proportions of b/tsDMARD-naïve patients were observed in the TNFi groups in all countries (range 46.2% [CA] to 81.9% [UK]). Patients in the IL-17A groups were more likely to be on monotherapy than patients in the TNFi groups (except in FR). There were no clear trends in baseline disease activity for patients initiating IL-17As or TNFis, although country-specific differences were observed. Conclusion The PRO-SPIRIT baseline characteristics described offer important insights into country-specific patient demographics and treatment patterns when initiating or switching to a new b/tsDMARD in a real-world setting. Between-country variations observed in PRO-SPIRIT baseline characteristics may be due to differences in healthcare systems and/or the evolution of treatment options for patients with PsA in each country. Disclosure N. Gullick: Consultancies; AbbVie,Novartis, UCB. Honoraria; AbbVie, Eli Lilly, Janssen, Novartis, UCB. Grants/research support; AbbVie, Astra Zeneca, Eli Lilly, Novartis. M. Sheesh: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. C. Laedermann: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. M. Ngantcha: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. B. Gittens: Corporate appointments; Eli Lilly and Company. K. Ng: Corporate appointments; Eli Lilly and Company. Shareholder/stock ownership; Eli Lilly and Company. W. Tillett: Consultancies; Abbvie, Amgen, Eli Lilly and Company, GSK, Janssen, Novartis, Ono Pharma, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Amgen, Eli Lilly and Company, GSK, Janssen, Novartis, Pfizer, UCB. Grants/research support; Janssen, UCB, Pfizer, Eli Lilly and Company. J. Morel: Consultancies; Pfizer, AbbVie, Boerhinger Ingelheim, Galapagos, GSK. Member of speakers’ bureau; Biogen, Amgen, Bristol Myers Squib, Eli Lilly and Company, Novartis, Sanofi, MSD, Mylan, Fresenius Kabi, Roche, Union Chimique Belge, Janssen, Medac, Nordic Pharma. Grants/research support; Fresenius Kabi. E. Lubrano: Member of speakers’ bureau; Abbvie, Janssen Cilag, Lilly, UCB, Pfizer, Novartis. R. Alten: Consultancies; AbbVie, BMS, Celltrion, Galapagos, Eli Lilly and Company, Novartis, Pfizer, Roche, UC. Member of speakers’ bureau; AbbVie, BMS, Celltrion, Galapagos, Eli Lilly and Company, Novartis, Pfizer, Roche, UCB. L. Kristensen: Consultancies; Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly and Company, Janssen. Member of speakers’ bureau; Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly and Company, Janssen. Grants/research support; Pfizer, Abb- Vie, UCB, Gilead, Biogen, Novartis, Eli Lilly and Company, Janssen. V. Chandran: Consultancies; AbbVie, Eli Lilly, Novartis, Amgen, Janssen. Grants/research support; AbbVie. A. Martinez-Ferrer: Grants/research support; Eli Lilly and Company. B. Kirkham: Consultancies; Abbvie, Eli Lilly and Company, Galapagos, Novartis. Member of speakers’ bureau; Abbvie, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly and Company, Novartis.

Bimekizumab Versus Secukinumab Continuous Maintenance of PASI 90 and PASI 100 Responses through One Year in Patients with Moderate to Severe Plaque Psoriasis: Post-HOC Results from the BE RADIANT Phase 3b Trial

Introduction: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL‑17A.[1] Secukinumab (SEC) is a widely used monoclonal IgG1 antibody that targets IL-17A. BE RADIANT was the first phase 3 study to compare inhibition of IL-17A and IL-17F with inhibition of IL-17A alone. Patient (pt) surveys have confirmed that maintaining a long-lasting response is a key treatment goal for patients who have already achieved skin clearance.[2,3] Here, we assess the efficacy of BKZ vs SEC in continuously maintaining an improvement of ≥90% in the Psoriasis Area and Severity Index (PASI 90), and PASI 100 responses, at every visit from Week (Wk)16 to Wk48 of treatment in pts with moderate to severe plaque psoriasis. Procedure/study: BE RADIANT was a phase 3b, randomized trial, consisting of a 48-week double-blinded, active comparator-controlled period followed by an open-label extension.[4] Pts were randomized 1:1 to BKZ 320 mg every 4 wks (Q4W) or SEC (weekly to Wk4 then Q4W). At Wk16, BKZ-randomized pts either continued to receive BKZ 320 mg Q4W or switched to BKZ 320 mg every 8 wks (Q8W). This analysis includes pts who achieved PASI 90 or 100 at Wk16 and continued to receive study medication at Wk16 or later, reported with BKZ dose groups pooled. We report the proportion of responders who continued to achieve their response at every study visit up to and including Wk48. Missing data were imputed as non-response. Results: At baseline, 373 pts were randomized to BKZ, and 370 were randomized to SEC. At Wk16, 319/373 (85.5%) BKZ-randomized and 273/370 (73.8%) SEC-randomized pts achieved PASI 90; 230/373 (61.7%) and 180/370 (48.6%) achieved PASI 100. PASI 90 was continuously maintained at each study visit from Wk16–Wk48 by 242/319 (75.9%) BKZ-treated and 177/273 (64.8%) SEC-treated Wk16 responders. PASI 100 was continuously maintained through Wk48 by 139/230 (60.4%) BKZ-treated and 93/180 (51.7%) SEC-treated Wk16 responders. Conclusion: A higher proportion of pts treated with BKZ continuously maintained their Wk16 PASI 90 and PASI 100 responses at every visit during the first treatment year compared to SEC. Funding: UCB Pharma. Medical writing support: Costello Medical.

Targeting Common Inflammatory Mediators in Experimental Severe Asthma and Acute Lung Injury.

Neutrophils, known to be mobilized and activated in high amounts through Il-17 stimulation, are a key factor for clinical manifestation and imbalance of redox systems favoring a dominant oxidative state in both severe asthma and acute lung injury (f). The aim of this study was to evaluate in mice, the effect of Secukinumab (SECU) in a model of ovalbumin-induced asthma exacerbated with LPS administration to induce ALI, compared to dexamethasone (DEXA), already known for its benefit in both asthma and ALI. Results on cytokine levels for specific Th1, Th2 and Th17 revealed an interplay of immune responses. For Th1 effector cytokines in BALF, DEXA treatment increased TNF-α levels, but TNF-α was not modified by SECU; DEXA and SECU significantly decreased IFN-γ and IL-6 levels. For typical Th2 cytokines, DEXA significantly increased Il-4, Il-5 and Il-13 levels, while SECU significantly inhibited Il-5 levels. Both SECU and DEXA significantly decreased Il-17 levels. Cytokine level changes in lung tissue homogenate were partly similar to BALF cytokines. Conclusion: in addition to DEXA, SECU possesses the ability to modulate inflammatory cytokine release and to decrease Th17 responses in ALI overlapped on exacerbated asthma in mice.

Long-term efficacy, safety, and drug survival of secukinumab in patients with psoriasis in Turkey: a retrospective analysis of real-world experience.

Secukinumab (SEC) has been shown to be highly effective and safe in the treatment of moderate to severe plaque psoriasis (PsO), but data on SEC's long-term drug survival are limited. To analyse the survival rate of SEC and its predictive factors of survival, together with the drug safety and efficacy. Data of 268 patients who received SEC between May 2018 and April 2022 with moderate to severe psoriasis and/or psoriatic arthritis were analysed retrospectively. Psoriasis Area Severity Index (PASI) was used to define effectiveness. Drug survival was examined using the Kaplan-Meier analysis and Cox regression analysis was used to analyse predictive factors. PASI 75/90/100 responses achieved at week 16 (89.5%, 78%, and 16.2%, respectively) were well maintained at week 52 (96.3%, 90.7%, and 15.4%, respectively). The drug survival probability rates for SEC were 94.4% at 12 months, 88.4% at 24 months, 78.6% after 3 years, 52.7% after 4 years. Concomitant treatments, dose escalation and family history of psoriasis were associated with a higher risk for SEC withdrawal. Close monitoring may improve SEC survival in psoriasis patients who require dose escalation and concomitant drugs.

Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.

To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.

Course of uveitis in patients with ankylosing spondylitis during the interleukin 17 inhibitors therapy

Background. Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the effects of interleukin 17 inhibitors (iIL17) on uveitis in AS continue to accumulate. Objective – to evaluate the effect of iIL17 therapy on the course of uveitis in AS. Material and methods. 73 patients (pts) with AS (New York criteria, 1984), who received iIL17 (57 – secukinumab (SEC), 22 – netakimab (NTK)) for at least 1 year were included in the study. The average age of pts at the time of inclusion in the study was 41.93±8.95 years, the average duration of AS was 10.75±6.22 years. There were 40 (56.7%) men and 33 (43.3%) women among the pts. HLA-B27 was detected in 62/73 (85%), coxitis in 58 (79%), enthesitis in 63 (86.3%), peripheral arthritis in 57 (78%), psoriasis in 7 (9.5%), inflammatory bowel disease (IBD) in 3 (4.1%); in 6 (8.2%) the disease started before the age of 16; 19 (26%) pts had at least 1 episode of uveitis during the course of the disease. The rates of uveitis was estimated by comparing the number of incidences per 100 patient-years before the start of bDMARDs therapy and during iIL17 using. Result. The incidence rate of uveitis before the start of bDMARDs therapy for all pts was 8.3 per 100 pt-years (95% CI: 0.065–0.107), during iIL17 therapy – 9.2 per 100 pt-years (95% CI: 0.06–0.15; p=0.72). The incidence rate of uveitis among pts used SEC was 10.1 per 100 patient-years (95% CI: 0.079–0.13) before the start of bDMARDs therapy, during SEC using – 9.4 per 100 pt-years (95% CI: 0.05–0.15; p=0.74). The incidence rate of uveitis among pts used NTK was 4.8 per 100 pt-years (95% CI: 0.028–0.08) before the start of bDMARDs therapy, during the NTK using – 7.1 per 100 pt-years (95% CI: 0.019–0,22; p=0.3). For patients with a history of uveitis, the incidence rate of uveitis before the start of therapy with bDMARDs was 22.5 per 100 pt-years (95% CI: 0.18–0.28), during iIL17 therapy – 29.1 per 100 pt-years (95% CI: 0.18–0.43; p=0.29). Occurrences of uveitis were observed in 4 of 57 pts (7%) during the using of SEC, and in 1 of 25 pts (4%) – during the NTK therapy. 1 case of new-onset uveitis was recorded during the using of SEC. Conclusion. There were no significant differences in the incidence rates of uveitis during iIL17 using compared with non-biological therapy. iIL17 have not demonstrated a significant effect on the course of uveitis in AS in the study group.

Safety of secukinumab in the treatment of patients with axial spondyloarthritis and concurrent hepatitis B virus infection or latent tuberculosis infection.

To evaluate the safety of secukinumab (SEC) in the treatment of patients with axial spondyloarthritis (axSpA) and concurrent hepatitis B virus (HBV) infection or latent tuberculosis infection (LTBI). This is a retrospective cohort study. Adult axSpA patients with HBV infection or LTBI receiving SEC treatment for at least 3months from March 2020 to July 2022 in Guangdong Provincial People's Hospital were included. Patients were screened for HBV infection and LTBI before SEC treatment. During follow-up, reactivation of HBV infection and LTBI was monitored. Relevant data were collected and analyzed. A total of 43 axSpA patients with HBV infection or LTBI were included, of whom 37 were with HBV infection, 6 were with LTBI. Six out of thirty-seven (16.2%) patients with axSpA and concurrent HBV infection exhibited HBV reactivation after 9.0 ± 5.7months of SEC treatment. Among them, 3 patients had chronic HBV infection and received anti-HBV prophylaxis, 2 patients had chronic HBV infection but did not receive anti-HBV prophylaxis, and 1 patient had occult HBV infection and did not receive antiviral prophylaxis. None of the 6 axSpA patients with LTBI developed reactivation of LTBI, whether received anti-TB prophylaxis or not. HBV reactivation can occur in axSpA patients with different types of HBV infection undergoing SEC treatment, whether receive antiviral prophylaxis or not. Close monitoring of HBV reactivation in axSpA patients with HBV infection undergoing SEC treatment is mandatory. Anti-HBV prophylaxis may be beneficial. In contrast, SEC may be safe in axSpA patients with LTBI, even in patients not receiving anti-TB prophylaxis. Key Points •Currently, most evidence about the safety of SEC in patients with HBV infection and LTBI were from patients with psoriasis. Our study adds data about the safety of SEC in Chinese axSpA patients with concurrent HBV infection or LTBI in real-world clinical setting. •Our study showed that HBV reactivation can occur in axSpA patients with different types of HBV infection undergoing SEC treatment, whether receive antiviral prophylaxis or not. •Close monitoring of serum HBV markers, HBV DNA load, and liver function is mandatory in axSpA patients with chronic, occult, and resolved HBV infection undergoing SEC treatment. Anti-HBV prophylaxis may be beneficial in all HBsAg-positive patients and HBsAg-negative, HBcAb-positive patients at high risk of HBV reactivation who are receiving SEC therapy. •None of the axSpA patients with LTBI, whether received anti-TB prophylaxis or not, developed reactivation of LTBI in our study. SEC may be safe in axSpA patients with LTBI, even in patients not receiving anti-TB prophylaxis.

When to start secukinumab treatment in patients with axial spondyloarthropathy: Before or after anti-TNFα treatment?

Introduction and objectivesThis study aimed to evaluate the efficacy of secukinumab (SEC) in axial spondyloarthropathy (axSpA) in anti-TNFα naïve and anti-TNFα experienced patients. It also focused on the duration of SEC treatment and its side effects. Patients and methodsThe patients with axSpA treated with SEC and followed up in our outpatient clinic from May 2018 through October 2021 were included in this study. All patients in the study also fulfilled the ASAS classification criteria for axSpA. Patients were separated into two groups according to whether they received prior anti-TNFα therapy. While anti-TNFα naïve patients comprised group 1, anti-TNFα experienced patients were included in group 2. Pre- and post-treatment BASDAI scores were reported and compared. ResultsEighty-four axSpA patients (42 men; duration of the disease: 86.86±65.35 months in group 1 and 160.65±97.4 months in group 2) were treated with SEC. 45.5% of anti-TNFα naïve patients and 56.5% of anti-TNFα experienced patients were still on SEC therapy in October 2021. Duration of SEC treatment was 12.5±7.9 months in group 1 and 17.19±12 months in group 2 (p=0.098). The differences between pre-and post-treatment BASDAI scores were statistically significant in both groups (p<0.001). While patients in group 1 did not develop any adverse effects, three patients in group 2 experienced alopecia, uveitis, and recurrent pneumonia after SEC treatment. ConclusionOur study's efficacy and safety data on the use of SEC were reassuring in both anti-TNFα naïve and anti-TNFα experienced patients. However, further studies are still needed to determine the appropriate timing to begin SEC treatment.

IL-17 inhibitor-associated inflammatory bowel disease: A study based on literature and database analysis.

Objective: Few real-world studies have shown clear association between interleukin (IL)-17 inhibitors and inflammatory bowel disease (IBD) onset. This study investigated the reporting prevalence and evaluated the clinical features and management of IL-17 inhibitor-related IBD events. Methods: We used the US FDA Adverse Event Reporting System database and retrieved data, from 2015 to 2022, on IL-17 inhibitors to identify gastrointestinal inflammatory events and conduct disproportionality analyses by estimating the reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs). Furthermore, case reports and case series, from 2015 to 30 November 2022, on IBD induced by IL-17 inhibitors were collected for retrospective analysis. Results: A total of 388 cases of primary suspected IL-17 inhibitor-associated gastrointestinal events were reported (268 IBD and 120 colitis), including 348 cases involving secukinumab (SEC), 36 cases involving ixekizumab (IXE), and 4 cases involving brodalumab (BRO). Statistically significant reporting rates of total IBD events were observed for SEC and IXE (ROR = 2.13, 95% CI [1.96-2.30] and ROR = 2.79, 95% CI [2.39-3.27], respectively), whereas BRO did not trigger a safety signal. Twenty-nine studies, which included 34 cases, showed evidence of IBD, following SEC (79.4%) and IXE (20.6%) treatment. The median age was 42years; typical initial symptoms included diarrhea (90.9%), abdominal pain (57.6%), bloody diarrhea (51.5%), and fever (36.4%). The median time to onset of IBD symptoms was 2.9months. Some cases were accompanied by elevated white blood cell (WBC) count (87.5%), erythrocyte sedimentation rate (ESR; 85.7%), C-reactive protein (CRP; 100%), and fecal calprotectin (FC; 100%). Cessation of IL-17 inhibitors plus treatment with corticosteroids and TNF antagonists, as either monotherapy or in combination, could lead to complete clinical remission. The median time to remission after IL-17 inhibitor discontinuation was 4weeks. Conclusion: IL-17 inhibitor treatment is associated with exacerbation and new onset of IBD and colitis. Obtaining a detailed patient history before initiation of treatment and monitoring gastrointestinal symptoms and intestinal inflammatory biomarkers during IL-17 inhibitor treatment is important for safe use of these drugs.

Comparison of Real-World Costs, Healthcare Resource Utilization, and Comorbidity-Related Costs Between Ixekizumab and Secukinumab Among Biologic-Experienced Patients with Psoriasis Over 18 Months in the USA.

Data on real-world healthcare costs for ixekizumab (IXE) and secukinumab (SEC) in biologic-experienced patients with psoriasis are limited. This study compared real-world costs and healthcare resource utilization between IXE and SEC in biologic-experienced patients with psoriasis over an 18-month follow-up period in the USA. Adult patients with a diagnosis of psoriasis between 1 March, 2015 and 31 October, 2019 were identified using health insurance claims data from IBM Watson Health MarketScan®. The index date was the date of the first IXE or SEC claim. Biologic-experienced patients with one or more pre-period claims for biologic drugs were identified. Inverse probability of treatment weighting was used to reduce cohort imbalances. All-cause and psoriasis-related direct healthcare costs along with index drug costs were estimated during the follow-up and reported as per patient per month. Discount factors published by the Institute for Clinical and Economic Review were applied to psoriasis-related biologics to adjust pharmacy costs. A total of 411 IXE and 780 SEC users were included. After weighting, all-cause inpatient admissions were similar between IXE (9.5%) and SEC users (10.3%). Weighted, mean ± standard deviation per patient per month all-cause healthcare costs were higher in IXE users ($6670 ± $2910) than in SEC users ($6239 ± $3903; p = 0.049). Psoriasis-related and monthly index drug costs were higher in IXE users ($5609 ± $2009; p < 0.001 and $4688 ± $1994; p < 0.001, respectively) than in SEC users ($5095 ± $2291 and $3853 ± $1977, respectively). After Institute for Clinical and Economic Review adjustment, mean per patient per month all-cause ($4363 ± $2576 vs $4398 ± $3517) and psoriasis-related costs ($3302 ± $1264 vs $3253 ± $1504) were similar between the groups. Institute for Clinical and Economic Review- and adherence-adjusted mean per patient per month index drug costs were similar between IXE and SEC users (p = 0.339). Institute for Clinical and Economic Review-adjusted all-cause and psoriasis-related costs were comparable between IXE and SEC users among biologic-experienced patients over an 18-month follow-up period.

Real-World Retention and Clinical Effectiveness of Secukinumab for Axial Spondyloarthritis: Results From the Canadian Spondyloarthritis Research Network.

Axial spondyloarthritis (axSpA) is a chronic, immune-mediated, inflammatory condition consisting of 2 clinical subsets: nonradiographic axSpA and ankylosing spondylitis, the latter having an estimated prevalence of 0.2% to 1% in Canada. Secukinumab (SEC) received Health Canada approval in 2016 for the treatment of adults with axSpA who have responded inadequately to conventional treatment, and has demonstrated efficacy and safety through extensive clinical trials. However, there is limited evidence on its real-world use in Canada. The objective of this study was to use the Canadian Spondyloarthritis (CanSpA) Research Network to describe real-world retention and effectiveness of SEC in the Canadian axSpA population. This was an observational cohort study of Canadian patients with axSpA aged 18 to 65 years within the CanSpA network who had received treatment with SEC. Patients were indexed on the first date of SEC initiation. Retention and clinical effectiveness were assessed at 12 months postindex. Clinical effectiveness was measured as the proportion in remission and change in disease activity using multiple clinical indices. A total of 146 patients were included. Overall retention was estimated at 62.9%. Low disease activity (ie, Bath Ankylosing Spondylitis Disease Activity Index < 4) was achieved in 29.2% of patients, and 2% had achieved remission based on the Ankylosing Spondylitis Disease Activity Score. Bath Ankylosing Spondylitis Metrology Index scores improved by more than 60% from baseline to 12 months. The results of this real-world study of Canadian patients with axSpA, one of the first of its kind, support the effectiveness of SEC for treatment of axSpA. The CanSpA network presents an opportunity to continue building and improving the real-world evidence base for treatment of Canadian patients with spondyloarthritis.

Comparative Efficacy of Biologic Disease-Modifying Anti-Rheumatic Drugs for Non-Radiographic Axial Spondyloarthritis: A Systematic Literature Review and Bucher Indirect Comparisons.

Biologic disease-modifying anti-rheumatic drugs (bDMARDs), including certolizumab pegol (CZP), are effective treatment options for the management of non-radiographic spondyloarthritis (nr-axSpA). In the absence of head-to-head comparisons in nr-axSpA, we conducted a systematic literature review (SLR) and indirect treatment comparison (ITC) to better understand the comparative efficacy of CZP vs. other bDMARDs. Literature searches were conducted in October 2020 in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in patients with nr-axSpA who had failed at least one non-steroidal anti-inflammatory drug and were treated with bDMARDs. Outcomes of interest included the Assessment of Spondyloarthritis international Society (ASAS), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Disease Activity Index (BASDAI), and spinal pain score. Comparative efficacy was examined using a series of Bucher ITCs in subgroups matched by prior exposure to bDMARDs, disease duration, baseline C-reactive protein (CRP) levels/magnetic resonance imaging (MRI) status, and timepoints, to ensure comparability between studies. At 12-16weeks, treatment with CZP was significantly more likely to achieve ASAS20/40 response and ASDAS-inactive disease status vs. etanercept (ETN), ixekizumab (IXE), and secukinumab (SEC). CZP showed statistically significant improvement in BASDAI, BASFI, and total spine pain score over adalimumab (ADA), ETN, and IXE, and in BASFI over SEC. Among patients with objective signs of inflammation (OSI; elevated CRP levels and/or inflammation on MRI at baseline), CZP had a statistically significant advantage over ETN and SEC (with or without loading dose) in achieving ASAS40, whereas the comparisons with other bDMARDs did not show any statistically significant differences. In the overall matched population, CZP performed significantly better than most comparators in improving the clinical outcomes. Among patients with OSI, CZP was found to be superior to SEC (in the MRI-/CRP + and MRI + /CRP- subgroups) and ETN (in the MRI + /CRP- subgroup) and it was comparable to golimumab and IXE across the different OSI subgroups.

Economic Evaluation of Selected Interleukin Inhibitors Versus Methotrexate for Moderate-to-Severe Plaque Psoriasis From the Philippine Payer Perspective

ObjectivesWe conducted an economic evaluation of interleukin inhibitors (ILIs) guselkumab, ixekizumab (IXE), secukinumab (SEC), and ustekinumab to a methotrexate (MTX) comparator for biologic-naive adult Filipino patients with moderate-to-severe chronic plaque psoriasis. MethodsA 1-year decision tree and 5-year Markov model were used to estimate incremental cost-effectiveness ratios (ICERs) in Philippine pesos (PHP) per Psoriasis Area Severity Index improvement of at least 75%. For health technology assessment purposes, we also estimated the budget impact of subsidies for SEC to a Government of the Philippines (GoP) payer. Deterministic and probabilistic sensitivity analyses were performed. Data sources included global literature and local intervention prices. ResultsAll ILIs were more effective but also more expensive than MTX. In the base case, only IXE and SEC were cost-effective treatments at a gross domestic product–benchmarked threshold, yielding ICERs of PHP468 098.01 and PHP483 525.32 per PASI responder, respectively. GUS and UST were less likely to be cost-effective throughout a range of simulated thresholds. ICERs were most responsive to discontinuation rates and drug prices. Full subsidy of SEC for 5 years would cost the GoP PHP1.83 billion more than a similar subsidy for MTX. ConclusionsILIs were clearly more effective than MTX, but only IXE and SEC were potentially cost-effective for a GoP payer. Any case in which SEC is fully subsidized is more expensive to the GoP than the base case. This study was limited by a lack of country-specific effectiveness data, underestimation of comparator costs, exclusion of noncutaneous and quality-of-life effects, and indirect costs.

Using natural language processing to explore characteristics and management of patients with axial spondyloarthritis and psoriatic arthritis treated under real-world conditions in Spain: SpAINET study.

Spondyloarthritis (SpA) is a group of related but phenotypically distinct inflammatory disorders that include axial SpA (axSpA) and psoriatic arthritis (PsA). Information on the characteristics and management of these patients in the real world remains scarce. To explore the characteristics and management [disease activity assessment and treatment with secukinumab (SEC) or other biologic disease-modifying antirheumatic drugs (bDMARDs)] of axSpA and PsA patients using natural language processing (NLP) in Electronic Health Records (EHRs). National, multicenter, observational, and retrospective study. We analyzed free-text and structured clinical information from EHR at three hospitals. All adult patients with axSpA, PsA or non-classified SpA from 2018 to 2021 with minimum follow-up of three months were included when starting SEC or other bDMARDs. Clinical variables were extracted using EHRead® technology based on Systemized Nomenclature of Medicine-Clinical Terms (SNOMED CT) terminology. Out of 887,735 patients, 758 were included, of which 328 had axSpA [58.5% male; mean (SD) age of 50.7 (12.7) years], 365 PsA [54.8% female, 53.9 (12.4) years], and 65 non-classified SpA. Mean (SD) time since diagnosis was 36.8 (61.0) and 24.1 (35.2) months for axSpA and PsA, respectively. Only 116 axSpA patients (35.3%) had available Ankylosing Spondylitis Disease Activity Score (ASDAS) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at bDMARD onset, of which 61 presented active disease. Disease Activity in PSoriatic Arthritis (DAPSA) or Disease Assessment Score - 28 joints (DAS-28) values at bDMARD onset were available for only 61 PsA (16.7%) patients, with 23 of them having active disease. The number of patients with available tender joint count or swollen joint count assessment was 68 (20.7%) and 59 (18%) for axSpA, and 115 (31.5%) and 119 (32.6%) for PsA, respectively. SEC was used in 63 (19.2%) axSpA patients and in 63 (17.3%) PsA patients. Using NLP, the study showed that around one-third of axSpA and one-sixth of PsA patients have disease activity assessments with ASDAS/BASDAI or DAPSA/DAS-28, respectively, highlighting an area of improvement in these patients' management.