Efficacy and safety of secukinumab in Japanese patients with active ankylosing spondylitis: 24-week results from an open-label phase 3 study (MEASURE 2-J)

Kishimoto, Mitsumasa; Taniguchi, Atsuo; Fujishige, Ayako; Kaneko, Shuhei; Haemmerle, Sibylle; Porter, Brian; Kobayashi, Shigeto

doi:10.1080/14397595.2018.1538004

Cited by 28 publications

(33 citation statements)

References 38 publications

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“…Regarding LoBT and dosages employed, our data on the clinical response about treatment with SCK were consistent with our previous short-term experience as well as that of RCTs [18][19][20][21][22], since no differences in clinical response or retention rate were observed between biologic-naïve subjects and in patients formerly exposed to anti-TNF-α agents as well as between patients undergoing SCK 150 mg/4 w vs. 300 mg/4 w. Furthermore, no differences in clinical response or drug retention emerged between psoriatic and nonpsoriatic patients or between subjects with radiographic vs. non-radiographic axSpA. Although these results were obtained from a fairly small cohort and therefore must be interpreted with caution, our findings again support the adequacy of SCK in the management of axSpA manifestations.…”

Section: Discussionsupporting

confidence: 89%

“…Therefore, the need to find alternative treatments for these patients has led to the development of further drugs able to block another pivotal cytokine involved in axSpA inflammation, such as interleukin-(IL-) 17 [17]. The human anti-IL-17A monoclonal antibody secukinumab (SCK) has been approved for the treatment of ankylosing spondylitis (AS), after proving its effectiveness in 5 multicentre phase III trials, including 4 randomized double blind trials and their extensions (MEASURE 1 [18], MEASURE 2 [18], MEASURE 3 [19], MEASURE 4 [20], and MEASURE 2-J [21]).…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Gentileschi

Rigante

Sota

et al. 2020

Mediators of Inflammation

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Objectives. The primary aim of our study was to evaluate long-term efficacy of secukinumab (SCK) in patients with axial spondyloarthritis (axSpA); secondary aims were to evaluate drug retention rate and to identify differences in the clinical and laboratory assessment according to axSpA clinical features, dosage administered, and biologic treatment lines. Patients and Methods. We collected clinical, demographical, and treatment data from 39 patients affected by axSpA consecutively treated with SCK. Laboratory assessment was based on inflammation parameters; clinical assessment was performed with the Ankylosing Spondylitis Disease Activity Score- (ASDAS-) CRP and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were recorded at baseline and every 3 months for the first year and then every 6 months in the second year. Results. Twelve males and 27 females were enrolled; both BASDAI and ASDAS-CRP showed a statistically significant reduction during the observation period (p<0.0001 and p<0.0001, respectively). C-reactive protein significantly decreased (p=0.006), with significant reduction at the post hoc analysis between baseline and both 6-month evaluation (p=0.02) and 24-month visit (p=0.036). No statistical significance was observed in BASDAI and ASDAS-CRP improvement (p=0.482 and p=0.164, respectively) between different dosages administered. No significant differences emerged in the BASDAI and ASDAS-CRP variations between biologic-naïve patients and subjects previously failing to tumour necrosis factor (TNF) inhibitors (p=0.53 and p=0.148, respectively). At the end of our observation, 7 out of 39 patients discontinued SCK. The global retention rate at the end of the study period was 78.2%, without any significant differences between biologic-naïve and anti-TNF-failure patients (p=0.619) or between subjects administered with different SCK dosages (p=0.614). No adverse events were reported. Conclusions. In our cohort, SCK has proved a remarkable effectiveness regardless biologic treatment line and dosages employed. As suggested by the notable drug retention rate, SCK has been able to maintain its effectiveness over a considerable long period of treatment.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Gentileschi

Rigante

Sota

et al. 2020

Mediators of Inflammation

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“…Similarly, cytokines levels were strongly interrelated in this AS cohort, reflecting their interaction in mitigating disease in AS patients [40–42], but there was a complete disconnect between cytokine levels and clinical disease activity, laboratory findings, and patient-reported health measures. Other, but not all, studies have reported a similar lack of clinical association for cytokines [1, 42, 43], but given the efficacy of anti-cytokine therapy in AS [6, 44, 45], it is hard to reconcile this discrepancy between pathophysiological and clinical findings. We have earlier also shown that TNF levels do not predict response to TNFi treatment in AS [18], but given the increased levels of TNF mRNA in sacroiliac joints [9], it can be argued that there is no or only limited overflow of site-specific inflammation markers in AS similar to the lack of specific biomarkers found in rheumatoid arthritis [46].…”

Section: Discussionmentioning

confidence: 99%

Disease Activity and Patient-Reported Health Measures in Relation to Cytokine Levels in Ankylosing Spondylitis

Nossent

Johnsen²,

Bakland

2019

Rheumatol Ther

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Introduction Ankylosing spondylitis (AS) is a lifelong condition where spinal inflammation causes chronic back pain and restriction of spinal function. While proinflammatory cytokines participate in the disease process, their relation with disease activity, spinal function, and quality of life is less well understood. Methods Cross-sectional study of serum levels of four inflammatory cytokines (IL-6, TNF, IL-23, and IL-17A) in AS patients not on biologics. Disease characteristics and simultaneous spinal function tests and patient-reported health measures (Bath Functional Index (BASFI), Dougados Functional Index (DFI), Modified Health Assessment Questionnaire (MHAQ), and routine laboratory parameters were recorded. The composite ASDAS-CRP score was used to classify disease activity as absent, low, or high. Results In 164 AS patients (age 46 years, 70.1% males, 90.9% HLAB27 positive, ASDAS-CRP 1.8), disease activity was classified as inactive in 14%, low in 54%, and high in 31%. ASDAS-CRP correlated well with MHAQ, DFI, BASFI, and spinal mobility across patients with low and high disease activity (all p < 0.05). Cytokine levels did not correlate with ASDAS-CRP, ESR, BASFI, or spinal mobility scores and were comparable between patients with no, low, or high disease activity regardless of gender or disease duration (all p > 0.2). Conclusions A large proportion of AS not on biologics have active disease far into the disease course. This impacts negatively on quality of life, work ability, and spinal mobility. Serum cytokine levels are poor markers for these central disease features in AS management. Funding Abbott Norway AS and Arthritis Foundation of Western Australia. Electronic supplementary material The online version of this article (10.1007/s40744-019-0161-7) contains supplementary material, which is available to authorized users.

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“…11 Interleukin (IL)-17 cytokines play a pathophysiological role in axSpA. 12 Clinical trials have demonstrated the efficacy and safety of IL-17 inhibitors in the treatment of AS [13][14][15][16][17][18][19][20][21][22][23] and nr-axSpA. 24 Inhibition of IL-17A and IL-17F prevents inflammation and pathological and new bone formation.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial

Wei¹,

Kim²,

Kishimoto³

et al. 2021

Ann Rheum Dis

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ObjectiveTo investigate the efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA).MethodsIn a multicentre, placebo-controlled phase 3 study (NCT02985983) conducted at 48 sites across Japan, Korea and Taiwan, patients with axSpA were randomised 1:1 to receive subcutaneous brodalumab 210 mg (n=80) or placebo (n=79) at baseline, weeks 1 and 2 and every 2 weeks thereafter, during the 16-week double-blind period. The primary endpoint was the proportion of patients with Assessment of SpondyloArthritis International Society (ASAS) 40 response at week 16. Secondary endpoints included the proportion of patients with ASAS 20 response and change in Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) at week 16 and safety.ResultsASAS 40 response rate (n/N; 95% CI) was 43.8% (35/80; 32.7, 55.3) with brodalumab vs 24.1% (19/79; 15.1, 35.0) with placebo (rate difference, 19.7% (5.3, 34.1); p=0.018 by stratified Cochran-Mantel-Haenszel test). ASAS 20 response rate (n/N; 95% CI) was 67.5% (54/80; 56.1, 77.6) vs 41.8% (33/79; 30.8, 53.4) and least squares mean change (95% CI) from baseline (brodalumab, 2.660; placebo, 2.716) in ASDAS-CRP was –1.127 (–1.322, –0.931) with brodalumab vs –0.672 (–0.872, –0.473) with placebo at week 16. Treatment-emergent adverse events were reported in 44 (55%) and 45 (57%) patients in the brodalumab and placebo groups, respectively.ConclusionBrodalumab demonstrated a significant improvement at week 16 in patients with active axSpA. Safety of brodalumab was consistent with that reported in previous global/Japanese psoriasis studies.

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Efficacy and safety of secukinumab in Japanese patients with active ankylosing spondylitis: 24-week results from an open-label phase 3 study (MEASURE 2-J)

Cited by 28 publications

References 38 publications

Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Disease Activity and Patient-Reported Health Measures in Relation to Cytokine Levels in Ankylosing Spondylitis

Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial

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