Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorated clinical symptoms and MRI findings of a patient with ankylosing spondylitis

Shima, Yoshihito; Tomita, Tadanori; Ishii, Taeko; Morishima, Atsuyoshi; Maeda, Yukihide; Ogata, Atsushi; Kishimoto, Tadamitsu; Tanaka, Toshio

doi:10.1007/s10165-011-0416-9

Cited by 20 publications

(4 citation statements)

References 16 publications

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“…After 6 months, active knee inflammation and bone marrow edema also disappeared from the review images. In addition, leukocytosis, mild anemia, and low serum albumin levels observed before treatment were significantly improved, and no adverse events occurred throughout the treatment period ( 39 ).…”

Section: Discussionmentioning

confidence: 98%

Therapeutic potential of single-nucleotide polymorphism-mediated IL6R inhibitors in ankylosing spondylitis treatment

Chen,

Xu,

Que

et al. 2024

Front. Med.

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ObjectiveInterleukin-6 (IL-6) is a multiple-effect cell factor implicated in the etiopathogenesis of several rheumatologic disorders. The blockade of the IL-6 pathway via IL6R inhibitors effectively treats these disorders. However, the clinical significance of the IL6R blockade for ankylosing spondylitis (AS) therapy remains controversial. With advances in genomics, increasing evidence has revealed the role of heritability in the etiology of disease, and Mendelian randomization (MR) analyses are being used more broadly to infer causation. Therefore, this MR study aims to evaluate the potential therapeutic utility of IL6R-targeted approaches in AS.MethodsThe C-reactive protein (CRP) level was used as an exposure factor, and rheumatoid arthritis (RA) was used as a positive control. As-related genome-wide association study (GWAS) data were used as the primary outcome of drug-targeted MR analyses to test the relation between IL6R blockers and AS. Inverse variance weighting (IVW) is the primary analytical approach. Various sensitivity tests were performed to check the robustness and trustworthiness of the causality estimation, including consistency, heterogeneity, and pleiotropy analyses. In addition, repeated analysis was conducted using different GWAS data related to exposures and outcomes to examine the results for stability.ResultsAccording to the IVW results, IL6R inhibitors significantly reduced the risk of AS in ukb-b-18194 (OR: 0.995, 95% CI 0.993–0.996, P = 5.12 × 10−08) and ukb-a-88 (OR: 0.994, 95% CI 0.993–0.996, P = 6.25 × 10−15). Moreover, repeated analyses were performed using different exposure-related GWAS data, yielding similar results, ukb-b-18194 (OR: 0.995, 95% CI 0.993–0.997, P = 1.25 × 10−06) and ukb-a-88 (OR: 0.995, 95% CI 0.994–0.997, P = 7.81 × 10−09). Heterogeneity analyses and pleiotropy analyses indicated no significant heterogeneity or pleiotropy.ConclusionThis MR analysis result further validates that the IL-6 pathway may contribute to the pathogenesis of AS and that the inhibition of IL6R reduces the risk of AS. These findings may guide future studies and provide more favorable drug treatment options for people at high risk of AS.

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Section: Discussionmentioning

confidence: 98%

Therapeutic potential of single-nucleotide polymorphism-mediated IL6R inhibitors in ankylosing spondylitis treatment

Chen,

Xu,

Que

et al. 2024

Front. Med.

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“…Serum IL-6 levels significantly decreased after adalimumab administration for 1 (12.5 %) patient only, whereas levels remained normal for 5 (62.5 %) patients. Therefore, even after the significant efficacy of cytokine therapy (TNF blockers and anti-IL-6 receptor antibody [ 21 ]), other, yet unknown, factors may explain the pain and disease activity in SpA. Until we have a better understanding of the underlying mechanisms, we suggest the use of serum TNF-α and IL-6 levels to determine the appropriate timing of treatment and to monitor disease activity among patients with greater disease activity and abnormally high cytokine levels.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics of Japanese patients with axial spondyloarthritis, and short-term efficacy of adalimumab

Otsuka

Morita

Yamada

2015

Journal of Orthopaedic Science

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BackgroundAnkylosing spondylitis (AS) is rarer in Japan than in Europe, probably because the European criteria, not well known by Japanese general physicians, regard AS as a progressive stage of axial spondyloarthritis (SpA). HLA-B27 is an important diagnostic marker of SpA; however, the incidence of the HLA-B27 allele is as low as 0.4 % in Japan. For Japanese SpA patients, other HLA alleles and clinical findings are required for earlier definitive diagnosis, for determining appropriate treatment timing, and for disease monitoring.MethodsWe investigated the HLA-B alleles of 36 patients clinically diagnosed with SpA. For 8 axial SpA patients we evaluated the short-term efficacy of subcutaneous adalimumab injections (40 mg every other week for ≥11 months). Treatment efficacy was evaluated by use of the Bath Ankylosing Spondylitis Activity Index (BASDAI) score, and serum TNF-α and IL-6 levels were measured pre and post-treatment.ResultsAmong the 36 Japanese SpA patients, the HLA-B27 allele occurred infrequently (5.6 %) whereas the HLA-B44 and 61 alleles were the most frequently detected (25.0 %). We also detected severe bamboo spine on radiography in the absence of the HLA-B27 allele. All 8 patients with axial SpA experienced significant symptom improvement after adalimumab treatment; the HLA-B27 allele was absent from these patients. Serum TNF-α and IL-6 levels were elevated in cases with remarkable inflammatory pain and high disease activity. These cytokines decreased after therapy, however. Most patients with normal cytokine levels at baseline retained these low levels.ConclusionsThe findings reveal the short-term efficacy of adalimumab. The remarkably low incidence of HLA-B27 among our patients indicates that HLA-B distribution is different from that in other countries. Serum TNF-α and IL-6 levels were not effective as biomarkers for cases without high disease activity, and further research with larger samples is needed. The efficacy of TNF blockers, however, suggested a potential localized TNF effect was present among SpA patients.

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“…Первое упоминание об использовании иИЛ6 в терапии АС относится к концу прошлого века [23]. В дальнейшем были представлены описания единичных случаев применения данного лечения при спондилоартритах с положительным эффектом [24][25][26][27][28][29]. Предполагают, что ТЦЗ может быть эффективным у больных АС, которые рефрактерны к иФНОα и имеют высокий уровень СРБ.…”

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A case of effective use of interleukin 6 inhibitors in patients with ankylosing spondylitis with secondary amyloidosis

Эрдес¹,

Румянцева²,

Agafonova³

et al. 2021

Sovremennaâ revmatologiâ

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Ineffectiveness of interleukin 6 inhibitors (iIL6), tocilizumab (TCZ) and sarilimumab in ankylosing spondylitis (AS) was shown in randomized clinical trials. However, there is ample evidence that IL6 is actively involved in the pathogenesis of this disease. In addition, the efficacy of iIL6 in patients with secondary AA-amyloidosis was established.Objective: to analyze the results of TCZ administration in AS, complicated by secondary AA-amyloidosis.Patients and methods. The analysis included 6 patients with AS with secondary AA-amyloidosis. All patients were HLA-B27 positive male. The average age of patients was 44±9.2 years, the average age of the disease onset was 16.3±7.9 years, the average duration of AS was 26.0±7.5 years. All 6 patients had pathomorphologic confirmed secondary AA-amyloidosis: all had kidney affection, 5 patients also had gastrointestinal tract affection and 2 had heart affection. As a first biological drug TCZ was prescribed in 2 patients, and 4 patients had previously received one or more inhibitors of tumor necrosis factor α. The average duration of TCZ treatment was 27.6 [3.0; 36.0] months.Results and discussion. During TCZ therapy, the level of CRP (M±σ) significantly decreased: from 81.1±74.5 to 1.2±0.8 mg/L (p<0.05), as well as daily proteinuria (Me [25th ; 75th percentile]): from 1.8 [1.0; 2.1] to 0.2 [0.1; 0.3] g/day (p<0.05) and AS activity indices – BASDAI (M±σ): from 6.2±1.6 to 3.3±0.9 (p<0.05 ); ASDAS-CRP (M±σ) from 4.6±1.1 to 2.04±0.7 (p<0.05). Positive dynamics was also noted in relation to a decrease in the number of patients with inflammatory back pain, arthritis and coxitis. A case of clinical and laboratory remission of AS on TCZ treatment is described. Conclusion. The presented data show that in certain clinical situations iIL6 can be highly effective in AS.

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Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorated clinical symptoms and MRI findings of a patient with ankylosing spondylitis

Cited by 20 publications

References 16 publications

Therapeutic potential of single-nucleotide polymorphism-mediated IL6R inhibitors in ankylosing spondylitis treatment

Therapeutic potential of single-nucleotide polymorphism-mediated IL6R inhibitors in ankylosing spondylitis treatment

Clinical characteristics of Japanese patients with axial spondyloarthritis, and short-term efficacy of adalimumab

A case of effective use of interleukin 6 inhibitors in patients with ankylosing spondylitis with secondary amyloidosis

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