Changes in serum interleukin-6 levels as possible predictor of efficacy of tocilizumab treatment in rheumatoid arthritis

Aizu, Motohiko; Mizushima, Ichiro; Nakazaki, Satoshi; Nakashima, Akikatsu; Kato, Takashi; Murayama, Takashi; Kato, Shunsuke; Katsuki, Yasuo; Ogane, Kunihiro; Fujii, Hiroshi; Yamada, Kazunori; Nomura, Hideki; Yachie, Akihiro; Yamagishi, Masakazu; Kawano, Mitsuhiro

doi:10.1080/14397595.2017.1370766

Cited by 17 publications

(11 citation statements)

References 19 publications

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“…The reduced effects of Tocilizumab in hyperglycemic patients may due to the higher plasma IL-6 levels. Previous study evidenced that tocilizumab efficacy was inversely proportional to the baseline IL-6 levels in patients with rheumatoid arthritis (5). Accordingly, our data evidence that hyperglycemic patients had IL-6 levels at admission 5-fold higher as compared to the normoglycemic patients.…”

supporting

confidence: 66%

Negative impact of hyperglycemia on Tocilizumab therapy in COVID-19 patients

Marfella

Paolisso

Sardu

et al. 2020

Preprint

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Tocilizumab is used for treating moderate-severe Covid-19 pneumonia by targeting IL-6 receptors (IL-6R) and reducing cytokine release, but the pooled rate ratio among diabetic patients with adverse vs those with the more favorable course was 2.26. To date, the hyperglycemia has been shown to increase IL-6 and IL-6R, which has been suggested as a severity predictor in lung diseases of Covid-19 patients. However, there are no data about the effects of tocilizumab therapy on outcomes of hyperglycemic Covid-19 patients with pneumonia. To investigate this unsolved need, 475 Covid-19 positive patients were retrospectively studied since March 1st, 2020. Among them, 78 patients with pneumonia disease and treated with tocilizumab were further evaluated for a severe outcome (encompassing both the use of mechanical ventilation and/or death). Thirty-one (39.7%) hyperglycemic and 47 (60.3%) normoglycemic Covid-19 positive patients (blood glucose levels >140 mg/dl, at admission and/or during hospital stay) were evaluated. Noteworthy, 20 (64%) of hyperglycemic and 11 (23.4%) of normoglycemic patients were also diabetics (P<0.01). At admission, more elevated IL-6 levels in hyperglycemic patients were found and persists even after Tocilizumab administration. In a risk adjusted Cox-regression analysis, Tocilizumab in hyperglycemic did not attenuate the risks of severe outcome as did in normoglycemic patients (p<0.009). Therefore, we could conclude that reduced effects of Tocilizumab in hyperglycemic patients may due to the higher plasma IL-6 levels. Interestingly, when we added IL-6 levels in a Cox regression model the significance for the tocilizumab effect was lost (p<0.07). In this context, our observations evidence that optimal Covid-19 infection management with tocilizumab is not achieved during hyperglycemia both in diabetic and non-diabetic patients.

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supporting

confidence: 66%

Negative impact of hyperglycemia on Tocilizumab therapy in COVID-19 patients

Marfella

Paolisso

Sardu

et al. 2020

Preprint

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“…In rheumatoid arthritis, IL-6 <30 pg/mL after 12 weeks predicted remission after 52 weeks 4 5. In contrast, others reported a link between lower serum IL-6 at TCZ stop and subsequent GCA flares 3.…”

mentioning

confidence: 97%

Serial IL-6 measurements in patients with tocilizumab-treated large-vessel vasculitis detect infections and may predict early relapses

Berger¹,

Rebholz-Chaves

Recher³

et al. 2019

Ann Rheum Dis

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“…In this setting, TCZ through its targeting of the IL-6 pathways is a blocker of the IL-6 signal transduction pathway and can be used in patients with severe Covid-19 [8]. Notably, based on a previous study conducted in patients with rheumatoid arthritis, TCZ efficacy was shown to be inversely proportional to baseline IL-6 levels [9]. Moreover, in Covid-19 patients, TCZ treatment led to a significant decline in inflammatory markers, with radiological improvement and reduced ventilator support requirements [10].…”

mentioning

confidence: 99%

Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients

Marfella

Paolisso

Sardu

et al. 2020

Diabetes & Metabolism

115

102

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To calm the inflammatory storm, tocilizumab (TCZ) has been used in the treatment of moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release [1]. Yet, despite the optimal management of Covid-19 infection with treatments including TCZ, the pooled rate ratio for diabetes patients with adverse disease courses vs. those with more favourable courses was 2.26 [2]. An important factor in any infection outcomes in patients with diabetes may be glucose control [2]. Indeed, hyperglycaemia is associated with higher levels of IL-6 and IL-6Rs [3], both of which are predictors of severe lung disease in Covid-19 patients [1]. However, at this time, there are no data on the effects of TCZ on outcomes in hyperglycaemic Covid-19 patients with moderate-to-severe respiratory illness. To investigate this unresolved need, 475 Covid-19-positive patients, admitted to infectious disease departments (University of Bologna, University Vanvitelli Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, were retrospectively studied. The study protocol was approved by the Ethics Committees of the relevant Institutional Review Boards. The diagnosis of Covid-19 was established according to World Health Organization (WHO) interim guidance and confirmed by RNA detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the hospitals' microbiology laboratories. Of the Diabetes & Metabolism 46 (2020) 403-405

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Changes in serum interleukin-6 levels as possible predictor of efficacy of tocilizumab treatment in rheumatoid arthritis

Abstract: Serum IL-6 levels from 12 to 24 weeks after TCZ initiation better reflect the efficacy of TCZ at 52 weeks.

Cited by 17 publications

References 19 publications

Negative impact of hyperglycemia on Tocilizumab therapy in COVID-19 patients

Negative impact of hyperglycemia on Tocilizumab therapy in COVID-19 patients

Serial IL-6 measurements in patients with tocilizumab-treated large-vessel vasculitis detect infections and may predict early relapses

Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients

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