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

Berger, Christoph T.; Rebholz-Chaves, Birke; Recher, Mike; Manigold, Tobias; Daikeler, Thomas

doi:10.1136/annrheumdis-2018-214704

Cited by 38 publications

(24 citation statements)

References 5 publications

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“…2 As a consequence of the blockade of the IL-6 pathway, acute-phase reaction proteins (erythrocyte sedimentation rate, C-reactive protein and fibrinogen) remained in the lowest range during the TCZ treatment period (figure 1A). Similar to Berger's study, the median (IQR) IL-6 concentration increased from 1.5 (1.5-12.7) at W0 to 20.6 (8.3-38.5) pg/mL at the last TCZ infusion (W12) (p=0.021; figure 1B), but this increase was less significant than the increase reported by Berger CT et al 1 About 3 months after TCZ was discontinued (W26), median (IQR) IL-6 concentration had normalised to 1.5 (1.5-1.5) pg/mL ( figure 1B). In our study, 2/6 (33.3%) patients with low serum IL-6 (< 12.9 pg/mL) at W12 relapsed during the follow-up period versus 8/13 (61.5%) patients with high IL-6 (≥12.9 pg/mL) at week 12 which did not reach significance (p=0.35).…”

supporting

confidence: 83%

“…We read with great interest the letter published by Berger et al in which the authors showed that relapse-free survival for giant cell arteritis (GCA) treated with tocilizumab (TCZ) was longer in patients with an interleukin (IL) 6 decline (slope ≤0.1). 1 In contrast with Berger et al, 1 IL-6 levels at the last TCZ infusion were not found to predict the risk of relapse in our phase 2 prospective open-label clinical trial that included 20 patients with GCA (19/20 patients with new-onset GCA) treated with prednisone and TCZ (8 mg/kg/4 weeks from inclusion to week 12 (W12)). These patients were followed for 52 weeks, and IL-6 levels were monitored by luminex (eBioscience) at inclusion (W0), W12 and W26.…”

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confidence: 75%

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Analysis of IL-6 measurement in patients with GCA treated with tocilizumab should consider concomitant treatment with prednisone

Samson

Bonnotte

2019

Ann Rheum Dis

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We thank Marion Ciudad for her help in dosing interleukin-6. We thank Serge Monier from the Plateforme de Cytométrie, Institut Fédératif de Recherche 100, Université de Bourgogne. We thank Suzanne Rankin for her help in reviewing the manuscript. Collaborators We thank Marion Ciudad for her help in dosing IL-6. We thank Serge Monier from the Plateforme de Cytométrie, Institut Fédératif de Recherche 100, Université de Bourgogne. We thank Suzanne Rankin for her help in reviewing the manuscript. Contributors MS and BB included patients, collected data, performed IL-6 dosages, analysed data and drafted the manuscript. Funding The study was funded by the French Ministry of Health (Programme Hospitalier de Recherche Clinique [PHRC] 2012) and registered with ClinicalTrials. gov, number NCT01910038. Competing interests None declared. Patient consent for publication Not required.

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supporting

confidence: 83%

contrasting

confidence: 75%

Analysis of IL-6 measurement in patients with GCA treated with tocilizumab should consider concomitant treatment with prednisone

Samson

Bonnotte

2019

Ann Rheum Dis

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“…According to the serum IL‐6 data obtained from several patients in this trial (Table ), sustained suppression of IL‐6 production might be related to drug‐free remission, as indicated in the DREAM study of rheumatoid arthritis . A report has described the importance of longitudinal IL‐6 measurements, which may be helpful to predict relapse or continuous remission after the discontinuation of TCZ in the management of large‐vessel vasculitis …”

Section: Discussionmentioning

confidence: 82%

Tocilizumab monotherapy for polymyalgia rheumatica: A prospective, single‐center, open‐label study

et al. 2019

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| INTRODUC TI ONPolymyalgia rheumatica (PMR) is a systemic inflammatory disease of unknown etiology. It mainly affects elderly people and rarely arises in people younger than 50 years old. Typical clinical features of PMR include proximal myalgia (particularly in the shoulder girdles), morning stiffness of the trunk, and elevated erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) levels. 1,2 Glucocorticoids (GC) remain the mainstay therapy for PMR 2,3 because they produce dramatic responses in most patients. However, approximately half of patients with PMR experience relapse after tapering of the GC dose. 2,4 Moreover, long-term GC therapy can produce substantial adverse events, such as osteoporotic compression fractures of the spine, diabetes, infections and cardio-cerebral vascular events. 2,5,6 Abstract Objectives: Polymyalgia rheumatica (PMR) is a systemic inflammatory disease in the elderly of unknown etiology. While glucocorticoids are the mainstay of treatment for PMR, various glucocorticoid-related adverse events are common. Recently, several studies have reported the efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, for PMR treatment in addition to an accompanying reduction, or even tapering-off, of glucocorticoids in some cases. The objective of this study was to elucidate the efficacy of TCZ monotherapy in the absence of glucocorticoids for PMR. Method:We conducted a 2-year, prospective, single-center, open-label pilot study of TCZ monotherapy in patients with PMR. TCZ (8 mg/kg) was administered at fortnightly intervals for the first 2 months and monthly over the next 10 months.Subsequently, patients were observed for another year without any treatment. The primary endpoints were the remission rates at weeks 12 and 52, and the secondary endpoints were the relapse rate and safety over the total 104 weeks.Results: Thirteen patients were included in this study. Four of these patients achieved remission at week 12 (remission rate 31%). Four patients withdrew from the study due to adverse events (n = 2) and inefficacy (n = 2). At week 52, all 9 patients who had completed the first year achieved remission. Eight patients completed the drug-free second year, with 7 maintaining remission.Conclusions: TCZ monotherapy is well tolerated and can lead to remission in most patients with PMR in the absence of glucocorticoids. K E Y W O R D Sglucocorticoid, interleukin-6, monotherapy, polymyalgia rheumatica, tocilizumab agents. We used 15 infusions of TCZ. However, if fewer TCZ infusions are sufficient to control PMR and TCZ treatment could be ceased, then these cost problems would be negated. Therefore, the optimal number of infusions of TCZ required to control PMR activity must be determined in the future. In addition, as TCZ monotherapy is expected to reduce adverse events related to GCs, such as osteoporosis, diabetes, dyslipidemia, and so on, the additional costs associated with the treatment of these adverse events will be reduced.Several limitations of our study warran...

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“…This is in line with our data (as well as Gloor et al 2 ), as absolute levels were also not associated with relapse outcome in our study (median 38.3 vs 36.1 vs 39.8 pg/mL for 'no', 'early' and 'late relapse'). 3 Instead, we found that a longitudinal decline (ie, the slope over several measurements) of IL-6 levels during therapy related to later relapses. Since Samson and Bonnotte did not analyse longitudinal measurements, the direct comparison is not possible.…”

mentioning

confidence: 58%

Longitudinal versus cross-sectional IL-6 measurements in tocilizumab-treated GCA. Response to: ‘Analysis of IL-6 measurement in GCA patients treated with tocilizumab should consider concomitant treatment with prednisone’ by Samson and Bonnotte

Berger

Daikeler

2019

Ann Rheum Dis

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Provenance and peer review Commissioned; internally peer reviewed. Correspondence response Figure 1 Stratification of interleukin 6 (IL-6) blood levels based on daily cortisone dose or age. IL-6 plasma levels in subjects: (A) receiving or ≥20 mg of daily prednisone (PDN) in early time-points (left) and before tocilizumab (TCZ) was stopped (right); (B) younger versus older than 70 years of age. (C) Correlation matrix of: 'n TCZ'=total numbers of TCZ doses received, IL-6 after the second dose and IL-6 before TCZ was stopped, as well as daily prednisone doses at the time of TCZ start and discontinuation. Values indicate Spearman r correlation coefficients. 'PDN at start' versus 'IL-6 after second dose' (p=0.008), 'PDN at stop' versus 'n TCZ' (p=0.042) and 'IL-6 after second dose' versus 'at TCZ stop' (p=0.029) were significant.

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

Cited by 38 publications

References 5 publications

Analysis of IL-6 measurement in patients with GCA treated with tocilizumab should consider concomitant treatment with prednisone

Analysis of IL-6 measurement in patients with GCA treated with tocilizumab should consider concomitant treatment with prednisone

Tocilizumab monotherapy for polymyalgia rheumatica: A prospective, single‐center, open‐label study

Longitudinal versus cross-sectional IL-6 measurements in tocilizumab-treated GCA. Response to: ‘Analysis of IL-6 measurement in GCA patients treated with tocilizumab should consider concomitant treatment with prednisone’ by Samson and Bonnotte

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