Sustained tocilizumab-induced hypofibrinogenemia and thrombocytopenia. Comment on: “Tocilizumab-induced hypofibrinogenemia: A report of 7 cases” by Martis et al., Joint Bone Spine 2016, doi: 10.1016/j.jbspin.2016.04.008

Vitiello, Gianfranco; Battaglini, Carolina Orsi; Radice, Anna; Carli, G; Micheli, Serena; Cammelli, Daniele

doi:10.1016/j.jbspin.2017.02.012

Cited by 11 publications

(7 citation statements)

References 2 publications

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“…Previous researches have shown that hypo brinogenemia in patients mainly occurs after 1-4 doses of TCZ treatment and FIB levels can return to normal after discontinuation of treatment 3,5,22,23 , which is consistent with the ndings of our study. Our results indicated that a majority of rheumatic diseases patients experienced hypo brinogenemia within 3 months of receiving TCZ treatment, and among these patients, 65.63% (21/32) were able to recover their FIB levels to normal.…”

Section: Fib Level In the Fib-reduced Group At Different Time Pointssupporting

confidence: 93%

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia

An,

Ma,

Yuan

et al. 2024

Clin Rheumatol

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The objective of this study was to analyze the changes in plasma brinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypo brinogenemia and its possible risk factors, and establish a nomogram model for predicting the probability of hypo brinogenemia in rheumatoid arthritis (RA) patients treated with TCZ. MethodsClinical data of patients treated with TCZ at the department of Rheumatology and Immunology, the First A liated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypo brinogenemia in several rheumatic diseases at different time points. The risk factor of hypo brinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypo brinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software. ResultsA total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypo brinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 38.25 ± 16.92 years. Hypo brinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypo brinogenemia typically occurs within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypo brinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypo brinogenemia in RA patients receiving TCZ. ConclusionAlthough bleeding symptoms were not observed in this study, the incidence of hypo brinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypo brinogenemia after TCZ treatment in RA patients.

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Section: Fib Level In the Fib-reduced Group At Different Time Pointssupporting

confidence: 93%

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia

An,

Ma,

Yuan

et al. 2024

Clin Rheumatol

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“…Martis et al 12 have reported that TCZ-induced hypofibrinogenemia has occurred after an average of eight doses (4–48 doses) 11 . TCZ-induced hypofibrinogenemia occurred after one to four doses of TCZ in most patients in our center.…”

Section: Discussionmentioning

confidence: 99%

“…TCZ had been initially expected to normalize fibrinogen levels. However, TCZ-induced hypofibrinogenemia has been reported recently in adult cases and limited small case series with rheumatoid arthritis (RA) or giant cell arteritis (GCA) 11 , 12 . TCZ-induced hypofibrinogenemia has never been reported in children with SJIA.…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab-induced hypofibrinogenemia in patients with systemic-onset juvenile idiopathic arthritis

Ling

Yang

2023

Sci Rep

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Systemic juvenile idiopathic arthritis (SJIA) is a chronic inflammatory disease of childhood with elevated serum IL-6 levels. As an inhibitor of IL-6R, tocilizumab (TCZ) has been approved to treat SJIA patients. TCZ-induced hypofibrinogenemia has been only reported in adult cases and limited small case series with rheumatoid arthritis or giant cell arteritis. Here, we describe the incidence of TCZ-induced hypofibrinogenemia in SJIA patients and its possible influence on bleeding risk. SJIA patients with TCZ treatment in Shenzhen Children’s hospital were retrospectively reviewed. Only those with the data on serum fibrinogen levels were included. Data on clinical manifestations, laboratory parameters, management, and sJADAS10-ESR score were collected. Laboratory data were extracted following the start of TCZ therapy at 2, 4, 8, 12, and 24 weeks thereafter. Seventeen SJIA patients with TCZ treatment were included. Thirteen (76.47%, 13/17) had hypofibrinogenemia. The lowest serum fibrinogen levels were even below 1.5 g/L in seven (41.17%, 7/17) patients. Among four patients without MTX treatment, two had obvious hypofibrinogenemia. Although five patients had already stopped steroid treatment 24 weeks after TCZ treatment, three of them still had hypofibrinogenemia. Only P14 had mild nasal mucosal bleeding occasionally. Coagulation tests were regularly performed in eight patients, of these, six had hypofibrinogenemia, which occurred following one to four doses of TCZ; continuation of TCZ treatment hadn’t further aggravated hypofibrinogenemia. Serum fibrinogen levels were not decreased consistently with the improvement of sJADAS10-ESR score in more than half of these eight patients. Factor XIII was detected in six patients and none was identified with Factor XIII deficiency. TCZ alone may induce hypofibrinogenemia in SJIA patients. Continuation of TCZ treatment may be safe for most SJIA patients. But for SJIA patients with indications of surgery or complicated with MAS, the risk of hemorrhage should be regularly evaluated during TCZ treatment. The association between TCZ-induced hypofibrinogenemia and factor XIII deficiency remains uncertain.Trial registration: Not applicable; this was a retrospective study.

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“…3 Although hypofibrinogenemia does not seem to be related to an increased hemorrhagic risk, the drug was in any case suspended due to low platelet count. 29 Concerning the risk of infections, whether this can be attributed to the biological agent or to the combination of TCZ and GCs remains unknown. 7…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab in Giant Cell Arteritis: A Real-Life Retrospective Study

et al. 2018

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This study aims to evaluate (1) the efficacy and safety of tocilizumab (TCZ) as a steroid-sparing agent in patients with giant cell arteritis (GCA) and (2) the usefulness of F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up and to detect disease activity. We retrospectively evaluated 12 patients with GCA treated with TCZ (8 mg/kg/mo). Pre- and posttherapy data about clinical signs and symptoms, laboratory results, FDG-PET imaging study, and the mean glucocorticoid (GC) dose were used to assess disease activity. Tocilizumab achieved complete disease remission in all patients. Mean FDG-PET-detected standard uptake value decreased from 2.05 ± 0.64 to 1.78 ± 0.45 ( P = .005). In 2 patients in whom temporal arteries color Doppler sonography examination was consistent with temporal arteritis, the hypoechoic halo disappeared after TCZ treatment. Mean GC dose was tapered from 26.6 ± 13.4 mg/d to 3.3 ± 3.1 mg/d ( P< .0001). One-half of the patients discontinued GC therapy. Three patients experienced severe adverse reactions and had to stop TCZ therapy. In accordance with previous reports, TCZ is an effective steroid-sparing agent for GCA, although careful monitoring of adverse drug reactions is needed. F-fluorodeoxyglucose positron emission tomography could be used to monitor disease activity in TCZ-treated patients, but prospective studies are needed to confirm these data.

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Sustained tocilizumab-induced hypofibrinogenemia and thrombocytopenia. Comment on: “Tocilizumab-induced hypofibrinogenemia: A report of 7 cases” by Martis et al., Joint Bone Spine 2016, doi: 10.1016/j.jbspin.2016.04.008

Cited by 11 publications

References 2 publications

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia

Tocilizumab-induced hypofibrinogenemia in patients with systemic-onset juvenile idiopathic arthritis

Tocilizumab in Giant Cell Arteritis: A Real-Life Retrospective Study

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