BACKGROUND Tocilizumab is a humanized monoclonal antibody against the interleukin-6(IL-6)receptor that is commonly used to treat large vessel vasculitis and antineutrophil cytoplasmic antibody-related small vessel vas...BACKGROUND Tocilizumab is a humanized monoclonal antibody against the interleukin-6(IL-6)receptor that is commonly used to treat large vessel vasculitis and antineutrophil cytoplasmic antibody-related small vessel vasculitis.However,tocilizumab in combination with glucocorticoids for successfully treating granulomatosis with polyangiitis(GPA)has rarely been reported.CASE SUMMARY Here,we report a 40-year-old male patient who suffered GPA for 4 years.He was treated with multiple rounds of drugs,including cyclophosphamide,Tripterygium wilfordii,mycophenolate mofetil,and belimumab,with no improvement.In addition,he exhibited persistently high IL-6 levels.After tocilizumab treatment,his symptoms improved,and his inflammatory marker levels returned to normal.CONCLUSION Tocilizumab may be effective for treating GPA.展开更多
BACKGROUND Since its initial detection in 2019,coronavirus disease 2019(COVID-19)pneumonia has rapidly spread throughout the world in a global pandemic.However,reports of COVID-19 pneumonia among patients following ki...BACKGROUND Since its initial detection in 2019,coronavirus disease 2019(COVID-19)pneumonia has rapidly spread throughout the world in a global pandemic.However,reports of COVID-19 pneumonia among patients following kidney transplantation have been limited and no uniform treatment guidelines for these patients have yet to be established.CASE SUMMARY Here,we report the case of a 39-year-old patient recovering from kidney transplantation who contracted perioperative COVID-19 pneumonia that was successfully controlled with oral paxlovid and a single intravenous drip infusion of tocilizumab following the discontinuation of immunosuppressive drugs.CONCLUSION Given the rapid spread of severe acute respiratory syndrome coronavirus 2 infections,clinicians should be aware of the potential for more cases of COVID-19 among patients following kidney transplantation and be familiar with appropriate treatment options and likely clinical outcomes.展开更多
Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg...Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg/mL,3.0 mg/mL,5.0 mg/mL) for 24 h.then cells were cultured in ischemia environment for 24 h and reperfusion environment for 1 h.The MTT and flow cytometry were used to detect the proliferation and apoptosis of human cardiac myocytes,respectively.The mRNA and protein expressions of Bcl-2 and Bax were measured by qRT-PCR and western blot,respectively.Results:Compared to the negative group,pretreated by tocilizumab could significantly enhance the proliferation viability and suppress apoptosis of human cardiac myocytes after suffering ischemia reperfusion injury(P<0.05).The expression of Bcl-2 in tocilizumab treated group were higher than NC group(P<0.05).while the Bax expression were lower(P<0.05).Conclusions:Tocilizumab could significantly inhibit apoptosis and keep the proliferation viability of human cardiac myocytes after suffering ischemia reperfusion injury.Tocilizumab may obtain a widely application in the protection of ischemia reperfusion injury.展开更多
AIM: To examine the therapeutic effects of tocilizumab on experimental corneal transplantation and its effect on Treg/Th17 balance. METHODS: Allograft corneal graft was performed between host Sprague Dawley and Wistar...AIM: To examine the therapeutic effects of tocilizumab on experimental corneal transplantation and its effect on Treg/Th17 balance. METHODS: Allograft corneal graft was performed between host Sprague Dawley and Wistar donor rats.The rats were randomly divided into four groups: normal,autograft, allograft, and allograft treated with tocilizumab.Kaplan-Meier was performed to draw the survival curve.The protein levels of interleukin-17A(IL-17A), vascular endothelial growth factor(VEGF), and forkhead box protein3(Foxp3) were measured by immunohistochemistry.The mRNA levels of IL-17A, VEGF, retinoid-related orphan receptor gammat(RORγt), interleukin-6(IL-6) and Foxp3 were detected by reverse transcription real-time polymerase chain reaction(RT-PCR). The Treg and Th17 cells were investigated by flow cytometry. RESULTS: The survival time of tocilizumab group was(24±1.27 d) longer than that of allograft group(10±0.55 d).Moreover, immunohistochemical examination revealed that IL-17A and VEGF protein levels in the allograft group were significantly higher than that of tocilizumab group(P<0.01),while Foxp3 levels in the allograft group was significantly lower than that of the tocilizumab treated group(P<0.001).Flow cytometry showed that the number of Th17 cellsin allograft group was significantly higher than that in tocilizumab group(P<0.001). Meanwhile, the number of Tregs was significantly lower than in tocilizumab group(P<0.001). Simultaneously, Foxp3 m RNA expression level in corneal tissues of tocilizumab treated group was significantly higher than other groups(P<0.001). CONCLUSION: These findings suggest that tocilizumab may promote corneal allograft survival, possibly by modulating Treg-Th17 balance.展开更多
BACKGROUND Human herpes virus-8(HHV-8)-negative,idiopathic multicentric Castleman disease(iMCD)is a rare and life-threatening disorder driven by proinflammatory cytokines,which is still poorly understood.Pulmonary par...BACKGROUND Human herpes virus-8(HHV-8)-negative,idiopathic multicentric Castleman disease(iMCD)is a rare and life-threatening disorder driven by proinflammatory cytokines,which is still poorly understood.Pulmonary parenchyma lesion is a rare condition in iMCD,which mainly manifests as lymphocytic interstitial pneumonia and is an indicator of severe iMCD.Cutaneous lesion is also very rare and mainly occurs in Asians.There have been few reports of iMCD patients with both skin and lung parenchyma involvement.CASE SUMMARY We present a Chinese man who complained about a 3-year history of intermittent dry cough and a 2-year history of diffuse reddish-brown maculopapules.Laboratory examination revealed polyclonal hypergammaglobulinemia and hypercytokinemia including interleukin 6.Chest computed tomography revealed small patchy shadows with ground-glass nodules scattered in two lobes and mediastinal lymphadenopathy.The pathological result of the lymph node was consistent with the plasma cell type of Castleman disease.As serum human immunodeficiency virus test and HHV-8 staining of the lymph node were negative,the patient was finally diagnosed with HHV-8 negative i MCD.He was treated with tocilizumab at an intravenous(i.v.)dose of 8 mg/kg every 2 wk combined with methylprednisolone at an i.v.dose of 80 mg/d initially with gradual dose tapering.Partial remission was achieved 9 mo later.CONCLUSION i MCD with lung parenchyma and skin involvement is a rare condition that requires clinicians'attention and awareness for early diagnosis.展开更多
The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments...The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments.The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis(RA)patients administered intravenously or subcutaneously with tocilizumab.The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer.The serum tocilizumab was rapidly digested by immobilized trypsin for 30 min.The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min.The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 μg/mL.The intra-and inter-day accuracy and relative standard deviation(RSD)were 90.7%-109.4%and<10%,respectively.The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 μg/mL,respectively.The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay,although a systematic error was observed between these methods.In conclusion,a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocilizumab concentrations in RA patients was developed.展开更多
COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest tha...COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.展开更多
BACKGROUND The main pathophysiological basis of coronavirus disease 2019(COVID-19)causing respiratory failure is a cytokine storm and interleukin-6(IL-6)is an important component of the COVID-19 cytokine storm.As a sp...BACKGROUND The main pathophysiological basis of coronavirus disease 2019(COVID-19)causing respiratory failure is a cytokine storm and interleukin-6(IL-6)is an important component of the COVID-19 cytokine storm.As a specific antagonist of IL-6,tocilizumab may block the cytokine storm of COVID-19.The Diagnosis and Treatment Guidelines of New Coronavirus Pneumonia(7 th Edition)includes tocilizumab as a recommended drug for immunotherapy in severe and critical COVID-19 patients.However,the specific clinical efficacy of tocilizumab in the treatment of COVID-19 patients is worth studying.AIM To determine the clinical efficacy of tocilizumab in inhibiting the cytokine storm in COVID-19.METHODS In total,19 severe and critical COVID-19 patients were enrolled in this study,and were treated with tocilizumab in Optical Valley Campus of Hubei Maternal and Child Health Care Hospital from February 20 to March 31,2020.The imaging manifestations and clinical data before and after treatment were analyzed retrospectively,including routine peripheral venous blood tests,routine blood biochemical tests,coagulation test,C-reactive protein(CRP),IL-6,and arterial blood gas analysis.RESULTS Of the 19 patients in this group,13(68.4%)had significantly improved symptoms of COVID-19(5 patients were discharged directly and 8 patients were transferred after improvement)following treatment.One case was invalid,1 case was exacerbated,and 4 deaths(21.1%)were observed(all critical cases).The lymphocyte count,CRP,lactic acid,oxygenation index,fibrinogen(FIB)and IL-6 levels were significantly different in the improved group.CONCLUSION Tocilizumab treatment is effective against IL-6 in COVID-19 patients,but it does not completely inhibit the inflammation and cytokine storm in all patients with COVID-19.In the clinical treatment of COVID-19 patients,attention should be paid to the timing of drug administration and other adjuvant treatments.展开更多
To determine the effect of tocilizumab (TCZ) on reactive oxygen species (ROS) in 11 patients with rheumatoid arthritis (RA), reactive oxygen metabolites (d-ROM) were measured using a Free Radical Elective Evaluator. T...To determine the effect of tocilizumab (TCZ) on reactive oxygen species (ROS) in 11 patients with rheumatoid arthritis (RA), reactive oxygen metabolites (d-ROM) were measured using a Free Radical Elective Evaluator. The Disease Activity Score (DAS28) and matrix metalloproteinase-3 (MMP-3) level were also evaluated. d-ROM measured 392 ± 110 Carratelli units [U. CARR] on initiation of TCZ, and significantly decreased to 237 ± 82, 248 ± 88, and 226 ± 91 U.CARR after 3, 6, and 12 months, respectively展开更多
Objective:To compare the efficacy of pulsed-dose corticosteroids(≥250 mg methylprednisolone,3 days)and tocilizumab in treating COVID-19-related hyperinflammation.Methods:This prospective observational study included ...Objective:To compare the efficacy of pulsed-dose corticosteroids(≥250 mg methylprednisolone,3 days)and tocilizumab in treating COVID-19-related hyperinflammation.Methods:This prospective observational study included RT-PCR positive COVID-19 patients with acute respiratory distress syndrome,who were admitted to the COVID-19 Adult Intensive Care Unit of Prof Dr.Murat Dilmener Emergency Hospital(Istanbul,Turkey)between December 1,2020 and February 28,2021.Clinical,laboratory and radiological examinations were used to diagnose COVID-19 associated hyperinflammation.Three cohort groups were formed:the pulsed-dose corticosteroids group(250 mg methylprednisolone for 3 days),the tocilizumab group(8 mg/day single dose or 400 mg/day for 2 days),and the combined group(pulsed-dose corticosteroid+tocilizumab).The difference in mortality rates among the groups was compared primarily.The most common cause(s)of death was determined.Furthermore,adverse events(secondary infection,acute kidney injury,arrhythmia,gastrointestinal system bleeding)for 28 days were recorded.Results:A total of 60 patients were included in this study,with 20 patients in each group.There was no statistically significant difference between the 3 groups in mortality rates(55%in the pulsed corticosteroid group,60%in the tocilizumab group,50%in the combined group,χ2=0.404,P=0.817).Infectious causes were found to be the most common cause of mortality in all the three groups,and no difference was found between them(χ2=0.404,P=0.817).There was also no difference in the development of adverse events such as secondary infection,acute kidney injury,arrhythmia,and gastrointestinal bleeding among the groups(P>0.05).Conclusions:Corticosteroids can be used instead of tocilizumab to treat hyperinflammation in COVID-19 patients with acute respiratory distress syndrome.展开更多
BACKGROUNDThe majority of patients with coronavirus disease 2019 (COVID-19) have goodprognoses, but some develop a critical illness that can lead to death. Evidenceshows severe acute respiratory syndrome is closely re...BACKGROUNDThe majority of patients with coronavirus disease 2019 (COVID-19) have goodprognoses, but some develop a critical illness that can lead to death. Evidenceshows severe acute respiratory syndrome is closely related to the inducedcytokine storm. Interleukin-6 is a key player;its role in systemic inflammation iswell known.AIMTo evaluate the effect of tocilizumab (TCZ), an interleukin-6 receptor antagonist,on the outcomes for patients with COVID-19 pneumonia.METHODSPubMed, EMBASE, SCOPUS, Web of Science, MedRxiv, Science Direct, and theCochrane Library were searched from inception to 9th June 2020 for observationalor prospective studies reporting results of hospitalized adult patients withCOVID-19 infection treated with TCZ. Effect sizes were reported as odds ratios(ORs) with 95% confidence intervals (CIs), and an OR less than 1 was associatedwith a better outcome in those treated with TCZ.RESULTSOverall 13476 patients (33 studies;n = 3264 received TCZ) with COVID-19pneumonia and various degree of severity were included. Outcome wasimproved with TCZ. In the primary analysis (n = 19 studies reporting data),mortality was reduced in patients treated with TCZ (OR = 0.64, 95%CI: 0.47-0.87;P < 0.01). In 9 studies where risk of death with TCZ use was controlled for othervariables mortality was reduced by 57% (OR = 0.43, 95%CI: 0.27-0.7;P < 0.01).Intensive care need (mechanical ventilation) was also reduced (OR = 0.36, 95%CI:0.14-0.89;P = 0.02).CONCLUSIONIn COVID-19-infected patients treated with TCZ, outcome may be improvedcompared to those not treated with TCZ.展开更多
Modulation of the interleukin-6 pathway with tocilizumab has been demonstrated to be highly effective in substantial numbers of patients suffering from rheumatoid arthritis (RA), and juvenile idiopathic arthritis. A p...Modulation of the interleukin-6 pathway with tocilizumab has been demonstrated to be highly effective in substantial numbers of patients suffering from rheumatoid arthritis (RA), and juvenile idiopathic arthritis. A pivotal role of the IL-6 pathway has been also established in other autoimmune conditions including psoriasis and psoriatic arthritis, becoming attractive targets for therapeutic IL-6 inhibition. Here, we describe the first case of tocilizumab treatment in a RA-patient suffering from concomitant severe psoriasis, who achieved remission of RA, whereas no improvement of psoriatic lesions could be observed.展开更多
Objective:To study the clinical efficacy of tocilizumab combined with leflunomide in the treatment of rheumatoid arthritis.Methods:114 patients with rheumatoid arthritis admitted from May 2015 to April 2018 were rando...Objective:To study the clinical efficacy of tocilizumab combined with leflunomide in the treatment of rheumatoid arthritis.Methods:114 patients with rheumatoid arthritis admitted from May 2015 to April 2018 were randomly divided into control group(n=57)and observation group(n=57).The control group was treated with leflunomide.On the basis of this,the observation group was treated with tocilizumab for 12 weeks.Functional indicators,erythrocyte sedimentation rate(ESR),rheumatoid factor and inflammatory factors were evaluated and adverse reactions were recorded.Results:The total treatment efficiency of the observation group(89.47%)was significantly higher than that of the control group(75.44%)(P<0.05).Morning stiffness time,joint pain score,joint swelling score,ESR,serum C-reactive protein(CRP),rheumatoid factor(RF),tumor necrosis factor(TNF-α),and interleukin-1 were observed in the observation group and the control group.The levels of IL-1),IL-6,IL-8 and other indicators were lower than those before treatment.The indexes of the observation group were significantly lower than those before treatment(P<0.05),and after treatment The morning stiffness time,joint pain score,joint swelling score,ESR,CRP,RF,TNF-α,IL-1,IL-6,IL-8 and other indicators in the observation group were significantly lower than those in the control group(P<0.05).The incidence of adverse reactions in the observation group was 14%,and the incidence of adverse reactions in the control group was 17.54%.Toltuzumab combined with leflunomide in the treatment of rheumatoid arthritis did not increase the probability of adverse reactions.Conclusion:The use of tocilizumab combined with leflunomide in the treatment of rheumatoid joints has good efficacy and safety.This may be related to a significant reduction in inflammatory factors TNF-α,IL-1,IL-6,IL-8 and the like.展开更多
Takayasu arteritis is a large vessel vasculitis of the young women with giant cells and granuloma formation. The diagnosis and management of the disease are really not so easy because of the insidious onset and the di...Takayasu arteritis is a large vessel vasculitis of the young women with giant cells and granuloma formation. The diagnosis and management of the disease are really not so easy because of the insidious onset and the difficulties in assessment of disease activity. Nearly 60% of the patients are corticosteroid resistant or dependent and relapses are very frequent during taper of the dose [1]. The novel biologic agents as Anti-TNF, Rutiximab and Tocilizumab provide acceptable response rates with low toxicity. Herein, we reviewed the efficacy of Tocilizumab in Takayasu arteritis.展开更多
文摘BACKGROUND Tocilizumab is a humanized monoclonal antibody against the interleukin-6(IL-6)receptor that is commonly used to treat large vessel vasculitis and antineutrophil cytoplasmic antibody-related small vessel vasculitis.However,tocilizumab in combination with glucocorticoids for successfully treating granulomatosis with polyangiitis(GPA)has rarely been reported.CASE SUMMARY Here,we report a 40-year-old male patient who suffered GPA for 4 years.He was treated with multiple rounds of drugs,including cyclophosphamide,Tripterygium wilfordii,mycophenolate mofetil,and belimumab,with no improvement.In addition,he exhibited persistently high IL-6 levels.After tocilizumab treatment,his symptoms improved,and his inflammatory marker levels returned to normal.CONCLUSION Tocilizumab may be effective for treating GPA.
基金Supported by Guiyang Science and Technology Program,No.2019-9-1-39.
文摘BACKGROUND Since its initial detection in 2019,coronavirus disease 2019(COVID-19)pneumonia has rapidly spread throughout the world in a global pandemic.However,reports of COVID-19 pneumonia among patients following kidney transplantation have been limited and no uniform treatment guidelines for these patients have yet to be established.CASE SUMMARY Here,we report the case of a 39-year-old patient recovering from kidney transplantation who contracted perioperative COVID-19 pneumonia that was successfully controlled with oral paxlovid and a single intravenous drip infusion of tocilizumab following the discontinuation of immunosuppressive drugs.CONCLUSION Given the rapid spread of severe acute respiratory syndrome coronavirus 2 infections,clinicians should be aware of the potential for more cases of COVID-19 among patients following kidney transplantation and be familiar with appropriate treatment options and likely clinical outcomes.
基金supported by a grant from the Health Department Foundation of Zhejiang Province(2010KYA102)
文摘Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg/mL,3.0 mg/mL,5.0 mg/mL) for 24 h.then cells were cultured in ischemia environment for 24 h and reperfusion environment for 1 h.The MTT and flow cytometry were used to detect the proliferation and apoptosis of human cardiac myocytes,respectively.The mRNA and protein expressions of Bcl-2 and Bax were measured by qRT-PCR and western blot,respectively.Results:Compared to the negative group,pretreated by tocilizumab could significantly enhance the proliferation viability and suppress apoptosis of human cardiac myocytes after suffering ischemia reperfusion injury(P<0.05).The expression of Bcl-2 in tocilizumab treated group were higher than NC group(P<0.05).while the Bax expression were lower(P<0.05).Conclusions:Tocilizumab could significantly inhibit apoptosis and keep the proliferation viability of human cardiac myocytes after suffering ischemia reperfusion injury.Tocilizumab may obtain a widely application in the protection of ischemia reperfusion injury.
基金Supported by Science and Technology Planning Project of Guangdong Province (No.2017A020211005)Science and Technology Programme of Guangzhou, China 2016 (No.201607010386)
文摘AIM: To examine the therapeutic effects of tocilizumab on experimental corneal transplantation and its effect on Treg/Th17 balance. METHODS: Allograft corneal graft was performed between host Sprague Dawley and Wistar donor rats.The rats were randomly divided into four groups: normal,autograft, allograft, and allograft treated with tocilizumab.Kaplan-Meier was performed to draw the survival curve.The protein levels of interleukin-17A(IL-17A), vascular endothelial growth factor(VEGF), and forkhead box protein3(Foxp3) were measured by immunohistochemistry.The mRNA levels of IL-17A, VEGF, retinoid-related orphan receptor gammat(RORγt), interleukin-6(IL-6) and Foxp3 were detected by reverse transcription real-time polymerase chain reaction(RT-PCR). The Treg and Th17 cells were investigated by flow cytometry. RESULTS: The survival time of tocilizumab group was(24±1.27 d) longer than that of allograft group(10±0.55 d).Moreover, immunohistochemical examination revealed that IL-17A and VEGF protein levels in the allograft group were significantly higher than that of tocilizumab group(P<0.01),while Foxp3 levels in the allograft group was significantly lower than that of the tocilizumab treated group(P<0.001).Flow cytometry showed that the number of Th17 cellsin allograft group was significantly higher than that in tocilizumab group(P<0.001). Meanwhile, the number of Tregs was significantly lower than in tocilizumab group(P<0.001). Simultaneously, Foxp3 m RNA expression level in corneal tissues of tocilizumab treated group was significantly higher than other groups(P<0.001). CONCLUSION: These findings suggest that tocilizumab may promote corneal allograft survival, possibly by modulating Treg-Th17 balance.
基金National Natural Science Foundation of China,No.81801600Shanghai Sailing Program,No.18YF1414500。
文摘BACKGROUND Human herpes virus-8(HHV-8)-negative,idiopathic multicentric Castleman disease(iMCD)is a rare and life-threatening disorder driven by proinflammatory cytokines,which is still poorly understood.Pulmonary parenchyma lesion is a rare condition in iMCD,which mainly manifests as lymphocytic interstitial pneumonia and is an indicator of severe iMCD.Cutaneous lesion is also very rare and mainly occurs in Asians.There have been few reports of iMCD patients with both skin and lung parenchyma involvement.CASE SUMMARY We present a Chinese man who complained about a 3-year history of intermittent dry cough and a 2-year history of diffuse reddish-brown maculopapules.Laboratory examination revealed polyclonal hypergammaglobulinemia and hypercytokinemia including interleukin 6.Chest computed tomography revealed small patchy shadows with ground-glass nodules scattered in two lobes and mediastinal lymphadenopathy.The pathological result of the lymph node was consistent with the plasma cell type of Castleman disease.As serum human immunodeficiency virus test and HHV-8 staining of the lymph node were negative,the patient was finally diagnosed with HHV-8 negative i MCD.He was treated with tocilizumab at an intravenous(i.v.)dose of 8 mg/kg every 2 wk combined with methylprednisolone at an i.v.dose of 80 mg/d initially with gradual dose tapering.Partial remission was achieved 9 mo later.CONCLUSION i MCD with lung parenchyma and skin involvement is a rare condition that requires clinicians'attention and awareness for early diagnosis.
基金supported by the Japan Society for the Promotion of Science KAKENHI(Grant No.:JP19H00349).
文摘The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments.The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis(RA)patients administered intravenously or subcutaneously with tocilizumab.The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer.The serum tocilizumab was rapidly digested by immobilized trypsin for 30 min.The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min.The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 μg/mL.The intra-and inter-day accuracy and relative standard deviation(RSD)were 90.7%-109.4%and<10%,respectively.The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 μg/mL,respectively.The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay,although a systematic error was observed between these methods.In conclusion,a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocilizumab concentrations in RA patients was developed.
基金Project FIS PI-17/00547(Instituto CarlosⅢ,Ministerio de Economía y Competitividad,Spain),which means that it was also partially supported by European Regional Development Funds(ERDF)the University of Granada(Spain)for the support。
文摘COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.
文摘BACKGROUND The main pathophysiological basis of coronavirus disease 2019(COVID-19)causing respiratory failure is a cytokine storm and interleukin-6(IL-6)is an important component of the COVID-19 cytokine storm.As a specific antagonist of IL-6,tocilizumab may block the cytokine storm of COVID-19.The Diagnosis and Treatment Guidelines of New Coronavirus Pneumonia(7 th Edition)includes tocilizumab as a recommended drug for immunotherapy in severe and critical COVID-19 patients.However,the specific clinical efficacy of tocilizumab in the treatment of COVID-19 patients is worth studying.AIM To determine the clinical efficacy of tocilizumab in inhibiting the cytokine storm in COVID-19.METHODS In total,19 severe and critical COVID-19 patients were enrolled in this study,and were treated with tocilizumab in Optical Valley Campus of Hubei Maternal and Child Health Care Hospital from February 20 to March 31,2020.The imaging manifestations and clinical data before and after treatment were analyzed retrospectively,including routine peripheral venous blood tests,routine blood biochemical tests,coagulation test,C-reactive protein(CRP),IL-6,and arterial blood gas analysis.RESULTS Of the 19 patients in this group,13(68.4%)had significantly improved symptoms of COVID-19(5 patients were discharged directly and 8 patients were transferred after improvement)following treatment.One case was invalid,1 case was exacerbated,and 4 deaths(21.1%)were observed(all critical cases).The lymphocyte count,CRP,lactic acid,oxygenation index,fibrinogen(FIB)and IL-6 levels were significantly different in the improved group.CONCLUSION Tocilizumab treatment is effective against IL-6 in COVID-19 patients,but it does not completely inhibit the inflammation and cytokine storm in all patients with COVID-19.In the clinical treatment of COVID-19 patients,attention should be paid to the timing of drug administration and other adjuvant treatments.
文摘To determine the effect of tocilizumab (TCZ) on reactive oxygen species (ROS) in 11 patients with rheumatoid arthritis (RA), reactive oxygen metabolites (d-ROM) were measured using a Free Radical Elective Evaluator. The Disease Activity Score (DAS28) and matrix metalloproteinase-3 (MMP-3) level were also evaluated. d-ROM measured 392 ± 110 Carratelli units [U. CARR] on initiation of TCZ, and significantly decreased to 237 ± 82, 248 ± 88, and 226 ± 91 U.CARR after 3, 6, and 12 months, respectively
文摘Objective:To compare the efficacy of pulsed-dose corticosteroids(≥250 mg methylprednisolone,3 days)and tocilizumab in treating COVID-19-related hyperinflammation.Methods:This prospective observational study included RT-PCR positive COVID-19 patients with acute respiratory distress syndrome,who were admitted to the COVID-19 Adult Intensive Care Unit of Prof Dr.Murat Dilmener Emergency Hospital(Istanbul,Turkey)between December 1,2020 and February 28,2021.Clinical,laboratory and radiological examinations were used to diagnose COVID-19 associated hyperinflammation.Three cohort groups were formed:the pulsed-dose corticosteroids group(250 mg methylprednisolone for 3 days),the tocilizumab group(8 mg/day single dose or 400 mg/day for 2 days),and the combined group(pulsed-dose corticosteroid+tocilizumab).The difference in mortality rates among the groups was compared primarily.The most common cause(s)of death was determined.Furthermore,adverse events(secondary infection,acute kidney injury,arrhythmia,gastrointestinal system bleeding)for 28 days were recorded.Results:A total of 60 patients were included in this study,with 20 patients in each group.There was no statistically significant difference between the 3 groups in mortality rates(55%in the pulsed corticosteroid group,60%in the tocilizumab group,50%in the combined group,χ2=0.404,P=0.817).Infectious causes were found to be the most common cause of mortality in all the three groups,and no difference was found between them(χ2=0.404,P=0.817).There was also no difference in the development of adverse events such as secondary infection,acute kidney injury,arrhythmia,and gastrointestinal bleeding among the groups(P>0.05).Conclusions:Corticosteroids can be used instead of tocilizumab to treat hyperinflammation in COVID-19 patients with acute respiratory distress syndrome.
文摘BACKGROUNDThe majority of patients with coronavirus disease 2019 (COVID-19) have goodprognoses, but some develop a critical illness that can lead to death. Evidenceshows severe acute respiratory syndrome is closely related to the inducedcytokine storm. Interleukin-6 is a key player;its role in systemic inflammation iswell known.AIMTo evaluate the effect of tocilizumab (TCZ), an interleukin-6 receptor antagonist,on the outcomes for patients with COVID-19 pneumonia.METHODSPubMed, EMBASE, SCOPUS, Web of Science, MedRxiv, Science Direct, and theCochrane Library were searched from inception to 9th June 2020 for observationalor prospective studies reporting results of hospitalized adult patients withCOVID-19 infection treated with TCZ. Effect sizes were reported as odds ratios(ORs) with 95% confidence intervals (CIs), and an OR less than 1 was associatedwith a better outcome in those treated with TCZ.RESULTSOverall 13476 patients (33 studies;n = 3264 received TCZ) with COVID-19pneumonia and various degree of severity were included. Outcome wasimproved with TCZ. In the primary analysis (n = 19 studies reporting data),mortality was reduced in patients treated with TCZ (OR = 0.64, 95%CI: 0.47-0.87;P < 0.01). In 9 studies where risk of death with TCZ use was controlled for othervariables mortality was reduced by 57% (OR = 0.43, 95%CI: 0.27-0.7;P < 0.01).Intensive care need (mechanical ventilation) was also reduced (OR = 0.36, 95%CI:0.14-0.89;P = 0.02).CONCLUSIONIn COVID-19-infected patients treated with TCZ, outcome may be improvedcompared to those not treated with TCZ.
文摘Modulation of the interleukin-6 pathway with tocilizumab has been demonstrated to be highly effective in substantial numbers of patients suffering from rheumatoid arthritis (RA), and juvenile idiopathic arthritis. A pivotal role of the IL-6 pathway has been also established in other autoimmune conditions including psoriasis and psoriatic arthritis, becoming attractive targets for therapeutic IL-6 inhibition. Here, we describe the first case of tocilizumab treatment in a RA-patient suffering from concomitant severe psoriasis, who achieved remission of RA, whereas no improvement of psoriatic lesions could be observed.
基金Science and Technology Research and Development Program of Affiliated Hospital of Yan'an University(2018PT-09).
文摘Objective:To study the clinical efficacy of tocilizumab combined with leflunomide in the treatment of rheumatoid arthritis.Methods:114 patients with rheumatoid arthritis admitted from May 2015 to April 2018 were randomly divided into control group(n=57)and observation group(n=57).The control group was treated with leflunomide.On the basis of this,the observation group was treated with tocilizumab for 12 weeks.Functional indicators,erythrocyte sedimentation rate(ESR),rheumatoid factor and inflammatory factors were evaluated and adverse reactions were recorded.Results:The total treatment efficiency of the observation group(89.47%)was significantly higher than that of the control group(75.44%)(P<0.05).Morning stiffness time,joint pain score,joint swelling score,ESR,serum C-reactive protein(CRP),rheumatoid factor(RF),tumor necrosis factor(TNF-α),and interleukin-1 were observed in the observation group and the control group.The levels of IL-1),IL-6,IL-8 and other indicators were lower than those before treatment.The indexes of the observation group were significantly lower than those before treatment(P<0.05),and after treatment The morning stiffness time,joint pain score,joint swelling score,ESR,CRP,RF,TNF-α,IL-1,IL-6,IL-8 and other indicators in the observation group were significantly lower than those in the control group(P<0.05).The incidence of adverse reactions in the observation group was 14%,and the incidence of adverse reactions in the control group was 17.54%.Toltuzumab combined with leflunomide in the treatment of rheumatoid arthritis did not increase the probability of adverse reactions.Conclusion:The use of tocilizumab combined with leflunomide in the treatment of rheumatoid joints has good efficacy and safety.This may be related to a significant reduction in inflammatory factors TNF-α,IL-1,IL-6,IL-8 and the like.
文摘Takayasu arteritis is a large vessel vasculitis of the young women with giant cells and granuloma formation. The diagnosis and management of the disease are really not so easy because of the insidious onset and the difficulties in assessment of disease activity. Nearly 60% of the patients are corticosteroid resistant or dependent and relapses are very frequent during taper of the dose [1]. The novel biologic agents as Anti-TNF, Rutiximab and Tocilizumab provide acceptable response rates with low toxicity. Herein, we reviewed the efficacy of Tocilizumab in Takayasu arteritis.
