Successful treatment of granulomatosis with polyangiitis using tocilizumab combined with glucocorticoids:A case report

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.

Successful treatment of a case of COVID-19 pneumonia following kidney transplantation using paxlovid and tocilizumab

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.

托珠单抗联合泼尼松和甲氨蝶呤治疗难治性中重度类风湿关节炎临床评价

目的探讨托珠单抗联合泼尼松、甲氨蝶呤治疗难治性中重度类风湿关节炎(RA)的临床疗效。方法选取医院2020年3月至2022年3月收治的难治性中重度RA患者145例,采用分层随机法分为观察组(72例)和对照组(73例)。两组患者均口服醋酸泼尼松片、甲氨蝶呤片,观察组患者加用托珠单抗注射液静脉滴注。两组均连续治疗3个月。结果治疗后,两组患者的关节疼痛评分、肿胀评分均显著降低,晨僵持续时间均显著缩短,疾病活动指数28量表评分均显著降低,Fugl-Meyer运动功能评价量表评分均显著升高,类风湿因子、C反应蛋白水平及红细胞沉降率均显著降低,基质金属蛋白酶-3水平均显著降低,金属蛋白酶组织抑制因子-1水平均显著升高(P<0.05);且观察组患者上述指标改善程度均更显著(P<0.05)。观察组与对照组不良反应发生率相当(11.11%比8.22%,P>0.05)。结论托珠单抗联合泼尼松、甲氨蝶呤治疗难治性中重度RA,可有效缓解患者的关节炎性症状,降低血清炎性指标水平,改善关节活动能力和关节损伤。

托珠单抗注射液致过敏性休克1例分析

目的 分析托珠单抗注射液致过敏性休克的特点,为临床合理用药提供参考。方法 报道1例儿童使用托珠单抗导致过敏性休克的案例,通过文献回顾托珠单抗导致过敏性休克的情况,并分析原因及防治措施。结果 根据患者的临床表现及药物与用药时间的关联性,考虑托珠单抗导致过敏性休克,患者经有效抗过敏治疗后,过敏性休克症状得到缓解。结论 临床应用托珠单抗应警惕过敏性休克等过敏情况,对严重过敏患者应禁止使用。

Tocilizumab对肺动脉高压大鼠IL-6及survivin的影响

目的观察tocilizumab对肺动脉高压大鼠白细胞介素-6(IL-6)和survivin的表达水平的影响。方法通过腹腔注射野百合碱诱导建立肺动脉高压大鼠模型,观察tocilizumab对肺动脉高压大鼠IL-6和survivin的表达水平的影响。结果 Tocilizumab干预组大鼠和空白对照组大鼠mPAP、IL-6和survivin含量明显低于实验对照组,P<0.05。Tocilizumab干预组肺动脉血管内膜轻度水肿,血管壁轻度增厚。IL-6和survivin在实验对照组大鼠肺组织和血清中表达强烈,在tocilizumab干预组大鼠肺组织少量表达,而空白对照组大鼠肺组织不表达。结论 Tocilizumab可有效抑制野百合碱可诱导肺动脉高压大鼠IL-6和survivin的表达,抑制肺动脉高压的发生。

托珠单抗治疗儿童难治性多相性髓鞘少突胶质细胞糖蛋白抗体相关疾病2例病例报告并文献复习

背景国外病例报告及病例系列报告表明,托珠单抗(TCZ)可能对其他免疫抑制剂效果欠佳的难治性髓鞘少突胶质细胞糖蛋白抗体相关疾病(MOGAD)有一定疗效,但多为成人研究,目前国内尚无儿童相关报道。目的 总结2例应用TCZ治疗的难治性MOGAD患儿的临床特点及疗效,并对TCZ治疗MOGAD患者的疗效及安全性进行文献复习。设计病例报告并文献复习。方法 报告北京大学第一医院儿科收治的2例应用TCZ治疗难治性MOGAD患儿的病例资料,总结其临床特点及TCZ的疗效及安全性。以“MOGAD”、“抗髓鞘少突胶质细胞糖蛋白抗体”等和“TCZ”、“白细胞介素6受体拮抗剂”及相应英文检索词于PubMed、Embase、Web of Science、Cochrane、万方数据库、中国知网数据库、维普数据库检索中英文文献,检索时间为建库至2023年11月。主要结局指标TCZ的疗效及安全性。结果 2例MOGAD患儿分别于6岁6月龄和3岁7月龄起病,应用TCZ时的病程分别为9年3个月和6年6个月,此前分别出现11次和5次急性脱髓鞘事件发作,1例规律应用TCZ 14个月期间未出现复发,停用后复发,再次间断应用10个月期间复发1次;1例规律应用2年4个月未出现复发。2例治疗期间均未出现严重不良反应。文献复习纳入9项研究(含本文)共27例MOGAD患者,4例(14.8%)出现复发,27例治疗后年复发率均明显下降。应用TCZ治疗过程中最常见的不良反应为感染及高脂血症,无因严重不良反应而停止治疗的患者。Meta分析共纳入5项研究(含本文)23例患者,TCZ治疗MOGAD的无复发率为87%(95%CI:72%~100%)。结论 TCZ对其他传统免疫抑制剂治疗效果欠佳的难治性多相性MOGAD患儿有效且耐受性好,但仍需大样本的前瞻性研究进一步证实。

IL-6/IL-6R抑制剂在免疫炎症性皮肤疾病的应用

白细胞介素-6(IL-6)是一种前炎症因子,与细胞表面受体或细胞外可溶性受体结合后,激活多种信号通路,通过调节免疫炎症细胞的增殖、分化和功能,而参与多种皮肤疾病的发生、发展。近年来,IL-6/IL-6受体(IL-6R)抑制剂在皮肤病领域的应用引起了广泛关注,尤其是最早上市的托珠单抗(Tocilizumab,TCZ),在治疗系统性硬化症、成人still病、白塞病、系统性红斑狼疮、银屑病关节炎、特应性皮炎等疾病中有一定疗效。本文就IL-6/IL-6R抑制剂,尤其是TCZ在皮肤科疾病治疗中的应用,包括疗效、安全性和不良反应进行综述,以了解其应用现状并展望其应用前景。

甲状腺相关眼病治疗中不同单克隆抗体有效性与安全性的系统评价再评价

目的:全面评估甲状腺相关眼病(thyroidassociated ophthalmopathy,TAO)治疗中利妥昔单克隆抗体(rituximab,RTX)、托珠单克隆抗体(tocilizumab,TCZ)、替妥木单克隆抗体(teprotumumab,TMB)的有效性和安全性。方法:采用系统评价再评价方法,系统检索PubMed、Embase、Cochrane Library数据库中关于TAO治疗的系统评价/Meta分析,检索时间均为建库至2024年1月。分别采用PRISMA 2020声明、AMSTAR 2量表和GRADE工具评估纳入研究的报告质量、方法学质量及证据质量。结果:当前关于TAO治疗中3种单克隆抗体的系统评价在报告规范性、方法学质量和证据质量方面仍存在不足。目前仍缺少3种单克隆抗体直接比较的证据,基于间接比较证据,TCZ可能是最好的治疗方法,其次为TMB和RTX。有效性方面,TCZ、TMB可显著降低临床活动性评分、眼球突出度及生活质量,TCZ显著降低复视发生,RTX显著降低疾病应答,RTX及TCZ显著改善疾病失活率,RTX在复视、眼睑裂变化、NOSPECS评分与生活质量方面无显著差异。安全性方面的结论尚不一致,TCZ和TMB可能增加不良事件的发生率,而RTX在安全性方面与糖皮质激素或安慰剂相比无显著差异。结论:本研究为TAO治疗中3种单克隆抗体的选择提供循证依据。尽管TCZ在有效性方面可能具有优势,但考虑到现有证据的限制性,未来仍需更多高质量研究进一步验证和比较不同单克隆抗体在TAO治疗中的有效性和安全性。

托珠单抗治疗COVID-19导致继发感染风险的Meta分析

目的通过Meta分析评估托珠单抗(tocilizumab,TCZ)治疗新型冠状病毒感染(corona virus disease2019,COVID-19)导致的继发感染风险,为托珠单抗在COVID-19患者中应用的安全性提供循证依据。方法在The Cochrane Library、PubMed、Web of Science、中国知网、中国生物医学文献数据库以及万方数据库中检索了2019年12月19日至2022年12月30日期间使用托珠单抗治疗COVID-19患者的相关研究,筛选并提取文献中发生继发感染的数据,利用RevMan 5.4.1进行Meta分析。结果共筛选了1691篇参考文献,纳入18项研究,涉及3933名患者。托珠单抗+标准治疗组继发感染发生率为19.14%(331/1729),标准治疗组继发感染发生率为12.11%(267/2204)。Meta分析结果显示,托珠单抗+标准治疗组继发感染发生率高于标准治疗组[RR=1.35,95%CI(1.05,1.74),P=0.02]。亚组分析显示,使用不同剂量的托珠单抗发生继发感染的风险不同。托珠单抗给药剂量为400~800 mg/d的亚组继发感染发生率明显高于标准治疗组,差异具有统计学意义[RR=1.48,95%CI(1.19,1.84),P=0.0004];≤400 mg/d继发感染发生率也显著高于标准治疗组,差异具有统计学意义[RR=1.87,95%CI(1.28,2.72),P=0.001];托珠单抗给药剂量为6~8 mg/kg亚组与标准治疗组比较差异无统计学意义。结论与标准治疗相比,托珠单抗可能增加COVID-19患者发生继发感染的风险,临床给药前应仔细评估使用托珠单抗治疗的利益和风险。但是,目前仍需要更多大样本、高质量的研究来进一步评估。

不同生物制剂治疗类风湿性关节炎有效性及安全性的网状Meta分析

目的:临床中治疗类风湿性关节炎的生物制剂多种多样,其疗效及安全性差异尚不明确,文章旨在比较不同生物制剂治疗类风湿性关节炎的有效性及安全性的差异。方法:检索中国知网、维普、万方、中国生物医学文献系统数据库、PubMed、Cochrane图书馆、Web of Science和Embase数据库的文献,收集各数据库建库至2022-10-01符合要求的关于类风湿性关节炎生物制剂治疗的随机对照试验。运用EndNote软件筛选文献,RevMan 5.3软件对纳入的文献进行质量评价;采用Stata 14.2软件对ACR20(美国风湿学会20%缓解率)、ACR50(美国风湿学会50%缓解率)、ACR70(美国风湿学会70%缓解率)、红细胞沉降率及不良反应指标进行直接Meta分析及网状Meta分析。结果:共纳入符合要求的文献39篇,5篇低风险文献,4篇含高风险文献,剩余30篇含有风险未知偏倚,共13种治疗措施。网状Meta分析结果:①在ACR20方面,英夫利昔单抗联合甲氨蝶呤(OR=5.54,95%CI:1.33-23.01,P<0.05)、阿巴西普+甲氨蝶呤片(OR=3.21,95%CI:1.13-9.10,P<0.05)、托珠单抗(OR=2.95,95%CI:1.61-5.44,P<0.05)的治疗效果均优于甲氨蝶呤片,且排名靠前;ACR20概率排序结果为:英夫利昔单抗+甲氨蝶呤片>阿巴西普+甲氨蝶呤片>托珠单抗>培塞利珠单抗>依那西普+甲氨蝶呤片。②在ACR50方面,依那西普联合甲氨蝶呤片(OR=4.04,95%CI:2.13-7.66,P<0.05)、英夫利昔单抗联合甲氨蝶呤片(OR=4.79,95%CI:1.19-19.26,P<0.05)、托珠单抗联合甲氨蝶呤片(OR=3.54,95%CI:1.36-9.22,P<0.05)治疗效果优于甲氨蝶呤片,且排名靠前;ACR50概率排序结果为:依那西普+甲氨蝶呤片>英夫利昔单抗+甲氨蝶呤片>托珠单抗+甲氨蝶呤片>托珠单抗>培塞利珠单抗+甲氨蝶呤片。③在ACR70方面,英夫利昔单抗联合甲氨蝶呤片(OR=8.00,95%CI:2.31-27.69,P<0.05)、依那西普联合甲氨蝶呤片(OR=4.26,95%CI:2.51-7.21,P<0.05)、托珠单抗+甲氨蝶呤片(OR=3.51,95%CI:1.82-6.80,P<0.05)的治疗效果优于甲氨蝶呤片;ACR70概率排序结果为英夫利昔单抗+甲氨蝶呤片>依那西普+甲氨蝶呤片>托珠单抗+甲氨蝶呤片>培塞利珠单抗>阿达木单抗+甲氨蝶呤片。④在红细胞沉降率方面,依那西普联合甲氨蝶呤片(SMD=-9.23,95%CI:-16.55至-1.92,P<0.05)治疗效果优于依那西普及甲氨蝶呤片(SMD=14.59,95%CI:7.28-21.91,P<0.05)。红细胞沉降率概率排序结果为依那西普+甲氨蝶呤片>英夫利昔单抗+甲氨蝶呤片>依那西普>阿达木单抗+甲氨蝶呤片>甲氨蝶呤片。⑤在不良反应方面,安慰剂(OR=0.62,95%CI:0.39-0.99,P<0.05)优于英夫利昔单抗和培塞利珠单抗(OR=0.44,95%CI:0.25-0.78,P<0.05)。不良反应概率排序结果为安慰剂>英夫利昔单抗>依那西普+甲氨蝶呤片>培塞利珠单抗>依那西普。结论:基于39篇随机对照试验的文献证据表明,英夫利昔单抗联合甲氨蝶呤片(高级强推荐)在临床中可作为治疗类风湿性关节炎首选,有效性及安全性相对较好,依那西普联合甲氨蝶呤片(高级强推荐)可作为次选。

Systemic juvenile idiopathic arthritis–associated lung disease: A retrospective cohort study

BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.

视神经脊髓炎谱系疾病合并结缔组织病的托珠单抗疗效评价

目的评价托珠单抗(tocilizumab,TCZ)治疗合并结缔组织病(connective tissue disease,CTD)的水通道蛋白4抗体(anti-aquaporin 4-immunoglobulin,AQP4-IgG)阳性的视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)患者的疗效和安全性。方法6例病情活跃(入组前12个月内至少有1次NMOSD发作)且合并CTD的血清AQP4-IgG阳性的NMOSD患者,其中4例患者合并系统性红斑狼疮(systemic lupus erythematosus,SLE)、2例患者合并原发性干燥综合征(primary Sjogren s syndrome,pSS),所有患者均按体重8 mg/kg的剂量静脉输注TCZ治疗,每个月1次,疗程至少7个月。观察每例患者在TCZ治疗的7个月期间NMOSD的年复发率(annual relapse rate,ARR)、扩展的残疾状态量表(expanded disability status scale,EDSS)评分、血清AQP4-IgG滴度、外周血B细胞水平以及CTD的活动情况。结果6例患者在TCZ治疗期间均无NMOSD复发,治疗后ARR由中位数(四分位数)0.3(0,1.2)次/年降至0次/年,但差异无统计学意义(Z=-1.826,P=0.068),EDSS评分显著降低〔由中位数(四分位数)3.5(2.5,4.7)分降至2.0(0.8,3.1)分,Z=-2.220,P=0.026〕,血清AQP4-IgG滴度显著下降〔由中位数(四分位数)1∶100(1∶83,1∶320)降至1∶21(0,1∶49),Z=-2.201,P=0.028〕,外周血B细胞计数降低〔由中位数(四分位数)116(75,201)个/L降至37(19,97)个/L,Z=-2.201,P=0.028〕。治疗期间CTD维持临床稳定。1例患者出现白细胞及中性粒细胞数目严重减低,使用药物治疗后恢复,所有患者均未发生感染等不良反应。结论TCZ对于治疗合并CTD的NMOSD患者具有较好的疗效及安全性。

ST5100TCZ型道路除障车液压系统的设计

通过分析道路除障车各执行机构动作的特点与要求,拟定了液压传动系统的工作原理图。本文可为改装汽车的液压传动系统设计提供理论依据。

TCZ联合IMD治疗RRA的疗效和对ESR、CRP、IgG水平的影响

目的研究托珠单抗(TCZ)联合艾拉莫德(IMD)治疗难治性类风湿性关节炎(RRA)的疗效和对血沉(ESR)、血清C反应蛋白(CRP)、免疫球蛋白G(IgG)水平的影响。方法将76例RRA患者随机分为给予TCZ+IMD治疗的联合组(38例)和给予IMD治疗的IMD组(38例),比较两组临床疗效和治疗前后ESR、血清CRP、IgG水平变化。结果治疗1、3个月后,联合组疾病活动度评分(DAS28评分)、临床症状、临床疾病活动指数(CDAI)评分改善幅度均大于IMD组(P<0.05);ESR及血清IgG、CRP水平降低幅度也均大于IMD组(P<0.05)。结论 TCZ联合IMD可有效改善RRA患者临床症状,减少机体炎症反应,改善患者关节活动度。

抗类风湿关节炎药——Tocilizumab

美国食品药品管理局(FDA)批准Tocilizumab用于治疗类风湿性关节炎,该药适用于使用其他已获批的治疗药物无效的成年中重度类风湿性关节炎患者。Tocilizumab通过抑制白细胞介素-6受体的活性而发挥作用。基于其临床研究显示的严重安全性问题,Tocilizumab仅被推荐用于其他治疗无效的患者。在进行的对类风湿性关节炎成年患者治疗的临床试验中显示Tocilizumab的有效性和安全性。该文通过检索国外文献,对Tocilizumab药理学、药动学、临床试验、不良反应及药物相互作用等进行论述。

Protective function of tocilizumab in human cardiac myocytes ischemia reperfusion injury

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.

Tocilizumab promotes corneal allograft survival in rats by modulating Treg-Th17 balance

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.

Idiopathic multicentric Castleman disease with pulmonary and cutaneous lesions treated with tocilizumab:A case report

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.

LC-MS/MS method for the quantitation of serum tocilizumab in rheumatoid arthritis patients using rapid tryptic digestion without IgG purification

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.

Clinical efficacy of tocilizumab treatment in severe and critical COVID-19 patients

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.