Effects of temporarily suspending low-dose methotrexate treatment for 2 weeks after SARS-CoV-2 vaccine booster on vaccine response in immunosuppressed adults with inflammatory conditions: protocol for a multicentre randomised controlled trial and nested mechanistic substudy (Vaccine Response On/Off Methotrexate (VROOM) study).
Effects of temporarily suspending low-dose methotrexate treatment for 2 weeks after SARS-CoV-2 vaccine booster on vaccine response in immunosuppressed adults with inflammatory conditions: protocol for a multicentre randomised controlled trial and nested mechanistic substudy (Vaccine Response On/Off Methotrexate (VROOM) study).
复制标题
DOI：
10.1136/bmjopen-2022-062599
复制
发表时间：
2022-05-03
期刊：
影响因子：
2.9
通讯作者：
Cook, Jonathan Alistair
中科院分区：
文献类型：
--
作者：
Abhishek, Abhishek;Boyton, R. J.;McKnight, Aine;Coates, Laura;Bluett, James;Barber, Vicki S.;Cureton, Lucy;Francis, Anne;Appelbe, Duncan;Eldridge, Lucy;Julier, Patrick;Peckham, Nicholas;Valdes, Ana M.;Rombach, Ines;Altmann, Daniel M.;Nguyen-Van-Tam, Jonathan;Williams, Hywel C.;Cook, Jonathan Alistair
目前尚不清楚在接种COVID-19疫苗后暂时中断长期免疫抑制治疗是否会提高疫苗应答。本研究的目的是评估SARS-CoV-2疫苗加强剂后每周低剂量甲氨蝶呤治疗中断2周与持续治疗自身免疫性炎症性疾病的成人相比是否能增强免疫应答。一项开放标签、务实、前瞻性、平行组、随机对照优效性试验，包括内部可行性评估和嵌套机制子研究，将在大约25家英国医院的风湿病和皮肤科诊所进行。样本量为560例，以1：1的比例随机分配至干预组和常规护理组。主要结果指标是在加强免疫前（基线）、加强免疫后4周（主要结果）和12周（次要结果）收集的抗棘突受体结合域（RBD）抗体水平。其他次要结局指标为患者对疾病活动性、疾病发作及其治疗的总体评估、EuroQol 5维5水平（EQ-5D-5L）、自我报告的中断或继续甲氨蝶呤治疗的依从性、SARS-CoV-2中和抗体滴度（机制子研究）和口服甲氨蝶呤生化依从性（机制子研究）。将在获得额外资金的情况下，对基线和第4周和第12周的B细胞记忆和T细胞应答进行分析。将对随机分组（即意向治疗）的组进行主要分析。将使用混合效应模型估计研究组之间抗加标RBD抗体水平的差异，允许在受试者内进行重复测量。模型将根据随机因素和既往SARS-CoV-2感染状态进行调整。本研究获得了利兹西部研究伦理委员会和健康研究管理局的批准（REC参考号：21/HRA/3483，IRAS 303827）。要求受试者在参加试验前提供书面知情同意书。将通过同行审查出版物、通讯和会议进行传播。将向决策者通报结果。ISRCTN11442263。
It is unknown if a temporary break in long-term immune-suppressive treatment after vaccination against COVID-19 improves vaccine response. The objective of this study was to evaluate if a 2-week interruption in low-dose weekly methotrexate treatment after SARS-CoV-2 vaccine boosters enhances the immune response compared with continuing treatment in adults with autoimmune inflammatory conditions. An open-label, pragmatic, prospective, parallel group, randomised controlled superiority trial with internal feasibility assessment and nested mechanistic substudy will be conducted in rheumatology and dermatology clinics in approximately 25 UK hospitals. The sample size is 560, randomised 1:1 to intervention and usual care arms. The main outcome measure is anti-spike receptor-binding domain (RBD) antibody level, collected at prebooster (baseline), 4 weeks (primary outcome) and 12 weeks (secondary outcome) post booster vaccination. Other secondary outcome measures are patient global assessments of disease activity, disease flares and their treatment, EuroQol 5- dimention 5-level (EQ-5D-5L), self-reported adherence with advice to interrupt or continue methotrexate, neutralising antibody titre against SARS-CoV-2 (mechanistic substudy) and oral methotrexate biochemical adherence (mechanistic substudy). Analysis of B-cell memory and T-cell responses at baseline and weeks 4 and 12 will be investigated subject to obtaining additional funding. The principal analysis will be performed on the groups as randomised (ie, intention to treat). The difference between the study arms in anti-spike RBD antibody level will be estimated using mixed effects model, allowing for repeated measures clustered within participants. The models will be adjusted for randomisation factors and prior SARS-CoV-2 infection status. This study was approved by the Leeds West Research Ethics Committee and Health Research Authority (REC reference: 21/HRA/3483, IRAS 303827). Participants will be required to give written informed consent before taking part in the trial. Dissemination will be via peer review publications, newsletters and conferences. Results will be communicated to policymakers. ISRCTN11442263.
登录
查看更多内容
影响因子：
27.4
作者：
Park, Jin Kyun;Lee, Min Ah;Lee, Eun Bong
通讯作者：
Lee, Eun Bong
影响因子：
2.9
作者：
Edwards CJ;Campbell J;van Staa T;Arden NK
通讯作者：
Arden NK
影响因子：
27.4
作者：
Park, Jin Kyun;Lee, Yun Jong;Lee, Eun Bong
通讯作者：
Lee, Eun Bong
影响因子：
27.4
作者：
Bitoun, Samuel;Nocturne, Gaetane;Mariette, Xavier
通讯作者：
Mariette, Xavier
影响因子：
5.5
作者：
Abhishek, Abhishek;Doherty, Michael;Grainge, Matthew J.
通讯作者：
Grainge, Matthew J.