key: cord-0922392-efrwsbwq authors: Santosa, Amelia; Xu, Chuanhui; Arkachaisri, Thaschawee; Kong, Kok Ooi; Lateef, Aisha; Lee, Tau Hong; Leong, Keng Hong; Low, Andrea Hsiu Ling; Sriranganathan, Melonie K.; Tan, Teck Choon; Teng, Gim Gee; Thong, Bernard Yu‐hor; Fong, Warren; Lahiri, Manjari title: Recommendations for COVID‐19 vaccination in people with rheumatic disease: Developed by the Singapore Chapter of Rheumatologists date: 2021-05-10 journal: Int J Rheum Dis DOI: 10.1111/1756-185x.14107 sha: 7af263134c9daef1cdbd65465953e1b7eb33bad7 doc_id: 922392 cord_uid: efrwsbwq AIM: People with rheumatic diseases (PRD) remain vulnerable in the era of the COVID‐19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against SARS‐CoV‐2 in PRD. METHODS: Systematic literature reviews were performed to evaluate: (a) outcomes in PRD with COVID‐19; (b) efficacy, immunogenicity and safety of COVID‐19 vaccination; and (c) published guidelines/recommendations for non‐live, non‐COVID‐19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: The consensus comprises 2 overarching principles and 7 recommendations. Vaccination against SARS‐CoV‐2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommend that eligible PRD and household contacts be vaccinated against SARS‐CoV‐2. We conditionally recommended that the COVID‐19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommend that the COVID‐19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post‐vaccination antibody titers against SARS‐CoV‐2 need not be measured. Any of the approved COVID‐19 vaccines may be used, with no particular preference. CONCLUSION: These recommendations provide guidance for COVID‐19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low‐level evidence. Novartis (Novavax® or NVX-CoV2373) 11 and Bharat Biotech (BB-152 or Covaxin®), 12 The CWG sent out preselected topics to the TFP and sought their input on additional clinically important topics. Considering the TFP's input, the CWG selected the following core topics relevant to clinical decision-making for COVID-19 vaccination: 1. Are PRD at increased risk of adverse outcomes from COVID-19? A recent systematic review and meta-analysis of global data showed that PRD remain vulnerable, with substantial rates of severe outcomes. 3 The overall rates of hospitalization, oxygen support, ICU admission and fatality among COVID-19 infected patients with rheumatic diseases were 58% (95% CI 48%-67%), 33% (95% CI 21%-47%), 9% (95% CI 5%-15%) and 7% (95% CI 3%-11%), respectively, which are comparable with data from the COVID-19 Global Rheumatology Alliance (GRA) physician registry. The fatality rate was higher both in this meta-analysis and the COVID-19 GRA (7.0% and 6.7%, respectively) than that (3.4%) of general population infected with COVID-19 in the WHO database, although age, gender and comorbidities were not matched. 3 D'Silva et al reported a higher risk of hospitalization, ICU admission, mechanical ventilation, acute kidney injury, renal replacement therapy and death based on TriNetX, a multi-center research network with real-time electronic health record data across 35 healthcare organizations in the US. 15 The authors concluded that these outcomes were likely mediated by a higher comorbidities burden in PRD, such as hypertension, diabetes mellitus, chronic kidney disease and asthma. 2. Are existing approved vaccines against SARS CoV2 safe, immunogenic and efficacious in PRD? COVID-19, immunosuppression, people with rheumatic diseases, SARS-CoV-2, vaccination Two mRNA vaccines are currently approved by the US FDA and Singapore HSA. It is known that selected DNA and RNA molecules have the unique property to activate the immune system, through activation of Toll-like receptors. 16 It has been shown that the innate immune response would be suppressed by nucleoside modification of RNA, as the innate immune system detects RNA lacking nucleoside modification as a means of selectively responding to bacteria or viruses. 17 vaccine trials to date are summarized in Table 1 . [4] [5] [6] 9, 10, 12, 19, 20 There are currently no available data on the immunogenicity and efficacy of COVID-19 vaccination in PRD. Table 2 ). [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] The definitions of PRD and immunomodulatory drugs considered in this recommendation are summarized in Table 3 . The CWG met to formulate and finalize preliminary statements The final consensus statement was circulated to the TFP after the consensus meeting and was approved by all members. The final consensus statements consist of 2 overarching principles and 7 recommendations. They are summarized in Table 4 . 1. Vaccination in PRD should be aligned with prevailing national policy. The knowledge on COVID-19 vaccination is rapidly evolving protection is not well established at present, we conditionally recommend that titers not be measured. 6 . We strongly recommend that household contacts be vaccinated against SARS-CoV-2. Level of evidence as defined: High -very unlikely to change confidence in the estimate of effect by an additional study; Moderate -likely to change confidence in the estimate of effect by an additional study; Low -highly likely to change confidence in the estimate of effect by an additional study; Very low -not sure about confidence in the estimate of effect c Level of evidence as defined: 1a -meta-analysis of randomized controlled trials (RCT); 1b -RCT; 2 -prospective controlled intervention study without randomization; 3 -descriptive/analytic study (including case-control, cross-sectional, case series); 4 -expert committee reports or opinion or clinical experience of respected authorities or both d GRADE level of evidence. 32 e Level of evidence as defined: High -consistent evidence from well performed RCTs or exceptionally strong evidence from unbiased observational studies; Moderate -evidence from RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from unbiased observational studies; Low -evidence for at least 1 critical outcome from observational studies, RCTs with serious flaws or indirect evidence; Very low -evidence for at least 1 critical outcome from unsystematic clinical observations or very indirect evidence. Timing /DMARD cessation We conditionally recommend that any of the approved COVID-19 vaccines may be used, with no particular preference. The various SARS-CoV-2 vaccines in development are non-live vaccines. The anticipated risk-benefit ratio should therefore be similar for vaccinations to be recommended without preference for any particular vaccine. However, long-term follow-up in PRD will be needed to ascertain longer term efficacy and safety of the various vaccines. Overarching principles Vaccination in people with rheumatic diseases should be aligned with prevailing national policy. The decision for vaccination should be individualized, and should be explained to the patient, to provide a basis for shared decision-making between the healthcare provider and the patient. meta-analysis of global data Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine FDA Briefing Document Janssen Ad26. 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