How are people with rheumatism vaccinated?

*For medical professional reading reference only

Compared with the 2019 EULAR guidelines, what are the differences between the 2022 ACR guidelines?

Both autoimmune disorders and receiving immunosuppressive therapy leave patients with rheumatism in an immunocompromised state, which puts rheumatism patients at constant risk of higher infection risk

Expanded indications for specific vaccines in patients with rheumatism on immunosuppressants

Inactivated vaccine is conditionally recommended for all patients with rheumatism, regardless of disease activity

Comments:

The 2019 European League Against Rheumatism (EULAR) recommendation on vaccination of adult patients with autoimmune diseases states that vaccination of patients with rheumatism should preferably be performed during periods of disease quiescence

1.

Remarks: The above recommendations are conditional recommendations, and discontinuation recommendations are recommended when disease activity permits

B-cell-targeted biologics (eg, rituximab) can severely affect vaccine-elicited humoral immunity, thereby reducing vaccine efficacy

(regardless of disease activity)

1.
For patients taking ≤10mg/d prednisone, it is strongly recommended that there is no need to postpone the vaccination of influenza vaccine and other inactivated vaccines;

2.
For patients taking >10mg but <20mg/d prednisone, it is conditionally recommended that it is not necessary to postpone the vaccination of influenza vaccine and other inactivated vaccines;

3.
For patients taking prednisone ≥ 20 mg/d, it is conditionally recommended that it is not necessary to postpone the vaccination of influenza vaccine, but it is recommended to postpone the vaccination of other inactivated vaccines
.

Comments:
In the 2019 EULAR recommendations for the vaccination of adults with autoimmune diseases: Vaccination of patients with rheumatic diseases should preferably be performed during periods of disease quiescence
.

In 2006, the CDC and the Advisory Committee on Immunization also proposed: In order to obtain the maximum immune response and avoid complications, a large amount of corticosteroids (prednisone ≥ 20 mg per day) should be administered for 1 month
.
The recommendations of the ACR in 2022 clearly stated that the recommendations for patients who only use glucocorticoids need not be completely based on the premise of disease quiescence; and for patients taking prednisone ≥ 20 mg/d, it is conditionally recommended that influenza does not need to be postponed.
Vaccination, but it is recommended to postpone other inactivated vaccines
.

This is another big relief for the vaccination of patients on glucocorticoids such as prednisone
.

For patients with rheumatism who are receiving immunosuppressive therapy,

Conditional recommendation to postpone the use of live attenuated vaccines

For patients with rheumatism, it is conditionally recommended to receive live attenuated virus vaccine (see the table below) after drug withdrawal for a period of time, and it is recommended to continue to suspend taking immunosuppressive drugs within 4 weeks after vaccination
.
 

Remarks: JAK = Janus kinase; TNF = tumor necrosis factor; IL = interleukin; IVIG = intravenous immunoglobulin G; IV = intravenous injection; the
details are as follows:

1.
For patients using glucocorticoids, live attenuated vaccines can be administered at least 4 weeks after drug withdrawal, and continue to be discontinued for 4 weeks after receiving live attenuated vaccines; but for daily doses equivalent to prednisone <20mg/day or Attenuated vaccination may be critical in the subset of patients (usually infants weighing <10 kg) with <2 mg/kg/day or glucocorticoid therapy one day apart (i.
e.
, "low-level immunosuppression"), if the patient is discontinued There is a high risk of disease recurrence or adrenal insufficiency following glucocorticoids, and continuation of these low-dose steroids may be considered for attenuated vaccines
.

2.
，4，4；≤0.
4mg/kg/≤3mg/kg/（），，
。

3.
，，4，4；

4.
JAK，1，4；

5.
TNF、IL-17、IL-12/23、IL-23，BAFF/Bly，，4；FDA，（，12，2）
。

6.
IL-6IL-1（，，），，4；，DMARD，，
。

7.
，Anifrolumab，，4；，FDA，
。

8.
For patients using rituximab, the live attenuated vaccine can be vaccinated at least 6 months after the drug is discontinued, and the live attenuated vaccine should be discontinued for 4 weeks before administration
.

9.
For patients using human immunoglobulin (IVIG), if the dose is 300-400mg/kg, it is recommended to stop the live attenuated vaccine for at least 8 months; if the dose is 1000mg/kg, it is recommended to stop at least 8 months.
Live attenuated vaccines can be administered after 10 months of medication; if the dose is 2000 mg/kg, it is recommended to receive live attenuated vaccines after drug withdrawal for at least 11 months
.

Likewise, all live attenuated vaccines should wait at least 4 weeks before dosing; the recommendation to discontinue IVIG prior to vaccination is aimed at improving vaccine efficacy, not safety concerns
.

That is to say, in some cases in specific practice, such as during the period of measles epidemic, it is better to vaccinate in advance, rather than mechanically delay vaccination as recommended
.

Comments:
Common live attenuated vaccines such as measles, rubella, mumps, and shingles may be critical for adults with rheumatism and children with rheumatism
.

For the vaccination of live attenuated vaccines, the 2019 EULAR recommends that live attenuated vaccines should be used with caution in patients with rheumatism
.

Guidelines from the Infectious Diseases Society of America recommend that vaccination with live attenuated vaccines be supported in patients receiving low-level induction of immunosuppression
.

These treatments include: low-dose prednisone (<2 mg/kg: maximum dose ≤20 mg/day) or equivalent doses of other drugs; methotrexate (≤0.
4 mg/kg weekly); azathioprine [≤3 mg /(kg d)], but did not give detailed recommendations for specific situations and novel biological agents
.
This update provides more specific and feasible recommendations on the timing of the use of live attenuated vaccines
.

Because B-cell-targeting biologics (eg, rituximab) can severely affect vaccine-evoked humoral immunity, previous guidelines have recommended that rheumatic patients should be vaccinated prior to the use of anti-B-cell biologics.
Vaccination schedules for patients receiving rituximab are unclear
.

The 2022 ACR guidelines give detailed discontinuation recommendations for the use of live attenuated vaccines in patients treated with rituximab
.
The guideline update also gives relevant recommendations for the use of human immunoglobulin for injection vaccines, but the reason for this regulation is not safety, but effectiveness
.

Because gamma globulin is a blood product, it has a certain impact on vaccination
.

After the application of blood products, the antibodies of the blood products enter the human body and may specifically bind to the antigens in the vaccine, interfering with the immune response of the body to the vaccine
.

The higher the antibody titer contained in blood products and the higher the dose, the longer the antibody decay in the body and the longer the impact on subsequent vaccination
.

However, the above effects are mainly due to live attenuated vaccines, and have little effect on common inactivated vaccines.
Therefore, the discontinuation recommendations for human immunoglobulin in this guideline are only reflected in live attenuated vaccines
.

use of biological agents during pregnancy,

When to get live attenuated rotavirus vaccine after birth

1.
If a tumor necrosis factor inhibitor (TNFi) is used in the second and third trimesters of pregnancy, the newborn can be vaccinated with live attenuated rotavirus vaccine within 6 months after birth;

2.
If rituximab is used in the second and third trimesters of pregnancy, the rotavirus vaccine should not be vaccinated within 6 months after birth.
It is recommended to receive rotavirus vaccine after 6 months of birth
.

Note: Exposure to intrauterine biologics, when to receive live attenuated rotavirus vaccine after birth

Comments:
The 2019 EULAR recommendations on vaccination of adults with autoimmune diseases state that if patients with rheumatism are treated with biologics in the second and third trimesters of pregnancy (TNFi is more common), then neonates should be avoided within the first 6 months of life.
Live virus vaccine
.

Because these biological agents may enter the fetus through the placenta in late pregnancy, affecting fetal immune function
.
However, rotavirus enteritis is a common disease in pediatric emergency department, with a high incidence every year.
It is common in late autumn and early winter, which seriously threatens the health of newborns.
Therefore, it is generally necessary for newborns to be injected with rotavirus vaccine.
Rotavirus vaccine is a preventive measure.
The vaccine for rotavirus enteritis is mainly vaccinated from 2 months to 3 years old.

Therefore, based on evidence-based medicine and clinical practice needs, the update of this guideline specifically proposes that if TNFi is used in the second and third trimesters of pregnancy, neonatal Live attenuated rotavirus vaccine can be given within 6 months of birth, not all live attenuated vaccines
.

At the same time, the guidelines also make detailed recommendations for the use of rituximab in the second and third trimesters of pregnancy
.

Summarize

It should be noted that the overall quality of the evidence supporting the above recommendations is low, so most of the above recommendations are conditional and require more evidence-based support
.

The use of these recommendations requires a trade-off between the patient's risk of developing vaccine-preventable disease and the risk of rheumatic disease recurrence, particularly when immunosuppressive vaccinations need to be withheld
.
Review the previous version of the rheumatism patient vaccination guide reviewed by the author - how to vaccinate patients with rheumatism? This is the real way to improve immunity! The author believes that the update of this guideline is of great significance to the guidance of rheumatology medical practice.
Although the level of evidence is low, this guideline update provides more detailed and specific recommendations, which are often more conducive to guiding clinical practice and giving more Lots of room for change
.
In clinical practice, decisions on vaccination and drug withdrawal often encourage doctors and patients to make joint decisions.
The update of this guideline also provides a more detailed basis for joint decision-making between doctors and patients.
bring more clinical benefits to patients
.
Reference: [1] 2022 American College of Rheumatology (ACR) Guideline for Vaccinations in Patients with Rheumatic and Musculoskeletal Diseases.
[2] FurerV, RondaanC, HeijstekMW, et al.
2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.
Ann Rheum Dis.
2019 Aug 14.
pii: annrheumdis-2019-215882.
[3]KrogerAT, AtkinsonWL, MarcuseEK, et al.
General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR Recomm Rep, 2006, 55.
[4]] Avery RK.
Vaccination of the immunosuppressed adult patient with rheumatologic disease.
Rheum Dis Clin North Am, 1999, 25(3): 567-584.
[5] Jonathan Lippiatt, et al.
Non-cervical human papillomavirus -relateddisease.
2013.
[6] Joel M Palefsky, et al.
Anal squamous intraepithelial lesions: Diagnosis, scree.
[7] National Health and Medical Research Council.
The Australian Immunisation Handbook.
9thed.
Canberra, Australia: Australian Government.
Publishing Service, 2008: 90.
Source of this article: Rheumatism and Immunity Channel of the Medical Community Author of this article: Yao Xiaoyan Review of this article: Deputy Chief Physician Chen Xinpeng

Where can I find more rheumatism clinical knowledge?
Come and have a look at the "Doctor Station"👇

Copyright statement
This article is original, please forward it to the circle of friends - End -
Call for manuscripts "Rheumatology Immunity Channel in the Medical Community" long-term recruitment of online authors, 1.
Clinical practical skills, misdiagnosed cases, clinical medication, and interesting content in rheumatology and immunology; 2.
Rheumatism Interesting diagnosis and treatment stories of immunologists; 3.
Significant progress in the field of rheumatology and immunization; 4.
Others (what rheumatologists are interested in
) Contributions are welcome to share! We will provide you with competitive royalties and a platform to showcase your talents
.

Submission email: yanjin@yxj.
org.
cn (reply to manuscripts) The medical community strives for the accuracy and reliability of its published content when it is approved, but does not regard the timeliness of the published content and the accuracy of the cited materials (if any) and completeness, etc.
, and do not assume any responsibility for the outdated content, possible inaccuracy or incompleteness of the cited information
.

Relevant parties are requested to check separately when adopting or using it as a basis for decision-making
.