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What recommendations are available regarding the timing of administration of the COVID-19 vaccine with regard to immunosuppressant medications?

Currently, there are 3 vaccines for coronavirus disease 2019 (COVID-19) available in the United States.1-3 The first COVID-19 vaccine available was developed by Pfizer and BioNTech, and approved by the U.S. Food and Drug Administration (FDA) for emergency use authorization (EUA) on December 11, 2020.4 It is a 2-dose series with each dose given 3 weeks apart.1 The vaccine contains a nucleoside-modified messenger RNA (mRNA) that encodes the viral spike (S) glycoprotein of SARS-CoV-2 virus, triggering an immune response. The second vaccine approved for EUA was the Moderna vaccine on December 18, 2020, a week after the Pfizer-BioNTech vaccine approval.4 Like the Pfizer-BioNTech vaccine, the Moderna vaccine uses mRNA technology and is a 2-dose series; however, each dose should be separated by 28 days.2 On February 27, 2021, the third vaccine was approved for EUA, and it was developed by Janssen/Johnson & Johnson.4 Unlike the first 2 EUA-approved COVID-19 vaccines, the Janssen vaccine is an adenovirus-vectored vaccine and is a single dose.3

While the efficacy of these vaccines has been established in the general population, patients receiving immunosuppressive therapy were excluded from pivotal vaccine trials.5-10 Therefore, no information related to drug interactions is provided in the EUA labeling for these COVID-19 vaccines.1-3 The EUA prescribing information for the Pfizer-BioNTech, Janssen, and Moderna COVID-19 vaccines all note that individuals receiving immunosuppressive therapy may have an attenuated response to the COVID-19 vaccine. Thus, it unknown whether certain medications will impact the safety or efficacy of the COVID-19 vaccines, and this has triggered frequently asked questions regarding management of immunosuppressive therapy at the time of vaccination. Of note, because the COVID-19 vaccines are not live vaccines, the Centers for Disease Control and Prevention (CDC) states that they can be administered safely to immunocompromised patients.11

General recommendations
To generate protective immunity from vaccination, a person needs an intact immune system.11,12 However, many therapies such as B-cell directed therapies (eg, CD20 or CD22 monoclonal antibodies, bispecific agents like blinatumomab, CD19- or CD22-directed CAR T-cell therapies, Bruton’s tyrosine kinase inhibitors), T-cell directed therapies (eg, calcineurin inhibitors, antithymocyte globulin, alemtuzumab), chemotherapy, and daily high-dose corticosteroids (prednisone-equivalent ≥20 mg) will limit the body’s ability to generate an immune response to a vaccine. Several organizations have made statements regarding the COVID-19 vaccine in patients on immunosuppressive therapy.11-21 These statements are typically disease state specific; however, the CDC and the American Society of Hematology (ASH) have made general recommendations about immunosuppressive therapy.

The CDC notes that patients receiving immunosuppressant medications can receive the COVID-19 vaccine.11 Data is lacking on optimal timing of the vaccine with regard to immunosuppressant therapy; therefore, there is no recommended minimum interval specific to the COVID-19 vaccine other than general best practices. The CDC general best practices for vaccination of immunocompromised people states that patients should ideally complete vaccination at least 14 days prior to starting immunosuppressive therapy. Patients on immunosuppressive therapy can still get the vaccine if they are not able to delay therapy, and decisions to delay therapy should be based on the risk of the individual’s underlying condition.

The ASH also provides recommendations for vaccinating patients on immunosuppressive therapy; however, the timeframes for separating vaccines from therapy differ slightly from the CDC.12 They recommend administering the vaccine at least 2 to 4 weeks prior to immunosuppressive therapy. If the patient is currently receiving or has received immunosuppressants, they suggest that clinicians consider delaying the vaccination for up to 6 months after treatment to prevent a diminished immune response to the vaccine. Additionally, ASH suggests using clinical judgement when deciding between vaccinating immunocompromised patients and deferring the vaccine to elicit the best immune response. The risks and benefits of vaccinating immunocompromised patients should be weighed on an individual basis. The decision should incorporate the incidence of COVID-19 in the community as well.

Solid organ transplantation
The American Society of Transplantation (AST) issued a statement on COVID-19 vaccines in patients receiving solid organ transplants in May 2021, which specifically states that patients should continue stable immunospressive regimens at the time of vaccination to avoid organ rejection.13 The AST suggests that it may be appropriate to defer the COVID-19 vaccine for 3 months when T- or B-cell ablative therapies, such as anti-thymocyte globulin or rituximab, were used during transplantation due to a potential decreased immune response.14 Multiple studies have reported an attenuated response to COVID-19 vaccines among solid organ transplant recipients; however recommendations still support vaccination of recipients and vaccination prior to transplant when possible.13 An early observational study at John Hopkins School of Medicine evaluated the safety of the first dose of the COVID-19 vaccine in 187 solid organ transplant recipients.22 Recipients were 6 years post-transplant on average, and their maintenance immunosuppression included tacrolimus (87%), mycophenolate (69%), azathioprine (11%), and steroids (55%). Fifty percent of participants received the Pfizer-BioNTech vaccine, and 50% received the Moderna vaccine. Adverse events in the study were consistent with those found in the COVID-19 randomized trials.

Inflammatory bowel disease
Patients with inflammatory bowel disease (IBD) on immune-modifying agents may have a reduced immune response to the vaccine, and prospective studies are in process to evaluate the true effect.15 A retrospective cohort study in the Veterans Health Administration evaluating the effectiveness of the mRNA COVID-19 vaccines in patients with IBD on immunosuppressive medications showed 80.4% vaccine effectiveness.23 This cohort included 14,697 patients on immunosuppressive medications (5-aminosalicylic acid [ASA] alone, 54.8%; anti-tumor necrosis factors [TNFs] alone, 19.9%; thiopurines, 10.7%), of which 7,321 patients received at least 1 vaccine dose (91.2% received both Pfizer doses, 88.7% received both Moderna doses).

Despite the potential for reduced effectiveness, the Crohn’s & Colitis Foundation states that patients receiving immunosuppressive agents should not defer vaccination because of immune-modifying treatment.15 Additionally, they state that patients receiving systemic corticosteroids should be advised about the potential decreased efficacy of the vaccine. Because the vaccine is not live, it is not expected to be associated with increased safety concerns in patients with IBD. Data from 246 IBD registry patients who received an mRNA COVID-19 vaccine showed that adverse events occurred in a similar frequency to that in the general population.24

Oncology and hematology
The American Society of Clinical Oncology (ASCO) recommends offering the vaccine to patients actively receiving cancer treatment, including chemotherapy and immunotherapy, as long as there is no other contraindication to the vaccine.16 The organization suggests providing the vaccine between cycles of therapy or after waiting periods for patients receiving stem cell transplants and immune globulin treatment to reduce possible risks and maintain efficacy of the vaccine. In general, the National Comprehensive Cancer Network (NCCN) COVID-19 Vaccination Advisory Committee recommends vaccinating cancer patients as the COVID-19 vaccine becomes available to them; however, there are some caveats to this recommendation based on the indication and therapy, which are described in Table 1.17 Memorial Sloan Kettering (MSK) Cancer Center, a National Cancer Institute (NCI) designated cancer center, has written interim guidelines for therapy and disease-specific recommendations for COVID-19 vaccination.18 The guideline provides more granular recommendations by medication and is endorsed by ASCO and the Leukemia and Lymphoma Society (LLS). Additionally, the LLS notes that certain lymphoma therapies, specifically rituximab and obinutuzumab, may impair the immune response to the COVID-19 vaccine as this has been observed with other vaccines.19 A summary of recommendations from the NCCN, MSK, and LLS is provided in Table 1.17-19

Recommendations for vaccination in oncology patients from various organizations generally align; however, there are several notable differences between the guidelines, including for cytotoxic chemotherapy in solid tumors.17-19 The NCCN recommends administering the vaccine when it is available to patients; whereas MSK provides various recommendations based on whether chemotherapy has already been initiated or completed. Another exception is with chronic lymphocytic leukemia (CLL) and B-cell depleting therapies. The NCCN recommends administering the vaccine when it is available to patients with symptomatic CLL. However, MSK recommends deferring the vaccine until 1 month after completing B-cell depleting therapy or until evidence of lymphocyte reconstitution. There are also various recommendations for rituximab administration based on indication; however, MSK recommends considering vaccination during times of high community transmission as it may still generate T-cell memory responses.

Table 1. Oncology immunosuppressants and COVID-19 vaccine administration recommendations.17-19
Circumstance of use
Anti-CD20 antibodies for HSCT (eg, rituximab)
Defer vaccine for at least 3 months after completing therapy.*
CAR T-Cell Therapy
Defer vaccine for at least 3 months after completing therapy.*
Chronic and Indolent B-cell depleting therapy (eg, rituximab, venetoclax, ibrutinib)
Asymptomatic CLL, Indolent lymphomas‡†

Symptomatic CLL




Administer vaccine series, hold B-cell depleting therapy for 1 month after completing vaccine series.

Defer vaccination for 1 month after completion of therapy or until there is evidence of lymphocyte reconstitution (ALC > 1.0 and/or B cell counts ≥50).§‖

Administer vaccine when available, no dosing or timing adjustments.

Administer vaccine when available, no dosing or timing adjustments.
Cytotoxic chemotherapy
Solid tumors

Administer vaccine when available, no dosing or timing adjustments recommended.**

Administer first dose of vaccine ≥14 days prior to initiating therapy, if feasible.
If already started chemotherapy, administer first dose vaccine between chemotherapy cycles and away from nadir.
If therapy completed, defer first dose of vaccine until nadir is resolved.
Hypomethylating agents
Consider for vaccination regardless of treatment status.
Immune checkpoint inhibitors
Solid tumors
Administer vaccine when available, no dosing or timing adjustments.††
Solid tumors
Administer vaccine when available, no dosing or timing adjustments.
Induction therapy
B-cell or T-cell ALL ‡‡, DLBCL and other aggressive B-cell lymphomas, T-cell lymphomas¶¶, AML***
Do not delay therapy for vaccination.
Intensive cytotoxic chemotherapy (eg, cytarabine and anthracycline-based induced regimens)
Hematologic malignancies (eg, AML)
Defer vaccine until ANC recovery.
Hematologic malignancies
Administer vaccine to patients receiving plasma therapy not specific to COVID-19.
Lymphocyte-depleting therapies (eg, rituximab, blinatumomab, ATG, alemtuzumab, high-dose melphalan with HSCT, cytoxan/fludarabine, anti-CD52 monoclonal antibody conditioning)
Hematologic malignancies (non-myeloma)


Complete vaccine series 14 days prior to initiation of lymphocyte-depleting therapy.
If already started lymphocyte-depleting therapy, it is reasonable to defer vaccination until 6 months after completion of therapy or until there is evidence of lymphocyte reconstitution (ALC >1.0 and/or B cell counts ≥50).

Defer vaccine until lymphocyte recovery is observed.
Maintenance therapies (eg, BTKi, JAKi)

Hematologic malignancies

Defer vaccine for at least 3 months post-HSCT, agents may blunt immune response to vaccine.†††

Administer vaccine when available.
Systemic corticosteroids
B- or T-ALL (induction therapy)

GVHD immunosuppressive treatment

Hematologic malignancy


Consider vaccination.‡‡‡

Consider delaying vaccine until immunosuppressive therapy is reduced and/or based on immunophenotyping of T-cell and B-cell immunity.

Vaccinate prior to therapy, if possible.
Targeted therapy
Solid tumors
Administer vaccine when available, no dosing or timing adjustments.

B- or T-ALL (induction therapy)



Consider for vaccination regardless of remission status.

Consider for vaccination.‡‡‡
Abbreviations: ALC=absolute lymphocyte count; ALL=acute lymphocytic lymphoma; AML=acute myeloid leukemia; ANC=absolute neutrophil count; ATG=anti-thymocyte globulin; BTKi= Bruton’s tyrosine kinase inhibitors; CAR=chimeric antigen receptor; CLL=chronic lymphocytic leukemia; CML=chronic myeloid leukemia; COVID-19=coronavirus disease 2019; DLBCL=diffused large B-cell lymphoma; GVHD=graft-versus-host disease; HSCT=hematopoietic stem cell transplant; IVIG=intravenous immunoglobulin; JAKi=Janus kinase inhibitors; LLS=Leukemia and Lymphoma Society; MDS=myelodysplastic syndromes; MPN=myeloproliferative neoplasm; MSK=Memorial Sloan Kettering; NCCN=National Comprehensive Cancer Network; TKI=tyrosine kinase inhibitor
* MSK also notes patient should be IVIG independent with B-cell count ≥50.
‡ In patients with indolent lymphomas requiring systemic therapy, MSK recommends treating the patient with induction therapy only.
†Defer vaccine series until completion of induction therapy and evidence of B-cell recovery from anti-CD20 depletion (ALC > 1.0 and/or B cell counts ≥50), assuming no additional treatment is immediately planned.
§ Consider vaccinating patients with symptomatic CLL where chronic therapy is required as it may still generate T-cell memory responses.
‖ Utilization of absolute lymphocyte count and/or B-cell count as a predictive biomarker has not been established.
¶ MSK recommends that clinicians consider vaccinating patients with MPN regardless of whether the patient is under observation or active treatment.
** Ideal timing of vaccine administration relative to chemotherapy cycles has not been established.   
†† Immune checkpoint inhibitors may theoretically exacerbate immune-related adverse events but no data to suggest this exists. Additionally, there are no data relating to the timing of vaccine administration.
‡‡ In patients with B-cell or T-cell ALL, administer vaccine series during maintenance therapy when there is evidence of hematopoietic count recovery.
¶¶ In patients with T-cell lymphomas, consider vaccinating during induction therapy after count recovery.
*** In patients with acute myeloid leukemia, consider vaccinating patients during consolidation therapy, vaccine should not be given during induction remission phase.
††† In graft-versus-host disease, consider delaying vaccine until immunosuppressive therapy is reduced and/or based on immunophenotyping of T-cell of B-cell immunity.
‡‡‡ See induction therapy section for more intensive regimens for B- or T-acute lymphocytic leukemia.

The American College of Rheumatology (ACR) published recommendations for the COVID-19 vaccine in patients with rheumatic and musculoskeletal diseases, which includes recommendations for managing immunomodulating medications around the time of vaccination.20 The ACR guidance is intended for patients that have sufficient disease control to allow for medication adjustments. The recommendations note that decision-making should be determined on a case-by-case basis. A summary of the ACR’s recommendations is provided in Table 2. The task force reached a moderate level of consensus for all recommendations, with the exceptions noted in Table 2. Experts from the Arthritis Foundation do not believe an interaction between disease-modifying antirheumatic drugs (DMARDs) and COVID-19 vaccines will cause safety concerns, as most vaccines will likely be non-live vaccines.25 However, they note that DMARDs have been shown to reduce the immune responses to other vaccines, but it is unknown whether delaying DMARD therapy will improve a patient’s immune response to the COVID-19 vaccine.

In addition to the ACR recommendations, several review articles have aimed to extrapolate data from the influenza, hepatitis B, pneumococcal, shingles, and tetanus vaccines to anticipate potential interactions between the COVID-19 vaccine and DMARDs.26,27 In general, these review articles came to similar conclusions as the ACR with a few notable considerations. Both review articles recommend decreasing steroid doses to ≤10 mg daily in well controlled patients prior to administering a vaccine, while the ACR does not recommend therapy adjustments. Additionally, these reviews suggest holding Janus kinase inhibitors and methotrexate for 2 weeks after vaccination, instead of the 1-week hold recommended by ACR.

For patients with psoriasis and psoriatic arthritis, the National Psoriasis Foundation recommends continuing biologic or oral therapies when receiving an mRNA COVID-19 vaccine, but does not make any mention of other vaccine types.21

Table 2. Rheumatology medications and COVID-19 vaccine administration recommendations.20
Timing consideration relative to COVID‑19 vaccination
Hydroxychloroquine*; Apremilast*; IVIG*; Glucocorticoids*†; Sulfasalazine; Leflunomide; Azathioprine; Cyclophosphamide (PO); TNFi; inhibitors of IL-6R, IL-1, IL-17, IL-12/23, IL-23; Belimumab; Calcineurin inhibitors (PO)
Administer vaccine when available, no dosing or timing adjustments.
Hold for 1 week following each vaccine dose.
Hold for 1 week after each mRNA vaccine dose and 2 weeks after single-dose.
Hold for 1 week after each vaccine dose.
Abatacept (SC)Hold 1 week prior to AND 1 week after the FIRST vaccine dose. No medication adjustments for the second vaccine dose.
Abatacept (IV) Administer the first dose of the vaccine 4 weeks after abatacept infusion (entire dosing interval) and hold the subsequent abatacept infusion by 1 week (5-week gap in total). No medication adjustments for the second vaccine dose.
Cyclophosphamide (IV)
Administer each dose of the vaccine approximately 1 week prior to cyclophosphamide, when feasible.
Administer vaccine series 4 weeks prior to next scheduled rituximab cycle, assuming that the patient’s COVID-19 risk is low or mitigated by preventive health measures (ie, self-isolation). After the vaccine series is complete, delay rituximab for 2 to 4 weeks, if disease activity allows.
Acetaminophen, NSAIDs
Hold for 24 hours prior to vaccination, if disease is stable. Can use post-vaccination without restrictions.
Abbreviations: CDC=Centers for Disease Control and Prevention; COVID-19=coronavirus disease 2019; IL=interleukin; IV=intravenous; IVIG= intravenous immunoglobulin; JAKi=Janus kinase inhibitors; MTX=methotrexate; NSAID=non-steroidal anti-inflammatory drug; PO=oral; SC=subcutaneous; TNFi=tumor necrosis factor inhibitor
* The level of task force consensus was strong-moderate for these medications, including prednisone-equivalent doses <20 mg/day of glucocorticoids.
† Consensus was not reached for the timing of vaccine administration and prednisone-equivalent doses ≥ 20 mg/day of glucocorticoids.
Based on CDC recommendations for vaccination in immunosuppressive patients, Soy and colleagues recommend administering vaccine 14 days prior to therapy.26

High-quality data and information evaluating drug interactions with the COVID-19 vaccine is lacking. Several medications may have potential concerns for interacting with the COVID-19 vaccine, especially immunosuppressants which are known to blunt vaccine effectiveness with non-COVID-19 vaccines. Many organizations have provided guidance for evaluating potential drug interactions with the COVID-19 vaccine and managing immunosuppressive therapy at the time of vaccination. Recommendations to alter or continue therapy are highly specific to the medication’s indication, and plans to alter therapy should be individualized to the patient’s clinical course. As more information becomes available, these recommendations are expected to evolve, and organization websites should be consulted for the most up-to-date recommendations.


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  20. Curtis JR, Johnson SR, Anthony DD, et al. American College of Rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases: version 2. Arthritis Rheumatol. Published online June 15, 2021. doi: 10.1002/art.41877
  21. Gelfand JM, Armstrong AW, Bell S, et al. National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: version 2-advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments. J Am Acad Dermatol. 2021;84(5):1254-1268. doi: 10.1016/j.jaad.2020.12.058
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  23. Khan N, Mahmud N. Effectiveness of SARS-COV-2 vaccination in a Veterans Affairs Cohort of inflammatory bowel disease patients with diverse exposure to immunosuppressive medications. Gastroenterology. Published online May 25, 2021. doi: 10.1053/j.gastro.2021.05.044
  24. Botwin GJ, Li D, Figueiredo J, et al. Adverse events following SARS-CoV-2 mRNA vaccination: among patients with inflammatory bowel disease. Am J Gastroenterol. Published online May 25, 2021. doi: 10.14309/ajg.0000000000001342
  25. COVID-19 FAQs: medications, treatments and vaccines. Arthritis Foundation. Updated May 11, 2021. Accessed June 17, 2021.
  26. Soy M, Keser G, Atagunduz P, et al. A practical approach for vaccinations including COVID-19 in autoimmune/autoinflammatory rheumatic disease: a non-systematic review. Clin Rheumatol. Published online March 22, 2021. doi: 10.1007/s10067-021-05700-z
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Prepared by:
Hunter Patton-Gentert, PharmD (Class of 2021)
University of Illinois at Chicago College of Pharmacy

Reviewed by:
Amanda Gerberich, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

July 2021

The information presented is current as June 15, 2021. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.