Abstract
The use of immunosuppressive therapies for immune-mediated disease is associated with an elevated risk of infections and related comorbidities. While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal, due in part to uncertainty about their efficacy or safety under these clinical situations. To address this concern, a multidisciplinary group of Canadian physicians with expertise in dermatology, gastroenterology, infectious diseases, and rheumatology developed evidence-based clinical guidelines on vaccinations featuring 13 statements that are aimed at reducing the risk of preventable infections in individuals exposed to immunosuppressive and immunomodulatory agents.
The use of immunosuppressive therapies, including certain conventional synthetic disease-modifying antirheumatic drugs (DMARD), targeted synthetic DMARD, and biologics, has improved disease control and quality of life for patients with autoimmune and inflammatory diseases. However, because these treatments may attenuate protective immunity, some patients are potentially at an increased risk of developing common and opportunistic infections, complicated by higher rates of related morbidity and mortality than age- and sex-matched control populations1,2,3,4. Although this risk can be significantly reduced with commercially available vaccines, physicians often hesitate to vaccinate these patients because of uncertainties regarding the safety and efficacy of immunization while being treated with immunosuppressive medications5,6,7,8,9.
This executive summary of the clinical recommendations provides guidance regarding the vaccination of adults receiving immunosuppressive medications for the treatment of immune-mediated diseases (IMD), or infants with intrauterine exposure to such agents.
MATERIALS AND METHODS
A Canadian multidisciplinary committee with expertise in gastroenterology (JKM, AB, BB, AHS), dermatology (KAP, MG, RB, VH), rheumatology (BH, JEP, JW, SJ), and infectious diseases (DK, DCV) developed guidelines on the management of vaccination in patients receiving immunosuppressive therapies. Literature searches by Synapse Medical Communications identified clinical trials, metaanalyses, systematic reviews, observational studies, case series, and existing guidelines published from 2009 to 2017 across multiple databases (Embase, MEDLINE, PubMed) as per the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system10. Reference lists were manually searched to identify relevant articles and included based on the committee’s discretion (Figure 1). Published studies were then reviewed by the committee and assessed according to the GRADE evidence levels10. The quality of evidence was rated as “high” (indicating that further research is unlikely to change the confidence in the estimate of effect), “moderate” (implying that further research is likely to have an effect on the confidence in the estimate of effect), “low” (suggesting that further research is likely to have a strong effect on the confidence in the estimate of effect), or “very low” (meaning that any estimate of effect is very uncertain).
Literature search methodology.
The Steering Committee [KAP (chair), JKM, DK, BH] developed the initial statements, which underwent 2 rounds of revisions according to feedback received from all authors. All 14 members voted on a Web-based platform to determine the level of agreement for each statement using a 5-point scale (strongly agree, agree, neutral, disagree, strongly disagree). Statements achieving ≥ 75% agreement were included in the guidelines. Of the 15 statements considered, 2 were rejected.
The strength of recommendations was evaluated according to the GRADE and rated as “strong” when desirable consequences clearly outweighed undesirable consequences, “conditional” when desirable consequences probably outweighed undesirable consequences, or “weak” when the balance between desirable and undesirable consequences was closely balanced or uncertain.
RESULTS
The developed guidelines consist of 13 statements addressing general immunization strategies for individuals exposed to biologic and/or nonbiologic immunomodulatory agents (Table 1)11. Of these, 10 statements focus on the management of adults with IMD who are considering age-appropriate primary and secondary immunizations with live or inactivated vaccines. Recommendations specifically regarding the use of the live attenuated herpes zoster vaccine are also provided. The remaining 3 statements pertain to the timing of routine childhood vaccinations in infants exposed to immunosuppressive drugs either in utero during the third trimester or through breastfeeding.
Guideline statements*.
In the full guideline document, each statement is followed by a discussion of the supporting evidence, as well as any existing recommendations or guidance from other physician organizations or societies11.
DISCUSSION
This document is intended to provide guidance on the vaccination of individuals exposed to immunosuppressive therapies. A robust discussion of these recommendations is provided in the full guideline document11.
These guidelines were developed according to the best data available to date. However, the body of evidence regarding the safety and efficacy of vaccination in this patient population is small and incomplete. Therefore, clinical judgment based on a careful assessment of patient factors and the risks and benefits of vaccination should always prevail when determining the best course of action for each individual.
Regular updates to the current guidelines will be necessary as new clinical trial data and treatment options emerge.
Acknowledgment
We thank Synapse Medical Communications, Oakville, Ontario, Canada, for providing medical writing assistance in the form of drafting and revising as per authors’ directions and in accordance with the standards set out by the International Committee of Medical Journal Editors. Medical writing support was funded by the Dermatology Association of Ontario.
Footnotes
Development of the vaccination guidelines was funded by the Dermatology Association of Ontario. The authors received no financial support for the research, authorship, and/or publication of this article. K. Papp is an advisory board participant, steering committee member, investigator, speaker, and/or consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck (MSD), Novartis, and Valeant/Bausch Health. D. Kumar is an investigator for GSK, Oxford Immunotec, and Qiagen. J.K. Marshall is an advisory board participant, speaker, and/or consultant for AbbVie, Janssen, Pfizer, and Takeda. R. Bissonnette is an advisory board participant, investigator, speaker, and/or consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Incyte, Janssen, and Pfizer, and is a shareholder of Innovaderm Research. A. Bitton is an advisory board participant, speaker, and/or investigator for AbbVie and Janssen. B. Bressler is an advisor and/or speaker for AbbVie, Allergan, Genentech, Janssen, Pfizer, and Takeda. M. Gooderham is an advisory board participant, investigator, consultant, and/or speaker for AbbVie, Amgen, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Genzyme, and Valeant Pharmaceuticals. S. Jamal is a consultant for BMS, Eli Lilly, and UCB, and has received research grants from Merck, AbbVie, and BMS. A.H. Steinhart is an advisory board participant, speaker, investigator, and/or consultant for AbbVie, Amgen, Arena Pharmaceuticals, Celgene, Ferring, Genentech, Hoffmann-La Roche, Hospira, Janssen, Merck, Pfizer, Pharmascience, Red Hill Biopharma, and Takeda. D.C. Vinh is an advisory board participant, speaker, consultant, and/or investigator for Avir Pharma, Cidara, CSL Behring Canada, Novartis Canada, and Shire Canada. J. Wade is an advisory board participant and consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Roche, Sanofi, and UCB.
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- Accepted for publication October 30, 2018.
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