Elsevier

Vaccine

Volume 30, Issue 8, 14 February 2012, Pages 1413-1424
Vaccine

Review
Are immunosuppressive medications associated with decreased responses to routine immunizations? A systematic review

https://doi.org/10.1016/j.vaccine.2011.11.109Get rights and content

Abstract

Background

Long-term immunosuppressive medications are being used more commonly for a variety of medical conditions, including immune-mediated diseases and organ transplantation. While these medications are often necessary, they are associated with an increased risk of serious infections. Vaccination may be a way to prevent a variety of infections but vaccine responses among patients receiving immunosuppressive therapies have been variable.

Purpose

To systematically review the literature describing immune responses among patients on immunosuppressive therapies to vaccinations including influenza, pneumococcal, meningococcal, hepatitis A and B, tetanus toxoid, pertussis, varicella, and zoster.

Data sources

English language citations in the MEDLINE and EMBASE databases from 1985 to 2010.

Study selection

Two reviewers independently screened titles and abstracts to identify prospective, controlled studies reporting pre- and post-vaccination titers of recommended vaccines in patients receiving long-term immunosuppressive therapies for full-text review.

Data extraction

Three reviewers independently assessed study characteristics including treatment regimens and pre- and post-vaccination titers.

Data synthesis

Of the 972 identified titles, fifteen met inclusion criteria. Ten studies assessed the effects of immunosuppressive medications on responses to influenza vaccine, four studies investigated responses following pneumococcal vaccination, and one study assessed both influenza and pneumococcal vaccination. Five of the studies that evaluated influenza vaccination showed partially diminished responses among individuals receiving immunosuppressive therapies, while one of the pneumococcal vaccine studies showed significantly decreased responses following vaccination. Patients treated with more than one immunosuppressive medication were the least likely to respond to vaccination.

Limitations

The heterogeneity of reported outcomes limits generalizeability.

Conclusions

Immunosuppressive therapy, particularly combination regimens, may blunt response to influenza and pneumococcal vaccinations. To ensure the best chance of response, immunizations should be administered prior to initiation of immunosuppressive medications whenever possible.

Highlights

► Immunosuppressive (IS) therapies increase risks of vaccine-preventable infections. ► Vaccine responses were reviewed for several IS therapies and health conditions. ► Most IS modestly blunt vaccine responses to influenza and pneumococcal disease. ► The greatest impact of IS is seen among patients receiving 2 or more IS therapies. ► Patients receiving IS should ideally be vaccinated prior to initiation of therapy.

Introduction

As part of the armamentarium against many disease states, more people are receiving an increasing array of immunosuppressive agents such as corticosteroids, 6-mercaptopurine, azathioprine, methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil and various monoclonal antibodies (anti-TNFα, anti-CD20 and others). Immune suppression increases the risk of people developing various vaccine-preventable infections, including influenza, pneumococcal pneumonia, varicella, herpes zoster and heptatitis B [1], [2], [3], [4]. Patients with inflammatory diseases (inflammatory bowel disease and rheumatological disorders) and organ transplant recipients commonly require long-term immunosuppression which may further increase their risk for developing serious infections. In an attempt to decrease this risk, the Centers for Disease Control and Prevention (CDC) recommend that immunosuppressed patients be brought up to date against vaccine preventable infections [5], [6]. However, the response to immunizations in patients receiving immunosuppressive therapy is unclear. It also is likely that the response to immunization varies depending on the specific immunosuppressive drug or regimen administered. This has led some groups to advocate checking post-vaccination titers to ensure an adequate immunological response following immunization [7].

To better delineate the response to vaccination among immunosuppressed patients and if response varies by immunosuppressive regimen, we performed a systematic review of prospective, controlled studies that assessed pre- and post-vaccination titers among children and adults receiving various immunosuppressive therapies.

Section snippets

Search strategy

We conducted a systematic search of published, English-language studies from January 1, 1985 through January 2010 using MEDLINE and EMBASE, based on methods outlined in the Cochrane Collaborative Working Group on Systematic Reviews [8]. A search strategy was created to capture commonly used immunosuppressive therapies, conditions in which such therapies might be used, and routine vaccines (Table 1).

Study selection and data collection process

Two independent reviewers (NA, KO) screened article titles and abstracts in duplicate to assess

Search results

The MEDLINE and EMBASE database searches were performed for a 15 year period ending January 2010, and yielded 972 titles (Fig. 1). Of these, 45 abstracts met inclusion criteria, and these manuscripts were reviewed. Among these, 29 studies were excluded for not meeting inclusion criteria, resulting in 15 publications included in the final review. [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23] While all studies were prospective, only 2 studies involved

Discussion

We aimed to determine the impact of immunosuppressive medications on immune responses to vaccines in at-risk populations. We identified 14 relevant studies assessing responses to influenza and pneumococcal vaccines.

For influenza vaccination, 5 of 11 studies showed significantly decreased responses for at least one antigen in patients receiving immunosuppressive therapy [2], [3], [4], [5], [6]. Patients in these studies were treated for a variety of conditions with a variety of immunosuppressive

Acknowledgements

Gil Y. Melmed had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Funding. None. Financial disclosures. GYM: Jannsen (consultant), Abbott Labs (non-CME speaker), Amgen (consultant), Celgene (consultant). Contributors. Study concept and design was done by Gil Melmed. Acquisition of data was performed by all authors. Analysis and interpretation of data was done by Nikhil Agarwal, Robert Frenck, and Gil

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