The Immunogenicity and Safety of Zostavax® in Rheumatoid Arthritis Patients Using Abatacept
| Status: | Recruiting |
|---|---|
| Conditions: | Arthritis, Rheumatoid Arthritis, Shingles, Infectious Disease |
| Therapuetic Areas: | Dermatology / Plastic Surgery, Immunology / Infectious Diseases, Rheumatology |
| Healthy: | No |
| Age Range: | 50 - Any |
| Updated: | 2/3/2019 |
| Start Date: | May 8, 2014 |
| End Date: | December 2020 |
| Contact: | Amanda Brunton, MPH |
| Email: | brunton@ohsu.edu |
| Phone: | 503-494-6327 |
This investigator-initiated study will serve as a sub-study for the American College of
Rheumatology-sponsored VERVE protocol currently funded by the NIH. This double-blinded
multicenter randomized pragmatic trial is designed to determine whether Zostavax is safe and
effective in patients with rheumatoid arthritis (RA) currently using anti-tumor necrosis
factor (TNF) therapies. Inclusion/exclusion criteria for this sub-study mirror that of the
parent VERVE trial with the exception of abatacept therapy being allowed. Preliminary data
from the VERVE parent protocol enrolling patients using anti-TNF therapy is encouraging in
that few patients experienced adverse events (56 adverse events in 50 participants, out of
140 participants in total) and that 96.2% of these adverse events were considered either mild
or moderate. Importantly, there have been no instances of vaccine dissemination or zoster
events to date.
Rheumatology-sponsored VERVE protocol currently funded by the NIH. This double-blinded
multicenter randomized pragmatic trial is designed to determine whether Zostavax is safe and
effective in patients with rheumatoid arthritis (RA) currently using anti-tumor necrosis
factor (TNF) therapies. Inclusion/exclusion criteria for this sub-study mirror that of the
parent VERVE trial with the exception of abatacept therapy being allowed. Preliminary data
from the VERVE parent protocol enrolling patients using anti-TNF therapy is encouraging in
that few patients experienced adverse events (56 adverse events in 50 participants, out of
140 participants in total) and that 96.2% of these adverse events were considered either mild
or moderate. Importantly, there have been no instances of vaccine dissemination or zoster
events to date.
Recently, a live-attenuated vaccine (Zostavax®, Merck) to prevent herpes zoster (HZ) has been
developed and approved for use among individuals age 50 years or older, regardless of
previous HZ or varicella history. In a pivotal study of 38,456 older adults led by Dr.
Michael Oxman (a co-investigator in the parent VERVE trial and this immunogenicity pilot
sub-study), the vaccine reduced the incidence of HZ and postherpetic neuralgia (PHN) by >
50%.
Guidelines from the American Council on Immunization Practices (ACIP), based largely on
expert opinion (given the absence of data), recommend that patients who use methotrexate or
low to moderate doses of corticosteroids (up to 20mg/day prednisone) can receive this
vaccination safely. However, theoretical concerns regarding the safety of live vaccine use in
patients using biologic therapies have resulted in an ACIP recommendation that the vaccine is
contraindicated in patients receiving such medications. Similarly, given a lack of data, the
American College of Rheumatology (ACR) endorsed this contraindication in the updated ACR 2012
recommendations for biologic and non-biologic disease modifying anti-rheumatic drug (DMARD)
use in RA patients (led by members of the project team for this present application).
Currently it is unknown if RA patients using biologics can safely receive this vaccine.
Despite the demonstrated efficacy and safety of the zoster vaccine observed in non-RA
patients, there are no prospective data critically examining the efficacy or safety of HZ
vaccination in RA patients. The zoster vaccine was not given to immunosuppressed patients in
the large Shingles Prevention Study (SPS); RA patients and others receiving biologics and
immunosuppressive agents including glucocorticoids and DMARDs were excluded. However, this
trial did show safety of the vaccine even for very elderly individuals including those older
than 70 years of age and with little evidence of remaining VZV-specific cell mediated
immunity (CMI). Moreover, live varicella vaccine has been safely given to children with HIV
infection. Recently, the investigators used the administrative databases of a national U.S.
Healthcare organization (Aetna) to conduct an observational study to examining Zostavax use
in patients with RA and other rheumatic diseases (e.g. spondyloarthropathies). Among a total
of 19,326 RA patients older than age 50, only 206 (1%) received zoster vaccine, suggesting
that clinicians may be uncomfortable using the vaccine in RA patients. Additionally,
approximately 60 vaccinated patients were using anti-TNF therapies within one month of
vaccination, and no cases of HZ were reported during this time frame. Some studies suggest an
elevated risk of HZ in RA patients using anti-TNF therapies, although HZ cases reported
within these cohorts of anti-TNF users do not show increased dissemination or complications,
suggesting that anti-TNF therapy might not necessarily increase the likelihood of VZV
dissemination in such patients. Theoretically, however, with downregulation of
interferon-gamma pathways associated with TNF blockade, an increase risk of HZ might be
expected in such patients. Lastly, limited head-to-head data collected to date suggests
abatacept might carry less risk of HZ and other opportunistic infections than does anti-TNF
therapy. Given the widespread use of anti-TNF and other biologic therapies like abatacept,
many RA patients and rheumatologists are unwilling to stop biologic therapy in order to
receive Zostavax. This represents a missed opportunity with regard to HZ prevention. Clearly,
given the high risk of HZ in the RA population, it would be highly beneficial to
prospectively evaluate the safety and efficacy of this vaccine in patients using biologic
therapy.
developed and approved for use among individuals age 50 years or older, regardless of
previous HZ or varicella history. In a pivotal study of 38,456 older adults led by Dr.
Michael Oxman (a co-investigator in the parent VERVE trial and this immunogenicity pilot
sub-study), the vaccine reduced the incidence of HZ and postherpetic neuralgia (PHN) by >
50%.
Guidelines from the American Council on Immunization Practices (ACIP), based largely on
expert opinion (given the absence of data), recommend that patients who use methotrexate or
low to moderate doses of corticosteroids (up to 20mg/day prednisone) can receive this
vaccination safely. However, theoretical concerns regarding the safety of live vaccine use in
patients using biologic therapies have resulted in an ACIP recommendation that the vaccine is
contraindicated in patients receiving such medications. Similarly, given a lack of data, the
American College of Rheumatology (ACR) endorsed this contraindication in the updated ACR 2012
recommendations for biologic and non-biologic disease modifying anti-rheumatic drug (DMARD)
use in RA patients (led by members of the project team for this present application).
Currently it is unknown if RA patients using biologics can safely receive this vaccine.
Despite the demonstrated efficacy and safety of the zoster vaccine observed in non-RA
patients, there are no prospective data critically examining the efficacy or safety of HZ
vaccination in RA patients. The zoster vaccine was not given to immunosuppressed patients in
the large Shingles Prevention Study (SPS); RA patients and others receiving biologics and
immunosuppressive agents including glucocorticoids and DMARDs were excluded. However, this
trial did show safety of the vaccine even for very elderly individuals including those older
than 70 years of age and with little evidence of remaining VZV-specific cell mediated
immunity (CMI). Moreover, live varicella vaccine has been safely given to children with HIV
infection. Recently, the investigators used the administrative databases of a national U.S.
Healthcare organization (Aetna) to conduct an observational study to examining Zostavax use
in patients with RA and other rheumatic diseases (e.g. spondyloarthropathies). Among a total
of 19,326 RA patients older than age 50, only 206 (1%) received zoster vaccine, suggesting
that clinicians may be uncomfortable using the vaccine in RA patients. Additionally,
approximately 60 vaccinated patients were using anti-TNF therapies within one month of
vaccination, and no cases of HZ were reported during this time frame. Some studies suggest an
elevated risk of HZ in RA patients using anti-TNF therapies, although HZ cases reported
within these cohorts of anti-TNF users do not show increased dissemination or complications,
suggesting that anti-TNF therapy might not necessarily increase the likelihood of VZV
dissemination in such patients. Theoretically, however, with downregulation of
interferon-gamma pathways associated with TNF blockade, an increase risk of HZ might be
expected in such patients. Lastly, limited head-to-head data collected to date suggests
abatacept might carry less risk of HZ and other opportunistic infections than does anti-TNF
therapy. Given the widespread use of anti-TNF and other biologic therapies like abatacept,
many RA patients and rheumatologists are unwilling to stop biologic therapy in order to
receive Zostavax. This represents a missed opportunity with regard to HZ prevention. Clearly,
given the high risk of HZ in the RA population, it would be highly beneficial to
prospectively evaluate the safety and efficacy of this vaccine in patients using biologic
therapy.
Inclusion Criteria:
- Currently treated with abatacept therapy at the time of enrollment.
- Eligible women must be post-menopausal (> 1 year since last menstrual period) or have
a surgical history of bilateral oophorectomy or hysterectomy.
- History of prior chicken pox (positive varicella IgG serology can be used to document
prior exposure)
Exclusion Criteria:
- Prior zostavax receipt
- Active contraindications to vaccination including allergy or sensitivity to gelatin or
any other vaccine component
- Acute illness or infection
- HIV/AIDS
- Current systemic corticosteroid use (including any oral or parenteral use in the
previous 28 days)
- Dose of DMARDs not stable for > 30 days
- Concomitant TNF antagonist use
- Receiving radiation or chemotherapy for cancer treatment
- Current leukemia, lymphoma, or other cancer affecting bone marrow or lymphatic system
cellular immunodeficiency
- Current use of anti-viral medications against the herpes virus family
- Received any live virus vaccine within 28 days prior to study entry
- Received any inactivated vaccine within 7 days prior to study entry
- Known household contacts who may be susceptible to a live virus vaccine (e.g. pregnant
women).
We found this trial at
1
site
3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Principal Investigator: Kevin L Winthrop, MD, MPH
Phone: 503-494-6327
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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