Shingles Vaccines for Rheumatoid Arthritis

(BMS-188667 Trial)

Recruiting at 4 trial locations

Overseen By Ryan Stadnik, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kevin Winthrop

Must be taking: Abatacept

Must not be taking: Corticosteroids, Methotrexate, TNF antagonists, Antivirals

Disqualifiers: HIV/AIDS, Cancer, Immunodeficiency, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

154 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain medications like systemic corticosteroids, methotrexate over 25 mg/week, TNF antagonists, or anti-viral medications against the herpesvirus family. If you are on these, you may need to stop or adjust them before joining the trial.

What data supports the effectiveness of the shingles vaccines for rheumatoid arthritis?

The research does not provide direct evidence for the effectiveness of shingles vaccines in rheumatoid arthritis, but it highlights the success of biologic therapies in improving treatment options for rheumatoid arthritis, suggesting that targeted therapies can be effective in managing immune-related conditions. ^{1 2 3 4 5}

Is the shingles vaccine safe for people with rheumatoid arthritis?

The shingles vaccine, Shingrix, is generally safe for people with rheumatoid arthritis, although it may cause mild side effects like pain at the injection site, fatigue, and fever. Serious side effects are rare, and the vaccine is preferred over the live vaccine, Zostavax, especially for those who are immunocompromised. ^{6 7 8 9 10}

How is the Shingrix vaccine treatment different for rheumatoid arthritis patients?

Shingrix is a unique shingles vaccine because it is a recombinant (genetically engineered) vaccine that is safe for use in immunocompromised individuals, such as those with rheumatoid arthritis. Unlike live vaccines, it uses a non-live component, making it suitable for people with weakened immune systems. ^{7 9 11 12 13}

What is the purpose of this trial?

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 or Shingrix are 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.

Eligibility Criteria

This trial is for rheumatoid arthritis patients aged 18+ for Shingrix and 50+ for Zostavax, using abatacept. Women must be post-menopausal or have had certain surgeries, or if of childbearing potential, use contraception and test negative for pregnancy. Exclusions include allergy to vaccine components, acute illness, HIV/AIDS, recent corticosteroids or anti-herpesvirus meds, cancer treatments affecting bone marrow/lymphatic system, recent live/inactivated vaccines.

Inclusion Criteria

I am currently being treated with abatacept.

I am currently being treated with abatacept.

I am 50 years old or older.

Exclusion Criteria

I am currently undergoing radiation or chemotherapy for cancer.

My dose of DMARDs has not been stable for more than 30 days.

I am currently using TNF blockers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive either the live zoster vaccine (Zostavax) or the non-live zoster vaccine (Shingrix) or a placebo

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after vaccination, with assessments at 6 weeks and 1 year post-vaccination

1 year

2 visits (in-person)

Treatment Details

Interventions

• Placebo Injection
• Shingrix
• Zostavax

Trial Overview The study tests the safety and effectiveness of two shingles vaccines—Zostavax and Shingrix—in rheumatoid arthritis patients on abatacept therapy. It's a double-blinded trial where participants are randomly assigned to receive either the vaccine or a placebo injection without knowing which one they get.

Participant Groups

Group I: Varicella Zoster Vaccine (Zostavax) Experimental Treatment 1 Intervention

Live zoster vaccine injection will be administered as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm at the baseline visit

Group II: Varicella Zoster Vaccine (Shingrix) Experimental Treatment 1 Intervention

Non-live zoster vaccine injection will be administered twice, 8 weeks apart, as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm at the baseline visit

Group III: Placebo Injection (Shingrix Comparator) Placebo Group 1 Intervention

Saline injection will be administered twice, 8 weeks apart, as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm at the baseline visit

Group IV: Placebo Injection (Zostavax Comparator) Placebo Group 1 Intervention

Saline injection will be administered as a single 0.65-mL dose subcutaneously in the deltoid region of the upper arm at the baseline visit

Shingrix is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Shingrix for:

• Prevention of shingles in healthy adults over age 50 and in immunocompromised adults over age 18

Approved in European Union as Shingrix for:

• Prevention of herpes zoster (shingles) and postherpetic neuralgia (PHN) in adults 50 years of age and older

Approved in Canada as Shingrix for:

• Prevention of herpes zoster (shingles) in adults 50 years of age and older

Who Is Running the Clinical Trial?

Kevin Winthrop

Lead Sponsor

Trials

4

Recruited

760+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Findings from Research

Combination therapy using two or more biologic agents may provide better treatment outcomes for rheumatoid arthritis (RA) compared to single-agent therapies, as suggested by animal model data showing synergistic effects.

While there are potential risks associated with combination biologic therapies, such as increased toxicity and infection risk, careful clinical trials in patients with earlier stages of RA could lead to effective treatments with a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future use of biologic therapies in combination for the treatment of rheumatoid arthritis. Strand, V.[2005]

Abatacept and rituximab have been shown to significantly improve treatment outcomes for rheumatoid arthritis patients who do not respond well to traditional tumor necrosis factor inhibitors, with one-year clinical trial data indicating better efficacy and reduced joint damage compared to placebo.

While both therapies have a safety profile that includes infusion reactions and infections, premedication with corticosteroids can help reduce the risk of infusion reactions associated with rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the place of recently approved T cell-targeted and B cell-targeted therapies in the treatment of rheumatoid arthritis? Lessons from global clinical trials. Smolen, JS.[2015]

SHINGRIX, a non-live herpes zoster vaccine, is safe for patients on immunosuppressive therapy, making it a suitable option for those with inflammatory bowel disease who are at higher risk for infections.

A case report of a 74-year-old woman with ulcerative proctosigmoiditis revealed blistering autoimmune skin disorders following SHINGRIX vaccination, suggesting a potential, though previously unreported, adverse effect of the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blistering autoimmune skin reaction following SHINGRIX vaccination in an ulcerative colitis patient: Case report and literature review. Bell, H., Kamal, N., Wong, U.[2021]

The recombinant zoster vaccine (RZV; Shingrix) is effective and recommended for adults aged 50 and older, showing a safety profile consistent with prelicensure trials, where serious adverse events were similar to placebo rates.

In the first 8 months post-licensure, out of 3.2 million doses distributed, 4,381 adverse event reports were received, with common reactions being fever and injection site pain, but no unexpected safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix) - United States, October 2017-June 2018. Hesse, EM., Shimabukuro, TT., Su, JR., et al.[2020]

Shingrix® is a highly effective recombinant zoster vaccine that significantly reduces the risk of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged 50 and older, with efficacy remaining strong even after 4 years.

While Shingrix® is associated with more side effects than a placebo, such as injection-site reactions and fatigue, these reactions are generally mild to moderate and transient, making it a well-tolerated option for preventing HZ and PHN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Zoster Vaccine (Shingrix®): A Review in Herpes Zoster. Syed, YY.[2022]

The pilot study involving 10 patients with systemic lupus erythematosus (SLE) showed that the herpes zoster vaccine (Zostavax) was safe, with no cases of herpes zoster, serious adverse events, or SLE flares reported after vaccination.

While the vaccine elicited a measurable immune response in patients with mild SLE, the antibody titers increased significantly only in the control group, suggesting that while the vaccine is safe for SLE patients, its immunogenicity may be lower compared to healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herpes zoster vaccination in SLE: a pilot study of immunogenicity. Guthridge, JM., Cogman, A., Merrill, JT., et al.[2021]

The herpes zoster subunit vaccine (HZ/su) is highly effective, reducing the risk of developing shingles by over 90% compared to a placebo, making it a strong preventive measure for adults aged 50 and older.

The vaccine has a comparable safety profile to other vaccines, with common side effects including injection site pain and mild systemic reactions like fatigue and headache, supporting its routine use as recommended by the Advisory Committee on Immunization Practices (ACIP).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine. James, SF., Chahine, EB., Sucher, AJ., et al.[2019]

This study aims to evaluate the immune response to the Shingrix vaccine in 308 patients, including those with liver cirrhosis and liver transplant recipients, to understand how immunosuppression affects vaccine efficacy.

By measuring specific antibody and T cell responses at multiple time points, the research seeks to establish a routine test for monitoring vaccination success and its correlation with clinical protection against shingles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiza-Titre increase and enhanced immunity through an adjuvanted, recombinant herpes zoster subunit vaccine in patients with liver cirrhosis and post-liver transplantation: a study protocol for a prospective cohort study. Vollmer-Raschdorf, S., Rashidi-Alavijeh, J., Voigt, S., et al.[2023]

The Zoster Vaccine Recombinant, Adjuvanted (Shingrix) is effective in preventing herpes zoster in adults aged 50 and older, and its use has been expanded to include adults aged 18 and older who are immunocompromised, making it the first vaccine approved for this group.

With moderate to high efficacy and a good safety profile, Shingrix has the potential to significantly reduce the incidence of herpes zoster and its complications, as recommended by health authorities like the FDA and ACIP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. Anderson, TC., Masters, NB., Guo, A., et al.[2022]

References

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The future use of biologic therapies in combination for the treatment of rheumatoid arthritis. [2005]

5. Canada pubmed.ncbi.nlm.nih.gov

What is the place of recently approved T cell-targeted and B cell-targeted therapies in the treatment of rheumatoid arthritis? Lessons from global clinical trials. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Blistering autoimmune skin reaction following SHINGRIX vaccination in an ulcerative colitis patient: Case report and literature review. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of the Zoster Vaccine Recombinant Adjuvanted in Rheumatoid Arthritis and Other Systemic Rheumatic Disease Patients: A Single Center's Experience With 400 Patients. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix) - United States, October 2017-June 2018. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Recombinant Zoster Vaccine (Shingrix®): A Review in Herpes Zoster. [2022]

10. Canada pubmed.ncbi.nlm.nih.gov

Herpes zoster vaccination in SLE: a pilot study of immunogenicity. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Tiza-Titre increase and enhanced immunity through an adjuvanted, recombinant herpes zoster subunit vaccine in patients with liver cirrhosis and post-liver transplantation: a study protocol for a prospective cohort study. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. [2022]