Affiliations

Advocate Lutheran General Hospital

Abstract

Background/Significance:

Many new treatment options for ulcerative colitis (UC) have become available in recent years, including dual-mechanism strategies and single-agent approaches. Among available treatments, JAK– STAT inhibitors carry an increased risk of herpes zoster (HZ) with an associated FDA Black Box warning.

Purpose:

This study aims to compare FDA-approved UC therapies and their relative association with HZ using reported data from the FDA Adverse Event Reporting System database (FAERS).

Methods:

The FAERS database consists of voluntarily reported post-marketing adverse drug reactions (ADRs). 32,229,802 total reports from Jan 1968 to September 2025 were evaluated. Reports of ADRs of all FDA approved UC therapies including mesalamine, sulfasalazine, balsalazide, olsalazine, methotrexate, azathioprine, 6-mercaptopurine, infliximab, adalimumab, certolizumab, folimumab, vedolizumab, ustekunumab, mirikizumab, risankizumab, guselkumab, ozanimod, etrasimod, tofacitinib, and upadacitnib along with combination infliximab with methotrexate, infliximab with azathioprine, adalimumab with azathioprine, and golimumab with azathioprine were reviewed. Cases of reported HZ in the treatment of UC were collected and only medications with documented reports were included in this study. Using the OpenVigil program, signals for these ADRs were determined using reporter odds ratios (RORs) calculated with the following formula: ROR = (a/c)/(b/d) (a: drug with ADR, b: all drugs with ADR, c: all ADRs for the drug, d: other drugs with other ADRs.) A ROR >1 indicates that an ADR frequency is not occurring by chance alone, suggesting a significant post-marketing signal.

Results:

The JAK-STAT inhibitor tofacitinib showed increased risk of HZ with 58 total reports (ROR 2.79). In addition, methotrexate (ROR 1.83), azathioprine (ROR 1.74), 6-mercaptopurine (ROR 2.4), infliximab (ROR 2.49), and combination therapies of infliximab with methotrexate (ROR 2.61) and infliximab with azathioprine (ROR 2.91) demonstrated increased risk. Alternatively, there is a statistically significant decreased risk of HZ with treatment of adalimumab (ROR 0.61) and vedolizumab (ROR 0.54).

Conclusion:

Tofacitinib was shown to have an increased risk of HZ in our study. No other medications used in the treatment of UC also demonstrated an increased risk. Of interest, adalimumab and vedolizumab demonstrated a protective association with HZ.

Presentation Notes

Presented at Scientific Day; May 20, 2026; Milwaukee, WI.

Full Text of Presentation

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Document Type

Poster


 

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May 20th, 12:00 AM

Herpes Zoster Infection as an Adverse Reaction to Treatments for Ulcerative Colitis: A Review of Reports to the FDA Adverse Events Reporting System (FAERS)

Background/Significance:

Many new treatment options for ulcerative colitis (UC) have become available in recent years, including dual-mechanism strategies and single-agent approaches. Among available treatments, JAK– STAT inhibitors carry an increased risk of herpes zoster (HZ) with an associated FDA Black Box warning.

Purpose:

This study aims to compare FDA-approved UC therapies and their relative association with HZ using reported data from the FDA Adverse Event Reporting System database (FAERS).

Methods:

The FAERS database consists of voluntarily reported post-marketing adverse drug reactions (ADRs). 32,229,802 total reports from Jan 1968 to September 2025 were evaluated. Reports of ADRs of all FDA approved UC therapies including mesalamine, sulfasalazine, balsalazide, olsalazine, methotrexate, azathioprine, 6-mercaptopurine, infliximab, adalimumab, certolizumab, folimumab, vedolizumab, ustekunumab, mirikizumab, risankizumab, guselkumab, ozanimod, etrasimod, tofacitinib, and upadacitnib along with combination infliximab with methotrexate, infliximab with azathioprine, adalimumab with azathioprine, and golimumab with azathioprine were reviewed. Cases of reported HZ in the treatment of UC were collected and only medications with documented reports were included in this study. Using the OpenVigil program, signals for these ADRs were determined using reporter odds ratios (RORs) calculated with the following formula: ROR = (a/c)/(b/d) (a: drug with ADR, b: all drugs with ADR, c: all ADRs for the drug, d: other drugs with other ADRs.) A ROR >1 indicates that an ADR frequency is not occurring by chance alone, suggesting a significant post-marketing signal.

Results:

The JAK-STAT inhibitor tofacitinib showed increased risk of HZ with 58 total reports (ROR 2.79). In addition, methotrexate (ROR 1.83), azathioprine (ROR 1.74), 6-mercaptopurine (ROR 2.4), infliximab (ROR 2.49), and combination therapies of infliximab with methotrexate (ROR 2.61) and infliximab with azathioprine (ROR 2.91) demonstrated increased risk. Alternatively, there is a statistically significant decreased risk of HZ with treatment of adalimumab (ROR 0.61) and vedolizumab (ROR 0.54).

Conclusion:

Tofacitinib was shown to have an increased risk of HZ in our study. No other medications used in the treatment of UC also demonstrated an increased risk. Of interest, adalimumab and vedolizumab demonstrated a protective association with HZ.

 

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