What is the risk of developing shingles in patients taking Dupilumab (dupilumab), particularly those over 50 years old or with a history of varicella-zoster virus infection?

Risk of Shingles with Dupilumab

Dupilumab does not increase the risk of herpes zoster (shingles) and actually demonstrates lower rates compared to JAK inhibitors used for atopic dermatitis. This stands in stark contrast to JAK inhibitors like tofacitinib, upadacitinib, and abrocitinib, which carry established increased risk of herpes zoster infection.

Comparative Risk Profile

Dupilumab Safety Data

• In head-to-head studies, patients with atopic dermatitis treated with dupilumab showed lower rates of herpes zoster infection compared to those on JAK inhibitors (abrocitinib and upadacitinib). 1

• The prevalence of herpes zoster infections in atopic dermatitis patients on oral JAK inhibitors was <3%, while dupilumab served as the comparator with lower rates. 1

• Comprehensive safety data from over 7,000 patient-years of dupilumab use across eight phase 3 trials showed that serious infections were actually more frequent with placebo than with dupilumab. 2

• One small case series (n=10) reported varicella-zoster virus meningitis in 1 patient and herpes simplex virus uveitis in another, but these were isolated cases in a very small cohort with severe, long-lasting atopic dermatitis. 3

JAK Inhibitor Comparison (Context for Understanding Risk)

• Herpes zoster is an established complication of JAK inhibitors, with rates appearing dose-dependent for some agents. 1

• JAK1/2 inhibition impairs cellular cytotoxicity by blocking interferon-γ signaling, which compromises the body's ability to fight viral pathogens like varicella-zoster virus. 1

• Zoster vaccination (Shingrix) should be considered before starting JAK inhibitor therapy, particularly for patients aged >50 years or those at high risk. 1

Clinical Implications for Patients Over 50

Vaccination Recommendations

• All adults aged ≥50 years should receive the recombinant zoster vaccine (Shingrix) regardless of medication status, as this is standard preventive care. 4, 5

• The recombinant zoster vaccine demonstrates >90% efficacy against herpes zoster and ≥89% efficacy against post-herpetic neuralgia, with protection sustained over at least 4 years. 6

• Shingrix is administered as a two-dose series with the second dose given 2-6 months after the first dose. 5

• Unlike JAK inhibitors, there is no specific urgency to vaccinate before starting dupilumab, as dupilumab does not increase herpes zoster risk. 1

Special Considerations for History of VZV Infection

• Prior varicella-zoster virus infection (chickenpox) does not contraindicate dupilumab use. 4

• Patients with prior shingles episodes should still receive Shingrix vaccination, as having shingles once does not provide reliable protection against future episodes (10-year cumulative recurrence risk of 10.3%). 5

• Vaccination should be administered at least 2 months after an acute shingles episode has resolved. 5

Mechanism of Differential Risk

The key distinction lies in the mechanism of action:

• Dupilumab blocks IL-4 and IL-13 signaling (type 2 inflammation pathway), which does not significantly impair cellular immunity against viral pathogens. 1

• JAK inhibitors block interferon-γ signaling and cellular cytotoxicity pathways, directly compromising antiviral defense mechanisms. 1

• This mechanistic difference explains why herpes zoster risk is elevated with JAK inhibitors but not with dupilumab. 1

Common Pitfalls to Avoid

• Do not confuse dupilumab's safety profile with that of JAK inhibitors—they have fundamentally different mechanisms and risk profiles for herpes zoster. 1

• Do not delay standard age-appropriate Shingrix vaccination in patients on dupilumab, but understand this is routine preventive care, not a medication-specific requirement. 5

• Do not use the live-attenuated zoster vaccine (Zostavax) in any immunocompromised patient—only Shingrix (recombinant vaccine) is appropriate, though dupilumab patients are not considered significantly immunocompromised for this purpose. 4, 5

• Be aware that the small case series reporting VZV complications 3 involved patients with severe, long-lasting atopic dermatitis and previous eye disease, representing a high-risk subset that may not be generalizable.