Immunosuppressive Drugs: Affect on Hepatitis A Vaccine Immunogenicity

Gloved hand holding glass vial and syringe
Gloved hand holding glass vial and syringe
Researchers suggest that novel biologicals should be explored as a treatment alternative to hepatitis vaccination for patients who are being treated with immunosuppressive drugs.

Studies that evaluate hepatitis A vaccine immunogenicity in treatment with immunosuppressive agents show that an impaired immune response follows hepatitis A vaccination in patients taking immunosuppressive drugs, especially after a single vaccine dose, and in organ transplant recipients. Taking this into consideration, vaccinations should take place before immunosuppressive therapy, according to a study published in Travel Medicine and Infectious Diseases.

In healthy individuals, hepatitis A vaccines are very immunogenic. This systematic review and meta-analysis assessed the immunogenicity of hepatitis A vaccination in adults on immunosuppressive drugs while adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registering the review protocol with the PROSPERO systematic protocol registry (ID: CRD42018102607). Included for analysis were randomized controlled trials and studies that reported seroconversion and seroprotection data, or quantitative antibody levels after hepatitis A vaccination for adults taking immunosuppressive drugs.

The analysis included 17 studies with a total of 1332 participants. In healthy individuals, seroconversion rates ranged from 90% to 94% after the initial vaccine dose and 100% after the second. In contrast, seroconversion rates varied widely in patients taking drugs to prevent organ rejection, ranging from 0% to 67% 4 to 8 weeks after receiving the initial vaccine dose, and from 0% to 97% 4 to 8 weeks after receiving the second. In patients using either conventional immunomodulators, TNF-α inhibitors, or both, seroconversion rates ranged from 6% to 100% after the initial vaccine, and 48% to 100% after the second dose. In a meta-analysis, patients using a TNF-α inhibitor were more likely to seroconvert after the initial hepatitis A vaccine dose compared with patients using a conventional immunomodulator (odds ratio, 12.1; 95% CI, 2.14-68.2), although this analysis included only 82 participants from 2 studies, and no significant differences in seroconversion rate were seen after the second vaccine dose.

Despite the high degree of heterogeneity in the available studies, both methodologically and clinically, investigators concluded, “Overall, we report a reduced serologic response following HepA vaccination in these patients, especially after the first dose of vaccine, resulting in uncertain protection against HepA. Therefore, HepA vaccination should be considered prior to start of immunosuppressive therapy in patients with future travel plans. If this is not feasible, it is necessary to perform antibody assessment after vaccination. There is an urgent need for well-designed clinical trials investigating the response to alternative hepatitis vaccination regimens and long-term immunogenicity in patients using immunosuppressive drugs, including novel biologicals.”

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Garcia Garrido HM, Veurink AM, Leeflang M, Spijker R, Goorhuis A, Grobusch MP. Hepatitis A vaccine immunogenicity in patients using immunosuppressive drugs: A systematic review and meta-analysis [published online September 12, 2019]. Travel Med Infect Dis. doi: 10.1016/j.tmaid.2019.101479