JYNNEOS™ effectiveness as post-exposure prophylaxis against mpox: Challenges using real-world outbreak data.

Background: JYNNEOS vaccine has been used as post-exposure prophylaxis (PEP) during a mpox outbreak in New York City (NYC). Data on effectiveness are limited.

Methods: Effectiveness of a single dose of JYNNEOS vaccine administered subcutaneously ≤ 14 days as PEP for preventing mpox disease was assessed among individuals exposed to case-patients from May 22, 2022-August 24, 2022. Individuals were evaluated for mpox through 21 days post-exposure. An observational study was conducted emulating a sequence of nested "target" randomized trials starting each day after exposure. Results were adjusted for exposure risk and race/ethnicity. Analyses were conducted separately based on last (PEP) and first (PEP) exposure date. We evaluated the potential to overestimate PEP effectiveness when using conventional analytic methods due to exposed individuals developing illness before they can obtain PEP (immortal time bias) compared to the target trial.

Results: Median time from last exposure to symptom onset (incubation period) among cases that did not receive PEP was 7 days (range 1-16). Time to PEP receipt was 7 days (range 0-14). Among 549 individuals, adjusted PEP and PEP effectiveness was 19 % (95 % Confidence Interval [CI], -54 % to 57 %) and -7% (95 % CI, -144 % to 53 %) using the target trial emulation, respectively, and 78 % (95 % CI, 50 % to 91 %) and 73 % (95 % CI, 31 % to 91 %) using conventional analysis.

Conclusions: Determining PEP effectiveness using real-world data during an outbreak is challenging. Time to PEP in NYC coupled with the observed incubation period resulted in overestimated PEP effectiveness using a conventional method. The target trial emulation, while yielding wide confidence intervals due to small sample size, avoided immortal time bias. While results from these evaluations cannot be used as reliable estimates of PEP effectiveness, we present important methodologic considerations for future evaluations.