Withholding JAK, IL-17 inhibitors fails to improve COVID-19 vaccine booster response
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WASHINGTON — Withholding Janus kinase or interleukin-17 inhibitors from patients with rheumatoid arthritis or spondyloarthritis does not significantly benefit COVID-19 booster response, according to data presented at ACR Convergence 2024.
“This trial, COVER, is a pragmatic platform trial conducted under a master protocol that randomized patients with rheumatoid arthritis or spondyloarthritis to hold or continue their TNF inhibitor, IL-17 inhibitor, abatacept, or JAK inhibitor for 2 weeks at the time that they received a COVID booster,” Jeffrey Curtis, MD MS MPH, of the University of Alabama at Birmingham division of clinical immunology and rheumatology, told Healio.
“There is prior evidence, particularly for methotrexate, that this type of temporary interruption of an immunomodulator may boost vaccine response to COVID or other vaccines, such as influenza,” he added. “This trial intended to fill in that evidence gap as to whether holding these other medications might similarly help boost vaccine response.”
To examine the impact of withholding JAK inhibitors, IL-17 inhibitors, abatacept (Orencia, Bristol Myers Squibb), or TNF inhibitors for 2 weeks on COVID-19 booster response, Curtis and colleagues enrolled patients with either RA or SpA from the Excellence Network in Rheumatology (ENRGY), a research network of U.S.-based rheumatology practices. Patients who had previously received at least two primary doses of an mRNA COVID-19 vaccine were randomized 1:1 to either withhold or continue JAK inhibitor or biologic therapy for 2 weeks following a COVID-19 booster dose.
The researchers measured anti-receptor binding domain (RBD) IgG antibodies before and 6 weeks after the 2-week hold. They then compared mean log-transformed differences from before and after the booster dose, noting the geometric mean fold rise (GMFR) for each intervention group and therapy. Additionally, the researchers used linear regression to assess changes in COVID-19 RBD antibody levels, adjusting for age, sex, BMI, methotrexate and steroid use, and time from booster. The occurrence of patient-reported flares was also examined.
In all, Curtis reported data for 232 patients treated with a JAK inhibitor and 121 treated with IL-17 inhibition.
In the JAK inhibitor group, report of a flare following a booster occurred in 34% of patients who withheld therapy for 2 weeks, and in 9% of those who continued therapy (P < .0001), according to the researchers. For the IL-17 group, flare following booster occurred in 30% of patients in the hold group and in 16% of those in the continuation group (P = .20).
Further results showed that after a vaccine booster dose, RBD antibody titers increased significantly in patients treated with JAK inhibitors (P < .0001) and IL-17 inhibitors (P < .0001). In addition, all treatment groups showed a GMFR greater than 3, according to the findings.
In addition, the mean increase in anti-RBD titers was not significantly different by drug group in the hold vs. continuation arms. This trend persisted before and after the adjusted analysis.
The researchers observed a decreased effect change in RBD antibodies for JAK inhibition ( = –0.42; P = .018) and abatacept ( = –0.73; P < .001), referent to IL-17 inhibition and steroid use ( = -0.31; P = .041). BMI ( = 0.015; P = .039) was associated with a higher change in antibody levels, according to the researchers.
“The key takeaways were that although some medications such as abatacept and JAK inhibition blunted vaccine response compared to TNF inhibition or IL-17 inhibition, holding any of them for 2 weeks did not provide sufficient benefit on vaccine immunogenicity to warrant this temporary interruption,” Curtis said. “Importantly, the rate of disease flare was appreciably greater in patients randomized to the 2-week interruption, particularly for JAK inhibitors, which have short half-lives and would be expected to wear off most quickly.
“This should be very practical information for rheumatology providers to not recommend any treatment gaps, even for short half-life immunomodulatory therapies at the time patients receive a new COVID vaccine dose,” he added.
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Curtis J. Abstract #1718. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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