2 Weeks off Methotrexate Boosts Zoster Response Save

Consider holding methotrexate for two weeks after each recombinant zoster vaccine dose when disease is stable, and give the vaccine before rituximab when timing allows. Those are the messages from a pair of abstracts presented by Ana Cristina Medeiros-Ribeiro of the HC-FMUSP group in São Paulo at ACR Convergence 2026. One asks how long the response lasts on immunosuppression. The other asks whether it can be improved.

Abstract 0898 followed the group's phase 4 cohort for 12 months: 1,113 immunosuppressed patients with autoimmune rheumatic disease and 380 non-immunosuppressed controls. Anti-gE IgG fell about 71% in both groups between the early and 12-month measurements, and patients stayed lower throughout (2.1 vs 3.6 at month 12, p<0.001), still 10 times above baseline. Rituximab had the largest negative effect on the 12-month titer (ratio 0.45), followed by prednisone above 7.5 mg/day (0.76). Active surveillance found nine zoster cases, seven in patients and two in controls, 6.4 vs 5.2 per 1,000 patient-years (p=0.79). The seven patients with breakthrough zoster had lower early titers (2.4 vs 7.4) and were more often on prednisone at vaccination (85.7% vs 39.2%). Seven events make that comparison exploratory.

Abstract 0899 tackles the second question through the T cells, the main defense against zoster. In the group's randomized, investigator-blinded trial, a two-week methotrexate hold after each dose had already doubled antibody concentrations (10.6 vs 5.5) without worsening disease activity. In this substudy of 38 patients with low disease activity or remission, gE-specific CD4 T-cell responders six weeks after the second dose reached 95% with the hold (n=20) and 67% with continued methotrexate (n=18, p=0.038). The gain came from IL-2 and TNF-α producing cells. Patients on rituximab in the prior year were excluded.

The hold is the better supported of the two messages. Thirty-eight patients is a small substudy, but it points the same way as the randomized antibody data, and the cost to the patient is two weeks off one drug. Durability is less settled. No correlation of protection exists for zoster, so a falling titer is a signal to follow and not yet a reason to revaccinate. Nine events in one year cannot tell us whether a gap in titers becomes a gap in zoster.

In a patient with stable disease, and when the clinical picture allows, I would consider holding methotrexate for two weeks after each dose. In a patient heading to rituximab, the vaccine goes first when timing allows. The number to follow is zoster incidence beyond year one in patients with low early titers.