Data from one of the first studies to look at immune responses in patients with RA was presented at EULAR 2023.
The adjuvanted recombinant varicella zoster vaccine Shingrix was recommended by PBAC in March this year for inclusion on the National Immunisation Program for adults with immunocompromise.
However, there’s actually little data on immunogenicity in people with autoimmune conditions.
At EULAR 2023, Professor Kevin Winthrop of Oregon Health and Science University presented the results of what he said was one of the first studies to look at immune responses in patients with RA using the vaccine (OP0225).
“The varicella zoster virus causes shingles later in life, and we all know that there is a great unmet need in rheumatoid arthritis and other autoimmune conditions where the risk is elevated by the disease itself,” Professor Winthrop told delegates.
“And then it’s further elevated, of course, by some of the DMARDs that you all use, most notably JAK inhibitors and anifrolumab.”
The trial was a sub-study of the long-term extension SELECT-COMPARE trial, and included 95 patients who were taking 15mg upadacitinib as well as background methotrexate, with about half also taking corticosteroids. They were mostly female and mostly white with a mean age of 62 years. Median disease duration was around 12 years, with an average of four years on upadacitinib.
The patients were given two Shingrix doses, 12 weeks apart. Antibody titres were collected four weeks after the first dose (week four) and four weeks after the second (week 16).
The primary endpoint was the humoral response at week 16, with a “satisfactory response” defined as a ≥4-fold increase in anti gE humoral titre, based on the ZOE Shingrix trials conducted in the general population. Secondary endpoints were humoral response at week four, and cell-mediated response at weeks four and 16.
Satisfactory humoral responses to the vaccine occurred in 64% (95% CI: 55–74) of patients at week four, increasing to 88% (95% CI: 81–95) at week 16.
“So the responses were actually quite decent,” said Professor Winthrop.
“To give you some context, if you look at the phase 3 trials that were done in immunocompetent individuals, this is a little bit diminished. It was about 98% or so in that general population. So this is pretty good response, but it’s maybe slightly lower than what we’d expect in a general population.”
The researchers also looked at age and concomitant corticosteroid use.
“It was nice to see really no difference whether you’re older or younger, or whether you’re on steroids or not on steroids. We got about the same percentage of people with a satisfactory response, it was all around 85 to 90%.”
The cell-mediated responses were also a little lower than what would be seen in the general population, but “still pretty high”, with two-thirds achieving a satisfactory response – around one-third lower than the general population.
In terms of safety, there were very few adverse events and no serious adverse events, and side effects were mainly “reactogenicity” – headache, myalgia and fatigue after the vaccine – and two instances of RA flare.
“In conclusion, this is really the largest and most robust data we have in terms of how this vaccine works in patients with RA, and in particular patients on JAK inhibitors or methotrexate. We had reasonable responses, about two-thirds had a cell-mediated response and about 88% achieved a satisfactory humoral response.”
Professor Winthrop suggested further research was needed to look at differences in patients taking or not taking methotrexate, and also the effect of temporarily holding methotrexate or the JAK inhibitor.
“And then lastly, we don’t know what this means with regards to efficacy. These responses might be perfectly adequate for efficacy, we just don’t know. They might be diminished, and we might be able to do better. So, this is just the start, and it’s exciting data.”
OP0225 Evaluation of response to adjuvanted recombinant zoster vaccine vaccination in patients with rheumatoid arthritis receiving upadacitinib: results from a randomized trial sub-study. (DOI: 10.1136/annrheumdis-2023-eular.2386)
