Patients with rheumatoid arthritis (RA) who are treated with Janus ki- nase inhibitors (JAKi) have the high- est risk of developing herpes zosteramong disease-modifying antirheumaticdrugs (DMARDs), according to new datafrom the German biologics registry RABBITto be presented on 5 June.
The crude incidence rateof herpes zoster per 1,000patient-years was 24.9with JAKi compared withjust 5. 8 for controls takingconventional synthetic(cs) DMARDs. The risk ofherpes zoster was also increased with other biologic(b) and targeted synthetic(ts) DMARDs that were assessed, with crude rates per1,000 patient-years of 10. 4for monoclonal antibodytumour necrosis factor inhibitors (TNFis),10. 5 for B-cell–targeted therapies, 9. 4 forT-cell co-stimulation modulators, 9.0 forsoluble TNF receptors, and 8. 5 for interleu-kin (IL)- 6 inhibitors.
After adjustment for age, sex, and theuse of glucocorticoids, JAKi treatmentwas associated with more than a threefoldhigher risk of infection, compared withthe control population (hazard ratio [HR] =3.55; P < .0001). Adjusted HR for the otherRA treatments were also increased butwere only significant for monoclonal TNFi(HR = 1.55; P = .0009) and B-cell–targetedtherapies (HR = 1.45; P = .0155).
“The general risk of herpes zoster is
higher in patients with rheumatoid arthritis
when you compare it with the general
population, and if you think of all the
treatments that RA patients get, then the
risk is further increased with bDMARD
Strangfeld of the German Rheumatism Re-
search Center, Berlin, said in an interview.
Dr. Strangfeld and fellow RABBIT investigators have previously looked at therisk of herpes zoster in patients treatedwith anti-TNF-alpha agents (JAMA.
2009;301[ 7]:737-44. doi:
They found that monoclonal
anti-TNF-alpha agents may
be associated with in-
creased risk of herpes zos-
ter, which is now confirmed
by the current analysis. The
reason for looking at herpes
zoster risk again is that
since that first analysis,
many more therapies have
become available for RA
during the past 10 years,
notably the tsDMARDs. In-
deed, these are the first European data on
the risk of herpes zoster with JAKi.
Dr. Strangfeld will present the findingsof the new analysis during the “Rheumatoid arthritis – Non biologic treatment andsmall molecules” abstract session. Theanalysis included 12,470 patients with RAenrolled in RABBIT from 2007 onwards andwho had been treated with monoclonalantibody TNFi, cell-targeted therapies, andtsDMARDs such as JAKi. In all, at the datacut off at the end of April 2019, 452 casesof herpes zoster were recorded in 433 patients, of which 52 cases were serious.
“What we found was quite in agree-
ment with the data that we know from
the U.S., from the observational studies,
for example from the Corrona database,”
Dr. Strangfeld stated. “There is a higher
risk associated with treatment with JAK
inhibitors, but we also saw that monoclo-
nal TNF antibodies as well as all the other
biologic DMARD treatments have a higher
risk of herpes zoster in RA patients com-
pared to csDMARD therapy.”
The key finding is that the risk of herpes
zoster is increased to some level, almost
regardless of which drug is chosen, Dr.
Strangfeld said. “This gives a clear message that systematic herpes zoster vaccination should be done in patients withRA,” she suggested.
Herpes zoster may not always be aserious event, Dr. Strangfeld said, “butit diminishes your quality of life; it canalso be associated with pain, and may befollowed by postherpetic neuralgia, whichis very painful.” With new herpes zostervaccinations available, it is now possibleto vaccinate patients more easily. “This isadvisable for all kinds of treatments,” shesaid.
RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, Bristol-Myers Squibb, Fresenius Kabi, Hexal,Lilly, Merck Sharp & Dohme, Mylan, Pfizer,Roche, Samsung Bioepis, Sanofi-Aventis,and UCB. Dr. Strangfeld disclosed actingas a speaker for AbbVie, Bristol-MyersSquibb, Pfizer, Roche, and Sanofi-Aventis.
Shingles risk appears highest with JAK-
inhibitor treatment for rheumatoid arthritis
“This gives a clear
should be done in
patients with RA.”