Herpes Zoster in rheumatoid arthritis patients receiving tofacitinib, a single center experience from Taiwan

Abstract

In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR + activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.

Herpes zoster in patients with inflammatory arthritides or ulcerative colitis treated with tofacitinib, baricitinib or upadacitinib: a systematic review of clinical trials and real-world studies

“…In RA, the overall HZ-rates in RCTs ranged between 0 and 12.4% for TOFA [ 36 , 39 , 40 , 42 – 44 , 53 – 56 ], 0–7% for BARI [ 33 – 35 , 37 , 61 – 66 ] and 0.5–7.4% for UPA [ 29 , 30 , 32 , 71 – 79 , 104 ]. Similar rates were reported in RWS: TOFA: 1.3–16.7% [ 41 , 46 – 50 , 52 , 57 ] and BARI: 1.3–6.2% [ 58 , 59 , 67 – 69 ]] (Table 3 ).…”

“…More details were provided by RWS. In 3 cohorts, most events occurred within the first 16 weeks of JAKi initiation [ 57 , 67 , 98 ], while in another 4 cohorts, the median/mean time to VZV reactivation since JAKi commencement ranged between 7 and 44 weeks [ 49 , 69 , 94 , 103 ].…”

“…Of note, most clinical trials excluded patients with a history of > 1 HZ episode or a single episode of disseminated HZ. Thus, the association of HZ history with a new HZ episode after exposure to JAKi was examined only in 1 RA cohort at which was found to be significant [ 57 ]. In accordance, an integrated analysis of the SELECT program for UPA in RA showed that the history of HZ was a significant risk factor for incident HZ (HR: 24.19; 95% CI, 15.94–36.72) [ 118 ].…”

“…Of note, the IR was higher in a Japanese open-label LTEs (7.1/100 PY) compared to a global one (2.3/100 PY) [ 40 , 45 ]. In RWS (mean observation period: 24–81.6 weeks), the incidence ranged between 1.3 and 16.7% and the IR between 1.4 and 6.5/100 PY [ 41 , 46 – 52 , 57 – 59 ]. Finally, in a post-marketing surveillance study for TOFA in RA, 7 HZ events out of 9291 adverse events were reported [ 60 ].…”

“…Among the included studies, only 2 clinical trials and 4 RWS provided information about patients’ previous HZ history. In 5 of them, less than 15% of patients who developed HZ during JAKi treatment had history of an HZ event [ 30 , 34 , 47 , 57 , 67 , 94 , 103 ]. In contrast, in a cohort with 125 RA patients, 100% (7/7) of patients who developed HZ during TOFA treatment had HZ history compared to 14.4% (17/118) of those who did not develop HZ during TOFA therapy (p < 0.001)[ 57 ].…”