Background/Purpose: Compared to the general population, RA patients (pts) have an increased risk of herpes zoster (HZ) due to their disease and various DMARD therapies including JAK inhibitors.¹ The aim of this analysis was to evaluate HZ in RA pts treated with baricitinib (bari), an oral JAK1/JAK2 inhibitor in development for treatment of RA.^2,3

Methods: Data were pooled from completed Phase (Ph) 1, 2, and 3 studies, and an ongoing long-term extension (LTE) study of bari in RA pts (data cutoff January 1, 2016). HZ events were identified using MedDRA preferred terms related to HZ. The incidence of HZ was evaluated for all RA pts who ever received bari (any dose, including LTE data), pts in the 6 randomized, placebo [PBO]-controlled studies (0-24 weeks, DMARD-inadequate responders), and pts in individual active-controlled studies with MTX (DMARD-naive: RA BEGIN) and adalimumab (ADA; MTX-inadequate responder: RA BEAM). Incidence rate (IR) was calculated as the number of pts with an HZ event per 100 patient-years of observation (PYO) with exposure censored at event date. The Mantel-Haenszel method was used for between treatment group comparisons, controlling for the study effect.

Results: In the All Bari group (1 Ph 1, 3 Ph 2, 4 Ph 3, and 1 ongoing LTE; 3492 pts, 5141 PYO), treatment-emergent HZ was reported in 170 pts (IR=3.3) (Figure 1). In the PBO-controlled studies HZ rates for bari 4 mg were significantly increased compared to PBO (IR difference [95%CI]: 3.2 [1.0, 5.4]) but were comparable to ADA in RA-BEAM. The majority of HZ events (95%) were reported as mild or moderate in severity; few were disseminated or complicated (7 distributed beyond primary or adjacent cutaneous dermatomes, 2 associated with facial nerve palsy, no visceral events). Rates appeared higher in Japan and in patients with advancing age, but not with longer RA duration, or corticosteroid use (Tables 1 and 2), and decreased with prolonged exposure.

Conclusion: In these integrated analyses, treatment with bari was associated with an increased risk of HZ compared to PBO, with an overall IR of 3.3/100 PYO in patients with RA. Rates appeared to diminish with prolonged exposure. References: ¹Smitten AL et al. Arthritis Rheum 2007;57:1431-1438. ²Dougados M et al. Ann Rheum Dis 2015;74(S2):79.  ³Taylor PC et al. Arthritis Rheumatol 2015;67(S10):3927-3928.