Sex: U
Vaccine: VARZOS
Symptoms: Herpes zoster cutaneous disseminated
Clinical narrative: This literature marketed report has been received from an author in a published article. Background/Purpose: Tofacitinib was an oral Janus Kinase inhibitor for the treatment of rheumatoid arthritis (RA). Clinical guidelines recommended using live zoster vaccine (LZV) to prevent shingles in RA, but this vaccine had not been previously studied in RA patients and the effect of tofacitinib on humoral or cell mediated live vaccine response was unknown. Methods: To evaluate the effect of tofacitinib upon the immune response and safety of LZV, we recruited patients aged equal to or greater than 50 years with active RA (equal to or greater than 4 tender/painful joints and equal to or greater than 4 swollen joints) despite methotrexate (MTX) therapy (24 months of treatment with 15-25 mg/week before screening). Patients with prior history of zoster vaccination were excluded, as were those receiving any vaccine in the 6 weeks prior to randomization. After screening, eligible patients were given LZV and then randomized to either tofacitinib 5 mg BID or placebo (PBO) to start 2-3 weeks post-vaccination with continuation of background MTX. The authors measured both humoral (varicella-zoster virus [VZV]-specified IgG via gpELISA) and cell-mediated responses (VZV-specific T cell enumeration via ELISPOT) prior to vaccination (baseline, day of vaccination), and then at 2, 6, and 14 weeks post-vaccination. The primary endpoint was an assessment of the geometric mean fold rise (GMFR) in VZV-specific IgG titer at 6 weeks post-vaccination. Secondary endpoints included the proportion of patients achieving a 21.5 fold rise in VZV-specific IgG titer 6 weeks post-vaccination. Exploratory endpoints included the GMFR in VZV-specific T cells (spot-forming cells/10^6 peripheral blood mononuclear cells [PBMCs] by ELISPOT between baseline and 6 weeks post-vaccination. Patients were followed for 12 weeks after randomization for safety. Results: 112 patients were randomized into PBO (n=57) and tofacitinib arms (n=55). Most PBO (93%) and tofacitinib (98%) pts were evaluable for immune response endpoints. Pts were similar with regard to sex, age, baseline disease activity, and baseline VZV immune measures (i.e. IgG, ELISPOT). The GMFR in VZV-specific IgG titer at 6 weeks was 2.11 for tofacitinib patients and 1.74 for PBO pts. The GMFRs both in tofacitinib and PBO patients were comparable with the GMFRs in healthy people 250 years as indicated in the LZV labels. The proportion of patients developing a 1.5 fold post-vaccination rise in IgG titer at 6 weeks trended higher for tofacitinib (57.4%) versus PBO (43.4%). For cell-mediated immune responses, the VZV specific T cell GMFR at 6 weeks increased similarly for tofacitinib patients (1.50) and PBO patients (1.29). SAEs occurred in 0 (0%) and 3 (5.5%) of PBO and tofacitinib arms respectively. This report refers to one patient (equal to or greater than 50 years, gender unknown) in the study developed cutaneous dissemination with Zoster Vaccine Live (manufacturer unknown) (dose, frequency, route and lot# not reported) that occurred 2 days after starting tofacitinib (5 mg bid) (16 days post-vaccination) (drug interaction). Subsequently, this patient was found to lack pre-existing immunity to VZV, consistent with vaccine-induced disease. This event resolved after tofacitinib discontinuation and antiviral therapy. Conclusion: Patients starting tofacitinib had similar VZV-specific humoral and cell-mediated immune responses to LZV as compared to PBO-treated patients. Vaccination appeared safe in all patients but one who lacked preexisting VZV immunity. The author considered drug interaction to be related to Zoster Vaccine Live (manufacturer unknown) and tofacitinib. Additional information has been requested.