SAT0220 Evaluation of live zoster vaccine in a subset of patients with rheumatoid arthritis treated with tofacitinib with or without methotrexate, and adalimumab with methotrexate: results from a phase 3b/4 randomised trial
Authors: L. H. Calabrese, C. Abud-Mendoza, S. Lindsey, S.-H. Lee, L. Takiya, N. Iikuni, K. Soma, Z. Luo, R. Fleischmann
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Patients (pts) with RA are at increased risk for herpes zoster (HZ) and this risk is further increased with tofacitinib treatment.<sup>1</sup> <h3>Objectives:</h3> To evaluate the effect of live zoster vaccination (LZV) on HZ rates in a subset of methotrexate inadequate responder (MTX-IR) pts with RA who received tofacitinib with or without MTX, or adalimumab (ADA) with MTX in the ORAL Strategy randomised controlled trial (RCT).<sup>2</sup> <h3>Methods:</h3> ORAL Strategy (NCT02187055) was a Phase 3b/4, 1-year, triple-dummy active-comparator-controlled RCT. Pts were randomised 1:1:1 to receive tofacitinib 5 mg twice daily (BID; tofa mono), tofacitinib 5 mg BID+MTX (tofa+MTX), or subcutaneous ADA 40 mg every other week + MTX (ADA+MTX); target MTX dose was 15–25 mg/week. In countries where LZV was available, pts aged ≥50 years received LZV at the investigator's discretion, 28 days before the first dose of study drug. HZ incidence rates (IR; pts with events per 100 pt-years) and 95% confidence intervals (CI) were calculated for each treatment arm and for vaccinated vs non-vaccinated pts. <h3>Results:</h3> Of 1146 pts who received study drug (mean age: 50.1 years), 216 received LZV (proportion of pts who received LZV by treatment group: tofa mono: 18.0%; tofa+MTX: 19.9%; ADA+MTX: 18.7%) 28 days before randomisation in this RCT; 30 pts self-reported prior vaccination (Table). No pts had zoster-like lesions within 42 days of vaccination; 1 pt had vaccination site erythema. In the overall study population, HZ IR was similar between tofa mono and ADA+MTX and numerically higher (overlapping CI) with tofa+MTX. IRs were generally similar for pts who received LZV (18.8% of pts were vaccinated) vs those who did not (81.2%) (Table). Overall, 18/1146 pts had HZ. Among vaccinated pts, 3 (1.4%) had HZ: no events were serious and 1 (0.5%) event was multidermatomal (tofa mono). Among pts not vaccinated, 15 (1.6%) had HZ: there were 2 (0.2%) serious HZ events (tofa+MTX: n=1; ADA+MTX: n=1), 2 (0.2%) multidermatomal events (tofa mono: n=1; ADA+MTX: n=1) and 1 (0.1%) disseminated event (ADA+MTX). <h3>Conclusions:</h3> In MTX-IR pts with RA, LZV was well-tolerated. HZ IR was numerically similar between tofa mono and ADA+MTX and higher with tofa+MTX. HZ rates were generally similar in pts who received LZV vs those not vaccinated. LZV has shown efficacy in prevention of HZ in 51% (pts ≥60 years old) and 70% (50–59 years old) of immunocompetent adults.<sup>3</sup> Efficacy of LZV could not be fully evaluated as a minority (&lt;20%) of pts received LZV and not all geographic regions studied in other tofacitinib studies were represented. <h3>References</h3> [1]Winthrop, et al. Arthritis Rheumatol2014;66:2675–84. [2]Fleischmann, et al. Lancet2017;390:457–68. [3]Hales, et al. MMWR Morb Mortal Wkly Rep2014;63:729–31. <h3>Acknowledgements:</h3> Study sponsored by Pfizer Inc. Medical writing support was provided by D Binks of CMC and funded by Pfizer Inc. <h3>Disclosure of Interest:</h3> L. Calabrese Grant/research support from: Celgene, Crescendo, Consultant for: Celgene, Crescendo, Speakers bureau: Celgene, Crescendo, C. Abud-Mendoza Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Speakers bureau: Bristol-Myers Squibb, Merck-Serono, Pfizer Inc, Roche, UCB, S. Lindsey Speakers bureau: Pfizer Inc, S.-H. Lee: None declared, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Z. Luo Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, and UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, and UCB