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Background and Aims Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. Methods Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event]. Results In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23–7.00] for placebo and 1.35 [0.16–4.87] and 0.64 [0.02–3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02–5.42], 2.05 [0.42–6.00], and 6.64 [3.19–12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24–2.27], 3.48 [2.79–4.30], and 0.15 [0.04–0.38], respectively. No SIs resulted in death. Conclusions During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.

Background Filgotinib (FIL) is an oral preferential Janus kinase (JAK) 1 inhibitor in development for the treatment of inflammatory diseases. FIL for the treatment of moderately to severely active ulcerative colitis (UC) was evaluated in the phase 2b/3, double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522) and its long-term extension (LTE) study (NCT02914535). Here we report safety results from the FIL UC program. Methods Patients received FIL 100 mg, FIL 200 mg or PBO (2:2:1) once daily orally for up to 11 weeks for induction (cohort 1). At week 11, FIL induction responders were rerandomized 2:1 to continue FIL or receive PBO maintenance for 47 weeks (cohort 2). Week 10 non-responders and patients with worsening disease during the maintenance study were eligible for open-label FIL in the LTE. Patients completing the maintenance study could continue blinded dosing in the LTE. Cohort 3 comprised cohorts 1 and 2 and the LTE. Exposure-adjusted incidence rates (EAIRs) and exposure-adjusted event rates (EAERs) per 100 patient-years (PYs) were calculated for treatment-emergent adverse events (AEs) by treatment group in cohorts 1 and 2 (EAIR) and cohort 3 (EAER). Results In cohort 1, 1069 patients received FIL and 279 patients received PBO; baseline characteristics were generally similar across treatment groups (overall mean age, 43 years; mean UC duration, 8.4 years; mean Mayo Clinic Score, 9.0). EAIRs for AEs of interest were similar across treatment groups in cohorts 1 and 2 (Table 1). Treatment exposure for PBO, FIL 100 mg or FIL 200 mg in cohort 3 (i.e. cohorts 1 + 2 + the LTE) was 318, 360 and 1207 PYs, and median treatment duration was 12, 11 and 67 weeks, respectively. One case of pulmonary embolism occurred with FIL 200 mg induction and three venous thrombosis cases occurred with PBO maintenance/LTE (cohort 3) (Table 2). EAERs for all infections were similar across treatment groups, the most common being nasopharyngitis (Table 2). Opportunistic infections were rare. EAERs for serious infections were low across treatment groups (2.2 [PBO], 3.5 [FIL 100 mg], 2.2 [FIL 200 mg]), the most common being appendicitis (Table 2). EAERs for herpes zoster (HZ) were low in all treatment groups (0.3 [PBO], 0.3 [FIL 100 mg], 1.8 [FIL 200 mg]) (Table 2). HZ infections were cutaneous only and only one was serious. EAIRs for all infections in cohorts 1 and 2 were generally numerically higher for both PBO and FIL in patients over (vs under) 65 years old and in those with (vs without) biologic treatment failure (Figure 1). Conclusion FIL was well tolerated in patients with UC. Aggregation of AEs typical for pan-JAK inhibition was not observed, consistent with preferential JAK-1 inhibition with FIL.

Background/Aims Baricitinib (BARI) is an oral selective inhibitor of Janus kinase (JAK)1/2, approved for treatment of moderate-to-severe- rheumatoid arthritis (RA) in adults. Here, we update the drug’s safety profile with data up to 8.4 years of treatment. Methods Long-term safety of BARI was assessed from 9 completed randomized trials(5 Ph3, 3 Ph2, 1 Ph 1b) and 1 ongoing long-term extension(LTE) study. Incidence rates(IRs) per 100 patient-years (PY) were calculated for all RA patients treated with ≥1 dose of BARI through 1-Sep-2019(All-BARI-RA set). IRs for deep vein thrombosis(DVT), pulmonary embolism(PE), and DVT and/or PE(DVT/PE) were also calculated for groups of patients while receiving BARI 2mg/4mg within All-BARI-RA. Major adverse cardiovascular events(MACE) were adjudicated in 5 Ph3 studies and the LTE. Results 3770 pts received BARI for 13,148 PY, with median and maximum exposure: 4.2 and 8.4 years, respectively. Overall IRs per 100 PY were: for any treatment-emergent adverse event (AE)(25.8); serious AE (including death)(7.2); temporary interruption due to AE (9.5); permanent discontinuation due to AE (4.8); death (0.52); serious infection (2.7); opportunistic infection (0.46)(excluding tuberculosis [TB], including multidermatomal herpes zoster [HZ]); TB (0.15); HZ (3.0); MACE (0.50); DVT (0.31); PE (0.24); DVT/PE (0.46); malignancies excluding non-melanoma skin cancer (NMSC)(0.91); NMSC (0.33); lymphoma (0.07); and gastrointestinal perforation (0.04). (IRs)[95% confidence intervals] for patients while receiving BARI 2mg (N = 1077) and BARI 4mg (N = 3400) were DVT 2mg (0.38)[0.18, 0.73] and 4mg (0.30)[0.21, 0.43]; PE 2mg (0.26)[0.09, 0.56] and 4mg (0.25)[0.16, 0.36]; and DVT/PE 2mg (0.47)[0.23, 0.84] and 4mg (0.46)[0.34, 0.61]. IRs for death tended to increase in later time intervals (beyond 192 weeks). No particular cause of death contributed to this increase. For all other safety topics of interest, across 48-week treatment intervals, IRs remained stable over time. Across safety topics, IRs were consistent with previous analyses. Conclusion In this update, with 3021 additional PY of exposure, BARI maintained a safety profile similar to that previously reported, with no increase of IRs across safety topics through exposures up to 8.4 years. Disclosure K.L. Winthrop: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, and UCB Pharma. Grants/research support; Bristol Myers Squibb and Pfizer. T. Takeuchi: Consultancies; AbbVie, Asahi Kasei Medical, Astellas, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis, Pfizer Japan, Taiho Pharmaceutical, Taiho Toyama Pharmaceutical, Takeda, and UCB Japan. G. Burmester: Consultancies; Eli Lilly and Company, Janssen, Novartis, and Pfizer. Grants/research support; Eli Lilly and Company. W. Deberdt: Shareholder/stock ownership; Eli Lilly and Company. D. Schlichting: Shareholder/stock ownership; Eli Lilly and Company. D. Mo: Shareholder/stock ownership; Eli Lilly and Company. C. Walls: Shareholder/stock ownership; Eli Lilly and Company. J.S. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro Pharma, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Eli Lilly and Company, Gilead Sciences, ILTOO Pharma, Janssen, MedImmune, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB Pharma. Grants/research support; AbbVie, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche.

Herpes zoster (HZ) or shingles occurs as a result of reactivation after a primary infection with varicella zoster virus (chickenpox). The burden of HZ in older adults in China is not well understood. We conducted a systematic literature review to understand the burden of disease related to HZ, its complications, and associated costs in China. Using publications retrieved from Chinese and English literature databases, we described incidence and prevalence of HZ, occurrence of HZ-related complications, and costs associated with HZ in mainland China, Taiwan, and Hong Kong. The data, although limited, indicate that the burden of disease due to HZ is substantial in China, with incidence rates that are comparable to the rest of the world. Recently, an adjuvanted recombinant HZ vaccine was approved for use in China. Disease prevention is likely to reduce the burden of disease, with potentially significant economic benefits. However, understanding the public health impact of vaccination in China will require extensive baseline information about incidence, complication rates, and associated costs. This review gives an overview of available research, but also reveals existing gaps. Well-designed observational studies are needed to quantify the total burden of disease and potential impact of prevention through vaccination. What is the context? Although Herpes zoster (shingles) is a common disease of older age, the burden of disease in China is not well described.32% of the Chinese population is aged 50 years and Older and this proportion is increasing. As a result of the ageing population, the public burden associated with shingles is expected to increase over time. Although Herpes zoster (shingles) is a common disease of older age, the burden of disease in China is not well described. 32% of the Chinese population is aged 50 years and Older and this proportion is increasing. As a result of the ageing population, the public burden associated with shingles is expected to increase over time. What is new? We accessed published studies in the English and Chinese language literature to explore available information describing shingles in China.The incidence of shingles in Taiwan, Hong Kong and mainland China appears to be similar to other countries, although reliable population-based data are currently sparse in Hong Kong and mainland China. We accessed published studies in the English and Chinese language literature to explore available information describing shingles in China. The incidence of shingles in Taiwan, Hong Kong and mainland China appears to be similar to other countries, although reliable population-based data are currently sparse in Hong Kong and mainland China. What is the impact? Data describing the disease burden due to shingles are currently heterogeneous throughout China. This review is a first step to determine those populations which could benefit most from shingles vaccination.Preventing shingles through vaccination could benefit the individual as well as provide potentially significant economic benefits for the individual, the employer and the economy. Data describing the disease burden due to shingles are currently heterogeneous throughout China. This review is a first step to determine those populations which could benefit most from shingles vaccination. Preventing shingles through vaccination could benefit the individual as well as provide potentially significant economic benefits for the individual, the employer and the economy.

Herpes zoster atau cacar api adalah suatu infeksi yang disebabkan oleh virus varicella zoster. Penyakit Herpes Zoster disebut juga cacar api karena akan muncul lepuhan pada kulit berupa garis atau area kecil disalah satu sisi wajah atau tubuh dan rasanya cukup panas seperti terbakar. Biasanya penderita mengalami keluhan berupa bercak kemerahan dan muncul gelembung-gelembung berisi air. Merancang sistem pakar agar dapat membantu user dalam mengenali gejala awal penyakit Herpes Zoster, serta mengetahui jenis penyakit Herpes Zoster yang mana dideritanya melalui hasil konsultasi secara langsung lewat sistem. Data yang digunakan dalam penelitian ini diperoleh dari hasil wawancara secara langsung dengan pakar yaitu dr.Qaira Anum Sp.KK dirumah sakit RSI. Ibnu Sina Padang selaku dokter spesalis penyakit kulit dan kelamin. Data yang diperoleh berupa data jenis penyakit Herpes Zoster, gejala dari masing-masing jenis penyakit Herpes Zoster, bobot dari masing-masing gejala yang ada, dan solusi atau pencegahan dari masing-masing jenis penyakit Herpes Zoster. Serta dalam penelitian ini dibantu dengan menggunakan metode Certainty Factor agar dapat mempermudah dalam proses penentuan jenis penyakit Herpes Zoster apa yang diderita oleh user yang melakukan konsultasi melalui sistem berdasarkan dari gejala yang dirasakan oleh masing-masing user. Hasil dari pengujian terhadap metode ini adalah terdapat 100% dari 10 data pengujian. Berdasarkan akurasi dari hasil identifikasi terhadap sistem ini, maka penelitian ini sangat tepat dalam tingkat mengidentifikasi tingkat akurasi penyakit Herpes Zoster pada manusia. Sistem pakar pengujian telah dapat mengidentifikasi penyakit Herpes Zoster secara spesifik. Melalui metode Certainty Factor ini, tingkat akurasi yang di dapat cukup akurat dan dapat membantu dokter hewan dalam meningkatkan akurasi untuk mengidentifikasi penyakit Herpes Zoster pada manusia.

Background: Herpes zoster is a distressing illness that significantly reduces patients’ quality of life. However, Costa Rican data regarding the clinical burden of herpes zoster and associated health care resource utilization is limited. This study aimed to assess the zoster-associated burden evaluating pain, impact on quality of life and health care resource utilization in a Costa Rican sample. Methods: Herpes zoster patients recruited in Costa Rica at a private geriatric practice were enrolled at various time points during a zoster episode and were actively followed over 6 months. Outcomes including zoster-associated pain, quality of life and health care resource utilization were assessed via patient self-reported questionnaires. Results: 50 zoster patients were included [68.0% female, mean (SD) age = 69.5 (10.8) years]. Zoster-associated pain decreased over time while quality of life improved though without full base recovery. The highest health care resource utilization included doctor’s office (98.0%), emergency room (60.0%) and specialists (60.0%) visits. Sixteen (32.0%) patients were hospitalized [mean (SD)= 4.3 (4.1) days]. Conclusion: Similar to other Latin American countries, high herpes zoster burden was observed in a private geriatric practice in Costa Rica, supporting the need for early intervention and preventive strategies, one of such could be the implementation of a HZ vaccination program. Resumen Justificación: El herpes zoster es una enfermedad estresante que reduce significativamente la calidad de vida de los pacientes. Sin embargo, datos relativos a la carga clínica de herpes zoster y la utilización de recursos de salud son limitados en Costa Rica. El objetivo de este estudio fue evaluar la carga asociada al herpes zoster evaluando dolor, impacto sobre la calidad de vida y utilización de recursos de salud en una muestra costarricense. Métodos: Pacientes con herpes zoster fueron reclutados en una práctica geriátrica privada en diferentes etapas de un episodio de zoster y fueron activamente seguidos durante 6 meses. Se evaluaron los resultados en el paciente, incluyendo el dolor asociado a zoster, calidad de vida y utilización de recursos de salud mediante cuestionarios autoadministrados. Resultados: Se incluyeron 50 pacientes con herpes zoster [68,0% mujeres, media de edad (SD) = 69.5 (10.8) años]. El dolor asociado a zoster disminuyó con el tiempo mientras que calidad de vida mejoró, aunque sin plena recuperación comparado con la calidad de vida inicial. La utilización de recursos de salud más alta fue visitas al consultorio (98.0%), visitas a sala de urgencias (60.0%) y visitas a especialistas (60.0%). Dieciséis pacientes (32.0%) fueron hospitalizados [media (SD) = 4.3 (4.1) días]. Conclusión: Similar a otros países de América Latina, se observó una alta carga de enfermedad debido a herpes zoster en una práctica privada geriátrica en Costa Rica, lo cual respalda la necesidad de la intervención temprana y uso de estrategias preventivas, una de las cuales podría ser la implementación de un programa de vacunación a herpes zoster.

Background Giant cell arteritis (GCA) has protean manifestations including temporal headache, visual disturbances, constitutional symptoms, jaw and tongue pain; symptoms which overlap with other conditions which mimic GCA. An important benefit of a fast-track clinic (FTC) is to rapidly exclude the diagnosis GCA to avoid inappropriate steroid exposure. We analysed data for patients referred with suspected GCA to our FTC where GCA diagnosis was subsequently excluded with fast-track ultrasound (US) and other investigations. Methods This retrospective data was extracted from the GCA fast-track electronic referral system at Southend University Hospital from January 2016 to July 2019. Results 1,057 patients were seen at the fast-track clinic in this study period (Table 1). 690 (65.28%) were females. Only 15% (159) of the participants had a confirmed diagnosis of GCA (majority using US but also with other investigations such as biopsy or PET CT). Non-GCA patients accounted for 85% (898) and had a variety of differential diagnoses. In 222 (23.7%) no additional diagnosis was made after excluding GCA and patients were referred back for an expectant follow-up and assessment should any new features develop. In 204 (22.7%), polymyalgia rheumatica (PMR) was diagnosed with classical clinical symptoms and US of bilateral glenohumeral joints or response to a trial of low dose oral steroids. Another major group had different types of headaches 141 (15.71%) at presentation mimicking GCA. This included migraine 79 (56.0%), cervicogenic 58 (41.13%) and cluster headaches 4 (2.83%). Infectious causes were limited to head and neck infections 89 (9.91%) such as periorbital swelling, shingles and sinusitis. Neurological causes such as cervical spondylosis, cranial nerve palsy and TIA contributed to 7.9%. Chronic pain and other causes contributed 74 (8.24%) and 97 (10.8%) respectively. Other causes included medication-related (33), stress (21), cancer (4), RS3PE (4), glaucoma (2) and ANCA-associated vasculitis (33). Conclusion An FTP clinic not only diagnoses GCA rapidly but is also able to rapidly screen non GCA and prevent unnecessary steroid treatment. It also requires a screening tool like GCA probability score to triage referrals to enable a more efficient service. Disclosures A. kayani None. A. Sebastian None. C. Ranasinghe None. M. Whitlock None. H. Hussain None. B. Dasgupta Consultancies; Roche, Sanofi, GSK. Grants/research support; Roche.

In the antiretroviral therapy era, herpes zoster incidence continued to decline in people living with HIV (PLWH). However, at 0.9 cases/100 person-years, rates in PLWH are substantially higher than the general US population; emphasizing the needs for studies of the subunit vaccine in PLWH.

Background Herpes Zoster Ophthalmicus (HZO) affects 10-20% of adults with herpes zoster; ≥ 50% of these cases manifest as serious ocular diseases. This 1-year prospective observational cohort study aims to determine patient-reported HZO symptoms as well as economic and quality of life burden among 300 HZO patients from 6 major US ophthalmology practices. Here, we report baseline data from 13 initial enrollees. Methods Inclusion criteria were: participants ≥ 18 years, diagnosis of clinically active HZO, English or Spanish speaking, be willing and able to respond to study assessments, not be enrolled in a concurrent interventional HZO trial. Information are collected via 1) a clinical assessment form completed by the practice (baseline) and 2) patient questionnaires (baseline, 3, 6, and 12 months) on symptoms, medications, healthcare use, vision function, depression, and work productivity impact. Baseline results are presented for patients recruited during the first 6 months of enrollment from the first 4 sites to go live: diagnoses, and patient-reported symptoms and outcomes (eight-item Patient Health Questionnaire [PHQ-8] for depressive symptoms, National Eye Institute 25-item Visual Function Questionnaire [NEI-VFQ-25] for vision-related quality of life, and Zoster Brief Pain Inventory [ZBPI] for pain). Results The mean age of participants is 71 years; 11 are female and 9 are retired. Seven participants are college graduates or hold other degrees. All have health insurance coverage, with most (10) having primary insurance through Medicare. HZO diagnoses (Table 1) were: keratitis (4), iridocyclitis (4), conjunctivitis (1), other HZO diagnosis (3), other ocular diagnosis (6). Patient-reported symptoms (Table 2) were: pain above the eye, sensitivity to light, redness, feeling of sand/grit in the eye (9 each). The mean overall PHQ-8 and NEI-VFQ-25 scores were 5.9 (Standard Deviation [SD]:4.5) and 74.6 (SD:13.9), respectively; the mean ZBPI score for worst pain severity was 3.3 (SD:3.8) (Table 3). Table 1. HZO Diagnosis at Baseline based on Clinical Assessment Form (N=13) Table 2. Patient-reported Symptoms in the HZO-Affected Eye at Baseline (N=13) Table 3. Patient-reported Outcomes: Depressive Symptoms, Vision-Related Quality of Life, and Herpes Zoster Pain at Baseline (N=13) Conclusion This study represents the first large scale effort to quantify HZO burden. Findings will inform development of a formal patient-reported symptom scale for use in research and clinical practice. Funding GlaxoSmithKline Biologicals SA (GSK study identifiers: 209235/HO-17-17967) Disclosures Laura T. Pizzi, PharmD, MPH, ORCID: 0000-0002-7366-7661, GlaxoSmithKline (Research Grant or Support) Soham Shukla, PharmD, ORCID: 0000-0002-4139-0856, GSK (Employee)Rutgers University (Employee) Brandon J. Patterson, PharmD, PhD, GSK (Employee, Shareholder) Debora A. Rausch, MD, ORCID: 0000-0001-9759-2687, GSK (Employee) Philip O. Buck, PhD, MPH, ORCID: 0000-0002-3898-3669, GSK (Employee, Shareholder) Ann P. Murchison, MD, MPH, GSK (Grant/Research Support)

Background In 2017, the Advisory Committee on Immunization Practices preferentially recommended adjuvanted recombinant zoster vaccine (RZV) for adults ≥ 50 years as a two-dose series 2–6 months apart.1 We evaluated two-dose RZV completion and factors associated with completion. Methods The study included Kaiser Permanente Southern California members ≥ 50 years who received an RZV dose during April-November 2018 and had continuous membership 12 months before to 9 months after the 1st RZV dose (RZV1). Completion was defined as receipt of the 2nd dose ≥4 weeks to 9 months after RZV1 (allowing a 3-month grace period). Characteristics including age at RZV1, sex, race/ethnicity, Medicaid status, neighborhood level income and education, distance from home to medical office, comorbidities, history of herpes zoster, health care utilization before and after RZV1, receipt of influenza vaccine, vaccination month (supply shortage proxy), concomitant vaccine, department administering RZV1, medical center, and medically attended local or systemic reaction, pain, or gout after RZV1 were compared between completers and non-completers. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with completion were estimated by multivariable logistic regression. Results Among 31,120 RZV1 recipients, 67.2% completed the series within 9 months. In adjusted analyses, higher completion was associated with White compared with Black or Hispanic race/ethnicity, higher neighborhood income and education, no chronic pulmonary disease, diabetes, or dementia, more outpatient visits and fewer emergency department visits before or after RZV1, no hospitalizations after RZV1, receipt of influenza vaccine, receipt of RZV1 in June-November rather than April-May 2018, no concomitant vaccine with RZV1, and receipt of RZV1 in Family Practice rather than Internal Medicine. Systemic reactions or pain after RZV1 was not associated with completion. Table 2. RZV Series Completion by Selected Characteristics During Follow-up of Members Aged ≥50 Years Who Received at Least One Dose of RZV at Kaiser Permanente Southern California in April-November 2018 Table 2. RZV Series Completion by Selected Characteristics During Follow-up of Members Aged ≥ 50 Years Who Received at Least One Dose of RZV at KPSC in April-November 2018 Figure 1. Factors Associated with RZV Series Completion of Members Aged ≥ 50 Years Who Received at Least One Dose of RZV at KPSC in April-November 2018 Conclusion Completion of RZV series appears moderate in the early phase of implementation. Despite similar accessibility in a health care system, completion varied by race/ethnicity, socioeconomic status, health status, and care seeking behavior, suggesting areas to target for improvement. Disclosures Hung-Fu Tseng, MPH, PhD, GlaxoSmithKlein (Research Grant or Support) Lei Qian, PhD, GlaxoSmithKlein (Research Grant or Support) Jun Wu, MD, MS, GlaxoSmithKlein (Research Grant or Support) Yi Luo, PhD, GlaxoSmithKlein (Research Grant or Support) Lina S. Sy, MPH, GlaxoSmithKlein (Research Grant or Support) Katia Bruxvoort, PhD, MPH, GlaxoSmithKlein (Research Grant or Support) Bradley Ackerson, MD, GlasoSmithKlein (Research Grant or Support)

Background Older and immunocompromised adults are at increased risk for herpes zoster (HZ) and often experience persistent, severe HZ-related pain, impacting their quality of life and activities of daily living. High vaccine efficacy (VE) of the adjuvanted recombinant zoster vaccine (RZV) in preventing HZ and reducing severe and clinically significant HZ-related pain has been shown in adults ≥ 50 years of age (YOA; ZOE-50 study; NCT01165177), ≥ 70 YOA (ZOE-70; NCT01165229) and ≥ 18 YOA undergoing autologous hematopoietic stem cell transplantation (ZOE-HSCT; NCT01610414). Methods In patients with confirmed HZ from the above phase III, randomized, placebo-controlled studies, we analyzed VE of RZV in reducing the duration of clinically significant HZ-related pain and in reducing the use and duration of HZ-related pain medication. Pain was assessed by the Zoster Brief Pain Inventory (ZBPI). Use of all HZ-related medication was recorded. Results VE in reducing the duration of clinically significant HZ-related pain (ZBPI pain score ≥3) during HZ episodes was 38.5% (p-value: 0.0099) in RZV-vaccinated patients from the ZOE-HSCT study compared to placebo. A similar trend (not statistically significant) was observed in the ZOE-50 (VE: 26.9%; p-value: 0.4318) and ZOE-70 (VE: 28.4%; p-value: 0.1877) studies. VE in reducing the use (Table 1) and duration (Table 2) of HZ-related pain medication was 39.6% (p-value: 0.0083) and 49.3%(p-value: 0.0404), respectively, in the ZOE-70 study; corresponding positive VE estimates were also seen in the ZOE-50 and ZOE-HSCT studies. Non-opioids were used by 61.2%, 44.3% and 22.1% of patients in the ZOE-50, ZOE-70 and ZOE-HSCT studies, respectively; weak opioids by 18.6%, 13.0% and 10.8% of patients, and strong opioids by 8.0%, 2.0% and 5.3% of patients (Table 3). Table 1. Reduction in the use of HZ-related pain medication in patients with confirmed HZ Table 2. Reduction in the duration of HZ-related pain medication use in patients with confirmed HZ Table 3. HZ-related medication types in patients with confirmed HZ Conclusion In addition to a high VE in preventing HZ in these studies, we also observed an attenuation of HZ-related pain, and thus lower use and duration of pain medication in breakthrough cases after RZV vaccination, thereby potentially improving patient quality of life. Funding: GlaxoSmithKline Biologicals SA Acknowledgment: Kristel Vercauteren/Sander Hulsmans (Modis c/o GSK) provided medical writing/editorial support Disclosures Joon Hyung Kim, MD, GSK (Employee, Shareholder) Robert Johnson, MD, FRCA, GSK (Other Financial or Material Support, I accept no fees but have had expense reimbursement in the past.) Martina Kovac, MD, GSK (Other Financial or Material Support, I was an employee of GSK at the time of the study) Anthony L. Cunningham, MBBS, MD, FRACP, FRCPA, GSK (Consultant) Srikanth Emmadi, MSc, GSK (Employee) Keith Sullivan, MD, FASTCT, GSK (Consultant) Alemnew F. Dagnew, MD, GSK group of companies (Employee, Shareholder) Desmond Curran, PhD, GSK (Employee, Shareholder) Anne Schuind, MD, GSK (Employee, Other Financial or Material Support, own GSK stock options or restricted shares as part of renumeration)

Background Recombinant Zoster Vaccine (RZV) was licensed in the United States (US) in October 2017 for the prevention of herpes zoster in adults ≥ 50 years of age (YOA). The vaccine is administered in a two-dose sequence with a 2- to 6-month interval; however, the Center for Disease Control & Prevention has advised against restarting a series after the prescribed window. This study describes an assessment of 2nd dose completion and compliance of RZV in the US. Methods Primary analysis was conducted on a cohort ≥ 50 YOA who received an initial RZV dose between October 2017 and September 2018 as indicated in the IQVIA longitudinal prescription claims or medical claims databases. Subjects were required to have ≥ 1 year of observable time post initial dose. A sensitivity analysis was conducted using all eligible subjects regardless of observable time post initial dose. Endpoints of analyses were monthly and cumulative 2nd dose label-compliant proportions at 6 months and completers by 12-month intervals and time to completion from initial RZV vaccine administration with stratifications by age, sex, claim source and payer type. Results The primary sample included 1,225,088 subjects, while the sensitivity analysis included 7,097,441 (Table 1). Overall, 2nd RZV dose completion was 70.4% within 6 months and 81.8% within 12 months. Minimal variation for 12-month completion was demonstrated across age (77.2–84.5%), sex (81.7–81.9%), and Commercial vs. Medicare (80.9–83.0%). However, larger variations were seen across claim sources and other payer type, with medical claims (64.9%), Medicaid patients (72.8%) and Cash patients (74.7%) having lower rates at 12 months (Table 2). Overall, the average time to completion was around 4 months regardless of stratification except by claims source, with medical claims taking 5 months on average to complete. The sensitivity analysis of the variable follow-up cohort demonstrated findings consistent with that of the primary sample. Conclusion Assessment of RZV suggests high levels of completion across age, sex, payer type and claim sources. More effort is needed to understand barriers to completion rates in Medicaid patients and settings where vaccination claims are processed outside of the vaccine recipient’s pharmacy benefit. Disclosures Brandon J. Patterson, PharmD, PhD, GSK (Employee, Shareholder) Chi-Chang Chen, PhD, MSPharm, GSK (Research Grant or Support) Catherine B. McGuiness, MA, MS, GSK (Research Grant or Support)Pfizer (Shareholder) Lisa I. Glasser, MD, GSK (Employee, Shareholder) Kainan Sun, MS, PhD, GSK (Research Grant or Support) Philip O. Buck, PhD, MPH, ORCID: 0000-0002-3898-3669, GSK (Employee, Shareholder)

Background Herpes zoster (HZ), or shingles, is a common neurocutaneous disease caused by the reactivation of latent varicella zoster virus that often includes rash and neuropathic pain that may last for months. Opioids and other analgesics may be prescribed. Recombinant zoster vaccine (RZV) is preferentially recommended for the prevention of HZ in adults aged 50 years and older. This study aimed to assess the impact of RZV vaccination on opioid and other analgesic prescription-related outcomes. Methods Estimates of analgesic prescription rates (opioids, benzodiazepines, and other analgesics) among HZ cases were established using Truven claims data from 2012-2018 for adults aged 50 years and older. HZ case avoidance with RZV vaccination was calculated using a previously published cost-effectiveness model. This data was included in a calculator assessing the impact of RZV vaccination on analgesic prescription-related outcomes (compared to no vaccination). Results Between 24.4% and 28.0% of HZ cases in the observed claims had at least one opioid prescription, dependent on age group (4.5%-6.5% and 8.6%-19.6% for benzodiazepines and other analgesics, respectively). The mean number of opioid prescriptions per person in each age group with at least one opioid prescription was between 1.7 and 1.9 (1.7-2.3 and 1.7-2.0 prescriptions for benzodiazepines and other analgesics, respectively). Assuming a 1-million-person population and 65% RZV coverage, the calculator predicts RZV vaccination will prevent 75,002 cases of HZ and will prevent 19,311 people from being prescribed at least 1 HZ-related opioid, 4,502 people from being prescribed benzodiazepines, and 12,201 people from being prescribed other analgesics. Additionally, 34,520 HZ-related opioid prescriptions will be avoided (9,413 benzodiazepine prescriptions; 22,406 other analgesic prescriptions). Conclusion HZ is associated with high levels of opioid, benzodiazepine, and other analgesic use. Primary prevention of HZ by vaccination could potentially reduce opioid and other medication exposure. Disclosures Jean-Etienne Poirrier, PhD, MBA, The GSK group of companies (Employee, Shareholder) Justin Carrico, BS, GlaxoSmithKline (Consultant) Jessica K. DeMartino, PhD, The GlaxoSmithKline group of companies (Employee, Shareholder) Katherine A. Hicks, MS, BSPH, GlaxoSmithKline (Scientific Research Study Investigator, GSK pays my company for my contractual services.) Saurabh P. Nagar, MS, RTI Health Solutions (Employee) Juliana Meyers, MA, GlaxoSmithKline (Other Financial or Material Support, This study was funded by GlaxoSmithKline.)

Background Previous studies on adult vaccination coverage found inter-state variability that persists after adjusting for individual demographic factors. Assessing the impact of state-level factors may help improve uptake strategies. This study aimed to: • Update previous estimates of state-level, model-adjusted coverage rates for influenza; pneumococcal; tetanus, diphtheria, and acellular pertussis (Tdap); and herpes zoster (HZ) vaccines (individually and in compliance with all age-appropriate recommended vaccinations) • Evaluate effects of individual and state-level factors on adult vaccination coverage using a multilevel modeling framework. Methods Behavioral Risk Factor Surveillance System (BRFSS) survey data (2015–2017) were retrospectively analyzed. Multivariable logistic regression models estimated state vaccination coverage and compliance using predicted marginal proportions. BRFSS data were then combined with external state-level data to estimate multilevel models evaluating effects of state-level factors on coverage. Weighted odds ratios and measures of cluster variation were estimated. Results Adult vaccination coverage and compliance varied by state, even after adjusting for individual characteristics, with coverage ranging as follows: • Influenza (2017): 35.1–48.1% • Pneumococcal (2017): 68.2–80.8% • Tdap (2016): 21.9–46.5% • HZ (2017): 30.5–50.9% Few state-level variables were retained in final multilevel models, and measures of cluster variation suggested substantial residual variation unexplained by individual and state-level variables. Key state-level variables positively associated with vaccination included health insurance coverage rates (influenza/HZ), pharmacists’ vaccination authority (HZ), presence of childhood vaccination exemptions (pneumococcal/Tdap), and adult immunization information system participation (Tdap/HZ). Conclusion Adult vaccination coverage and compliance continue to show substantial variation by state even after adjusting for individual and state-level characteristics associated with vaccination. Further research is needed to assess additional state or local factors impacting vaccination disparities. Funding GlaxoSmithKline Biologicals SA (study identifier: HO-18-19794) Disclosures Shannon Hunter, MS, GSK (Other Financial or Material Support, Ms. Hunter is an employee of RTI Health Solutions, who received consultancy fees from GSK for conduct of the study. Ms. Hunter received no direct compensation from the Sponsor.) Diana Garbinsky, MS, GSK (Other Financial or Material Support, The study was conducted by RTI Health Solutions, which received consultancy fees from GSK. I am a salaried employee at RTI Health Solutions and received no direct compensation from GSK for the conduct of this study..) Elizabeth M. La, PhD, RTI Health Solutions (Employee) Sara Poston, PharmD, The GlaxoSmithKline group of companies (Employee, Shareholder) Cosmina Hogea, PhD, GlaxoSmithKline (Employee, Shareholder)

Background No national vaccination program against herpes zoster (HZ) is currently in place in Norway. We aimed to quantify the burden of medically attended HZ to assess the need for a vaccination program. Methods We linked data from several health registries to identify medically attended HZ cases during 2008–2014 and HZ-associated deaths during1996–2012 in the entire population of Norway. We calculated HZ incidences for primary and hospital care by age, sex, type of health encounter, vaccination status, and co-morbidities among hospital patients. We also estimated HZ-associated mortality and case-fatality. Results The study included 82,064 HZ patients, of whom none were reported as vaccinated against HZ. The crude annual incidence of HZ was 227.1 cases per 100,000 in primary healthcare and 24.8 cases per 100,000 in hospitals. Incidence rates were higher in adults aged ≥50 years (461 per 100,000 in primary care and 57 per 100,000 in hospitals), and women than in men both in primary healthcare (267 vs 188 per 100,000), and hospitals (28 vs 22 per 100,000). Among hospital patients, 47% had complicated zoster and 25% had comorbidities, according to the Charlson comorbidity index. The duration of hospital stay (median 4 days) increased with the severity of comorbidities. The estimated mortality rate was 0.18 per 100,000; and in-hospital case-fatality rate was 1.04%. Conclusions Medically attended HZ poses a substantial burden in the Norwegian healthcare sector. The majority of the zoster cases occurred among adults aged ≥50 years – the group eligible for zoster vaccination – and increased use of zoster vaccination may be warranted, especially among persons with co-morbidities.

Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib have been demonstrated in patients with moderate to severe UC in three Phase 3 studies (OCTAVE Induction 1 and 2 [NCT01465763; NCT01458951]; OCTAVE Sustain [NCT01458574]) [1]. Here, we present updated efficacy and safety data of tofacitinib dose escalation in patients with UC participating in an ongoing, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) [2]. Methods We present updated data from the dose-escalation subpopulation of the OLE study (as of May 2019; database not locked) comprising patients who achieved clinical response (CR) following 8 weeks of tofacitinib 10 mg twice daily (BID) induction therapy, entered OCTAVE Sustain receiving tofacitinib 5 mg BID, experienced treatment failure between Week 8 and Week 52, and subsequently entered OCTAVE Open with escalation to tofacitinib 10 mg BID. Treatment failure was defined as an increase of ≥3 points from maintenance study baseline total Mayo score, plus an increase of ≥1 point in both rectal bleeding subscore and centrally read endoscopic subscore (ES), and an absolute ES of ≥2 after ≥8 weeks of maintenance therapy. CR, mucosal healing (MH) and remission (R) were evaluated at Months 2, 12, 24 and 36 of OCTAVE Open (non-responder imputation and last observation carried forward [NRI-LOCF] and observed data). Safety was evaluated throughout the study. Results Of 944 patients enrolled in the OLE study, the dose escalation subpopulation comprised 59 patients. In these patients, CR, MH and R rates 36 months after dose escalation were, respectively, 40.7%, 39.0% and 30.5% for NRI-LOCF and 95.2%, 86.4% and 66.7% for observed data (Table). Of these 59 patients, 29 had prior tumour necrosis factor inhibitor (TNFi) failure; in these patients, CR, MH and R rates at Month 36 were, respectively, 51.7%, 51.7% and 41.4% for NRI-LOCF, and 100.0%, 92,3% and 75.0% for observed data. Incidence rates for safety events and pt-years’ exposure are reported in the table. Conclusion For most patients who lost initial CR to tofacitinib 10 mg BID induction therapy while on tofacitinib 5 mg BID maintenance therapy, including those with prior TNFi failure, dose-escalation back to 10 mg BID recaptured CR by Month 2 and was generally maintained over 3 years. The safety profile with tofacitinib 10 mg BID in the dose-escalation subpopulation was generally consistent with that in the overall study population, although there was a numerically higher rate of herpes zoster. These analyses are limited by low pt numbers and the absence of a comparator arm. References

This cost-effectiveness study evaluates use of the recombinant adjuvanted zoster subunit vaccine among patients 50 years and older.

Background The adjuvanted recombinant zoster vaccine (RZV, GSK), indicated for the prevention of herpes zoster (HZ) in adults ≥ 50 years of age, received its first marketing authorization in October 2017. We reviewed the post-marketing spontaneous adverse event (AE) reports submitted to GSK’s worldwide safety database since RZV introduction. Methods Descriptive analyses were conducted on all spontaneous reports involving RZV from October 13, 2017 to February 10, 2019. Observed-to-expected analyses were performed for the outcomes of interest: all-cause mortality and the 2 most commonly reported potential immune-mediated diseases, Guillain–Barré syndrome (GBS) and Bell’s palsy. Data mining was done to detect quantitative signals by identifying RZV-AE pairings with disproportionate reporting or evidence of an unexpected time-to-onset distribution. Results Most of the15,638 spontaneous reports received were medically verified (75.2%), originated from the United States (81.7%) and were non-serious (95.3%). Reports were mainly from individuals 50–69 years old (62.1%) and females (66.7%), when documented (Figure 1). Of all reports, 12,059 (77.1%) described signs/symptoms and 3,579 (22.9%) described vaccination errors, majority of which were without associated signs/symptoms (2,961; 82.7%). Overall, the most commonly reported signs/symptoms were consistent with vaccine reactogenicity (such as injection-site reactions, pyrexia, pain, chills, headache, fatigue), which were previously reported after RZV (Table 1). The observed reporting rates of outcomes of interest likely represent temporary associated events that are occurring as background incidence in the general population. No unexpected reporting patterns were detected overall. The proportion of RZV vaccination errors over time, by country, is shown in Figure 2. Overall, most reports described errors in vaccine preparation and reconstitution (29.7%) (Table 2). Conclusion Overall, the safety profile of RZV, following the first year of post-marketing use, is reassuring and consistent with that observed in clinical trials. Ongoing surveillance will continue to monitor RZV safety, as it is an early stage in the implementation, when real-life data are limited. Funding: GlaxoSmithKline Biologicals SA. Disclosures All authors: No reported disclosures.

Background In October 2017, the Centers for Disease Control and Prevention (CDC) recommended the adjuvanted Recombinant Zoster Vaccine (RZV) for all adults aged ≥ 50 years, regardless of previous vaccination. Understanding patient preferences for herpes zoster (HZ) vaccination can inform providers, payers, and policymakers about barriers, hesitancies, and utilization of available vaccines. Methods A discrete choice experiment survey was completed by 1,454 US adults aged ≥50 years in January 2019, with targeted sampling quotas of African Americans (25%), recent influenza vaccine recipients (50%), and individuals with autoimmune disease or chronic comorbidities (37%), to enable subgroup analyses. HZ vaccine profiles were characterized using seven attributes: vaccine efficacy (VE), duration of protection, location of service, number of doses, injection-site reaction severity, systemic reactions duration, and out-of-pocket (OOP) costs. In a series of choice questions, respondents chose between a pair of hypothetical HZ vaccine profiles, determined by an efficient experimental design, and a no vaccination option. In a second series, respondents stated intentions to complete a 2-dose vaccination series, conditioned on varying levels of side effects experienced with a first dose and expected OOP costs. Differences across subgroups were explored. Results Respondents placed the greatest weight on OOP costs and VE when choosing among HZ vaccination options (Figure 1). African American respondents were more sensitive to increases in OOP costs than non-African American respondents (Figure 2). ~75% of respondents indicated they would complete the series of a two-dose HZ vaccine if the cost of completing the series was $8-$13. Second-dose compliance drops about 25% when OOP costs increase to $140–150. Conclusion OOP cost had the greatest influence on respondents’ intention to select and complete HZ vaccination. Efforts to remove financial barriers to improve implementation of the CDC recommendations for HZ vaccination should be considered. GlaxoSmithKline Biologicals SA, GSK study identifiers: 208677/HO-17-18066. Disclosures All authors: No reported disclosures.

Background More recent baseline epidemiological data for Herpes Zoster (HZ) in adults ≥ 50 years of age, obtained before the introduction of the adjuvanted Recombinant Zoster Vaccine (RZV), are needed for future evaluations of the impact of RZV on HZ epidemiology. Methods The study comprised five elements: (1) The incidence of HZ was estimated from immunocompetent adults ≥ 50 years of age not vaccinated with Zoster Vaccine Live who had incident HZ between 2011–2015. HZ was identified by International Classification of Diseases (ICD) codes from electronic health records (EHR) of 4.6 million Kaiser Permanente Southern California members; (2) Postherpetic neuralgia (PHN) was identified by validated survey and medical record review of laboratory-confirmed incident HZ cases recruited during 2012–2015 for HZ-related pain ≥ 90 days after initial HZ diagnosis; (3) HZ Ophthalmicus (HZO) with ocular complications was identified by ICD codes and keyword search in EHR among patients identified with HZO using a validated natural language processing algorithm; (4) The proportion of HZ-related non-PHN and non-HZO cutaneous, neurological or other complications was assessed by double abstraction of EHRs from a sample of 600 incident HZ cases; (5) Recurrent HZ was identified by having an HZ diagnosis with HZ antiviral medication ≥ 6 months after the most recent HZ diagnosis with HZ antiviral medication in a cohort initially diagnosed with HZ between 2007 and 2008 and followed through 2016. Results We identified 40,893 incident HZ cases with an overall incidence of 9.92 (95% confidence interval [CI]: 9.82–10.01) per 1000 person-years. The proportion of incident HZ cases with PHN and HZO with ocular involvement was 18.37% (95% CI: 14.90–21.84%) and 8.06% (95% CI: 7.80–8.32%), respectively. The proportion of cutaneous, neurological, and other complications was 7.20% (95% CI: 5.44–8.96%), 0.87% (95% CI: 0.79–0.95%), and 1.24% (95% CI: 1.15–1.33%), respectively. The incidence of recurrent HZ was 10.96/1000 person-years (95% CI: 10.18–11.79). Conclusion HZ is common among unvaccinated US adults ≥ 50 years of age, with PHN and HZO occurring most frequently among incident HZ cases. Funding GlaxoSmithKline Biologicals SA, GSK study identifier: HO-17-18378. Disclosures All authors: No reported disclosures.

Background The risk of herpes zoster (HZ) has been reported to vary by sex and ethnicity. In 2 large-scale clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) demonstrated high vaccine efficacy (VE) against HZ and post-herpetic neuralgia (PHN). We present a post-hoc analysis of RZV efficacy against HZ and PHN in the ZOE-50/70 population stratified by sex, geographic region and geographic ancestry/ethnicity. Methods The ZOE-50 and ZOE-70 studies were phase III, observer-blind, placebo-controlled trials conducted across 5 geographic regions. Adults ≥ 50 years of age (YOA; ZOE-50) and ≥ 70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Here, VE against HZ by sub-population was estimated from the ZOE-50 population (≥ 50 YOA) and the pooled ZOE-50/70 population (pooled ≥ 70 YOA), and VE against PHN by sub-population was evaluated in the pooled ≥ 70 YOA. Results VE was evaluated in 7,340 RZV and 7,413 placebo recipients ≥ 50 YOA (mean age: 62.3 [RZV], 62.2 [placebo] YOA) and 8,250 RZV and 8,346 placebo recipients in pooled ≥ 70 YOA (mean age: 75.5 [RZV, placebo] YOA). VE against HZ and PHN was similar for women and men in the ≥ 50 YOA and pooled ≥ 70 YOA (Tables 1 and 2). Point estimates for VE against HZ by geographic region ranged from 95.7% to 97.2% in ≥ 50 YOA and from 87.3% to 95.1% in pooled ≥ 70 YOA (Table 1). Point estimates for VE against PHN by geographic region ranged from 86.8% to 100% in pooled ≥ 70 YOA. VE was similar across geographic ancestry groups in pooled ≥ 70 YOA: VE point estimates against HZ ranged from 89.6% to 100% and VE against PHN ranged from 87.5% to 100% (Tables 1 and 2). VE against HZ was 88.1% and against PHN was 65.9% in Hispanic participants in pooled ≥ 70 YOA (Tables 1 and 2). Conclusion Acknowledging the limitations including the post-hoc character of these analyses and the small number of participants and cases available, our data suggest that RZV is efficacious against HZ and PHN irrespective of sex, geographic region, geographic ancestry, and ethnicity. Funding: GlaxoSmithKline Biologicals SA. Disclosures All authors: No reported disclosures.

Background The incidence of recurrent herpes zoster (HZ) and the relationship between initial and recurrent HZ are not clear. Methods The Miyazaki Dermatologist Society has surveyed ~5000 patients with HZ annually since 1997. A questionnaire regarding HZ and its recurrence was completed by the dermatologists. Results A total of 34 877 patients with HZ were registered at 43 clinics between June 2009 and November 2015. Among 16 784 patients seen at 10 of the 43 clinics, 1076 patients (6.41%) experienced recurrence. Herpes zoster was more frequent in female than in male patients (5.27 vs 4.25 in 1000 person-years, P < .001), as was HZ recurrence (7.63% vs 4.73%, P < .001). Two and three recurrences were observed in 49 and 3 patients, respectively. Recurrence in the same dermatome was observed in 16.3% of patients, and more frequently this occurred in the left side (P = .027). The number of HZ-experienced persons increased with age, and one third of the population had experienced HZ by the age of 80. Conclusions Recurrent HZ was observed in 6.41% of patients, with a higher incidence in women. Moreover, HZ experience reduced the HZ incidence to 31.7% of the incidence in the HZ-naive population.

Background One in three people in the U.S. will develop herpes zoster during their life. Zoster Vaccine Live (ZVL or Zostavax™), has been licensed in the U.S. since 2006 to prevent herpes zoster. ZVL protection has been shown to wane with time and estimates of effect can be imprecise. We performed a systematic review of the duration of efficacy and effectiveness of ZVL against herpes zoster (HZ). Methods We systematically searched PubMed, Embase, Cochrane, and clinicaltrials.gov for vaccine efficacy or effectiveness (VE) studies of ZVL. Two authors independently screened each title and abstract, and potential VE studies were reviewed in-depth. Eligibility criteria included original data on ZVL prevention of HZ in a general population of immunocompetent recipients ≤ 60 years old. Selected articles were abstracted, independently reviewed, and discrepancies adjudicated. We attempted to locate relevant unpublished work and contacted authors for additional data, where necessary. Measures of association were illustrated on a forest plot and converted to VE (1-hazard ratio or risk ratio or odds ratio). Results We screened 1302 articles; 17 underwent full text review and 8 met inclusion criteria and were abstracted for this review. Selected studies included 1 phase III randomized controlled trial, 2 quasi experimental and 5 observational studies. One experimental and 5 observational studies estimated VE during the period from vaccination up to 4 years following vaccination; estimates across studies ranged from 33%-55%. Two quasi experimental and 3 observational studies estimated VE for ≥ 4 years following vaccination; estimates ranged from 19%-40%; the median estimate was 24% (Figure). Pooled VE was not calculated due to heterogeneity in length of follow up, age distribution of study subjects, as well as adjustment for factors such as underlying medical conditions. Conclusion Most experimental and observational studies estimate VE just above 50% during the 3 years following receipt of ZVL. Beyond 3 years, ZVL protection wanes, with most studies estimating a VE of ≤24% after 4 years. Information on overall efficacy and duration of protection from ZVL will guide policy decisions regarding its use. Disclosures E. Belongia, Novavax: Investigator, Research support

Background Herpes zoster (HZ) incidence in blacks is 25%–65% lower than in whites in the United States. Since 2007 and the widespread introduction of Zostavax (ZVL), studies report plateauing or decreasing HZ incidence in the United States among persons ≥60 years. We examined HZ incidence and ZVL coverage trends by race among Medicare beneficiaries, in the pre- and post-vaccine era. Methods We used administrative health claims from a 5% sample of Medicare beneficiaries ≥65 years. We defined incident cases as HZ in the first diagnostic position, with no HZ code in the previous year, among beneficiaries enrolled in Part A and B, from 1992 to 2015. We calculated incidence of first HZ episode by dividing the number of cases by the total number of person-years (p-y). A case was a censoring event. We used Poisson regression to compare HZ incidence by race before and after 2007. We calculated vaccine coverage by dividing the total number of persons with ZVL in Medicare Part D by the number of eligible enrollees. Results We identified 266,745 first HZ episodes. Prior to 2007, HZ incidence increased among both blacks and whites. Although incidence was double in whites vs. blacks (10.3 vs. 5.0 cases/1000 p-y), the rate of increase was similar (P = 0.75). From introduction of ZVL to 2015, HZ incidence decreased 1.8%/year in whites and did not change significantly in blacks (P < 0.001) (figure). By 2015, ZVL uptake in Medicare among blacks was less than half that among whites (7.3% vs. 19.9%). Conclusion Incidence of HZ increased at a similar rate for black and white Medicare beneficiaries in the pre-vaccine era. In the post-vaccine era, incidence has decreased among whites and plateaued among blacks. Though the reasons for racial difference and temporal changes in HZ incidence remain unknown, ecologic association suggests higher vaccination rates may contribute to steeper HZ declines among whites in the post vaccine era. Disclosures All authors: No reported disclosures.

Objectives. Exposure to varicella zoster virus through close contact with people with chickenpox was suggested to boost specific immunity, reducing the risk of herpes zoster (HZ). Since the introduction of the varicella immunization program in the U.S. in 1995, varicella morbidity has decreased substantially. This article examines incidence and risk factors associated with self-reported HZ disease and whether exposure to chickenpox within the previous decade reduces the risk of shingles in this age group. Methods. In 2004, a national random-digit dial telephone survey was used to obtain information on self-reported HZ disease, demographic characteristics, and exposure to children with chickenpox in the past decade. National estimates of the incidence of shingles disease were calculated. Results. Incidence rate of self-reported HZ was 19 per 1,000 population per year. White individuals were 3.5 times more likely to report shingles than Hispanic individuals ( pConclusions. Incidence of HZ among individuals ≥65 years of age in the U.S. may be higher than previously described in the literature, with whites being at higher risk for the disease. Currently, the potential contribution of exposure to chickenpox as a mechanism for maintaining cell-mediated immunity against HZ may be limited to a small percentage of the population. Vaccination against HZ may represent the best means of decreasing this disease burden.