Background Shingrix™ (recombinant zoster vaccine) was licensed to prevent herpes zoster, dispensed as two doses given 2–6 months apart, among adults ages ≥50 years. Clinical trials yielded efficacy of >90% for confirmed herpes zoster,but post-market vaccine performance has not been evaluated. Efficacy of a single dose, delayed second dose, or among persons with autoimmune or general immunosuppressive conditions have also not been studied. We aimed to assess post-market vaccine effectiveness of Shingrix. Methods We conducted a cohort study among vaccinated and unvaccinated Medicare Part D community dwelling beneficiaries ages >65 years. Herpes zoster was identified using a medical office visit diagnosis with treatment, and postherpetic neuralgia using a validated algorithm. We used inverse probability of treatment weighting to improve cohort balance, and marginal structural models to estimate hazard ratios. Results We found a vaccine effectiveness of 70.1% (95% CI, 68.6–71.5) and 56.9% (95% CI, 55.0–58.8) for two and one doses, respectively. The two-dose vaccine effectiveness was not significantly lower for beneficiaries 80+ years, for second doses received at ≥180 days, or for individuals with autoimmune conditions. The vaccine was also effective among individuals with immunosuppressive conditions. Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4-81.8). Conclusions This large real-world observational study of effectiveness of Shingrix demonstrates the benefit of completing the two-dose regimen. Second doses administered beyond the recommended 6 months did not impair vaccine effectiveness.Our effectiveness estimates were lower than the clinical trials estimates, likely due to differences in outcome specificity.

IMPORTANCE Previous studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use.OBJECTIVE To examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings. DESIGN, SETTING, AND PARTICIPANTS This retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019. EXPOSURES Insulin glargine, insulin detemir, and NPH insulin. MAIN OUTCOMES AND MEASURESThe primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age. RESULTSOf the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use. CONCLUSIONS AND RELEVANCEIn this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.

ImportanceThe association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described.ObjectiveTo evaluate the association of PCV13 use with pneumonia, non–health care–associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older.Design, Setting, and ParticipantsThis cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022.ExposuresUse of PCV13 vaccination 14 days or more before pneumonia hospitalization.Main Outcomes and MeasuresDiscrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE).ResultsAt the end of follow-up (December 2017), 24 121 625 beneficiaries (13 593 975 women [56.4%]; 418 005 [1.7%] Asian, 1 750 807 [4.8%] Black, 338 044 [1.4%] Hispanic, 111 508 [0.5%] Native American, and 20 700 948 [85.8%] White individuals) were in the cohort; 4 936 185 (20.5%) had received PCV13 only, and 10 646 220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35 127 pneumonia (95% CI, 33 011-37 270), 24 643 non-HA pneumonia (95% CI, 22 761-26 552), and 1294 LP (95% CI, 797–1819) hospitalizations were averted through PCV13 use.Conclusions and RelevanceThe study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults.

BackgroundPneumococcal conjugate vaccine (PCV13) was recommended in series with PPSV23 for all US adults ≥65 years in late 2014. We evaluated effectiveness of PCV13 against invasive pneumococcal disease (IPD) among Medicare beneficiaries ≥65 years old to assess this new policy.MethodsWe linked records for IPD cases (pneumococcus isolated from sterile sites) in persons ≥65 years old identified through Active Bacterial Core surveillance with those of Medicare beneficiaries. Isolates were serotyped and classified as PCV13 (with or without cross-reacting type 6C), and nonvaccine types. We selected Medicare beneficiaries with no record of IPD or pneumonia as controls, and matched to cases on age, residence census tract, and length of Medicare enrollment; we included all eligible controls. Vaccination and medical histories were obtained through Medicare. We estimated vaccine effectiveness (VE) as 1 minus the IPD odds ratio for vaccinated (PCV13) vs. unvaccinated (no PCV13 or PPSV23) persons using conditional logistic regression, adjusted for sex and underlying conditions.ResultsFrom 2,246 IPD cases identified in 2015–2016, 1,017 (45%) were matched to Medicare beneficiaries. After excluding cases in persons residing in long-term care facilities or with <1 year of Medicare enrollment, we included 699 eligible cases and 10,152 controls in our analysis. PCV13-types (+6C) accounted for 164 (23%) cases, and serotype 3 was the most common PCV13-type. Case patients were more likely than controls to have one or more chronic (88% vs. 58%) or immunocompromising (54% vs. 32%) conditions present. Fourteen percent, 22%, and 8% of case patients, and 18%, 21%, and 8% of controls received PCV13 only, PPSV23 only, or both vaccines, respectively. PCV13-only VE against PCV13-types was 36% (95% CI −18, 65%). When we included type 6C with PCV13-types, VE was 67% (95% CI 11, 88%). PCV13 showed similar effectiveness against PCV13 type (+6C) IPD among adults >75 years of age (VE 61%, 95% CI 14, 82). VE was 26% (95% CI −58, 65%) against serotype 3 and 67% (95% CI 11, 88%) against other PCV13-types (+6C). PCV13 was not effective against nonvaccine types.ConclusionPCV13 was effective in preventing IPD caused by PCV13 types when excluding type 3; no effectiveness was demonstrated against serotype 3.Disclosures W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee. Pfizer: Member, Data Safety Monitoring Board, Consulting fee. Dynavax: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. SutroVax: Consultant, Consulting fee. Shionogi: Consultant, Consulting fee.

BackgroundEfficacy of 13-valent pneumococcal conjugate vaccine (PCV13) against pneumococcal pneumonia in adults aged >65 years was shown in a 2014 clinical trial. However, its benefits in countries with a mature PCV infant program remain unclear. In August 2014, PCV13 was recommended for all US adults aged >65 years. We evaluated the direct effect of this recommendation on pneumonia hospitalizations among the elderly.MethodsWe analyzed claims data from US Medicare beneficiaries aged >65 years enrolled in part A/B during September 1, 2014 through December 31, 2017. Participants were followed until they died, left part A/B, or developed a study outcome: community-acquired pneumonia (CAP), non-healthcare-associated CAP (non-HA CAP) or lobar pneumonia (LP). We identified outcomes using inpatient diagnosis codes, and vaccination status using procedure codes. We used discrete-time survival models, stratified by influenza season (October–April) and influenza vaccination status, to estimate incidence rate ratios (IRR) by pneumococcal vaccination status (PCV13-only vs. no pneumococcal vaccination). We adjusted for demographic factors, healthcare utilization, month/year of hospital discharge, and underlying conditions. We derived vaccine effectiveness (VE) and number of hospitalizations averted by PCV13 from the IRRs.ResultsOf 26.6 million beneficiaries in September 2014, 43.4% were male, 54.2% were aged 65–74 years, and 28.9% had a Charlson comorbidity score >3. PCV13 coverage increased from 0.8% in September 2014 to 41.5% in December 2017. Annual incidence of CAP, non-HA CAP, and LP are shown in the figure. PCV13-vaccinated persons were more likely to be older, sicker, and have received flu vaccine than unvaccinated persons. VE estimates for CAP, non-HA CAP, and LP ranged from 6.0–11.4%, 5.0–11.0%, and 1.3–11.0%, respectively. From September 2014 to December 2017, an estimated 28,600 (95% CI: 21,000–36,000) CAP, 18,700 (12,000–25,800) non-HA CAP and 1,100 (190–1,900) LP hospitalizations were averted.ConclusionWithin 40 months after implementation of the adult PCV13 program, 2.0% (28,600) of US CAP hospitalizations were averted. Despite PCV13 effectiveness against adult CAP, only a small fraction of CAP hospitalizations was prevented. Disclosures All authors: No reported disclosures.