Objective To evaluate the risks of herpes zoster (HZ) and herpes simplex virus infection (HSV) associated with tofacitinib compared to biologic agents among patients with rheumatoid arthritis (RA). Methods Using health plan data from 2010–2014, RA patients initiating tofacitinib or biologics with no history of HZ or HSV were identified. Incident cases of HZ or HSV within this cohort were identified. Crude incidence rates were calculated by drug exposure. Cox proportional hazards models evaluated the adjusted association between tofacitinib and HZ, and a composite outcome of HZ or HSV. Results A total of 2,526 patients initiating tofacitinib were compared with initiations of other biologics: anti-TNF (n=42,850), abatacept (n=12,305), rituximab (n=5,078), and tocilizumab (n=6,967). Tofacitinib patients were somewhat younger (mean age 55 years) versus those on other biologics, and somewhat less likely to use concomitant MTX (39% vs. 43–56%, depending on drug). Crude incidence of HZ associated with tofacitinib was 3.87/100py. After multivariable adjustment, HZ risk was significantly elevated, hazard ratio [HR] 2.01 (95%CI 1.40–2.88) compared to abatacept. Rates and adjusted HRs for all other RA biologics were comparable to each other and abatacept. Older age, female sex, prednisone >7.5mg/day, prior outpatient infection, and greater number of hospitalizations were also associated with increased HZ risk Incidence rates for the combined outcome were greatest for tofacitinib (7.61/100py) and significantly elevated after adjustment (HR=1.40, 95%CI 1.09–1.81). Conclusion The rate of zoster associated with tofacitinib was approximately double that observed in patients using biologics.

ObjectivesTofacitinib is a Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis, and has been investigated in psoriasis (PsO). Routine pharmacovigilance of an ongoing, open-label, blinded-endpoint, tofacitinib RA trial (Study A3921133; NCT02092467) in patients aged ≥50 years and with ≥1 cardiovascular risk factor identified a higher frequency of pulmonary embolism (PE) and all-cause mortality for patients receiving tofacitinib 10 mg twice daily versus those receiving tumour necrosis factor inhibitors and resulted in identification of a safety signal for tofacitinib. Here, we report the incidence of deep vein thrombosis (DVT), PE, venous thromboembolism (VTE; DVT or PE) and arterial thromboembolism (ATE) from the tofacitinib RA (excluding Study A3921133), PsA and PsO development programmes and observational studies. Data from an ad hoc safety analysis of Study A3921133 are reported separately within.MethodsThis post-hoc analysis used data from separate tofacitinib RA, PsO and PsA programmes. Incidence rates (IRs; patients with events per 100 patient-years’ exposure) were calculated for DVT, PE, VTE and ATE, including for populations stratified by defined baseline cardiovascular or VTE risk factors. Observational data from the US Corrona registries (including cardiovascular risk factor stratification), IBM MarketScan research database and the US FDA Adverse Event Reporting System (FAERS) database were analysed.Results12 410 tofacitinib-treated patients from the development programmes (RA: n=7964; PsO: n=3663; PsA: n=783) were included. IRs (95% CI) of thromboembolic events among the all tofacitinib cohorts’ average tofacitinib 5 mg and 10 mg twice daily treated patients for RA, respectively, were: DVT (0.17 (0.09–0.27) and 0.15 (0.09–0.22)); PE (0.12 (0.06–0.22) and 0.13 (0.08–0.21)); ATE (0.32 (0.22–0.46) and 0.38 (0.28–0.49)). Among PsO patients, IRs were: DVT (0.06 (0.00–0.36) and 0.06 (0.02–0.15)); PE (0.13 (0.02–0.47) and 0.09 (0.04–0.19)); ATE (0.52 (0.22–1.02) and 0.22 (0.13–0.35)). Among PsA patients, IRs were: DVT (0.00 (0.00–0.28) and 0.13 (0.00–0.70)); PE (0.08 (0.00–0.43) and 0.00 (0.00–0.46)); ATE (0.31 (0.08–0.79) and 0.38 (0.08–1.11)). IRs were similar between tofacitinib doses and generally higher in patients with baseline cardiovascular or VTE risk factors. IRs from the overall Corrona populations and in Corrona RA patients (including tofacitinib-naïve/biologic disease-modifying antirheumatic drug-treated and tofacitinib-treated) with baseline cardiovascular risk factors were similar to IRs observed among the corresponding patients in the tofacitinib development programme. No signals of disproportionate reporting of DVT, PE or ATE with tofacitinib were identified in the FAERS database.ConclusionsDVT, PE and ATE IRs in the tofacitinib RA, PsO and PsA programmes were similar across tofacitinib doses, and generally consistent with observational data and published IRs of other treatments. As expected, IRs of thromboembolic events were elevated in patients with versus without baseline cardiovascular or VTE risk factors, and were broadly consistent with those observed in the Study A3921133 ad hoc safety analysis data, although the IR (95% CI) for PE was greater in patients treated with tofacitinib 10 mg twice daily in Study A3921133 (0.54 (0.32–0.87)), versus patients with baseline cardiovascular risk factors treated with tofacitinib 10 mg twice daily in the RA programme (0.24 (0.13–0.41)).

Objective. The herpes zoster (HZ) vaccine is recommended for adults in the US ages ‡60 years who do not have weakened immune systems. It is unclear how the risk of HZ varies according to age and disease conditions in younger patients with autoimmune or inflammatory (AI) diseases. This study was undertaken to evaluate the age-stratified incidence of HZ in patients with AI diseases as compared to older adults for whom the HZ vaccine is currently recommended by the US Centers for Disease Control and Prevention.Methods. Using linked data obtained from patients who were insured by US commercial and government health care plans during the period 2007-2010, 7 cohorts of patients with AI diseases were assembled: systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), ankylosing spondylitis (AS), and gout. Two comparator cohorts were also assembled as controls: adult patients with diabetes and adult subjects without AI diseases or diabetic conditions. HZ was identified using diagnostic codes. Age-specific incidence rates (IRs) of HZ were calculated and compared to the IRs of HZ in control subjects ages 61-70 years who were without AI diseases or diabetic conditions.Results. After review of the linked data, the following number of enrollment periods were identified: 8,395 for patients with SLE, 7,916 for patients with IBD, 50,646 for patients with RA, 2,629 for patients with PsA, 4,299 for patients with PsO, 1,019 for patients with AS, 58,934 for patients with gout, 214,631 for control patients with diabetes, and 330,727 for control subjects without AI diseases and diabetic conditions. The respective highest and lowest IRs of HZ during the study were 19.9 per 1,000 person-years in the SLE cohort and 6.8 per 1,000 person-years in the gout cohort, as compared to an IR of 5.3 per 1,000 person-years in control subjects without AI diseases or diabetic conditions. The age-specific IRs of HZ in patients with RA and those with SLE ages ‡40 years were 1.5-2 times greater than those observed in

Objective The risks of hospitalized infection associated with biologic agents used to treat rheumatoid arthritis (RA) are unclear. The aim of this study was to determine whether the associated risk of hospitalized infections differed between specific biologic agents used to treat RA. Methods In a retrospective cohort study using Medicare data from 2006–2011 for all enrolled patients with RA, new episodes of treatment with etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab, and tocilizumab were identified. Patients were required to have received another biologic agent previously and to have been continuously enrolled in Medicare medical and pharmacy plans during the baseline period and throughout followup. Followup started on the date of initiation of treatment with the new biologic agent (after previous treatment with a different biologic agent) and ended on the date of the earliest hospitalized infection, at 12 months, after an exposure gap of >30 days, or at the time of death or loss of Medicare coverage. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) for hospitalized infection, adjusting for an infection risk score and other confounders. Results Of 31,801 new biologic treatment episodes in patients who had previously received another biologic agent, 12.0% were with etanercept, 15.2% with adalimumab, 5.9% with certolizumab, 4.4% with golimumab, 12.4% with infliximab, 28.9% with abatacept, 14.8% with rituximab, and 6.3% with tocilizumab. During followup, we identified 2,530 hospitalized infections; incidence rates ranged from 13.1 per 100 person‐years (abatacept) to 18.7 per 100 person‐years (rituximab). After adjustment, etanercept (HR 1.24, 95% confidence interval [95% CI] 1.07–1.45), infliximab (HR 1.39, 95% CI 1.21–1.60), and rituximab (HR 1.36, 95% CI 1.21–1.53) had significantly higher HRs for hospitalized infection compared with abatacept. Conclusion In RA patients with prior exposure to a biologic agent, exposure to etanercept, infliximab, or rituximab was associated with a greater 1‐year risk of hospitalized infection compared with the risk associated with exposure to abatacept.

No abstract