Baojin Zhu

Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus—the Hopkins Lupus Cohort

Objectives The impact of corticosteroids on the risk of organ damage in the context of clinical end points endorsed in some systemic lupus erythematosus (SLE) clinical trials is underexplored. Methods We analysed data from the Hopkins Lupus Cohort using Cox proportional hazards models to understand the impact of exposure to different corticosteroid doses on the risk of developing any new organ damage or any new organ damage at the individual organ systems over time. Results Mean prior prednisone dose, recent disease activity and immunosuppressant use during follow-up, as well as organ damage score at cohort entry, were significant independent predictors of the risk of developing any new organ damage. Even after adjustment for recent disease activity, there was a dose-response relationship across the different levels of exposure to prednisone during follow-up and the risk of developing any new organ damage. The risk more than doubled in patients exposed to a mean prior prednisone dose of ≥20 mg/day versus <7.5 mg/day (HR=2.514, p<0.001). It was estimated that a 1 mg/day increase in prior prednisone dose during follow-up was associated with a 2.8% increase in the risk of developing new organ damage. For individual organ systems, exposure to a mean prior prednisone dose of ≥7.5 mg/day versus <7.5 mg/day significantly increased the risk of developing cataracts (HR=2.41, p<0.001), osteoporotic fractures (HR=2.16, p<0.001) and cardiovascular damage (HR=1.54, p=0.041), but showed no significant difference for renal damage (HR=1.44, p=0.163) or for other individual organ systems. Conclusions Organ damage in SLE is multifactorial; corticosteroid treatment and disease activity play a role.

Prevalence and incidence rates of cardiovascular, autoimmune, and other diseases in patients with psoriatic or psoriatic arthritis: a retrospective study using Clinical Practice Research Datalink

Previous studies have demonstrated that patients with psoriasis have higher rates of comorbidities compared to the general population. Despite the clinical and economic burden of psoriatic disease, there have been few large‐scale observational studies focused on this condition.

Improvement of scalp and nail lesions with ixekizumab in a phase 2 trial in patients with chronic plaque psoriasis

Scalp and nail psoriasis have a major impact on quality of life and are traditionally resistant to therapy. Ixekizumab is a monoclonal antibody that targets IL‐17A, a key cytokine in psoriasis pathogenesis.

Factors associated with clopidogrel use, adherence, and persistence in patients with acute coronary syndromes undergoing percutaneous coronary intervention

Abstract Objective: Recent guidelines recommend use of aspirin and either clopidogrel or prasugrel for at least 12 months following use of drug-eluting or bare metal stents in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). This study evaluated factors associated with clopidogrel use and adherence in ACS patients following PCI. Research design and methods: The US employer-based MarketScan commercial claims database was used to examine factors associated with clopidogrel use and adherence. Adherence was defined as a medication possession ratio of 80% or higher. Multivariate logistic regression analyses were conducted to identify factors associated with clopidogrel use and adherence and included patient demographics, comorbidities, and prior beta-blocker, statin, and angiotensin converting enzyme inhibitor (BSI) use as factors. Results: A total of 10,465 patients aged 18–65 years who met inclusion criteria were hospitalized for ACS and underwent PCI between 01/01/2005 and 12/31/2006. Overall, the rate of clopidogrel use was 92.8% for ACS-PCI patients and 66.8% of the clopidogrel users were adherent. Receiving PCI without stenting (Odds Ratio [OR] = 3.28), comorbid hypertension (OR = 1.50), diabetes (OR = 1.49), and atrial fibrillation (OR = 1.91) were associated with decreased filled prescriptions for clopidogrel. Younger age (OR = 0.83) and prior use of clopidogrel (OR = 0.54) or other BSI medications (OR = 0.44) were associated with increased use of clopidogrel (all p values < 0.05). Factors significantly associated with non-adherence of clopidogrel were prior use of clopidogrel (OR = 1.40), prior hospitalization (OR = 1.34), chronic pulmonary disease (OR = 1.31), PCI without stenting (OR = 1.32), diabetes (OR = 1.17), and younger age (OR = 1.29). Prior use of BSI medications (OR = 0.82) increased adherence to clopidogrel. Conclusions: Prior use of clopidogrel, comorbid conditions such as diabetes and chronic pulmonary disease, prior hospitalization, PCI without stenting, and younger age had a negative impact on clopidogrel adherence. These findings may assist programs to improve thienopyridine compliance through a better understanding of patients’ disease profiles and concomitant medication use.

Itching is a significant problem and a mediator between disease severity and quality of life for patients with psoriasis: results from a randomized controlled trial.

In patients with moderate‐to‐severe psoriasis, health‐related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity.

Early clinical response as a predictor of subsequent response to ixekizumab treatment: results from a phase II study of patients with moderate‐to‐severe plaque psoriasis

Early identification of responsiveness to biologic treatments in psoriasis has significant clinical and economic implications.

Effect of pitavastatin vs. rosuvastatin on international normalized ratio in healthy volunteers on steady-state warfarin

Abstract Objective: Statins have been shown to impact international normalized ratio (INR) when coadministered with warfarin. The aim of this study was to assess the effect of pitavastatin compared with rosuvastatin on steady-state pharmacodynamics (PD) of warfarin by measuring INR in healthy adult subjects. Methods: Subjects received oral doses of warfarin 5 mg once daily on days 1 through 3. The dose was titrated on days 4 through 9 to reach a steady-state INR of 1.5 to 2.2. Warfarin was continued on days 10 through 21 and pitavastatin 4 mg or rosuvastatin 40 mg was administered once daily on days 14 through 22. After a 14-day washout period, the process was repeated with the alternate statin. Study number: NK-104-4.03US. Results: For pitavastatin, mean INR changed from 1.73 ± 0.18 (n = 42) on day 14 before starting statin dosing, to 1.78 ± 0.29 (n = 42) on day 22 at treatment end; the difference in INR was not significant (p = 0.219). For rosuvastatin, mean INR increased significantly from 1.74 ± 0.20 (n = 43) at baseline to 1.90 ± 0.30 (n = 43) at treatment end (p < 0.001). Rosuvastatin caused a significantly greater increase in INR than pitavastatin (p < 0.001). Conclusion: Steady-state INR during warfarin treatment did not change significantly when pitavastatin 4 mg was added to the regimen, while a significant increase was observed when rosuvastatin 40 mg was added. The effect of rosuvastatin on INR was significantly larger than the effect of pitavastatin. This study is limited because it was done in healthy volunteers. Further studies in patient populations are needed to better understand the clinical significance of the results.

Effect of Ixekizumab Treatment on Work Productivity for Patients With Moderate-to-Severe Plaque Psoriasis: Analysis of Results From 3 Randomized Phase 3 Clinical Trials

IMPORTANCE Therapies that reduce psoriasis symptoms may improve work productivity. OBJECTIVE To assess the effect of ixekizumab therapy on work productivity, measured by the Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO). DESIGN, SETTING, AND PARTICIPANTS Three multicenter, randomized double-blind phase 3 trials conducted during the following periods: December 2011 through August 2014 (UNCOVER-1), May 2012 through April 2015 (UNCOVER-2), and August 2012 through July 2014 (UNCOVER-3). Adult outpatients with moderate-to-severe chronic plaque psoriasis were included. INTERVENTIONS In UNCOVER-1, patients were randomized 1:1:1 to subcutaneous placebo or 80 mg ixekizumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 12 weeks; UNCOVER-2 and UNCOVER-3 also had an etanercept arm (50 mg twice weekly). Maintenance of initial ixekizumab response was evaluated in UNCOVER-1 and UNCOVER-2 during a randomized withdrawal period following week 12 through week 60. The WPAI-PSO questionnaire was administered at baseline and week 12 for all patients and at weeks 24, 36, 52, and 60 for patients in UNCOVER-1 and UNCOVER-2. MAIN OUTCOMES AND MEASURES Change in work productivity from baseline as measured by WPAI-PSO scores. RESULTS Across trials, 5101 patients consented; 3866 were randomized (mean [SD] age, UNCOVER-1, 45.7 [12.9] y, 68.1% male; UNCOVER-2: 45.0 [13.0] y, 67.1% male; UNCOVER-3: 45.8 [13.1] y, 68.2% male). At week 12 in UNCOVER-1, the ixekizumab Q4W and ixekizumab Q2W groups showed significantly greater improvements in WPAI-PSO scores (least squares mean change from baseline [SE]) relative to placebo: absenteeism (-3.5 [0.87], P < .001; -2.6 [0.84], P = .003, respectively, vs 0.2 [0.88]), presenteeism (-18.8 [1.28], P < .001; -18.3 [1.24], P < .001, vs 0.5 [1.30]), work productivity loss (-20.6 [1.38], P < .001; -19.8 [1.33], P < .001, vs -0.8 [1.40]), and activity impairment (-24.5 [1.18], P < .001; -25.2 [1.15], P < .001, vs 0.8 [1.18]). Similar results were obtained for UNCOVER-2 and UNCOVER-3, with the exception of absenteeism with ixekizumab Q4W in UNCOVER-2. Additionally, ixekizumab-treated patients showed significantly greater improvements in WPAI-PSO scores vs etanercept-treated patients: UNCOVER-2: presenteeism, work productivity loss, activity impairment (P < .001 both doses), UNCOVER-3: activity impairment (ie, regular activities outside of work) (ixekizumab Q2W; P = .009). Improvements in WPAI-PSO scores at week 12 were sustained to at least week 60. CONCLUSIONS AND RELEVANCE Ixekizumab-treated patients reported short- and long-term improvements in work productivity, which could lead to reduced productivity-related cost burden in patients with psoriasis. TRIAL REGISTRATION clinicaltrials.gov Identifiers: NCT01474512, NCT01597245, NCT01646177.

Treatment Patterns and Health Care Costs for Patients With Psoriatic Arthritis on Biologic Therapy: A Retrospective Cohort Study

BACKGROUND Biologic therapies have been used in patients with psoriatic arthritis (PsA) who have been inadequately treated with conventional disease-modifying anti-rheumatic drugs (DMARDs). OBJECTIVE Examine treatment patterns and health care costs among patients with PsAs who initiated biologic therapy either as monotherapy or adjunctively with traditional DMARDs. METHODS The MarketScan(®) database was used to identify adults with PsA who initiated therapy with a biologic (with first use identified as index date). Patients were required to have a 6-month pre-period with no biologic use and 1 year insurance eligibility pre- and post-index date. Cohorts of patients initiating biologic therapy either as monotherapy or adjunctively with traditional DMARDs were created. Medication use patterns including discontinuation, switching, and restarting were identified during the 1-year follow-up period. Cox proportional hazards models were conducted to compare time to discontinuation of index biologic, and logistic models were used to compare the rate of discontinuation and biologic switching between the 2 cohorts. All-cause and PsA-related costs were compared between the 2 cohorts using propensity score-adjusted bootstrapping methods. All comparisons were made after adjusting for age, sex, Charlson comorbidity index, and PsA-related total cost over 1-year pre-index date. RESULTS Among the 3164 PsA patients identified, 67.7% initiated biologics as monotherapy and 32.3% initiated biologics adjunctively with traditional DMARDs. The number of patients on pain medications, topical medications, and traditional DMARDs was significantly lower post index date compared to pre-index date (P < 0.01), while use of antihypertensives, antidiabetics, and statins increased after patients initiated biologic therapy. In 1-year post-period, approximately half of the patients (50.9%) who initiated a biologic continued their index biologic with an average time to discontinuation of 279.8 days for all patients. Rates of discontinuation, switching, and restart were 33.1%, 9.9%, and 6.1%, respectively, for all patients. Rates of switching and restart were similar between the 2 cohorts, but a significantly lower rate of discontinuation was observed in the biologic plus traditional DMARDs cohort than the biologic monotherapy cohort. Pharmacy expenditures were higher for the biologic + DMARD cohort than the biologic-monotherapy cohort (

A high level of clinical response is associated with improved patient‐reported outcomes in psoriasis: analyses from a phase 2 study in patients treated with ixekizumab

14,486 vs