Exploration of the Product of the 5-Point Investigator's Global Assessment and Body Surface Area (IGA × BSA) as a Practical Minimal Disease Activity Goal in Patients with Moderate-to-Severe Psoriasis.

BACKGROUND/AIMS: In the treat-to-target era, psoriasis disease activity measures that can be easily performed in routine clinical practice are needed. This retrospective pooled analysis explored cutoff values of the product of the 5-point Investigator's Global Assessment and percentage of affected body surface area (IGA × BSA) correlating with achievement of minimal disease activity (MDA). METHODS: Post hoc analysis of the phase 3 clinical trials ERASURE, FIXTURE, FEATURE, and JUNCTURE was conducted to determine associations between IGA × BSA and 2 MDA definitions (Psoriasis Area and Severity Index [PASI] 90 and Dermatology Life Quality Index [DLQI] 0/1, or PASI score ≤1 or BSA <3%) in patients with moderate-to-severe psoriasis receiving secukinumab 300 mg. For each definition of MDA, a range of possible cutoff values of IGA × BSA was examined at each time point. The optimal cutoff value was determined using Youden index (YI), calculated as (sensitivity + specificity - 1). RESULTS: For MDA defined as PASI 90 and DLQI 0/1, optimal IGA × BSA cutoffs were 2.10 at week 12 (YI, 0.60; sensitivity, 0.78; specificity, 0.82), 1.02 at week 24 (YI, 0.55; sensitivity, 0.73; specificity, 0.82), and 1.00 at week 52 (YI, 0.65; sensitivity, 0.79; specificity, 0.86). For MDA defined as PASI score ≤1 or BSA <3%, optimal IGA × BSA cutoffs were 2.98 at week 12 (YI, 0.91; sensitivity, 0.99; specificity, 0.92), 2.80 at week 24 (YI, 0.94; sensitivity, 0.99; specificity, 0.95), and 3.00 at week 52 (YI, 0.96; sensitivity, 1.00; specificity, 0.96). CONCLUSION: IGA × BSA could be a valid measure highly associated with achievement of MDA.

Treatment Changes in Patients With Moderate to Severe Psoriasis: A Retrospective Chart Review.

BACKGROUND: Psoriasis treatment involves topical medications, oral medications, phototherapy, and/or biologics. The treatments used depend on a myriad of factors that change over time. OBJECTIVE: To characterise the frequency of and reasons for treatment changes in patients with moderate to severe psoriasis. METHODS: A chart review examined treatment changes at 902 visits by 116 patients seen between January 1, 2010, and June 30, 2015, for moderate to severe psoriasis and the physicians' justifications for those changes. 'Treatment change' was defined as switching between, adding, or removing medication classes or switching within the oral or biologic class. RESULTS: There were 221 visits with treatment changes identified, and a change occurred every 4.1 visits. On average, there were 1.2 treatment changes per year. Patients treated for at least 1 year averaged 1 treatment change every 16 months. The most common type of change was from one biologic to another biologic (24.9%), followed by adding a nonbiologic to a biologic (18.6%). The most common reason for switching was poor control or flare of psoriasis. Affordability was a more common problem for biologics than for nonbiologic treatments. CONCLUSIONS: Biologic treatment options provide a major improvement over older systemic treatments, but patients still undergo frequent treatment changes to help control their disease.

Incidence rates of comorbidities among patients with psoriasis in the United States.

Psoriasis is associated with a substantial burden of comorbidities; however, incidence rates (IRs) of these comorbidities following psoriasis diagnosis are not well characterized. Using administrative claims data from the Truven Health Analytics MarketScan Commercial and Medicare Supplemental Databases between January 1, 2002 and September 30, 2015, we compared the incidence of newly diagnosed comorbidities among patients with psoriasis versus demographically matched (birth year, gender, and geographic region) control patients without psoriasis in the United States. Comorbidities of interest were identified using ICD-9-CM codes. A total of 114,824 matched pairs of patients with psoriasis and control patients were included. IRs of all selected comorbidities were significantly higher among patients with psoriasis compared with controls (P<0.05). The most common newly diagnosed comorbidities in both groups were hyperlipidemia (psoriasis versus control, IR per 1,000 patient-years, 127.5 versus 102.8) and hypertension (94.3 versus 80.6). The greatest differences in IRs between patients with psoriasis and controls were observed for rheumatoid arthritis (9.7 versus 3.1; IR ratio [IRR], 3.15) and psoriatic arthritis (24.0 versus 0.2; IRR, 151.57). In this real-world study, patients with psoriasis were more likely to develop new selected comorbidities after diagnosis compared with demographically matched patients without psoriasis.

Pharmacoepidemiology of Clinically Relevant Hypothyroidism and Hypertension from Sunitinib and Sorafenib.

BACKGROUND: Thyroid dysfunction and hypertension (HTN) have been sporadically reported with sunitinib (SUN) and sorafenib (SOR). Determination of the side effect incidence will enhance monitoring and management recommendations. METHODS: An observational cohort study was performed using deidentified pharmacy claims data from a 3-year period to evaluate patients prescribed SUN, SOR, or capecitabine (CAP; comparison group). The primary outcome was time to first prescription for thyroid replacement or HTN treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox proportional hazards models. RESULTS: A total of 20,061 patients were eligible for evaluation of thyroid replacement therapy, which was initiated in 11.6% of those receiving SUN (HR, 16.77; 95% CI, 13.54-20.76), 2.6% of those receiving SOR (HR, 3.47; 95% CI, 2.46-4.98), and 1% of those receiving CAP, with median time to initiation of 4 months (range, 1-35 months). A total of 14,468 patients were eligible for evaluation of HTN therapy, which was initiated in 21% of SUN recipients (HR, 4.91; 95% CI, 4.19-5.74), 14% of SOR recipients (HR, 3.25; 95% CI, 2.69-3.91), and 5% of CAP recipients, with median time to initiation of 1 month (range, 1-18 months) for SOR and 2 months (range, 1-25 months) for SUN. CONCLUSION: SUN and SOR significantly increased the risk for clinically relevant hypothyroidism; the risk was at least 4 times greater with SUN than with SOR. Patients receiving SUN and SOR had a similar elevated risk for clinically relevant HTN. These data provide robust measures of the incidence and time to onset of these clinically actionable adverse events. The Oncologist 2017;22:208-212Implications for Practice: The side effect profiles for novel therapies are typically used to create monitoring and management recommendations using clinical trial data from patient populations that may not represent those seen in standard clinical practice. This analysis using a large pharmacy claims database better reflects typical patients treated with sorafenib or sunitinib outside of a clinical trial. The findings of increased need for thyroid replacement in patients receiving sunitinib compared with sorafenib and a similar increase in need for hypertension therapy with both agents can be used to form clinically relevant monitoring recommendations for these agents.

Treatment modifying factors of biologics for psoriatic arthritis: a systematic review and Bayesian meta-regression.

OBJECTIVES: The aim of this study was to explore factors that modify treatment effects of non-conventional biologics versus placebo in patients with psoriatic arthritis. METHODS: A systematic literature review and meta-regression was conducted. The biologics included etanercept, infliximab, adalimumab, golimumab, certolizumab, ustekinumab, tocilizumab, anakinra, abatacept, rituximab, and secukinumab. Outcomes included American College of Rheumatology (ACR) 20 and 50, Psoriasis Area Severity Index (PASI) 75, and 36-Item Short Form Health Survey (SF-36) Physical and Mental Component Summaries (PCS and MCS). RESULTS: Twelve RCTs were eligible for meta-regression. Treatment effects for ACR-20 at 12 weeks were higher in trials with longer disease durations (OR=2.94), and lower in trials enrolling older patients (OR=0.48), and those recently published (OR=0.49). Treatment effects for ACR-50 at 12 weeks were higher in trials with more males (OR=2.27), but lower in trials with high prior anti-TNF use (OR=0.28) and recently published trials (OR=0.37). For PASI-75, trials with more male patients (24 weeks: OR=2.56), and with higher swollen and tender joint counts (12 weeks: OR=8.33; 24 weeks: OR=14.44) showed higher treatment effects, and trials with high prior anti-TNF use had lower effects (OR=0.41). Treatment effects for SF-36 PCS at 24 weeks were higher in trials with longer psoriasis disease durations (OR=2.95) and PsA disease durations (OR=4.76), and those published earlier (OR=4.19). CONCLUSIONS: Our analyses show that differences in baseline characteristics may explain some of the differences in response to biologics versus placebo across different trials. Accounting for these factors in future studies will likely be important.

Burden and treatment patterns of advanced basal cell carcinoma among commercially insured patients in a United States database from 2010 to 2014.

BACKGROUND: The burden of advanced basal cell carcinoma (aBCC) is not fully understood. OBJECTIVE: To compare BCC disease burden and treatment patterns for aBCC with those for non-aBCC. METHODS: A retrospective, insurance claims-based study design was used. Adults with ≥2 claims associated with a BCC diagnosis (ICD-9-CM 173.x1) separated by ≥30 days on or after October 1, 2011, were classified as aBCC or non-aBCC by using an algorithm based on metastasis diagnosis, radiation therapy use, and medical oncologist/other specialist use. Non-aBCC and aBCC patients were matched 1:1 on the basis of age, sex, and region, and assigned the same index date (date of first qualifying diagnosis or event). Comparisons were made using Wilcoxon signed-rank (continuous variables) and McNemar's (categorical variables) tests. RESULTS: In total, 847 matched aBCC/non-aBCC patient pairs were selected (mean age 75 years; 57% men; locally advanced BCC, n = 826; metastatic BCC, n = 21). During the 12-month study period following the index date, aBCC patients had a significantly higher mean Charlson Comorbidity Index (P = .0023), significantly higher mean numbers of outpatient/dermatologist/medical oncologist visits (all P < .0001), and significantly higher mean total/medical/inpatient/outpatient/BCC treatment costs (all P < .05). LIMITATIONS: This study only included information from a database on commercial insurance and Medicare claims. The algorithm criteria might have restricted patient numbers; data were not fully reflective of targeted therapy era. CONCLUSIONS: aBCC patients had a higher disease burden than non-aBCC patients. Cost differences were largely driven by higher BCC treatment costs, specifically radiation therapy.

Drivers of Healthcare Costs Among the Costliest Patients With Psoriasis Over Three Years in a United States Health Plan.

OBJECTIVE: To compare patients with psoriasis by cost level over 3 years.

METHODS: Psoriasis patients in a large US health plan in 2011-2013 were identified. Four groups were created by healthcare costs excluding biologics: patients having top 10% of costs in all 3 years (Top), top 10% in 2 of 3 years (High), bottom 90% in 2 of 3 years (Medium), and bottom 90% in all 3 years (Bottom). Comorbidities, utilization, and costs between groups were compared.

RESULTS: The study included 18,653 patients: 514 (3%), 805 (4%), 2,443 (13%), and 14,891 (80%) patients in the Top, High, Medium, and Bottom groups, respectively. Significantly more patients in the Top vs Bottom group had diabetes (31.1% vs 9.4%), cardiovascular disease (26.5% vs 4.3%), psoriatic arthritis (25.7% vs 10.7%), depression (27.8% vs 6.9%), and anxiety (22.0% vs 7.9%) in 2011 (all P less than 0.05). Patients in the Top group had more unique 2011 prescriptions (17.7 vs 6.6; P less than 0.001) than the Bottom group, but similar biologic use (22.4% vs 21.6%). Patients in the Top, High, Medium, and Bottom groups had mean 2011 total costs of $68,913, $40,575, $24,292, and $8,815, and contributed to 14%, 13%, 23%, and 51% of the overall costs, respectively. Mean total costs increased 14-18% over time for all groups. Although mean 2011 total costs for patients in the Top group were 7.8 times of those in the Bottom group, psoriasis-related costs were less disparate ($8,716 vs $4,541). Compared with patients in the Bottom group, those in the Top group were more likely to have any 2011 hospitalization (36.8% vs 2.6%; psoriasis-related: 11.1% vs 0.7%) or emergency visit (50.8% vs 20.8%; psoriasis-related: 3.9% vs 1.0%).

CONCLUSION: The costliest patients with psoriasis had significantly higher prevalence of comorbidities, prescription fills, inpatient and emergency utilization, but not biologic medication use or biologic costs.

J Drugs Dermatol. 2017;16(7):651-658.

Incidence and prevalence of basal cell carcinoma (BCC) and locally advanced BCC (LABCC) in a large commercially insured population in the United States: A retrospective cohort study.

BACKGROUND: Accurate evaluation of basal cell carcinoma (BCC) in the United States was not possible before the 2011 release of BCC-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. OBJECTIVE: We sought to describe BCC (including locally advanced BCC [LABCC]) incidence/prevalence and the characteristics of patients in a commercially insured US population. METHODS: This retrospective cohort study used Truven Health MarketScan database insurance claims. Patients, aged 18 years or older with 2 or more BCC claims at least 30 days apart from October 1, 2011, to September 30, 2012, were continuously enrolled in medical and pharmacy benefits for 12 months before and after the index claim. A specific algorithm was used to classify patients with LABCC. RESULTS: A total of 56,987 patients with BCC were identified (39,035 incident cases; 17,952 prevalent cases). Age-adjusted BCC incidence and prevalence were 226.09 and 342.64 per 100,000 persons, respectively. These values project to 542,782 patients (incidence) and 822,593 patients (prevalence) in the 2012 US population. LABCC was uncommon (471 cases identified; projected US incidence and prevalence: 4399 and 7940 patients, respectively). LIMITATIONS: Use of medical claims data and retrospective analysis are limitations. CONCLUSION: In a study designed to distinguish patients with LABCC from the general BCC population based on BCC-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes, 0.8% were found to have LABCC, the majority having pre-existing disease.

Treatment patterns and costs for anti-TNFα biologic therapy in patients with psoriatic arthritis.

BACKGROUND: Real-world data regarding anti-tumor necrosis factor alpha (anti-TNFα) biologic therapy use in psoriatic arthritis (PsA) are limited; therefore, we described treatment patterns and costs of anti-TNFα therapy in PsA patients in the United States. METHODS: PsA patients (N = 990) aged ≥18 years who initiated anti-TNFα therapy were selected from MarketScan claims databases (10/1/2009 to 9/30/2010). Number of patients on first- (n = 881), second- (n = 72), or third- or greater (n = 37) line of anti-TNFα therapy, persistence, time-to-switch or modification, pharmacy and medical costs (measured per patient per month [PPPM]) for each line of therapy were observed during the 3-year follow-up. RESULTS: PsA patients receiving only one line of anti-TNFα therapy remained on first-line for ~17 months while those who switched to second- or third- or greater persisted on first-line for ~11 to 12 months, respectively. Time to first-line modification was longer for patients who switched to third- or greater line therapy (7 months) than those who did not switch or switched to second-line (range, ~2 to 4 months). Time-to-switch and time to first-line modification was progressively shorter with each line of therapy for patients who received third- or greater line. PPPM medical costs were higher for patients who did not switch ($322) than those who switched to second- ($167) or third- or greater ($217) line. PPPM pharmacy costs were greater for patients with third- or greater line therapy ($2539) than those who did not switch ($1985) or switched to second-line ($2045). CONCLUSION: While the majority of patients received only one line of anti-TNFα therapy, a subset of patients switched to multiple lines of therapy during the 3-year follow-up period. Persistence and therapy modifications differed between these patients and those receiving only one line. Overall medical costs were highest for patients who did not switch, and pharmacy costs increased as patients switched to each new line of therapy.

Underuse of guideline-recommended long-term asthma management in children hospitalized to the intensive care unit: a multicenter observational study.

BACKGROUND: Despite the significant burden of childhood asthma, little is known about prevention-oriented management before and after hospitalizations for asthma exacerbation. OBJECTIVE: To investigate the proportion and characteristics of children admitted to the intensive care unit (ICU) for asthma exacerbation and the frequency of guideline-recommended outpatient management before and after the hospitalization. METHODS: A 14-center medical record review study of children aged 2 to 17 years hospitalized for asthma exacerbation during 2012-2013. Primary outcome was admission to the ICU; secondary outcomes were 2 preventive factors: inhaled corticosteroid (ICS) use and evaluation by asthma specialists in the pre- and posthospitalization periods. RESULTS: Among 385 children hospitalized for asthma, 130 (34%) were admitted to the ICU. Risk factors for ICU admission were female sex, having public insurance, a marker of chronic asthma severity (ICS use), and no prior evaluation by an asthma specialist. Among children with ICU admission, guideline-recommended outpatient management was suboptimal (eg, 65% were taking ICSs at the time of index hospitalization, and 19% had evidence of a prior evaluation by specialist). At hospital discharge, among children with ICU admission who had not previously used controller medications, 85% were prescribed ICSs. Furthermore, 62% of all children with ICU admission were referred to an asthma specialist during the 3-month posthospitalization period. CONCLUSION: In this multicenter study of US children hospitalized with asthma exacerbation, one-third of children were admitted to the ICU. In this high-risk group, we observed suboptimal pre- and posthospitalization asthma care. These findings underscore the importance of continued efforts to improve prevention-oriented asthma care at all clinical encounters.

Gut microbiology of UK care home residents: a cross-sectional analysis from a randomised controlled trial.

OBJECTIVE: To describe the prevalence of potentially clinically relevant gut pathogens and associations with the carriage of resistant organisms in UK care home residents. METHODS: Stool samples were collected pre-randomisation from care home residents participating in a randomised placebo-controlled trial. Cultivable clinically relevant bacteria were analysed. Antimicrobial susceptibility testing was performed by agar dilution (amoxicillin, co-amoxiclav, gentamicin, trimethoprim, nitrofurantoin, and ciprofloxacin). We also aimed to detect resistance to third-generation cephalosporins, carbapenems, and vancomycin. RESULTS: Stool samples were available for 159/310 residents participating in the trial (51%) from 23 care homes between 2016 and 2018. In total, 402 bacterial isolates were cultured from 158 stool samples and 29 different species were cultured. The five most common species were Escherichia coli (155/158, 98%), Pseudomonas aeruginosa (40/158, 25%), Enterococcus faecalis (35/158, 22%), Enterococcus faecium (30/158, 19%), and Proteus mirabilis (25/158, 16%). Enterobacterales isolates were cultured from 157 samples (99%), and resistance to at least one of the tested antimicrobials was found in 119 of these (76%). There were high levels of variation in outcomes by care home. DISCUSSION: We demonstrated that care home residents harbour significant levels of antimicrobial-resistant organisms in their stool. This work emphasises the importance of both enhanced infection control practices and antimicrobial stewardship programmes to support the appropriate use of antimicrobials in this setting.

Determination of pericardial adipose tissue increases the prognostic accuracy of coronary artery calcification for future cardiovascular events.

OBJECTIVES: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. METHODS: 145 patients (94 males, age 60 ± 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. RESULTS: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 ± 2,269 vs. 538 ± 1,150, p < 0.01), and the CAC score was highly correlated with the relative risk of a future cardiac event: 2.4 (1.8-3.7; p = 0.01) for scores >400, 3.5 (1.9-5.4; p = 0.007) for scores >800 and 5.9 (3.7-7.8; p = 0.005) for scores >1,600. When additionally a PAT volume >200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores >400, 4.0 (2.1-5.0; p = 0.006) for scores >800 and 7.1 (4.1-10.2; p = 0.005) for scores >1,600. CONCLUSIONS: The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification.

Interaction of Therapeutic d-Peptides with Aß42 Monomers, Thermodynamics, and Binding Analysis.

The aggregation of the amyloid-ß (Aß) peptide is a major hallmark of Alzheimer's disease. This peptide can aggregate into oligomers, proto-fibrils, and mature fibrils, which eventually assemble into amyloid plaques. The peptide monomers are the smallest assembly units and play an important role in most of the individual processes involved in amyloid fibril formation, such as primary and secondary nucleation and elongation. Several d-peptides have been confirmed as promising candidates to inhibit the aggregation of Aß into toxic oligomers and fibrils by specifically interacting with monomeric species. In this work, we elucidate the structural interaction and thermodynamics of binding between three d-peptides (D3, ANK6, and RD2) and Aß42 monomers by means of enhanced molecular dynamics simulations. Our study derives thermodynamic energies in good agreement with experimental values and suggests that there is an enhanced binding for D3 and ANK6, which leads to more stable complexes than for RD2. The binding of D3 to Aß42 is shown to be weakly exothermic and mainly entropically driven, whereas the complex formation between the ANK6 and RD2 with the Aß42 free monomer is weakly endothermic. In addition, the changes in the solvent-accessible surface area and the radius of gyration support that the binding between Aß42 and d-peptides is mainly driven by electrostatic and hydrophobic interactions and leads to more compact conformations.

Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM. METHODS: Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 ± 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed. RESULTS: The mean loss of FEV1 was -2.30 ± 0.52 ml/day before therapy and a significant mean gain of FEV1 of 1.19 ± 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV1 and FVC at baseline were 1.12 ± 0.15 l (36.1 ± 4.5%pred.) and 2.47 ± 0.25 l (69.2 ± 6.5%pred.), respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated (3 months ΔFEV1: 220 ± 82 ml, p = 0.024; 6 months ΔFEV1: 345 ± 58 ml, p = 0.001); (3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy. CONCLUSIONS: Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.

Characterization of insufficient responders to anti-tumor necrosis factor therapies in patients with moderate to severe psoriasis: real-world data from the US Corrona Psoriasis Registry.

OBJECTIVE: Biologic therapies have dramatically changed the management of moderate to severe psoriasis; however, few US real-world studies characterize the unmet needs of patients who do not respond to biologic therapies. This study examined the characteristics at enrollment of patients with moderate to severe psoriasis who had insufficient responses to anti-tumor necrosis factor therapies (anti-TNFs). METHODS: Patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated an anti-TNF at enrollment were stratified on the basis of body surface area (BSA) improvement to <3% or a 75% improvement from enrollment to the 6-month follow-up visit (response versus insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for those who received anti-TNFs. RESULTS: Of 180 anti-TNF initiators who had ≥1 follow-up visit, 50.6% were classified as responders. Logistic regression modeling showed that female sex was significantly associated with a decreased likelihood of achieving a response (OR = 0.534, 95% CI = 0.289-0.988, p = .046). CONCLUSION: Despite the small sample size and short follow-up period, these findings may help dermatologists to identify patients with moderate to severe psoriasis who have unmet treatment needs.

Characterization of insufficient responders to ustekinumab in patients with moderate-to-severe psoriasis in the US Corrona Psoriasis Registry.

OBJECTIVE: Biologic therapies have revolutionized the management of moderate-to-severe psoriasis; however, there are a limited number of US real-world studies characterizing patients based on response to these treatments. This study examined characteristics at enrollment and change in outcomes of US patients with moderate-to-severe psoriasis who achieved insufficient responses with ustekinumab. METHODS: This study included patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated ustekinumab at enrollment and who were stratified based on achievement of psoriasis body surface area improving to <3% or by 75% from enrollment to the 6-month follow-up visit (response vs insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for ustekinumab responders and insufficient responders. RESULTS: Of the 178 patients who initiated ustekinumab in the Corrona Psoriasis Registry and had ≥1 follow-up visit, 99 (55.6%) were classified as responders at the 6-month follow-up visit. Logistic regression modeling showed that increasing age was significantly associated with a decreased likelihood of achieving a response (OR, 0.981 [95%CI, 0.962-0.999]; p = .049). CONCLUSIONS: These findings may help dermatologists characterize patients with moderate-to-severe psoriasis who have inadequate responses to biologic treatments.

Relationships Between Age, Frailty, Length of Care Home Residence and Biomarkers of Immunity and Inflammation in Older Care Home Residents in the United Kingdom.

Aging is associated with changes to the immune system, collectively termed immunosenescence and inflammageing. However, the relationships among age, frailty, and immune parameters in older people resident in care homes are not well described. We assessed immune and inflammatory parameters in 184 United Kingdom care home residents aged over 65 years and how they relate to age, frailty index, and length of care home residence. Linear regression was used to identify the independent contribution of age, frailty, and length of care home residence to the various immune parameters as dependent variables. Participants had a mean age (±SD) of 85.3 ± 7.5 years, had been residing in the care home for a mean (±SD) of 1.9 ± 2.2 years at the time of study commencement, and 40.7% were severely frail. Length of care home residence and frailty index were correlated but age and frailty index and age and length of care home residence were not significantly correlated. All components of the full blood count, apart from total lymphocytes, were within the reference range; 31% of participants had blood lymphocyte numbers below the lower value of the reference range. Among the components of the full blood count, platelet numbers were positively associated with frailty index. Amongst plasma inflammatory markers, C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1ra), soluble E-selectin and interferon gamma-induced protein 10 (IP-10) were positively associated with frailty. Plasma soluble vascular cell adhesion molecule 1 (sVCAM-1), IP-10 and tumor necrosis factor receptor II (TNFRII) were positively associated with age. Plasma monocyte chemoattractant protein 1 was positively associated with length of care home residence. Frailty was an independent predictor of platelet numbers, plasma CRP, IL-1ra, IP-10, and sE-selectin. Age was an independent predictor of activated monocytes and plasma IP-10, TNFRII and sVCAM-1. Length of care home residence was an independent predictor of plasma MCP-1. This study concludes that there are independent links between increased frailty and inflammation and between increased age and inflammation amongst older people resident in care homes in the United Kingdom. Since, inflammation is known to contribute to morbidity and mortality in older people, the causes and consequences of inflammation in this population should be further explored.

Combination of the Probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis, BB-12 Has Limited Effect on Biomarkers of Immunity and Inflammation in Older People Resident in Care Homes: Results From the Probiotics to Reduce Infections iN CarE home reSidentS Randomized, Controlled Trial.

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [Lacticaseibacillus (previously known as Lactobacillus) rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67-97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3-1.6 × 109 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly (p = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%).

Time to treatment failure following initiation of fingolimod versus teriflunomide for multiple sclerosis: a retrospective US claims study.

Objective: Disease modifying therapies (DMTs) for multiple sclerosis (MS) aim to delay progression and reduce relapses. Evidence is limited on the comparative effectiveness of the oral DMTs fingolimod and teriflunomide. This study evaluated time to treatment failure among patients with MS who initiated fingolimod versus teriflunomide in real-world settings.Methods: The retrospective cohort included 18-64 year old patients diagnosed with MS who initiated fingolimod or teriflunomide during 12 September 2012 to 30 September 2015 within MarketScan Commercial and Medicare Claims. Patients were followed from treatment initiation (index date) until first treatment failure or censoring. Treatment failure was defined as the first occurrence of MS relapse (identified using a validated algorithm) or treatment discontinuation (≥60 day supply gap). Treatment failure was examined through Kaplan-Meier analysis and multivariable Cox regression adjusting for 1 year baseline factors (age, gender, plan type, region, index year, prior DMT use, baseline relapses, Charlson Comorbidity Index [CCI] and MS symptoms).Results: On average, patients treated with fingolimod (n = 2704) were younger (43.6 versus 49.8 years) with lower CCI (0.4 versus 0.7) and more relapses at baseline (0.46 versus 0.42) than those treated with teriflunomide (n = 1859). Median time to treatment failure was 19.5 months with fingolimod versus 9.6 months with teriflunomide (p < .001). After controlling key demographic and clinical characteristics through multivariable regression, fingolimod was associated with 38.9% lower hazards of treatment failure versus teriflunomide (adjusted hazard ratio = 0.611; 95% CI: 0.559-0.669; p < .001).Conclusions: In a large cohort of US adults with MS, controlling for key baseline characteristics, fingolimod was associated with significantly longer time to treatment failure and lower risk of treatment failure compared with teriflunomide.

In Vitro Effects of Live and Heat-Inactivated Bifidobacterium animalis Subsp. Lactis, BB-12 and Lactobacillus rhamnosus GG on Caco-2 Cells.

Probiotic-host interaction can be cell-to-cell or through metabolite production. Dead (inactive) organisms could interact with the host, leading to local effects and possible health benefits. This research examined the effects of live and heat-inactivated Bifidobacterium animalis subsp. lactis, BB-12 (BB-12) and Lactobacillus rhamnosus GG (LGG) on cultured Caco-2 cells focusing on epithelial integrity and production of inflammatory mediators. Live organisms increased transepithelial electrical resistance (TEER), a barrier-integrity marker, with LGG having a greater effect than BB-12. When mildly heat-treated, both organisms had a more modest effect on TEER than when alive. When they were heat-inactivated, both organisms had only a limited effect on TEER. Neither live nor heat-inactivated organisms affected production of six inflammatory mediators produced by Caco-2 cells compared to control conditions. Pre-treatment with heat-inactivated LGG or BB-12 did not alter the decline in TEER caused by exposure to an inflammatory cocktail of cytokines. However, pre-treatment of Caco-2 cells with heat-inactivated organisms alone or their combination decreased the production of interleukin (IL)-6, IL-18, and vascular endothelial growth factor. To conclude, while the live organisms improve the epithelial barrier using this model, neither live nor heat-inactivated organisms directly elicit an inflammatory response by the epithelium. Pre-treatment with heat-inactivated BB-12 or LGG can reduce some components of the response induced by an inflammatory stimulus.