Real-world use of bevacizumab-awwb, a bevacizumab biosimilar, in US patients with metastatic colorectal cancer.

Aim: Evaluated real world use of bevacizumab-awwb (MVASI®), a bevacizumab biosimilar, for treating metastatic colorectal cancer (mCRC). Materials & methods: Adult mCRC patients who received bevacizumab-awwb during the first year after market availability were identified from the ConcertAI oncology dataset. Results: Of 304 patients, 47% initiated bevacizumab-awwb as reference product (RP) naive patients and 53% received bevacizumab-awwb with prior exposure to RP. Overall, 78% received bevacizumab-awwb as first-line therapy; the proportion was higher (91%) in RP-naive patients. Among RP-experienced patients, 83% were transitioned from RP to bevacizumab-awwb in the same line without disease progression; of those, the majority (83%) were transitioned within 28 days. Conclusion: Early evidence from US oncology practices suggests clinical adoption of bevacizumab-awwb in treating mCRC patients.

Persistence on biologic DMARD monotherapy after achieving rheumatoid arthritis disease control on combination therapy: retrospective analysis of corrona registry data.

Biological disease-modifying antirheumatic drugs (bDMARDs) monotherapy may enhance adherence and decrease adverse events compared to combination therapy with conventional synthetic DMARDs (csDMARDs); however, persistence with bDMARD monotherapy has not been extensively studied. We explore persistence of etanercept monotherapy and monotherapy with other tumor necrosis factor inhibitors (TNFis) among patients first achieving remission/low disease activity (LDA) while on combination therapy with csDMARDs and a TNFi. Using Corrona registry data, the percentage of patients persistent with the index TNFi (etanercept versus other TNFis) over 6 and 12 months was determined. Factors influencing persistence and treatment patterns at 6 and 12 months were examined. Among 617 eligible patients, 56% of 182 patients on etanercept and 45% of 435 patients on other TNFis persisted with monotherapy at 6 months, 46% and 33%, respectively, at 12 months. Across first-line and subsequent biologic DMARDs, etanercept persistence was greater than other TNFi persistence by 10.8% (95% CI 2.1%, 19.6%) at 6 months and 11.4% (95% CI 0.9%, 21.9%) at 12 months. Patients on other TNFis were more likely to require reintroduction of csDMARD after 6 months (45% versus 35% for etanercept). Remission was the key predictor of persistence for both etanercept and other TNFi monotherapies. This retrospective, cohort study of registry data reflecting real-world practice indicates patients who achieve remission/LDA with combination csDMARD and TNFi therapy may successfully transition to TNFi monotherapy. Patients on etanercept monotherapy experienced greater persistence and less frequent reintroduction of a csDMARD than was observed for patients on other TNFi monotherapies.

Utility of administrative and clinical data to predict major change in medical treatment in US Veterans enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry.

OBJECTIVES: To examine factors associated with major therapeutic changes (MTC) among US Veterans with moderate/severe rheumatoid arthritis (RA) based on Disease Activity Score based on 28 joints (DAS28). METHODS: We used data from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry from 1/1/2006 through 12/31/2014. The index date was a clinic visit with DAS28 >3.2 (moderate/severe disease) following an 18-month pre-index period that included ≥2 DAS28 measurements ≥60 days apart. The patients were followed for MTC from 7 days pre-index through 90 days post-index. Poisson multivariable regression models were used to identify associations with MTC. Chart review of a subset of randomly selected patients explored factors that impacted therapeutic decisions. RESULTS: Among 941 patients, 396 (42.1%) had MTC. Of these, 369 (39.2%) patients had worsening DAS28 at index, 118 (12.5%) had DAS28 improvements, and 454 (48.2%) patients had no change in DAS28 versus pre-index DAS28. Of the patients with worsening DAS28, no change in DAS28, and improved DAS28, respectively, 50.5%, 62.6%, and 70.3% had no MTC. Regression analyses showed index DAS28, oral steroid or non-biologic disease-modifying anti-rheumatic drug (nbDMARD) use in the previous year were associated with an increased likelihood of MTC; use of nbDMARDs in the previous 90 days was associated with a decreased likelihood of MTC. The most common reason for not modifying therapy despite DAS28 >3.2 was a judgement of mild disease. CONCLUSIONS: Clinicians frequently do not institute major therapeutic changes despite DAS28 indicating moderate/severe disease activity; multiple factors are involved in real-world treatment decisions.

Persistence of tumor necrosis factor inhibitor or conventional synthetic disease-modifying antirheumatic drug monotherapy or combination therapy in psoriatic arthritis in a real-world setting.

This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as "existing use" starting before registry entry or "initiated use" starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with < 12 months of follow-up after first use. Among evaluable patients who initiated use of TNFi monotherapy (n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with < 12 months of follow-up after first use. After initiation of index therapy, most changes (19-27% of patients) were discontinuation; 4-13% switched biologic therapy during follow-up. The results of this analysis of real-world treatment patterns in a PsA patient registry suggest that nonpersistence for TNFi monotherapy, csDMARD monotherapy, or TNFi/csDMARD combination therapy occurs more commonly after initiation of therapy than in patients with existing therapy. Trial registration: NCT02530268.

A retrospective cohort study to evaluate the development of comorbidities, including psychiatric comorbidities, among a pediatric psoriasis population.

BACKGROUND/OBJECTIVE: Compared with the adult psoriasis population, knowledge about the incidence of comorbidities in the pediatric psoriasis population is limited. The objective of this study was to assess the prevalence and incidence of comorbidities, including psychiatric comorbidities, in patients with pediatric psoriasis. METHODS: In this claims-based, retrospective cohort study, patients with pediatric psoriasis were matched 1:3 with a nonpsoriasis cohort based on age, sex, and index date (the earliest of inpatient claims or the latter of two outpatient claims). RESULTS: Obesity, serious infection, and juvenile idiopathic arthropathy had higher prevalence and incidence rates in the psoriasis cohort than the nonpsoriasis cohort. Psychiatric comorbidities were also more common in the psoriasis cohort than the nonpsoriasis cohort, as were ulcerative colitis and Crohn disease. Stratifying the psoriasis cohort by disease severity-mild and moderate-to-severe-found no differences in incidence rates of comorbidities between the two subsets. CONCLUSION: The incidence rates of many comorbid conditions were higher for patients with pediatric psoriasis compared with patients without pediatric psoriasis, and similar between patients with moderate-to-severe and mild pediatric psoriasis.

Pregnancy and infant outcomes including major congenital malformations among women with chronic inflammatory arthritis or psoriasis, with and without etanercept use.

PURPOSE: Objectives were to quantify prevalence estimates of pregnancy and infant outcomes including major congenital malformations (MCMs) by etanercept (ETN) exposure among infants born to women with chronic inflammatory arthritis (cIA) or psoriasis (PsO). METHODS: Claims-based data delineated pregnancy exposures and outcomes of live or nonlive births among women with cIA and PsO (ETN exposed, unexposed) and general population (GP) comparators. Infant outcomes were determined for live-born infants covered by the mother's insurer. Medical records were obtained from all accessible mother-infant pairs with claims for MCMs and a random sample of mothers. Multivariable logistic regression estimated the odds ratios (ORs) of having at least one algorithm-defined MCM in the ETN-exposed cohorts versus unexposed comparators. RESULTS: Prevalence estimates for pregnancy outcomes were comparable across cIA and PsO cohorts. Algorithm-defined prevalence estimates of having at least one MCM were 6.1% (ETN exposed), 5.5% (unexposed), and 5.7% (GP cohort) for the cIA cohort; PsO cohort estimates were 2.0%, 4.2%, and 4.7%, respectively. The ETN-exposure ORs for having at least one algorithm-defined MCM among infants of cIA mothers was 1.03 (95%CI: 0.51-2.10) and 0.39 (95%CI: 0.05-2.98) among infants of PsO mothers. Logistic regression with inverse probability of treatment weighting that included disease state resulted in an OR of 0.65 (0.24, 1.72). CONCLUSIONS: Overall, this study did not identify any new safety concerns associated with the use of etanercept during pregnancy. Etanercept, along with the other TNFis, remains a treatment without well-controlled clinical trials in pregnant women. Patients should continue to consult their doctor regarding benefit risk decisions of TNFi therapy during pregnancy.

Dose relationship between oral glucocorticoids and tumor necrosis factor inhibitors and the risk of hospitalized infectious events among patients with rheumatoid arthritis.

The objective of this study was to evaluate the impact of oral glucocorticoid (GC) dose on rates of hospitalized infectious events (HIEs) among RA patients newly exposed to tumor necrosis factor inhibitor (TNFi) therapy. This retrospective cohort study used data from the MarketScan claims database. Incident and prevalent adult RA patients newly exposed to TNFi therapy were identified and assigned to three cohorts: no GC, low-dose GC (≤7.5 mg), and high-dose GC (>7.5 mg); patients could contribute exposure time to multiple cohorts if they changed dose or discontinued GC. The primary outcome was estimated incidence rate (IR) of HIEs per 100 patient-years of GC exposure. A total of 40,933 eligible patients were identified (mean age 53.0 years; 77.4% female). HIE risk increased with increasing GC dose: the IR [95% confidence interval (CI)] was 3.9 (3.63-4.13) for no GC; 6.4 (5.68-7.16) for low-dose GC; and 13.3 (11.9-15.5) for high-dose GC. Adjusted rate ratios (95% CI) were 1.4 (1.21-1.60) for low-dose vs no GC; 2.8 (2.32-3.34) for high-dose vs no GC, and 2.0 (1.66-2.45) for high-dose vs low-dose GC. The risk of HIEs increased with increasing age. HIE risk did not increase with longer exposure to GCs. Oral GCs, regardless of dose, significantly increased the risk of HIEs among RA patients newly initiating TNFi therapy. Steroid dosing must be considered when assessing infection risk in treatment decisions for RA patients.

OBSERVE-5: observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results.

BACKGROUND: OBSERVE-5 was a 5-year Food and Drug Administration-mandated surveillance registry of patients with psoriasis. OBJECTIVE: We sought to assess long-term etanercept safety and effectiveness. METHODS: Patients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events, serious infectious events, events of medical interest, psoriasis-affected body surface area, physician global assessment score, and Dermatology Life Quality Index score. Safety outcomes were assessed relative to data from the MarketScan database. RESULTS: For 2510 patients, 5-year cumulative incidence was 22.2% (95% confidence interval [CI] 20.3%-24.2%) for serious adverse events; 6.5% (95% CI 5.4%-7.7%) for serious infectious events; 3.2% (95% CI 2.3%-4.1%) for malignancies excluding nonmelanoma skin cancer; 3.6% (95% CI 2.7%-4.5%) for nonmelanoma skin cancer; 2.8% (95% CI 2.0%-3.6%) for coronary artery disease; 0.7% (95% CI 0.3%-1.2%) for psoriasis worsening; 0.2% (95% CI 0.0%-0.4%) for central nervous system demyelinating disorder; 0.1% (95% CI 0.0%-0.3%) for lymphoma and for tuberculosis; and 0.1% (95% CI 0.0%-0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, nonmelanoma skin cancer, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years. LIMITATIONS: No internal comparator group was included; rare events may not have been detected. CONCLUSION: No new safety signals were observed with long-term, real-world etanercept use.

Real-world outcomes among patients with metastatic colorectal cancer treated first line with a bevacizumab biosimilar (bevacizumab-awwb).

Background: Bevacizumab-awwb (MVASI®) was the first U.S. Food and Drug Administration-approved biosimilar to Avastin® (reference product [RP]) for the treatment of several different types of cancers, including metastatic colorectal cancer (mCRC), an indication approved based on extrapolation. Objectives: Evaluate treatment outcomes in mCRC patients who received first-line (1L) bevacizumab-awwb at treatment initiation or as continuing bevacizumab therapy (switched from RP). Design: A retrospective chart review study. Methods: Adult patients who had a confirmed diagnosis of mCRC (initial presentation of CRC on or after 01 January 2018) and initiated 1L bevacizumab-awwb between 19 July 2019 and 30 April 2020 were identified from the ConcertAI Oncology Dataset. A chart review was conducted to evaluate patient baseline clinical characteristics and effectiveness and tolerability outcomes during the follow-up. Study measures were reported stratified by prior use of RP: (1) naïve patients and (2) switchers (patients who switched to bevacizumab-awwb from RP without advancing the line of therapy). Results: At the end of study period, naïve patients (n = 129) had a median 1L progression-free survival (PFS) of 8.6 months [95% confidence interval (CI), 7.6-9.9] and a 12-month overall survival (OS) probability of 71.4% (95% CI, 61.0-79.5%). Switchers (n = 105) had a median 1L PFS of 14.1 months (95% CI, 12.1-15.8) and a 12-month OS probability of 87.6% (95% CI, 79.1-92.8%). During treatment with bevacizumab-awwb, 20 events of interest (EOIs) were reported in 18 naïve patients (14.0%) and 4 EOIs reported in 4 switchers (3.8%), of which the most commonly reported events were thromboembolic and hemorrhagic events. Most EOIs resulted in emergency department visit and/or treatment hold/discontinuation/switch. None of the EOIs resulted in death. Conclusion: In this real-world cohort of mCRC patients who were treated 1L with a bevacizumab biosimilar (bevacizumab-awwb), the clinical effectiveness and tolerability data were as expected and consistent with previously published findings from real-world studies of bevacizumab RP in mCRC patients.

Potential for Major Therapeutic Changes to Produce Significant Clinical Response Across a Broad Range of Disease Activity: An Observational Study of US Veterans With Rheumatoid Arthritis.

OBJECTIVE: To examine the impact of major therapeutic change (MTC) on clinical response across a broad range of disease activity in US veterans with rheumatoid arthritis (RA). METHODS: This historical cohort analysis evaluated patient visits from the Veterans Affairs RA registry between January 1, 2006 and September 30, 2017. Eligible patient visits were a rheumatology visit with 3 disease activity measures, including the Disease Activity Score in 28 joints, the Clinical Disease Activity Index, and the Routine Assessment of Patient Index Data 3; the follow-up visit for all 3 disease activity measures was 2-6 months later. The full population and a subset of patients with active disease (≥6 tender joints, ≥6 swollen joints) were evaluated. Clinical outcome was based on the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20). The effect of MTC on ACR20 response was presented as crude descriptive statistics and evaluated using standardized regression for population- and disease activity-level conditional effects. RESULTS: The full population comprised 1,208 patients (6,138 visits) and the active disease subpopulation included 383 patients (1,109 visits). Overall, visits with MTC were associated with increased likelihood of ACR20 response across all disease activity measures for the full population. Risk ratios for overall risk of ACR20 response for visits with MTC versus those without MTC ranged from 1.67 to 2.22 across disease activity measures among the full population and from 1.51 to 1.60 for the subpopulation with active disease. CONCLUSION: MTC was associated with clinical improvement, even among patients with longstanding RA who had received multiple prior therapies, which emphasizes the utility of therapy modifications for patients with established and active RA.

Maintenance of Sustained Low Disease Activity or Remission in Patients With Rheumatoid Arthritis Treated With Etanercept Monotherapy: Results from the Corrona Registry.

OBJECTIVE: The purpose of this study was to evaluate maintenance of remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) who achieved remission/LDA with etanercept (ETN) plus a conventional synthetic disease-modifying antirheumatic drug (csDMARD) and to compare patients who discontinued csDMARD to receive ETN monotherapy (Mono) with those remaining on combination therapy (Combo). METHODS: Patients from the Corrona RA registry between October 1, 2001, and August 31, 2017, were eligible. The index date for the Mono cohort was the csDMARD discontinuation date; the index visit for the Combo cohort was estimated from time between ETN initiation and csDMARD discontinuation in the Mono cohort. The main outcome calculated was maintenance of remission/LDA. Patients were censored if they switched to or added a biologic DMARD, discontinued ETN, when a csDMARD was reintroduced (Mono), or if methotrexate increased more than 5 mg/d (Combo). Trimming was used to balance demographic and clinical characteristics between groups. Cox regression models were adjusted for the remaining differences across groups. RESULTS: We identified 182 Mono and 403 Combo patients; 120 Mono and 207 Combo patients remained after trimming. Most patients (approximately 80%) were biologic medication-naive before initiating ETN. At 24 months postindex, modeled percentages of patients remaining in remission/LDA were 75% for Mono and 86% for Combo (overall adjusted P = 0.057). More patients were censored for therapy change in Mono than in Combo groups (37% versus 5%), largely due to reintroduction of csDMARDs in the Mono group. CONCLUSION: Many patients with RA who achieved remission/LDA on combination therapy maintained remission/LDA with ETN monotherapy for 2 years after csDMARD discontinuation. ETN monotherapy may be a viable option for patients who discontinue csDMARDs after achieving LDA/remission.

Empirical evidence of disease activity thresholds used to indicate need for major therapeutic change in US veterans with rheumatoid arthritis.

BACKGROUND: A previous analysis of the Veterans Affairs Rheumatoid Arthritis (VARA) registry showed that more than half of the patients with rheumatoid arthritis (RA) did not receive a major therapeutic change (MTC) despite moderate or severe disease activity. We aimed to empirically determine disease activity thresholds associated with a decision by rheumatologists and nurse practitioners to institute a MTC in patients with RA and to report the impact of that change on RA disease activity. METHODS: We analyzed data from the VARA registry between January 1, 2006, and September 30, 2017. Eligible patients had a visit with 3 disease activity measures (DAMs) recorded: Disease Activity Score for 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3). The Youden Index was used to identify disease activity thresholds that best discriminated rheumatologist/nurse practitioner decision to initiate MTC. Clinical outcome was 20% improvement in the American College of Rheumatology criteria (ACR20 response). The effect of MTC on ACR20 response was presented as crude descriptive statistics and evaluated using G-computation for marginal and conditional effects with established disease activity level combined with an empirical threshold from Youden analysis. RESULTS: The study population comprised 1776 patients (12,094 visits: 3077 with MTC, 9017 without MTC). Empirical thresholds (95% bootstrap confidence interval with 1000 replications) for MTC were 4.03 (3.70-4.36) for DAS28, 12.9 (10.4-15.4) for CDAI, and 3.81 (3.32-4.30) for RAPID3. Visits with MTC had increased likelihood of ACR20 response: risk ratios for ACR20 response for visits with MTC vs without MTC ranged 1.2-2.6 across DAMs; risk differences ranged 0.2-14.5%. CONCLUSIONS: MTC was associated with clinical improvement across all DAMs with the greatest change in patients with RA disease activity above the Youden threshold identified in this work. TRIAL REGISTRATION: VARA Registry, https://www.hsrd. RESEARCH: va.gov/research/abstracts.cfm?Project_ID=2141698764.

Incidence of Serious Infections and Design of Utilization and Safety Studies for Biologic and Biosimilar Surveillance.

BACKGROUND: There is a need for postmarketing evidence generation for novel biologics and biosimilars. OBJECTIVE: To assess the feasibility, strengths, and limitations of the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) Distributed Research Network (DRN) to examine the utilization and comparative safety of immune-modulating agents among patients with autoimmune diseases. METHODS: We conducted a retrospective cohort study among patients enrolled in health insurance plans participating in the BBCIC DRN between January 1, 2006, and September 30, 2015. Eligible patients were adult (≥18 years) new users of a disease-modifying nonbiologic and/or biologic agent with a prior diagnosis of rheumatoid arthritis (RA), other inflammatory conditions (psoriasis, psoriatic arthritis, ankylosing spondylitis), or inflammatory bowel disease (IBD). Follow-up started at treatment initiation and ended at the earliest of outcome occurrence (serious infection); treatment discontinuation; or switching, death, disenrollment, or end of study period. The study leveraged the FDA Sentinel System infrastructure for data management and analysis; descriptive statistics of patient characteristics and unadjusted incidence rates of study outcomes during follow-up were calculated. RESULTS: Eligible patient drug episodes included 111,611 with RA (75% female), 61,050 with other inflammatory conditions (51% female), and 30,628 with IBD (52% female). Across all 3 cohorts, approximately half of the patient drug episodes initiated a biologic (50% in RA; 60% in psoriasis, psoriatic arthritis, ankylosing spondylitis; and 55% in IBD). The crude incidence rate of serious infection was 9.8 (9.5-10.0) cases per 100 person-years in RA, 7.1 (6.8-7.5) in other inflammatory conditions, and 14.2 (13.6-14.8) in IBD patients. CONCLUSIONS: This study successfully identified large numbers of new users of biologics and produced results that were consistent with those from earlier published studies. The BBCIC DRN is a potential resource for surveillance of biologics. DISCLOSURES: This study was funded by the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC). HealthCore conducted this study in collaboration with Harvard Pilgrim Health Care. Zhang and Sridhar were employed by HealthCore at the time of this study. Haynes is employed by HealthCore funded by PCORI, the NIH, and the FDA. Barr and Eichelberger were employed by AMCP at the time of this study. Lockhart is employed by the BBCIC. Holmes and Clewell are employed by AbbVie. Accrott is an employee of and shareholder in Amgen. Marshall and Brown are employed by Harvard Pilgrim Health Care. Barr is a shareholder in Roche/Genentech. Curtis has received research grants from and consults with the following: Amgen, AbbVie, BMS, CORRONA, Lilly, Janssen, Myriad, Pfizer, Roche, Regeneron, and UCB. Brown has received research grants from GSK and Pfizer and consulting fees from Bayer, Roche, and Jazz Pharmaceuticals, along with funding from the Reagan-Udall Foundation for the FDA to conduct studies for medical product manufacturers, including Eli Lilly, Novartis, Abbvie, and Merck. Brown is also funded by PCORI, the NIH, and the FDA. McMahill-Walraven subcontracts with Harvard Pilgrim Health Care Institute for public health and safety surveillance distributed data network activtities and with the FDA, GSK, and Pfizer. She also reports fees from Reagan Udall Foundation for the FDA and the Patient Centered Outcomes Research Institute.

Risk of arterial thrombotic events in inflammatory bowel disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events. The risk of arterial thrombotic events in IBD, however, has been less well characterized. We explored whether Crohn's disease (CD) and ulcerative colitis (UC) are associated with a higher risk for thrombotic events involving the mesenteric, cardiac, or cerebral arteries. METHODS: Using the Thomson Reuters MarketScan Research claims database, we conducted a retrospective cohort study of IBD patients observed for the occurrence of pre-defined thrombotic events. For comparison, four non-IBD controls were age-, sex-, and index date-matched to each IBD case. The outcomes of interest were acute mesenteric ischemia, transient ischemic attack, cerebrovascular occlusion, atherosclerosis, peripheral vascular disease, and myocardial infarction. We performed a multivariate analysis adjusting for potential confounders for thrombotic events, including hypertension, diabetes, hyperlipidemia, and, in women, the use of contraceptives. We calculated the adjusted hazard ratios (HRs) for each event by comparing IBD patients with controls and used the log-rank test to determine statistical significance. RESULTS: The study included 17,487 IBD patients and 69,948 controls. Overall, IBD patients had a markedly increased risk of acute mesenteric ischemia (HR=11.2, P<0.001). IBD patients as a whole did not have an increased risk of other arterial thrombotic events, including myocardial infarction and transient ischemic attack, when compared with controls. However, women with IBD who were over the age of 40 years had a higher risk of myocardial infarction (HR=1.6, P=0.003). In addition, women with IBD below the age of 40 years who showed a significantly higher risk for stroke (HR=2.1, P=0.04). For all events, the risks in CD and UC were similar. CONCLUSIONS: Patients with IBD have a markedly increased risk of acute mesenteric ischemia. Subgroup analysis reveals that women over the age of 40 years with IBD are at increased risk of myocardial infarction, whereas those below the age of 40 years exhibit a two-fold higher risk for stroke. In contrast, men with IBD did not share these same risks for arterial thrombotic events.

Subsequent Cardiovascular Events Among Patients With Rheumatoid Arthritis, Psoriatic Arthritis, or Psoriasis: Patterns of Disease-Modifying Antirheumatic Drug Treatment.

OBJECTIVE: To examine disease-modifying antirheumatic drug (DMARD) treatments and estimate the risk of a subsequent cardiovascular (CV) event following an initial CV event in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis. METHODS: We analyzed data from MarketScan claims databases (January 1, 2006 to June 30, 2015) for adults with RA, PsA, or psoriasis and an initial/index CV event (acute myocardial infarction, stroke, or coronary revascularization) while receiving DMARDs (tumor necrosis factor inhibitor [TNFi] biologic DMARDs [bDMARDs], conventional synthetic DMARDs [csDMARDs], or non-TNFi bDMARDs). We studied DMARD treatment patterns following the index event and rates of subsequent CV events. We used Cox regression to investigate predictors of DMARD discontinuation and risk factors for subsequent CV events. RESULTS: Among 10,254 patients, 15.3% discontinued and 15.5% switched DMARD therapy after the index CV event. Independent predictors of DMARD discontinuation included a psoriasis diagnosis, renal disease, hypertension, heart failure, diabetes mellitus, older age, and baseline csDMARD or non-TNFi bDMARD use (versus TNFi bDMARDs). Rates per 1,000 patient-years of subsequent events were 75.2 (95% confidence interval [95% CI] 54.4-96.0) for patients taking TNFi bDMARDs, 83.6 (95% CI 53.3-113.9) for csDMARDs, and 122.4 (95% CI 60.6-184.3) for non-TNFi bDMARDs. A diagnosis of RA (versus psoriasis) and heart failure at baseline, but not a DMARD pattern after the index event, were independently associated with an increased risk of subsequent CV event. CONCLUSION: In this large nationwide study, nearly one-third of patients with RA, PsA, or psoriasis switched or discontinued DMARD therapy following a CV event. There was no association between DMARD class and the risk of a subsequent CV event.

Therapy with Biologic Agents After Diagnosis of Solid Malignancies: Results from the Corrona Registry.

OBJECTIVE: Guidelines suggest that rheumatoid arthritis (RA) patients with previously treated solid malignancy may be treated as patients without such history. The recommendation is based on limited evidence, and rheumatologists and patients are frequently hesitant to start or continue biologic therapy after a cancer diagnosis. The objective of this study was to describe biologic use in real-world patients with RA following a malignancy diagnosis. METHODS: RA patients enrolled in the Corrona registry and diagnosed with solid malignancy with at least 1 followup visit within 12 months after diagnosis were included in this analysis. The proportion of patients continuing or initiating biological/targeted synthetic disease-modifying antirheumatic drug (bDMARD/tsDMARD) after diagnosis was estimated. Median time to initiation of bDMARD/tsDMARD after diagnosis was calculated using the Kaplan-Meier method and the proportion initiating biologic treatment in 6-month time intervals was estimated using the life-table method. RESULTS: There were 880 patients who met inclusion criteria with 2585 person-years total followup time postdiagnosis. Of those, 367 (41.7%) were treated with bDMARD/tsDMARD within 12 months preceding malignancy, of whom 270 (30.7%) were taking such agents at first postdiagnosis visit. Forty-four (5%) switched biologic agents within 36 months and an additional 90 patients (10.2%) started a biologic. The majority of bDMARD/tsDMARD initiations during followup was a tumor necrosis factor inhibitor (TNFi; 53.5%). CONCLUSION: In real-world practice, nearly one-third of RA patients with a cancer diagnosis were treated with systemic therapy in the immediate visit after malignancy diagnosis and a considerable percentage of malignancy survivors initiated biologic therapy within 3 years. The majority of bDMARD/tsDMARD initiations post-malignancy diagnosis was a TNFi.

Prognosis and determinants of outcome following locoregional or distant recurrence in patients with cutaneous melanoma.

OBJECTIVE: Information on prognosis for patients with cutaneous melanoma after locoregional or distant recurrence is sparse and controversial. The aim of this study was to analyze factors influencing outcome after the development of a first relapse. METHODS: Information was extracted from the Sydney Melanoma Unit database for 873 melanoma patients with American Joint Committee on Cancer (AJCC) Stage I and II disease treated between 1960 and 2002 who relapsed following treatment of their primary melanoma. Clinical and pathologic factors predicting survival were analyzed using the Cox proportional hazards regression model. RESULTS: Initial presentation of recurrence was local: 95 patients (10.9%), in transit: 86 patients (9.9%), regional lymph node: 300 patients (34.4%), and distant: 392 patients (44.9%). Independent prognostic factors for survival of the 481 patients with only locoregional recurrence were type of recurrence, primary tumor ulceration, and patient age. Predictors for longer survival in the 392 patients with distant metastasis at the time of first presentation with recurrence were lung vs other sites and diagnosis of relapse after 1990 compared with diagnosis before 1980. CONCLUSIONS: The type of recurrence is the most important prognostic factor in melanoma patients who relapse. Primary tumor ulceration is the most important pathologic predictor. The results of this study suggest that management of distant metastases may have improved over the last 25 years, but many confounders and improved staging techniques make assessment of this unreliable.

Impact of Sustained Remission on the Risk of Serious Infection in Patients With Rheumatoid Arthritis.

OBJECTIVE: This retrospective analysis examined how sustained remission impacted risk of serious infections in patients with rheumatoid arthritis (RA) enrolled in a clinical registry. METHODS: Inclusion criteria included RA diagnosis, age ≥18 years, and ≥2 Clinical Disease Activity Index (CDAI) scores followed by a followup visit. Index date was the second of 2 visits in which a patient had sustained remission (CDAI ≤2.8), low disease activity (LDA; 2.8 < CDAI ≤10), or moderate-to-high disease activity (MHDA; CDAI >10). Followup extended from the index date until first serious infection (requiring intravenous antibiotics or hospitalization) or last followup visit. The crude incidence rate (IR) per 100 patient-years for serious infections was calculated for the sustained remission, LDA, and MHDA groups. The multivariable-adjusted incidence rate ratio (IRR) (adjusted for age, sex, and prednisone dose) compared serious infection rates across disease activity groups. RESULTS: Most patients were female (>70%); mean age was approximately 60 years. The crude IR (95% confidence interval [95% CI]) per 100 patient-years for serious infections was 1.03 (0.85-1.26) in the sustained remission group (n = 3,355), 1.92 (1.68-2.19) in the sustained LDA group (n = 3,912), and 2.51 (2.23-2.82) in the sustained MHDA group (n = 5,062). Compared to sustained remission, the serious infection rate was higher in sustained LDA (adjusted IRR 1.69 [95% CI 1.32-2.15]). Compared to sustained LDA, the serious infection rate was higher in sustained MHDA (adjusted IRR 1.30 [95% CI 1.09-1.56]). CONCLUSION: In this study, lower RA disease activity was associated with lower serious infection rates. This finding may motivate patients and health care providers to strive for remission rather than only LDA.

Impact of multiple lymphatic channel drainage to a single nodal basin on outcomes in melanoma.

OBJECTIVE: To determine the impact of multiple lymphatic channels (MLCs) on outcome in melanoma. DESIGN: Retrospective cohort study. SETTING: Academic tertiary care center. PATIENTS: Of 1198 consecutive selective sentinel lymphadenectomies performed from 1995 to 2000 for primary invasive melanoma, 502 patients were identified with extremity or truncal melanoma that drained to a single nodal basin. Three cohorts were formed based on lymphatic channels (none, single, and multiple). Tumors with drainage to multiple nodal basins as well as all head and neck tumors were excluded. MAIN OUTCOME MEASURES: Multiple variables, including patterns of lymphatic drainage, were analyzed for impact on disease-free and overall survival. RESULTS: Demographics were similar among groups, with a median follow-up of 5.6 years. Univariate analysis revealed MLCs as an independent risk factor for both disease-free (P = .04) and overall survival (P = .003). Multivariate analysis confirmed that tumor depth, sentinel lymph node status, and MLCs were risk factors for both disease-free and overall survival. Kaplan-Meier analysis showed worse survival in the MLCs group. CONCLUSIONS: Our study reveals that MLCs are an independent risk factor for recurrence and mortality in melanoma. Multiple lymphatic channels may facilitate the process of metastasis.

Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation.

BACKGROUND: Patients infected with hepatitis C virus (HCV) frequently develop renal failure after liver transplantation. OBJECTIVE: To describe renal histologic characteristics and concomitant clinical features in HCV-infected patients with end-stage cirrhosis. DESIGN: Case series. SETTING: Single-center liver transplant program in the United States. PATIENTS: 30 patients who received liver transplants for HCV-induced cirrhosis. INTERVENTION: Kidney biopsy during liver engraftment. MEASUREMENTS: Clinical data and laboratory tests of renal function within 6 months before liver transplantation. RESULTS: Twenty-five patients had immune-complex glomerulonephritis: membranoproliferative glomerulonephritis type 1 (n = 12), IgA nephropathy (n = 7), and mesangial glomerulonephritis (n = 6). Of these patients, 10 had normal serum creatinine levels, normal urinalysis results, and normal quantitative proteinuria. For 5 others, the only renal abnormality was an increased serum creatinine level. No patient had cryoglobulins in the blood or kidney. LIMITATIONS: This small observational study did not include patients with nonviral cirrhosis and did not document post-transplantation outcomes. CONCLUSIONS: Immune-complex glomerulonephritis was common in patients with end-stage HCV-induced cirrhosis and was often clinically silent. Its potential to cause renal failure after liver transplantation may be underappreciated.