Incident HIV-Associated Wasting/Low Weight Is Associated with Nearly Doubled Mortality Risk in the Modern ART Era.

HIV-associated wasting (HIVAW) is an underappreciated AIDS-defining illness, despite highly effective antiretroviral therapy (ART). We (a) assessed the association between incident HIVAW/low weight and all-cause mortality and (b) described virologic outcomes after people with HIV (PWH) experienced HIVAW/low weight while on ART. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, PWH without prior HIVAW/low weight who were active in care in 2016-2020 were followed through the first of the following censoring events: death, loss to follow-up, or study end (October 31, 2021). HIVAW/low weight was a diagnosis of wasting or low body mass index (BMI)/underweight or a BMI measurement <20 kg/m2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent HIVAW/low weight and mortality were estimated with extended Cox regression models. Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of HIVAW/low weight and 1,354 (2%) deaths among 62,314 PWH. PWH who experienced HIVAW/low weight had a significantly higher risk of death than those who did not (HR: 1.96; 95% CI: 1.68, 2.27) after adjusting for age, race, ethnicity, and changes in viral load (VL) and Veterans Aging Cohort Study Mortality Index scores over follow-up. Among 4,572 PWH on ART at HIVAW/low weight, 68% were suppressed (VL of <200 copies/mL); subsequent virologic failure was uncommon (7%). Among viremic PWH, 70% and 60% achieved suppression and undetectability (VL of <50 copies/mL), respectively, over follow-up. HIVAW remains a challenge for some PWH. Particular attention needs to be paid to HIVAW/low weight and virologic control to restore health and potentially reduce the risk of death.

Factors Associated With Disease-Modifying Therapy Adherence and Persistence in Multiple Sclerosis: A Scoping Literature Review.

BACKGROUND: Patients with multiple sclerosis (MS) receiving disease-modifying therapies (DMT) show published adherence rates of 27.0% to 93.8% and published persistence rates of 49.7% to 96.5%. Improvements in DMT adherence and persistence are key to optimizing MS care, and enhanced understanding could improve MS disease management and identify research gaps. This scoping literature review aims to examine the nature and findings of the literature evaluating factors associated with DMT adherence and persistence in patients with MS. METHODS: Eligible articles included in the literature review were quantitative clinical studies written in English, included adherence or persistence as primary outcomes, and accounted for covariates/confounders. The articles were assessed to identify factors associated with adherence/persistence and analyzed according to DMT type (self-injectable, oral, infusion). RESULTS: Fifty-eight studies (103,450 patients) were included. Study distribution by DMT type was self-injectable only (n = 41), oral only (n = 2), infusion only (n = 1), and more than 1 type (n = 14). Older age and previous DMT use were associated with increased adherence and/or persistence. Increased alcohol consumption, DMT adverse events, higher education, and higher body mass index were negatively associated with adherence and/or persistence. Greater number and severity of relapses was associated with increased adherence but decreased persistence. CONCLUSIONS: Most studies examined factors associated with adherence and persistence to self-injectable DMTs. These factors should be evaluated further for oral and infusion DMTs. Insights into the modifiable factors associated with adherence and persistence could guide treatment decisions and help improve adherence and clinical outcomes.

Definition, Burden, and Predictors of HIV-Associated Wasting and Low Weight in the OPERA Cohort.

We aimed to describe the prevalence, incidence, and predictors of HIV-associated wasting (HIVAW)/low weight among people with HIV (PWH) in the United States. We conducted an observational, clinical cohort analysis, utilizing prospectively collected electronic health record data obtained from the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort. HIVAW/low weight included a wasting or low body-mass index (BMI)/underweight diagnosis (ICD codes and title search) or BMI <20 kg/m2. Prevalence was estimated among adult PWH in care from 2012 to 2015 and 2016 to 2020. Incidence from January 1, 2016, to October 31, 2021, was estimated using univariate Poisson regression among eligible PWH without prior HIVAW/low weight. Demographic and clinical predictors of incident HIVAW/low weight were included in multivariable logistic regression models, stratified by antiretroviral therapy (ART) experience. The period prevalence of HIVAW/low weight was 12% in both 2012-2015 and 2016-2020. Among 67,119 PWH without any prior HIVAW/low weight, 7% experienced incident HIVAW/low weight a median 64 months from HIV diagnosis. In multivariable regression models, similar predictor patterns were observed among ART-naïve and ART-experienced PWH without any prior HIVAW/low weight: lower odds of HIVAW/low weight with older age, female sex, Black race, and Hispanic ethnicity and higher odds with Medicaid. Notably, there was a dose-response relationship between increasing Veterans Aging Cohort Study Mortality Index scores and incident HIVAW/low weight in both groups. Wasting/low weight remains a challenge for PWH and may be underappreciated by providers. Advanced HIV and comorbidities significantly predict incident HIVAW/low weight. Increasing awareness of HIVAW, especially among frailer PWH, could improve the care of affected PWH.

The Clinical and Economic Impact of Employees Who Are Care Partners of Patients with Multiple Sclerosis by Disease Severity.

Background: Research on employee care partners of patients with multiple sclerosis (MS) is limited. Objectives: The clinical and economic impact on employee care partners was evaluated by MS disease severity. Methods: Employees with spouses/domestic partners with MS from the Workpartners database (Jan. 1, 2010-Dec. 31, 2019) were eligible if: spouse/partner had at least 3 MS-related (ICD-9-CM/ICD-10-CM:340.xx/G35) inpatient/outpatient/disease-modifying therapy claims within 1 year (latest claim = index date); 6-month pre-index/1-year post-index enrollment; and age 18 to 64 years. Employee care partners' demographic/clinical characteristics and direct/indirect costs were compared across predetermined MS severity categories. Logistic and generalized linear regression modeled the costs. Results: Among 1041 employee care partners of patients with MS, 358 (34.4%) patients had mild MS, 491 (47.2%) moderate, and 192 (18.4%) severe. Mean (standard error [SE]) employee care partner age was 49.0 (0.5) for patients with mild disease, 50.5 (0.4) for moderate, 51.7 (0.6) for severe; percent female care partners was 24.6% [2.3%] mild, 19.8% [1.8%] moderate, 27.6% [3.2%] severe; and mean care partner Charlson Comorbidity Index scores 0.28 (0.05) mild, 0.30 (0.04) moderate, 0.27 (0.06) severe. More care partners of patients with moderate/severe vs mild MS had hyperlipidemia (32.6%/31.8% vs 21.2%), hypertension (29.5%/29.7% vs 19.3%), gastrointestinal disease (20.8%/22.9% vs 13.1%), depression (9.2%/10.9% vs 3.9%), and anxiety 10.6%/8.9% vs 4.2%). Adjusted mean medical costs were greater for employee care partners of patients with moderate vs mild/severe disease (P<.001). Pharmacy costs (SE) were lower for employee care partners of mild vs severe/moderate patients (P<.005). Sick leave costs (SE) were greater for employee care partners of mild/severe vs moderate patients (P<.05). Discussion: Employee care partners of patients with moderate/severe vs mild MS had more comorbidities (ie, hypertension, gastrointestinal disease, depression, and anxiety) and higher pharmacy costs. Employee care partners of patients with moderate vs mild/severe MS had higher medical and lower sick leave costs. Treatment strategies that improve patient outcomes may reduce employee care partner burden and lower costs for employers in some instances. Conclusions: Comorbidities and direct/indirect costs of employees whose spouses/partners have MS were considerable and varied with MS severity.

Patterns of Comorbidity and Multimorbidity Among Patients With Multiple Sclerosis in a Large US Commercially Insured and Medicare Advantage Population.

Background: Comorbidities are common in patients with multiple sclerosis (MS), thus increasing the complexity of disease management and economic burden and worsening their prognosis and quality of life. Real-world evidence comparing comorbidities and multimorbidity patterns of commercially insured vs Medicare enrollees with MS is lacking. Objective: To evaluate the patterns of comorbidity and multimorbidity among patients with MS in a US commercially insured and Medicare Advantage population. Methods: This retrospective observational cohort study was conducted using Aetna health claims data from January 1, 2015, to October 31, 2019. Eligibility criteria were (1) at least 3 MS-related inpatient/outpatient (ICD-10-CM: G35), or disease-modifying therapy claims within 1 year (date of first claim = index date); (2) Aetna commercial health plan or Medicare Advantage medical and pharmacy benefits at least 12 months pre-/post-index; and (3) age 18 and older. Commercially insured patients, Medicare Advantage patients younger than 65 years of age, and Medicare Advantage patients 65 years and older were compared. Results: Among 5000 patients (mean [SD] age, 52.6 [12.9]; 75.2% female), 53% had commercial insurance and 47% had Medicare Advantage (59.2% disabled age <65). Medicare Advantage patients were older (age <65: 53.3 [7.9]; age ≥65: 70.8 [5.2]) vs commercial (age, 45.7 [10.2]), had greater comorbidity burden (Charlson Comorbidity Index; age <65: 1.17 [1.64], age ≥65: 1.65 [1.95]) vs commercial (0.53 [1.02]) (all P < .0001). Symptoms specific to MS (ie, malaise, fatigue, depression, spasms, fibromyalgia, convulsions) were more common among patients younger than 65 (all P < .0001). Age-related and other comorbidities (ie, hypertension, hyperlipidemia, dyspepsia, osteoarthritis, osteoporosis, glaucoma, diabetes, cerebrovascular, cancer) were more common among patients 65 years and older Medicare Advantage (all P < .0001). Multiple comorbidities were highly prevalent (median, 4 comorbidities), particularly among Medicare Advantage patients younger than 65 (median, 6) and Medicare Advantage patients 65 and older (median, 7). Conclusions: Comorbidities and multimorbidity patterns differed between patients with MS with commercial insurance and patients with Medicare Advantage. Multimorbidity was highly prevalent among patients with MS and should be considered in the context of clinical decision making to ensure comprehensive MS management and improve outcomes.

Static and group-based trajectory analyses of factors associated with non-adherence in patients with multiple sclerosis newly-initiating once- or twice-daily oral disease-modifying therapy.

Background: Increased understanding of adherence may facilitate optimal targeting of interventions. Objective: To utilize group-based trajectory modeling (GBTM) to understand longitudinal patterns of adherence and factors associated with non-adherence in patients with multiple sclerosis (MS) newly-initiating once-/twice-daily oral disease-modifying therapy (DMT) (fingolimod, dimethyl fumarate, or teriflunomide). Methods: Commercial plan data were analyzed using proportion of days covered (PDC) to evaluate factors associated with non-adherence. GBTM clustered patient subgroups with similar longitudinal patterns of adherence measured by monthly PDC (≥80%) and multinomial logistic regression identified factors associated with adherence trajectory subgroups. Results: Among 7689 patients, 39.5% were non-adherent to once-/twice-daily oral DMTs. Characteristics associated with non-adherence (PDC<80%) included younger age, female, depression or migraine, switching during follow-up, more frequent dosing, relapse, and absence of magnetic resonance imaging. GBTM elucidated three adherence subgroups: Immediately Non-Adherent (14.9%); Gradually Non-Adherent (19.5%), and Adherent (65.6%). Additional factors associated with adherence (i.e. region, chronic lung disease) were identified and factors differed among trajectory subgroups. Conclusion: These analyses confirmed that a significant proportion of patients with MS are non-adherent to once-/twice-daily oral DMTs. Unique patterns of non-adherence and factors associated with patterns of adherence emerged. The approach demonstrated how quantitative trajectories can help clinicians develop tailored interventions.

The implications of suboptimal year-1 outcomes with disease-modifying therapy in employees with multiple sclerosis.

AIM: Multiple sclerosis (MS) poses a substantial employer burden in medically related absenteeism and disability costs due to the chronic and debilitating nature of the disease. Although previous studies have evaluated relapse, nonadherence, discontinuation, and switching individually, little is known about their overall collective prevalence and implications in employees with MS treated with disease-modifying therapies (DMTs). This study evaluated the proportion of employees with MS with suboptimal DMT year-1 outcomes and to quantify the clinical and economic burden of suboptimal year-1 outcomes from a US employer perspective. MATERIALS AND METHODS: Employees with MS were selected from the Workpartners database. Eligibility criteria were: ≥2 MS diagnosis claims (ICD-9-CM 340.xx/ICD-10-CM G35) from January 1, 2010-March 31, 2019, ≥1 once-/twice-daily oral or self-injectable DMT claim (first claim = index), continuous eligibility 6-months pre-/1-year post-index, no baseline DMT, and age 18-64 years. Suboptimal year-1 outcomes included: non-adherence (proportion of days covered <80%), discontinuation (gap >60 days), switch, or relapse (MS-related hospitalization, emergency room visit, or outpatient visit with corticosteroid). A two-part logistic-generalized linear model evaluated costs. RESULTS: Of 488 eligible patients, half (n = 247; 50.6%) had suboptimal year-1 outcomes (39.5% non-adherence, 9.8% discontinuation, 10.9% switching, 20.7% relapse; not mutually exclusive). Employees with suboptimal year-1 outcomes had higher all-cause medical ($12,730 vs. $6,428; p < 0.0001), MS-related medical ($5,444 vs. $2,652; p < 0.0001), non-DMT pharmacy ($2,920 vs. $2,169; p = 0.0199), sick leave ($1247 vs. $908; p = 0.0274), and short-term disability ($934 vs. $146; p = 0.0001) costs. Long-term disability ($751 vs. $0; p = 0.1250) and Workers' Compensation ($56 vs. $24; p = 0.1276) did not significantly differ. LIMITATIONS: Administrative claims lack clinical information. Results may not be generalizable to other patients or care settings. CONCLUSIONS: Half of the employees with MS in this sample had suboptimal year-1 outcomes (i.e. non-adherence, discontinuation, switching, or relapse). These suboptimal year-1 outcomes were associated with greater medical, sick leave, and short-term disability costs.

Live birth rates, infertility diagnosis, and infertility treatment in women with and without multiple sclerosis: Data from an administrative claims database.

BACKGROUND: Real-world data regarding live birth rates (LBRs) and infertility in women with multiple sclerosis (MS) are lacking. This study compared LBRs, infertility diagnoses, and infertility treatments in women with and without MS. METHODS: Using a retrospective US administrative claims database, patients 18-55 years with MS were matched 1:1 to patients without MS to compare LBRs, infertility diagnoses, and infertility treatments used between cohorts. RESULTS: Overall LBRs were lower in women with MS (n=96,937) versus women without (n=96,937; 5.0% vs 7.0%; p<0.0001). A greater proportion of women with MS than without had a diagnosis of infertility (8.5% vs 8.1%; p=0.0006). Fewer women with MS than without used any infertility treatment (1.0% vs 1.2%; p=0.0002). Among women with or without MS who received infertility treatments, no significant difference was observed in LBRs with oral (32.2% vs 31.5%; p=0.8536) or injectable (44.0% vs 49.3%; p=0.2603) treatment. CONCLUSION: Women with MS had a lower LBR, received more infertility diagnoses, and were less likely to receive infertility treatment than women without MS. There was no difference in LBRs following infertility treatment. Claims-data studies provide valuable exploratory analyses that reflect interactions between patients and the healthcare system.

Real-world adherence to, and persistence with, once- and twice-daily oral disease-modifying drugs in patients with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Nonadherence to disease-modifying drugs (DMDs) for multiple sclerosis (MS) is associated with poorer clinical outcomes, including higher rates of relapse and disease progression, and higher medical resource use. A systematic review and quantification of adherence and persistence with oral DMDs would help clarify the extent of nonadherence and nonpersistence in patients with MS to help prescribers make informed treatment plans and optimize patient care. The objectives were to: 1) conduct a systematic literature review to assess the availability and variability of oral DMD adherence and/or persistence rates across 'real-world' data sources; and 2) conduct meta-analyses of the rates of adherence and persistence for once- and twice-daily oral DMDs in patients with MS using real-world data. METHODS: A systematic review of studies published between January 2010 and April 2018 in the PubMed database was performed. Only studies assessing once- and twice-daily oral DMDs were available for inclusion in the analysis. Study quality was evaluated using a modified version of the Newcastle-Ottawa Scale, a tool for assessing quality of observational studies. The random effects model evaluated pooled summary estimates of nonadherence. RESULTS: From 510 abstracts, 31 studies comprising 16,398 patients with MS treated with daily oral DMDs were included. Overall 1-year mean medication possession ratio (MPR; n = 4 studies) was 83.3% (95% confidence interval [CI] 74.5-92.1%) and proportion of days covered (PDC; n = 4 studies) was 76.5% (95% CI 72.0-81.1%). Pooled 1-year MPR ≥80% adherence (n = 6) was 78.5% (95% CI 63.5-88.5%) and PDC ≥80% (n = 5 studies) was 71.8% (95% CI 59.1-81.9%). Pooled 1-year discontinuation (n = 20) was 25.4% (95% CI 21.6-29.7%). CONCLUSIONS: Approximately one in five patients with MS do not adhere to, and one in four discontinue, daily oral DMDs before 1 year. Opportunities to improve adherence and ultimately patient outcomes, such as patient education, medication support/reminders, simplified dosing regimens, and reducing administration or monitoring requirements, remain. Implementation of efforts to improve adherence are essential to improving care of patients with MS.

Early experience of implementing a national HIV pre-exposure prophylaxis service in Wales, United Kingdom 2017.

Background Pre-exposure prophylaxis (PrEP) was introduced in Sexual Health Services of the Welsh National Health Service (NHS Wales) in July 2017 as a 3-year pilot service. METHODS: Data were collected through the pre-existing Sexual Health in Wales Surveillance System, to which codes were added to capture PrEP eligibility, outcome of offer of PrEP, reasons for declining and adherence. Eligibility categories were defined based on nationally agreed criteria: men who have sex with men (MSM) and transgender people at high risk of HIV acquisition; partners of HIV-positive individuals not known to be virally suppressed; and heterosexuals reporting condomless intercourse with a HIV-positive individual not known to be virally suppressed. RESULTS: During the first 6 months, 516 people were eligible, 96% of which were MSM. Overall, 57% of those eligible (296/516) started PrEP. Reasons for declining PrEP were given by 88 (56%) of 157 people; 50 (57%) of whom did not believe themselves to be at risk. Of the available adherence assessments, 89% considered that all risk episodes had been covered. Persistence at 3 months was assessed for 141 people, of which 93 (66%) were still using PrEP. There were no HIV diagnoses in people taking PrEP during the first 6 months. Twenty-nine people were diagnosed with 37 episodes of sexually transmissible infections (STIs) while on PrEP. STI incidence was 105.7 per 100 person-years. CONCLUSIONS: The early trend indicates that implementation of PrEP is progressing as planned, and the service has been utilised by clients. This analysis can help refine implementation, inform planning and research around uptake, use and effect in Wales and internationally.

A real-world comparison of relapse rates, healthcare costs and resource use among patients with multiple sclerosis newly initiating subcutaneous interferon beta-1a versus oral disease-modifying drugs.

BACKGROUND: Administrative-claims data enable comparative effectiveness assessment using large numbers of patients treated in real-world settings. OBJECTIVE: To evaluate real-world relapses, healthcare costs and resource use in patients with MS newly initiating subcutaneous interferon beta-1a (sc IFNß-1a) v. oral disease-modifying drugs (DMDs: dimethyl fumarate, fingolimod, teriflunomide). METHODS: Patients from an administrative claims database (1 Jan 2012-31 Dec 2015) were selected if they: were 18-63 years old; had an MS diagnosis; had newly initiated sc IFNß-1a, dimethyl fumarate, fingolimod, or teriflunomide (first claim = index); had no evidence of DMD 12-months pre-index; and had 12-month eligibility pre- and post-index. Relapse was defined as an MS-related inpatient stay, emergency room visit, or outpatient visit with a corticosteroid prescription ± 7 days. Outcomes were evaluated using logistic regression and generalized linear models. RESULTS: A total of 4475 patients met inclusion criteria: 21.9% sc IFNß-1a, 51.0% dimethyl fumarate, 19.7% fingolimod, 7.4% teriflunomide. Teriflunomide patients had 1.357 (95% CI 1.000, 1.831; p = 0.0477) greater odds of 1-year relapse than sc IFNß-1a patients. Estimated mean all-cause 1-year costs were higher after fingolimod (US$72,376) v. sc IFNß-1a initiation (US$65,408; p < 0.0001). Non-DMD costs were not significantly different. CONCLUSION: Patients initiating sc IFNß-1a had better relapse outcomes v. teriflunomide, and lower all-cause costs v. fingolimod.

Relapses and disease-modifying drug treatment in pregnancy and live birth in US women with MS.

OBJECTIVE: To evaluate relapse rates and disease-modifying drug (DMD) treatment in US women with multiple sclerosis (MS) and a live birth. METHODS: This retrospective administrative claims database study used US commercial health plan data from women with MS and a live birth from January 1, 2006, to June 30, 2015. Relapses and DMD treatment were evaluated 1-year prepregnancy, during pregnancy, during puerperium (6 weeks postpregnancy), and 1-year postpregnancy. Relapse was defined as MS-related hospitalization, emergency room visit, or outpatient visit with corticosteroid prescription within 7 days. Generalized estimating equation models for longitudinal data tested for differences between prepregnancy vs the other time periods. RESULTS: A total of 2,158 patients were eligible. The odds of relapse declined during pregnancy (odds ratio [OR] 0.623, 95% confidence interval [CI] 0.521-0.744; p < 0.0001), increased during puerperium (OR 1.710, 95% CI 1.358-2.152; p < 0.0001), and ended at a higher level during the last 3 postpartum quarters (OR 1.216, 95% CI 1.052-1.406; p = 0.0081). The proportion of women with DMD treatment was rather low overall: approximately 20% prepregnancy, bottoming to 1.9% during the second trimester, and peaking at 25.5% 9 to 12 months postpartum. DMD treatment declined significantly during pregnancy (OR 0.171, 95% CI 0.144-0.203; p < 0.0001), remained lower during puerperium (OR 0.361, 95% CI 0.312-0.418; p < 0.0001), and ended at a higher level during the last 3 postpartum quarters (OR 1.259, 95% CI 1.156-1.371; p < 0.0001). CONCLUSIONS: The rate of MS relapse decreased during pregnancy, increased 6 months postpartum, and decreased 6 to 12 months postpartum. DMD treatment was uncommon in the year before pregnancy, further decreased immediately prepregnancy and during pregnancy, and increased postpartum.

Pregnancy rates and outcomes in women with and without MS in the United States.

OBJECTIVE: To compare pregnancy prevalence and complications in women with and without multiple sclerosis (MS). METHODS: This retrospective US administrative claims study used data from January 1, 2006, to June 30, 2015. All data for women with MS were included. A nationally representative 5% random sample from approximately 58 million women without MS was used to compute the dataset. Annual pregnancy rates, identified via diagnosis/procedure codes and adjusted for covariates, were estimated via logistic regression. Claims for pregnancy and labor/delivery complications were compared using propensity score matching. RESULTS: From 2006 to 2014, the adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%; the adjusted proportion without MS and with pregnancy decreased from 8.83% to 7.75%. The difference in linear trend (0.17% increase and 0.15% decrease in per-annum pregnancy rates) was significant (t statistic = 7.8; p < 0.0001). After matching (n = 2,115 per group), a higher proportion of women with MS than without had claims for premature labor (31.4% vs 27.4%; p = 0.005), infection (13.3% vs 10.9%; p = 0.016), cardiovascular disease (3.0% vs 1.9%; p = 0.028), anemia/acquired coagulation disorders (2.5% vs 1.3%; p = 0.007), neurologic complications (1.6% vs 0.6%; p = 0.005), sexually transmitted diseases (0.4% vs 0.1%; p = 0.045), acquired fetal damage (27.8% vs 23.5%; p = 0.002), and congenital fetal malformations (13.2% vs 10.3%; p = 0.004). CONCLUSIONS: Pregnancy rates in this population of women with MS have been increasing. High rates of claims for several peripartum complications were observed in women with and those without MS. Claims data provide knowledge of interactions patients have with the health care system and are valuable initial exploratory analyses.

Comorbidity in US patients with multiple sclerosis.

OBJECTIVE: To assess the trends in the prevalence of comorbidities in US patients with multiple sclerosis (MS), and the association of demographic characteristics with the presence of comorbidities. STUDY DESIGN: A retrospective analysis was conducted from a sample of 5 million patients from the IMS Health Real World Data Adjudicated Claims - US database. METHODS: Comorbidity in patients with MS was assessed by year (2006-2014), and logistic regression models evaluated the association of age, sex, and region with select comorbidities. RESULTS: The most common comorbidities from 2006 to 2014 were hyperlipidemia and hypertension (25.9%-29.7% of patients within an individual year), followed by gastrointestinal disease (18.4%-21.2% of patients) and thyroid disease (12.9%-17.1% of patients). The proportion with a claim for hyperlipidemia increased from 2006 to 2009, was stable from 2009 to 2011, and then declined from 2011 to 2014. The proportion with a claim for hypertension generally increased from 2006 to 2013, then declined from 2013 to 2014. The proportion with a claim for gastrointestinal disease, thyroid disease, and anxiety generally increased from 2006 to 2014. Claims for comorbidities were statistically significantly more likely among older age groups (p<0.05), with the exception of anxiety and alcohol abuse, which were statistically significantly less likely among older age groups. Claims for gastrointestinal disease (OR=0.75), thyroid disease (OR=0.36), chronic lung disease (OR=0.76), arthritis (OR=0.71), anxiety (OR=0.63), and depression (OR=0.69) were statistically significantly less likely among males versus females (all p<0.05). Claims for hyperlipidemia (OR=1.39), hypertension (OR=1.25), diabetes (OR=1.31), and alcohol abuse (OR=2.41) were significantly more likely among males (p<0.05). Many comorbidity claims were statistically significantly more likely in the Northeast and South compared with the Midwest and West. CONCLUSION: This study provides select comorbidity claims estimates in US patients with MS, and thus highlights the importance of comprehensive patient care approaches.

Factors associated with early initiation of disease-modifying drug treatment in newly-diagnosed patients with multiple sclerosis.

OBJECTIVE: To examine the time to first disease-modifying drug (DMD) treatment and to identify factors associated with early DMD initiation in newly-diagnosed patients with MS. METHODS: This retrospective cohort study included newly-diagnosed patients with MS from a US administrative claims database, aged 18-65 years, with a first MS diagnosis (ICD-9-CM code: 340.xx) between January 1, 2007 and June 30, 2013 (index date), continuous eligibility for 12 months pre- and 24 months post-index, and initiated DMD treatment within 2 years. Time to first DMD within 24 months post-index was evaluated. A logistic regression model predicted earlier initiation of DMD treatment (within 60 days of MS diagnosis). RESULTS: In total, 37.4% of patients initiated DMD treatment within 2 years of MS diagnosis and were included in the primary analysis (n = 7,124). Mean (standard deviation [SD]) time from MS diagnosis to first DMD was 112.6 (148.3) days (median = 51); 30.7% received first DMD in <30 days, 55.1% in <60 days, and 18.5% not until ≥180 days after diagnosis. Logistic regression found that younger age; not living in the Northeast; diagnoses of balance disorders, numbness, and optical neuritis; the absence of musculoskeletal diagnoses; and a neurologist visit or MRI within 90 days before diagnosis were associated with DMD initiation within 60 days. CONCLUSIONS: In this population of patients initiating DMD treatment within 2 years of MS diagnosis, mean time to first DMD was 112.6 days. Identifying factors associated with delayed treatment may provide better understanding of the reasons for delay, leading to improved disease management.

Development and validation of a claims-based measure as an indicator for disease status in patients with multiple sclerosis treated with disease-modifying drugs.

BACKGROUND: Administrative healthcare claims data provide a mechanism for assessing and monitoring multiple sclerosis (MS) disease status across large, clinically representative "real-world" populations. The estimation of MS disease status using administrative claims can be a challenge, however, due to a lack of detailed clinical information. Retrospective claims analyses in MS have traditionally used rates of MS relapses to approximate disease status. Healthcare costs may be alternate, broader claims-based indicators of disease activity because costs reflect multiple facets of care of patients with MS, and there is a strong correlation between quality of life of patients with MS and costs of the disease. This study developed, tested, and validated a healthcare cost-based measure to serve as an indicator of overall disease status in patients with MS treated with disease-modifying drugs (DMDs) utilizing administrative claims. METHODS: Using IMS Health Real World Data Adjudicated Claims - US data (January 2006-June 2013), a negative binomial regression predicted annual all-cause medical costs. Coefficients reaching statistical significance (p < 0.05) and increasing costs by ≥5% were selected for inclusion into an MS-specific severity score (scale of 0 to 100). Components of the score included rehabilitation services, altered mental state, pain, disability, stiffness, balance disorder, urinary incontinence, numbness, malaise/fatigue, and infections. Coefficient weights represented each predictor's contribution. The predictive model was derived using 50% of a random sample and tested/validated using the remaining 50%. RESULTS: Average overall predicted annual total medical cost was $11,134 (development sample, n = 11,384, vs. $10,528 actual) and $11,303 (validation sample, n = 11,385, vs. $10,620 actual). The model had consistent bias (approximately +$600 or +6% of actual costs) for both samples. In the validation sample, mean MS disease status scores were 0.24, 8.95, and 21.77 for low, medium, and high tertiles, respectively. Mean costs were most accurately predicted among less severe patients ($5243 predicted vs. $5233 actual cost for lowest tertile). CONCLUSION: The algorithm developed in this study provides an initial step to helping understand and potentially predict cost changes for a commercially insured MS population.

The association of timing of disease-modifying drug initiation and relapse in patients with multiple sclerosis using electronic health records.

OBJECTIVE: A large, US de-identified electronic health record (EHR) database (Optum-Humedica de-identified Electronic Health Record dataset) was used to evaluate whether earlier disease-modifying drug (DMD) treatment initiation was associated with improved outcomes in multiple sclerosis (MS). METHODS: Newly diagnosed patients from 1 January 2008 to 30 August 2014 (International Classification of Diseases, Ninth Revision, Clinical Modification code: 340.xx; first MS diagnosis = index date) with healthcare activity 1 year pre- and 2 years post-index, and who initiated DMD treatment during the 2 year follow-up period, were included. Patients were categorized as Early or Late Initiators (initiated DMD treatment ≤90 or >90 days following index, respectively). Relapse was determined by the presence of an MS-related hospitalization or an outpatient encounter with MS diagnosis and corticosteroid prescription within 7 days. RESULTS: A total of 4732 patients met the inclusion criteria: 2042 (43.2%) were Early Initiators and 2690 (56.8%) were Late Initiators. Similar baseline mean age (46.9 years for both cohorts) and Charlson Comorbidity Index scores (Early Initiators: 0.3, Late Initiators: 0.32) were observed. Average time to treatment was 20.9 ± 27.6 days for Early Initiators and 346.3 ± 181.1 days for Late Initiators. A significantly higher proportion of Late Initiators (n = 609; 22.6%) had a relapse during the 2 years following MS diagnosis compared with Early Initiators (n = 403; 19.7%; p = .0158). After controlling for covariates using multivariable logistic regression, late initiation of DMD treatment was associated with greater likelihood of relapse compared with early initiation (odds ratio 1.189; 95% CI: 1.031-1.371; p = .0172). CONCLUSIONS: Later initiation of DMD treatment (i.e. >90 days after MS diagnosis) in patients with MS was associated with a greater likelihood of relapse compared with earlier initiation. Early initiation of DMD treatment following a diagnosis of MS may have an effect on long-term outcomes.

An evaluation of adherence in patients with multiple sclerosis newly initiating treatment with a self-injectable or an oral disease-modifying drug.

OBJECTIVE: As the multiple sclerosis (MS) disease-modifying drug (DMD) treatment options have expanded to include oral therapies, it is important to understand whether route of administration is associated with DMD adherence. The objective of this study was to compare adherence to DMDs in patients with MS newly initiating treatment with a self-injectable versus an oral DMD. METHODS: This retrospective database study used IMS Health Real World Data Adjudicated Claims - US data between July 1, 2010 and June 30, 2014. Adherence was measured by medication possession ratio (MPR), calculated as the total number of treated days divided by the total number of days from the first treated day until the end of 12-month follow-up. A binary measure representing adherence (MPR ≥0.8) versus nonadherence (MPR <0.8) to therapy was used. Logistic regression evaluated the likelihood of adherence to index DMD type (self-injectable vs oral). Covariates included patient baseline characteristics (ie, age, sex, comorbidities) and index DMD type. RESULTS: The analysis included 7,207 self-injectable and 1,175 oral DMD-treated patients with MS. In unadjusted analyses, the proportion of patients adherent to therapy (MPR ≥0.8) did not differ significantly between the self-injectable (54.1%) and the oral DMD cohorts (53.0%; P=0.5075). After controlling for covariates, index DMD type was not a significant predictor of adherence (odds ratio [OR] 1.062; 95% confidence interval [CI]: 0.937-1.202; P=0.3473). Higher likelihood of adherence was associated with male sex (OR 1.20; 95% CI: 1.085-1.335; P=0.0005) and age groups older than 18-34 years (ORs 1.220-1.331; P<0.01). Depression was associated with a lower likelihood of adherence (OR 0.618; 95% CI: 0.511-0.747; P<0.0001). CONCLUSION: Male sex and age older than 18-34 years were significantly associated with a higher likelihood of adherence, while depression was associated with a lower likelihood of adherence. Index DMD type, stratified by the route of administration (self-injectable vs oral DMD), was not a significant predictor of DMD adherence.

Occult Uterine Sarcoma and Leiomyosarcoma: Incidence of and Survival Associated With Morcellation.

OBJECTIVE: To estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation. METHODS: We conducted a population-based cohort study. All uterine sarcomas from 2006-2013 in an integrated health care system were identified. Age- and race-specific incidences of occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed. Crude and adjusted risk ratios of recurrence and death associated with morcellation at 1, 2, and 3 years were estimated using Poisson regression with inverse probability weighting. RESULTS: There were 125 hysterectomies with occult uterine sarcomas identified among 34,728 hysterectomies performed for leiomyomas. The incidence of occult uterine sarcoma and leiomyosarcoma was 1 of 278 or 3.60 (95% confidence interval [CI] 2.97-4.23) and 1 of 429 or 2.33 (95% CI 1.83-2.84) per 1,000 hysterectomies. For stage I leiomyosarcoma (n=111), eight (7.2%) were power and 27 (24.3%) nonpower-morcellated. The unadjusted 3-year probability of disease-free survival for no morcellation, power and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P=.15); overall survival was 0.64, 0.75, and 0.68, respectively (P=.97). None of the adjusted risk ratios for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76) (5.12, 95% CI 1.33-19.76, P=.02). We had inadequate power to infer differences for all other comparisons including 3-year survival and power morcellation. CONCLUSION: Morcellation is associated with decreased early survival of women with occult leiomyosarcomas. We could not accurately assess associations between power morcellation and 3-year survival as a result of small numbers.