Charles Makin

Relapse rates in patients with multiple sclerosis switching from interferon to fingolimod or glatiramer acetate: a US claims database study.

Background Approximately one-third of patients with multiple sclerosis (MS) are unresponsive to, or intolerant of, interferon (IFN) therapy, prompting a switch to other disease-modifying therapies. Clinical outcomes of switching therapy are unknown. This retrospective study assessed differences in relapse rates among patients with MS switching from IFN to fingolimod or glatiramer acetate (GA) in a real-world setting. Methods US administrative claims data from the PharMetrics Plus™ database were used to identify patients with MS who switched from IFN to fingolimod or GA between October 1, 2010 and March 31, 2012. Patients were matched 1∶1 using propensity scores within strata (number of pre-index relapses) on demographic (e.g. age and gender) and disease (e.g. timing of pre-index relapse, comorbidities and symptoms) characteristics. A claims-based algorithm was used to identify relapses while patients were persistent with therapy over 360 days post-switch. Differences in both the probability of experiencing a relapse and the annualized relapse rate (ARR) while persistent with therapy were assessed. Results The matched sample population contained 264 patients (n = 132 in each cohort). Before switching, 33.3% of patients in both cohorts had experienced at least one relapse. During the post-index persistence period, the proportion of patients with at least one relapse was lower in the fingolimod cohort (12.9%) than in the GA cohort (25.0%), and ARRs were lower with fingolimod (0.19) than with GA (0.51). Patients treated with fingolimod had a 59% lower probability of relapse (odds ratio, 0.41; 95% confidence interval [CI], 0.21–0.80; p = 0.0091) and 62% fewer relapses per year (rate ratio, 0.38; 95% CI, 0.21–0.68; p = 0.0013) compared with those treated with GA. Conclusions In a real-world setting, patients with MS who switched from IFNs to fingolimod were significantly less likely to experience relapses than those who switched to GA.

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis

Abstract Objective: Achieving therapeutic goals in multiple sclerosis (MS) requires strict adherence to treatment schedules. This retrospective study analyzed persistence with, and adherence to, fingolimod compared with injectable/infusible disease-modifying therapies (DMTs) in patients with MS. Methods: Patients in the PharMetrics Plus™ US administrative claims database with at least one prescription for, or administration of, fingolimod, glatiramer acetate (GA), interferon (IFN), or natalizumab (index DMT) between October 1, 2010 and September 30, 2011 were included. Patients were naïve to index DMT (no claim in the previous 360 days) and had an MS diagnosis code within 360 days of the first index DMT prescription. Outcomes were persistence, risk of discontinuing index DMT (evaluated by a Cox proportional hazards model), adherence (measured using the medication possession ratio [MPR] and proportion of days covered [PDC] in patients with at least two index DMT prescriptions), and the risk of being non-adherent (MPR <80% and PDC <80%, assessed using a logistic regression model). Results: The study included 3750 patients (fingolimod, n = 889; GA, n = 1233; any IFN, n = 1341; natalizumab, n = 287). Discontinuation rates (fingolimod, 27.9%; GA, 39.5%; IFN, 43.7%; natalizumab, 39.5%; all p < 0.001) and risk of discontinuation were significantly higher (hazard ratios vs fingolimod [95% confidence interval]: GA, 1.75 [1.49–2.07]; IFN, 2.01 [1.71–2.37]; natalizumab, 1.53 [1.22–1.91]) for patients receiving other DMTs compared with fingolimod. The risk of being non-adherent was also lower for patients in the fingolimod cohort than the other treatment cohorts, irrespective of whether non-adherence was defined as MPR <80% (p < 0.05 for all) or PDC <80% (p < 0.05 for GA and IFN). Limitations: As with all studies assessing real-world treatment patterns it is unclear if medications were used as prescribed. Conclusions: In a real-world setting, persistence with, and adherence to, oral fingolimod was higher than for injectable and infusible DMTs.

Work and productivity loss related to herpes zoster

Abstract Objective: To estimate absenteeism and presenteeism-related work loss due to herpes zoster (HZ) among working individuals of 50–64 years of age. Methods: This telephone survey included individuals with ≥1 insurance claim for HZ in the past year in administrative claims data from five US commercial health plans. Demographic information, characteristics of the HZ episode; impact of HZ on activities of daily living (ADL), and work days loss and productivity were surveyed. Results: Responses were obtained from 153 of 1654 individuals who were contacted and were eligible for the survey (9.3%). Most had moderate or severe HZ (72.6%). Close to two-thirds reported some impact of HZ on ADL such as shopping, housework/chores, and social engagement. About half (51%) reported missing work due to HZ, and about an equal percentage reported little or much worse productivity than usual due to HZ while at work. On average, age-adjusted absenteeism- and presenteeism-related work loss was estimated at 31.6 hours, and 84.4 hours, respectively, with a combined work loss of 116.0 hours per HZ episode in a working person of 50–64 years of age. Work loss tended to increase with age and the duration and severity of the HZ episode. Conclusions: The study documents a substantial societal burden of HZ-related work and productivity loss. This is important information to take into consideration, in addition to the direct medical burden, when making policy decisions around vaccine prevention of HZ. Limitations: The study may potentially be subject to selection bias due to low survey response rate and since only those cases who sought care for a HZ episode were captured. The study may also be subject to respondent recall bias. Finally, since some respondents could still be having the HZ episode at the time of survey, the study may potentially have under-estimated the work and productivity loss.

Comparative effectiveness of fingolimod versus interferons or glatiramer acetate for relapse rates in multiple sclerosis: a retrospective US claims database analysis

Abstract Objective: Disease-modifying therapies, such as fingolimod, interferon (IFN) and glatiramer acetate (GA), have differing effects on relapse rates in patients with multiple sclerosis (MS), but little is known about the real-world differences in relapse rates with these treatments. This retrospective study assessed relapse rates in patients with active MS initiating fingolimod, IFN or GA therapy in a real-world setting. Methods: Using administrative claims data from the US PharMetrics Plus database, we identified previously treated and untreated patients with MS who initiated fingolimod, IFN or GA treatment between 1 October 2010 and 31 March 2011 and had experienced a relapse in the previous year. A claims-based algorithm was used to identify relapses over the persistence period in patients with 540 days of post-index continuous enrolment. A logistic regression model assessed the probability of having at least one relapse and a generalized linear model estimated differences in annualized relapse rates (ARRs). Results: The study enrolled 525 patients (fingolimod, n = 128; combined IFN/GA cohort, n = 397) of the 31,041 initially identified. Similar findings for fingolimod and IFN/GA were observed for the unadjusted proportion of patients experiencing relapses (31.3% vs. 34.0%, respectively; p = 0.5653) and ARRs (0.50 vs. 0.55, respectively) while persistent to treatment. After adjusting for baseline differences, fingolimod was associated with a 52% reduction in the probability of having a relapse (odds ratio, 0.48; 95% confidence interval [CI], 0.28–0.84; p = 0.0097) and a 50% reduction in ARR (rate ratio, 0.50; 95% CI, 0.34–0.75; p = 0.0006) compared with IFN/GA. Limitations: Identification of relapses is based on the claims in the database rather than on a clinical assessment. Conclusions: In a real-world setting, fingolimod was shown to be associated with significantly lower relapse rates than IFN/GA in patients with MS who had a history of relapses.

Treatment Frequency and Dosing Interval of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in the USA.

Purpose To compare treatment patterns of intravitreal ranibizumab and aflibercept for the management of neovascular age-related macular degeneration (nAMD) in a real-world setting over the first 12 months of treatment. Methods A proprietary clinical database was used to identify treatment-naïve patients with nAMD in the USA with claims for ranibizumab or aflibercept between November 1, 2011 and November 30, 2013 and with follow-up of at least 12 months. Patients were considered treatment-naïve if they had no anti-VEGF treatment code for 6 months before the index date. Mean numbers of injections and of non-injection visits to a treating physician were compared between the two treatment cohorts (ranibizumab or aflibercept). In addition, the mean interval between doses was also investigated. Results Patient characteristics were similar for those receiving either ranibizumab (n = 5421) or aflibercept (n = 3506) at the index date. The mean (± standard deviation) numbers of injections received by patients treated with ranibizumab (4.9 ± 3.3) or aflibercept (5.2 ± 2.9) were not clinically different. The mean number of non-injection visits was 2.8 ± 2.8 and 2.1 ± 2.5 for ranibizumab and aflibercept, respectively. Mean dosing interval was 51.0 days (± 41.8 days) in patients receiving ranibizumab and 54.1 days (± 36.0 days) in those receiving aflibercept. Results were robust to sensitivity analyses for definition of treatment-naïve, length of follow-up and treatment in the index eye only. Conclusions Limited data exist regarding real-world treatment patterns of aflibercept for the management of nAMD. Our results suggest that, in routine clinical practice, patients receive a comparable number of injections in the first year of treatment with ranibizumab or aflibercept.

Evaluation of Resource Utilization and Treatment Patterns in Patients with Actinic Keratosis in the United States.

OBJECTIVE To compare health care resource utilization and treatment patterns between patients with actinic keratosis (AK) treated with ingenol mebutate gel (IngMeb) and those treated with other field-directed AK therapies. METHODS A retrospective, propensity-score-matched, cohort study compared refill/repeat and adding-on/switching patterns and outpatient visits and prescriptions (health care resource utilization) over 6 months in patients receiving IngMeb versus those receiving imiquimod, 5-fluorouracil, diclofenac sodium, and methyl aminolevulinate or aminolevulinic acid photodynamic therapy (MAL/ALA-PDT). RESULTS The final sample analyzed included four matched treatment cohort pairs (IngMeb and comparator; n = 790-971 per treatment arm). Refill rates were similar except for imiquimod (15% vs. 9% for imiquimod and IngMeb, respectively; P < 0.05). MAL/ALA-PDT treatment repetition rates were higher than IngMeb refill rates (20% vs. 10%; P < 0.05). Topical agent add-on/switch rates were comparable. PDT had higher switch rates than did IngMeb (5% vs. 2%; P < 0.05). The IngMeb cohort had a significantly lower proportion of patients with at least one AK-related outpatient visit during the 6-month follow-up than did any other cohort: versus imiquimod (50% vs. 66%; P < 0.0001), versus 5-fluorouracil (50% vs. 69%; P < 0.0001), versus diclofenac sodium (51% vs. 56%; P = 0.034), and versus MAL/ALA-PDT (50% vs. 100%; P < 0.0001). There were significantly fewer AK-related prescriptions among patients receiving IngMeb than among patients in other cohorts. CONCLUSIONS Results based on the first 6 months after treatment initiation suggested that most field-directed AK therapies had clinically comparable treatment patterns except imiquimod, which was associated with higher refill rates, and PDT, which was associated with significantly more frequent treatment sessions and higher switching rates. IngMeb was also associated with significantly fewer outpatient visits than were other field-directed therapies.

Economic Burden of HIV Antiretroviral Therapy Adverse Events in the United States

Objective: To estimate health care costs associated with medical events identified as antiretroviral therapy (ART)-attributable adverse events (AEs). Methods: During September 2006 to June 2012, adults with ≥1 HIV International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code (042/V08), ≥1 claim for ART prescription (March 2007-June 2011; index date), and continuous health plan enrollment for ≥6 months pre- and ≥12 months postindex were included (IMS’ PharMetrics Plus Health Plan Claims Database). Patients with events of interest/ART claim during preindex period or with pregnancy/hepatitis C virus diagnosis/hepatitis B virus/cancer/tuberculosis during the study period were excluded. Postindex medical events were defined as first diagnosis code of event with ART claim ≤60 days prior to start of the event. Results: Differences in median total all-cause health care costs observed for diabetes/insulin resistance management (US

Exacerbations, health services utilization, and costs in commercially-insured COPD patients treated with nebulized long-acting β2-agonists

14 547 median all-cause health care costs during time periods identified as diabetes/insulin resistance medical events versus US

THU0435 Treatment Persistence with Subcutaneous Biologic Therapies in Patients with Psoriatic Arthritis (PSA)

11 237 without diabetes/insulin resistance events; P = .0021), lipid disorders (US

AB1091 Treatment Persistence with Subcutaneous Biologic Therapies in Patients with Rheumatoid Arthritis

12 825 versus US