Reasons for discontinuation of subcutaneous interferon ß-1a three times a week among patients with multiple sclerosis: a real-world cohort study.

BACKGROUND: Continuation of interferon (IFN) ß-based therapies is important for maximum treatment effectiveness in patients with multiple sclerosis (MS); however, few real-world data are available on discontinuation from IFN ß. The aim of this cohort analysis was to estimate real-world discontinuation rates up to 3 years among MS patients in the United States taking subcutaneous (sc) IFN ß-1a three times a week (tiw) and to identify whether the factors associated with discontinuation change over time. METHODS: Patient data were pooled from the MarketScan© Commercial and Medicare Supplemental healthcare claims databases. Patients with ≥1 multiple sclerosis diagnosis who were sc IFN ß-1a tiw naïve, had ≥1 year of continuous eligibility before treatment, and ≥1 prescription were followed from first prescription (index date) until date of discontinuation, switch, or end of observation. Treatment status was analysed at exactly 1, 2 or 3 years after index. Multivariable models were used to identify drivers of discontinuation. RESULTS: Data from 5956 patients were included; 2862 patients (48.1%) discontinued therapy. Discontinuation rates were 36.9% (1 year), 49.5% (2 years) and 55.8% (3 years). A greater proportion of discontinuing patients had poor adherence (<80% [94.0%] versus ≥80% [51.7%]) or were taking additional medication at follow-up versus the overall population. Factors independently associated with discontinuation irrespective of time on therapy were increasing number of magnetic resonance imaging scans (1 year adjusted odds ratio 1.45, 95% confidence interval 1.26-1.67; 2 years 1.18, 1.06-1.32; 3 years 1.20, 1.07-1.34) and adherence <80% versus ≥80% (1 year 180.95, 135.84-241.03; 2 years 135.80, 100.10-184.23; 3 years 174.89, 115.27-265.38). Factors associated only with early discontinuation (at 1 year) were ≥3 sets of laboratory investigations versus none (2.54, 1.20-5.38), and anxiolytic use at follow-up (1.40, 1.06-1.82). Factors associated only with later discontinuation (at 2 years and/or at 3 years) were antidepressant use at follow-up (2 years 1.46, 1.10-1.94) and greater number of relapses (2 years 1.60, 1.11-2.30; 3 years 2.31, 1.27-4.22). CONCLUSIONS: Potential drivers of discontinuation change over time. Improved awareness of the drivers of discontinuation could lead to targeted interventions to improve adherence.

Effectiveness, Healthcare Resource Utilization and Adherence to Subcutaneous Interferon Beta-1a According to Age in Patients With Multiple Sclerosis: A Cohort Study Using a US Claims Database.

Background: It is thought that older patients with multiple sclerosis (MS) may present with a different clinical disease phenotype, and therefore respond to subcutaneous interferon beta-1a (sc IFN ß-1a) differently to younger patients. However, few real-world data are available concerning the effectiveness of sc IFN ß-1a according to age. Using data from US claims databases, this cohort analysis aimed to determine the differences in relapse rates, healthcare utilization, treatment adherence, and discontinuation according to pre-defined age groups. Methods: Patient data were pooled from the IBM® MarketScan® Commercial Claims Database and Medicare Supplemental Database. Patients with a confirmed MS diagnosis who initiated treatment with sc IFN ß-1a between July 01, 2010 and December 31, 2015, along with at least 6 months continuous enrolment in a healthcare plan, were followed from first prescription (index date) until date of discontinuation, treatment switch, or end of observation period (1 year after index date). Results: Of the 5,340 patients included in the analysis, there was a high proportion of patients free from relapse across all age groups (range: 94.1-95.4%), with a numerical decrease in the number of MRI performed by age (mean: 0.25, 18-30 years; 0.20, 31-40 years; 0.16, 41-50 years; 0.14, ≥51 years). Adherence (≥80%) was seen to increase with age (77.6%, 18-30 years; 79.6%, 31-40 years; 81.3%, 41-50 years; 84.0%, ≥51 years), at the same time as a non-significant decrease in discontinuation (incidence rate: 79.91, 73.01, 71.75, 68.71%). Conclusion: The effectiveness of sc IFN ß-1a does not appear reduced as a consequence of age in this real-world setting. Older patients had lower discontinuation rates and reduced disease activity, reflected in lower relapse rates and fewer MRI scans compared with younger patients.

The association between exposure to interferon-beta during pregnancy and birth measurements in offspring of women with multiple sclerosis.

BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference.

Postmarketing Safety Profile of Subcutaneous Interferon Beta-1a Given 3 Times Weekly: A Retrospective Administrative Claims Analysis.

BACKGROUND: Health insurance administrative claims databases represent a valuable source of information regarding the safety profile of marketed products as used in actual clinical practice in a broader range of patients than that assessed in clinical trials. Interferon beta-1a administered subcutaneously 3 times weekly (IFN ß-1a SC tiw), which was approved in 2002 by the FDA for the treatment of relapsing-remitting multiple sclerosis (MS), has over a decade of postmarketing experience. To date, however, its postmarketing safety profile has not been described using a real-world evidence source such as administrative claims data. OBJECTIVE: To describe the safety profile of IFN ß-1a SC tiw as presented in its U.S. prescribing information (PI) for patients with MS initiating IFN ß-1a SC tiw therapy using data from U.S. health care administrative claims databases. METHODS: This study featured an observational and retrospective "new start" cohort design using data from the Truven MarketScan Commercial and Medicare Supplemental health care administrative claims databases. Patients were eligible for inclusion if they were aged ≥ 18 years; had ≥ 1 diagnosis for MS recorded between January 1, 2006, and December 31, 2012; had ≥ 2 prescriptions for IFN ß-1a SC tiw; and had ≥ 90 days of continuous eligibility pre-index date and ≥ 180 days of continuous eligibility post-index date. Patients with a prescription for IFN ß-1a SC tiw without a MS diagnosis were excluded. Patients were followed from first prescription for IFN ß-1a SC tiw (index date) until date of therapy switch or discontinuation, end of insurance eligibility, or end of observation period. Adverse events (AEs) examined were those listed in the Warnings and Precautions, Adverse Reactions, and Postmarketing Experience sections of the 2014 U.S. PI. Outcomes of interest were identified at the Medical Dictionary for Regulatory Activities (version 17.1) Preferred Term level and then coded to the corresponding ICD-9-CM criteria. Descriptive analyses of patient demographic, health status, health care utilization, and adherence status were performed, and incidence rates (IRs) per 100 person-years of labeled AEs with corresponding 95% CIs were calculated. The IR calculation was based on events that presented after therapy initiation and that were not present in the 90-day pre-index period. RESULTS: The top 6 AEs included influenza-like symptoms (IR = 15.65, 95% CI = 14.96-16.36); malaise (IR = 15.33, 95% CI = 14.65-16.04; fatigue (IR = 15.02, 95% CI = 14.35-15.72); abdominal pain (IR = 10.18, 95% CI = 9.67-10.70); chest pain (IR = 8.48, 95% CI = 8.03-8.95); and depression (IR = 7.75, 95% CI = 7.32-8.20). In contrast, the 6 lowest IRs were for maculo-papular rash (IR = 0.01, 95% CI = 0.00-0.04; injection-site necrosis (IR = 0.01, 95% CI = 0.00-0.03); erythema multiforme (IR = 0.01, 95% CI = 0.00-0.04); hypoesthesia (IR = 0.00, 95% CI = 0.00-0.02); Stevens-Johnson Syndrome (IR = 0.00, 95% CI = 0.00-0.02); and xerophthalmia (IR = 0.00, 95% CI = 0.00-0.02). CONCLUSIONS: Study results show strong convergence between the real-world safety profile of IFN ß-1a SC tiw and its U.S. label. Our findings demonstrate the value of using real-world evidence obtained from administrative claims to complement clinical trial and postmarketing surveillance data in order to characterize the safety profile of established products, such as IFN ß-1a SC tiw, in the postmarketing context.

Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study.

OBJECTIVE: To determine whether the use of metformin in type 2 diabetic patients with various kidney functions is associated with an increased risk of lactic acidosis (LA). RESEARCH DESIGN AND METHODS: This study was a retrospective analysis of U.K. patient records from the Clinical Practice Research Datalink database from 1 January 2007 to 31 December 2012. Inclusion criteria were 1) diagnosis of type 2 diabetes before 1 January 2007, 2) treatment with metformin, and 3) at least one assessment of renal function between 2007 and 2012. Renal function was assessed by glomerular filtration rate and categorized as normal (N), mildly reduced (Mi), moderately reduced (Mo), or severely reduced (Se) function. The outcome of the study was LA. RESULTS: A total of 77,601 patients treated with metformin for type 2 diabetes were identified. There were 35 LA events (10.37 [95% CI 7.22-14.42] per 100,000 patient-years) of which none were fatal and 23 were linked to a comorbidity. No significant difference in the incidence of LA was observed across N, Mi, Mo and Se renal function groups (7.6 [0.9-27.5], 4.6 [2.00-9.15], 17 [10.89-25.79], and 39 [4.72-140.89] cases per 100,000 patient-years, respectively). CONCLUSIONS: The overall LA incidence rate for patients on metformin in this study was within the range of rates reported in the literature for patients with type 2 diabetes, and no significant difference was observed among patients with N, Mi, Mo, and Se function.

[HIV and other sexually transmitted infections among migrant population in Spain: a scoping review]. / Infección VIH/Sida y otras infecciones de transmisión sexual en la población inmigrante en España: revisión bibliográfica.

BACKGROUND: Migration flows have the ability to disperse infectious agents and alter local epidemiologies. The aim of the study is to describe the socio-epidemiological, clinical and microbiology / molecular epidemiology of HIV / AIDS infection in the immigrant population. METHODS: Review of the literature following the methodology Scoping review. A literature search in Medline and MEDES, original items made in Spain, published between 1998-2012, with people from Latin America, sub-Saharan Africa, North Africa, Asia and / or Eastern Europe was conducted. RESULTS: 41 articles were selected. The most studied population was from Latin America (48.8%). Higher HIV prevalence than in native was observed in men who have sex with men from Latin America (18.1%), transvestite and transsexual sex workers from Latin America (23.3%), pregnant women (0.9%) and men and women from sub-Saharan Africa (9.1% and 7.5%). Risk behaviors were different depending on the country of origin and sex. The diagnostic delay of HIV infections reached 43%, with higher prevalence in immigrants from sub-Saharan Africa, which showed delayed diagnosis in 41% and resistance to anti-retroviral treatment in 13%. Immigrant women had more losses to follow up, worse immunological response to antiretroviral treatment and shorter time treatment failure. CONCLUSION: Higher prevalence of HIV is presented by subjects from sub-Saharan Africa, men who have sex with men and transgender and transvestite sex workers from Latin America. Also pregnant women. Delayed diagnosis and resistance to treatment are more common in individuals from sub-Saharan Africa. Immigrant women presented poorer response to antiretroviral treatment.