Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study

BACKGROUND: Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the long-term safety and efficacy of dupilumab in patients with AD. METHODS: This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated. RESULTS: Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life. LIMITATIONS: Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks. CONCLUSION: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD

Unintentional non-adherence to chronic prescription medications: How unintentional is it really?

<p>Abstract</p> <p>Background</p> <p>Unintentional non-adherence has been characterized as passively inconsistent medication-taking behavior (forgetfulness or carelessness). Our objectives were to: (1) study the prevalence and predictors of unintentional non-adherence; and (2) explore the interrelationship between intentional and unintentional non-adherence in relation to patients’ medication beliefs.</p> <p>Methods</p> <p>We conducted a cross-sectional survey of adults with asthma, hypertension, diabetes, hyperlipidemia, osteoporosis, or depression from the Harris Interactive Chronic Illness Panel. The analytic sample for this study included 24,017 adults who self-identified themselves as persistent to prescription medications for their index disease. They answered three questions on unintentional non-adherence (forgot, ran out, being careless), 11 questions on intentional non-adherence, and three multi-item scales assessing perceived need for medication (k = 10), perceived medication concerns (k = 6), and perceived medication affordability (k = 4). Logistic regression was used to model predictors of each unintentional non-adherence behavior. Baron and Kenny’s regression approach was used to test the mediational effect of unintentional non-adherence on the relationship between medication beliefs and intentional non-adherence. Bootstrapping was employed to confirm the statistical significance of these results.</p> <p>Results</p> <p>For the index disease, 62% forgot to take a medication, 37% had run out of the medication, and 23% were careless about taking the medication. Common multivariate predictors (p < .001) of the three behaviors were: (1) lower perceived need for medications; (2) more medication affordability problems; (3) worse self-rated health; (4) diabetes or osteoporosis (relative to hypertension); and (5) younger age. Unique statistically-significant predictors of the three behaviors were: (a) ‘forgot to take medications’ - greater concerns about the index medication and male gender; (b) ‘run out of medications’ - non-white race, asthma, and higher number of total prescription medications; (c) ‘being careless’ - greater medication concerns. Mediational tests confirmed the hypothesis that the effect of medication beliefs (perceived need, concerns, and affordability) on intentional non-adherence is mediated through unintentional non-adherence.</p> <p>Conclusions</p> <p>For our study sample, unintentional non-adherence does not appear to be random and is predicted by medication beliefs, chronic disease, and sociodemographics. The data suggests that the importance of unintentional non-adherence may lie in its potential prognostic significance for future intentional non-adherence. Health care providers may consider routinely inquiring about unintentional non-adherence in order to proactively address patients’ suboptimal medication beliefs before they choose to discontinue therapy all together.</p

Individual patients hold different beliefs to prescription medications to which they persist vs nonpersist and persist vs nonfulfill

Colleen A McHorney, Abhijit S GadkariU.S. Outcomes Research, Merck and Co. Inc., North Wales, PA, USAObjective: Our objective was to explore whether adults hold different beliefs about medications to which they persist vs nonpersist and persist vs nonfulfull.Methods: We conducted a cross-sectional survey of adults with asthma, hypertension, diabetes, hyperlipidemia, osteoporosis, or other cardiovascular disease from the Harris Interactive Chronic Illness Panel. A quota was set to obtain a sample of respondents who were persistent to a medication for one disease and nonpersistent or nonfulfilling to a medication for a second, different disease. Respondents completed 32 items yielding five multi-item scales: perceived need for medication (k = 12), side-effect concerns (k = 5), medication-safety concerns (k = 5), perceived disease severity (k = 3), and knowledge about the prescribed medication (k = 7). Respondents completed the 32 items twice &amp;ndash; once for their persistent medication and a second time for their nonpersistent or nonfulfilling medication. Paired sample t-tests (bivariate) and generalized estimating equations (GEE) models (multivariate) were used to test the study hypotheses.Results: Overall, 178 respondents were sampled for being persistent to one medication and nonpersistent to another, while 48 respondents were persistent to one medication and nonfulfilling to a second. For the medication to which an individual patient was persistent vs nonpersistent, there was significantly higher perceived need, fewer side-effect concerns, higher perceived disease severity, and better knowledge about the medication. For the medication to which an individual patient was persistent vs nonfulfilling, there was significantly higher perceived need, fewer side-effect concerns, and better knowledge about the medication.Conclusion: Individual patients hold different beliefs about medications to which they persist vs nonpersist or nonfulfill. Patients exhibit different medication-taking behaviors for different medications because they weigh the perceived risks and benefits for each medication separately. These results suggest that adherence interventions should be tailored to patients&amp;rsquo; beliefs about specific medications.Keywords: adherence, persistence with therapy, medication beliefs, chronic disease, primary nonadherence, medication nonfulfilmen

Treatment patterns in UK adult patients with atopic dermatitis treated with systemic immunosuppressants: data from The Health Improvement Network (THIN)

Background: There is limited understanding on patterns of systemic treatment in adults with moderate-to-severe atopic dermatitis (AD) in the UK. Objective: To characterize treatment patterns in adult AD patients prescribed immunosuppressants (IMMs) in the primary care setting. Results: Six hundred and fifty-six patients with AD (6.6%) were prescribed IMM in the analysis (mean age 52.1 years; 59.1% female; age-adjusted Charlson comorbidity index 1.4). Most prevalent (&gt;5%) conditions at baseline were depression (10.8%), contact dermatitis (10.7%), rheumatological disease (7.9%), skin/subcutaneous tissue disorders (6.4%), upper respiratory disease (5.8%), and psoriasis (5.2%). At baseline, up to 50% of patients were prescribed ≥1 IMM. During follow-up, 42.7% of patients were prescribed oral corticosteroids (OCSs), increasing in line with IMM exposure. The most commonly prescribed IMM was methotrexate (43.3%). Ciclosporin, the only approved IMM for AD, was prescribed to 16.9% of patients. Conclusions: The prevalence of comorbidities and high rate of IMM prescriptions demonstrate the impact of AD on quality of life. The frequency of OCS prescribing in AD patients treated with IMMs suggests a lack of disease control with existing therapies, and an unmet need for safe and effective targeted agents for long-term disease control.</p

Real-world utilization patterns of systemic immunosuppressants among US adult patients with atopic dermatitis.

At the time of this study, prior to the introduction of biologics in the US, systemic therapies used for the treatment of moderate-to-severe atopic dermatitis included off-label immunosuppressants and corticosteroids. Immunosuppressant therapy is associated with a substantial risk of side-effects, therefore needing clinical monitoring, and is likely to incur a significant healthcare burden for patients and payers. This retrospective cohort study based on claims data measured immunosuppressant use and its associated burden among US adult patients with atopic dermatitis covered under commercial or Medicare Supplemental insurance from January 01, 2010, to September 30, 2015. Overall, based on age, gender, region, and index year, 4201 control patients with atopic dermatitis without immunosuppressant use were matched with 4204 patients treated with immunosuppressants. The majority (68.5%) of patients using immunosuppressants were non-persistent with immunosuppressant treatment during the 12-month follow-up period after a mean (standard deviation) of 88.1 (70.7) days of immunosuppressant use; 72.3% required systemic steroid rescue treatment. Immunosuppressant users had higher incidence of immunosuppressant-related clinical events than controls; in addition, a larger proportion of immunosuppressant users versus controls developed cancer (0.28% vs 0.14%, respectively; P < 0.0001). Healthcare utilization and costs associated with clinical events and monitoring were also higher for immunosuppressant users compared with controls (total costs, $9516 vs$1630, respectively; P < 0.0001; monitoring costs, $363 vs$54, respectively; P < 0.0001). This study revealed that patients treated with systemic immunosuppressants often require systemic steroids or changes to treatment. The increase in immunosuppressant-related clinical events, including the need for increased monitoring with immunosuppressant treatment, compared with controls demonstrates a substantial treatment burden and highlights the unmet need for more effective long-term therapies for atopic dermatitis with improved safety profiles and reduced monitoring requirements