Lower Risk Of Discontinuation Research Articles

Paliperidone palmitate long‐acting injection – prospective year‐long follow‐up of use in clinical practice

To follow-up patients prescribed paliperidone palmitate long-acting injection (PP) over 1 year to determine factors predicting continuation with PP treatment. Naturalistic observation of patients registered as starting PP in a single healthcare unit in London, UK. Monovariate and multivariate (Cox regression) analysis of factors predicting continuation at 1 year. Data were available for 210 patients consecutively prescribed PP of whom 10 were lost to follow-up. At 1 year, 65% of 200 patients (176 with a diagnosis of schizophrenia or schizoaffective disorder) started on PP were still receiving it. The main reason for discontinuation was perceived ineffectiveness (52% of discontinuers); only 10 subjects (5% of total) discontinued because of adverse effects. Initiation as an out-patient [hazard ratio (HR) 0.39, 95%CI, 0.20, 0.67, P = 0.001]; being switched from risperidone (HR 0.56, 95%CI 0.32, 0.94, P = 0.026) and correct initiation (HR 0.56, 95%CI 0.34, 0.93, P = 0.024) were significantly associated with a lower likelihood of discontinuation. Paliperidone palmitate was effective and well tolerated in this naturalistic cohort. Optimising treatment by targeting PP for patients identified as having lower risk of discontinuation can give rise to continuation rates approaching 80% at 1 year.

Effectiveness of two formulations of oral olanzapine in patients with schizophrenia or bipolar disorder in a natural setting: results from a 1‐year European observational study

This study aims to assess the proportion of patients with schizophrenia or bipolar disorder who discontinued treatment with one of two oral formulations of olanzapine within 12 months in outpatient settings in Germany, Greece, and France. This 1-year, prospective, observational study included patients who had recently initiated treatment with olanzapine-coated tablets (OC) or the orodispersible (OD) formulation. Primary endpoint was olanzapine discontinuation for any reason. Clinical and functional status were also evaluated. Out of 927 enrolled patients, 903 were included in the analyses (612 patients with schizophrenia, 291 with bipolar disorder). Within 12 months, 46 of 903 patients discontinued olanzapine. Most (95%) patients remained on olanzapine for 12 months with similar rates for patients with either diagnosis (94.5% for schizophrenia, 94.9% for bipolar disorder) and for both formulations (93.7% with OC, 95.3% with OD). The only factor significantly associated with time to discontinuation was baseline disease severity. Patients with more severe disease at baseline had a lower discontinuation risk. There were significant improvements in functioning and well-being and non-significant improvements in therapeutic alliance and compliance. No significant difference was seen between discontinuation rates of the two formulations. Higher baseline severity was associated with a lower discontinuation rate.

Cost Effectiveness of Denosumab Compared with Oral Bisphosphonates in the Treatment of Post-Menopausal Osteoporotic Women in Belgium

Denosumab has recently been shown to be well tolerated, to increase bone mineral density (BMD) and to significantly reduce the risk of hip, vertebral and non-vertebral fractures in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial. It is becoming increasingly important to evaluate not only the therapeutic value of a new drug but also the cost effectiveness compared with the most relevant treatment alternatives. The objective of this study was to estimate the cost effectiveness of denosumab compared with oral bisphosphonates (branded and generic drugs) in the treatment of post-menopausal osteoporotic women in Belgium. Cost effectiveness of 3 years of treatment with denosumab was compared with branded risedronate and branded and generic alendronate using an updated version of a previously validated Markov microsimulation model. The model was populated with relevant cost, adherence and epidemiological data for Belgium from a payer perspective and the results were presented as costs per QALY gained (&U20AC;, year 2009 values). Analyses were performed in populations (aged ≥60 years) in which osteoporosis medications are currently reimbursed in many European countries, i.e. those with BMD T-score of -2.5 or less or prevalent vertebral fracture. Patients receiving denosumab were assumed to have a 46% lower risk of discontinuation than those receiving oral bisphosphonates, and the effect of denosumab after treatment cessation was assumed to decline linearly to zero over a maximum of 1 year. Denosumab was cost effective compared with all other therapies, assuming a willingness to pay of &U20AC;40 000 per QALY gained. In particular, denosumab was found to be cost effective compared with branded alendronate and risedronate at a threshold value of &U20AC;30 000 per QALY and denosumab was dominant (i.e. lower cost and greater effectiveness) compared with risedronate from the age of 70 years in women with a T-score of -2.5 or less and no prior fractures. The cost effectiveness of denosumab compared with generic alendronate was estimated at &U20AC;38 514, &U20AC;22 220 and &U20AC;27 862 per QALY for women aged 60, 70 and 80 years, respectively, with T-scores of -2.5 or less. The equivalent values were &U20AC;37 167, &U20AC;19 718 and &U20AC;19 638 per QALY for women with prevalent vertebral fractures. This study suggests, on the basis of currently available data, that denosumab is a cost-effective strategy compared with oral bisphosphonates (including generic alendronate) for the treatment of post-menopausal osteoporotic women, aged ≥60 years in Belgium. Denosumab therefore appears to have the potential to become a first-line treatment for post-menopausal women with osteoporosis. However, further studies would be required to evaluate the long-term safety and adherence of denosumab in real-world clinical practice as well as head-to-head effectiveness compared with oral bisphosphonates.

One-Year Contraceptive Continuation and Pregnancy in Adolescent Girls and Women Initiating Hormonal Contraceptives

To assess contraceptive discontinuation, switching, factors associated with method discontinuation, and pregnancy among women initiating hormonal contraceptives. This was a 12-month longitudinal cohort study of adolescent girls and women (n=1,387) aged 15 to 24 years attending public family planning clinics who did not desire pregnancy for at least 1 year and selected to initiate the patch, ring, depot medroxyprogesterone acetate, or pills. Participants completed follow-up assessments at 3, 6, and 12 months after baseline. Life table analysis was used to estimate survival rates for contraceptive continuation. Cox proportional hazards models were used to estimate factors associated with method discontinuation. The continuation rate (per 100 person-years) at 12 months was low for all methods; however, it was lowest for patch and depot medroxyprogesterone acetate initiators, 10.9 and 12.1 per 100 person years, respectively (P≤.003); continuation among ring initiators was comparable to pill initiators, 29.4 and 32.7 per 100 person-years, respectively (P=.06). Discontinuation was independently associated with method initiated and younger age. The only factors associated with lower risk of discontinuation were greater intent to use the method and being in school or working. The pregnancy rate (per 100 person-years) was highest for patch and ring initiators (30.1 and 30.5) and comparable for pill and depot medroxyprogesterone acetate initiators (16.5 and 16.1; P<.001). The patch and the ring may not be better options than the pill or depot medroxyprogesterone acetate for women at high risk for unintended pregnancy. This study highlights the need for counseling interventions to improve contraceptive continuation, education about longer-acting methods, and developing new contraceptives that women may be more likely to continue. II.

A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study

The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efavirenz and lopinavir regimens based on these measures. Patients starting a nevirapine, efavirenz or lopinavir-based cART regimen for the first time after 1 January 2000 were included in the analysis. Follow-up started ≥ 3 months after initiation of treatment if viral load was <500 HIV-1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers. A total of 603 patients (21%) started nevirapine-based cART, 1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no significant difference in the risk of discontinuation for any reason between the groups on nevirapine and efavirenz (P=0.43) or lopinavir (P=0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P=0.0002) and those on lopinavir a 63% (P<0.0001) lower risk of discontinuation because of treatment failure and a 31% (P=0.01) and 66% (P<.0001) higher risk, respectively, of discontinuation because of toxicities or patient/physician choice. There were no significant differences in the incidence of non-AIDS-related events, worsening anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels or increased total cholesterol. Compared with patients on nevirapine, those on lopinavir had an 80% higher incidence of high-density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P=0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P=0.39). The long-term durability of nevirapine-based cART, based on risk of all-cause discontinuation and development of long-term adverse events, was comparable to that of efavirenz or lopinavir, in patients in routine clinical practice across Europe who initially tolerated and virologically responded to their regimen.

TNF‐α Antagonist Survival Rate in a Cohort of Rheumatoid Arthritis Patients Observed under Conditions of Standard Clinical Practice

A cohort of rheumatoid arthritis (RA) patients in the Lombardy Rheumatology Network (LOHREN) registry and receiving anti-TNF therapy was evaluated after 6, 12, 24, and 36 months. Of the 1114 patients in the registry 1064 met the clinical criteria for inclusion with 519 receiving infliximab, 303 adalimumab, and 242 etanercept. The therapeutic survival curve of these patients showed that the likelihood of continuing anti-TNF therapy was 78.8% after 12 months, 65.2% after 24 months, and 52.9% after 36 months, with a risk of dropout similar for inefficacy and adverse events. There were 405 anti-TNF therapy discontinuations (38.1%): 180 (16.9%) due to inefficacy, 194 (18.2%) adverse events, and 31 (2.9%) other reasons. Four deaths (2 septicemia, 1 postinfective cerebritis, 1 heart failure) were considered to be related to anti-TNF therapy. Of the discontinuations, 219 (54.1%) occurred within the first 12 months: 110 due to adverse events, 89 inefficacy, and 20 due to other reasons. After 36 months, the likelihood of survival on etanercept (62.5%) was significantly greater than the likelihood of survival on infliximab (49.1%) or adalimumab (53.6%). A higher risk of therapy discontinuations due to adverse events was associated with increasing age, a corticosteroid > 5 mg/day, a high erythrocyte sedimentation rate (ESR), a higher risk of therapy discontinuations due to inefficacy was associated with the previous use of > or = 4 disease-modifying antirheumatic drugs (DMARDs) and a high ESR. Comorbidities, increasing DAS28 values and co-therapy with methotrexate were associated with a lower risk of discontinuation.

Risk of Discontinuation of Nevirapine due to Toxicities in Antiretroviral-Naive and -Experienced HIV-Infected patients with High and Low CD4+ T-cell Counts

Introduction It is unknown whether the increased risk of toxicities in antiretroviral-naive HIV-infected patients initiating nevirapine-based (NVPc) combination antiretroviral therapy (cART) with high CD4+ T-cell counts is also observed when NVPc is initiated in cART-experienced patients. Patients and methods 1,571 EuroSIDA patients started NVPc after 1/1/1999, with CD4+ T-cell counts and viral load measured in the 6 months before starting treatment, and were stratified into four groups based on CD4+ T-cell counts at initiation of NVPc (high [H], &gt;400/mm3 or &gt;250/mm3 for male or female, respectively, or low [L], ≤400/mm3 or ≤250/mm3 for male or female) and prior antiretroviral experience (antiretroviral-naive [N] or -experienced [E]). Cox proportional hazards models compared the risks of discontinuation of nevirapine due to toxicities or patient/physician choice (TOXPC). Results After adjustment, there was a significantly lower risk of discontinuation of nevirapine due to TOXPC in the HE group ( n=588; proportion discontinued by 3/12 months: 10/17%, respectively) than in HN (n=62; 21/32% respectively; overall relative hazard [RH]: 0.56; 95% confidence interval [CI]: 0.34–0.94; P=0.027). This difference was most pronounced during the first 3 months of NVPc (RH: 0.44; 95% CI: 0.23–0.87; P=0.017). There were no deaths in the 6 months after starting NVPc resulting from exposure to &lt;3 months of NVPc exposure within the HE group (incidence: 0; per 1,000 person-years follow up; 95% CI: 0–6.9). After adjustment, there were no differences between the HE and HN groups in discontinuation due to TOXPC in patients starting efavirenz-based cART (RH: 0.91; 95% CI: 0.60–1.38; P=0.66) or protease-inhibitor-based cART (RH: 1.13; 95% CI: 0.77–1.66; P=0.52). Conclusions Results from this non-randomized study suggest that NVPc might be safer to initiate in antiretro-viral-experienced than in antiretroviral-naive patients with high CD4+T-cell counts.

X-ray diffraction study of inorganic structural units in fossil wood

<h3>Background</h3> Adherence to maintenance 5-amino-salicylic-acid (5-ASA) therapy is associated with better health and quality of life of adolescents and young adults (AYA) diagnosed with Ulcerative Colitis (UC). However, little is known about rates of adherence and how often AYA discontinue oral 5-ASA treatment.¹ <h3>Aims</h3> To determine rates and predictors of oral 5-ASA adherence and risk of discontinuation amongst AYA diagnosed with UC. <h3>Methods</h3> A retrospective data analysis was performed within the UK Clinical Practice Research Datalink amongst AYA diagnosed with UC between 1998 and 2016 and and starting on oral 5-ASA treatment between the ages of 10 to 24 years. The proportion of individuals discontinuing treatment (first prescription gap of ≥ 90 days) in the first year of treatment and the median time until a first 90-day gap was estimated using Kaplan-Meier analysis. Adherence, measured as proportion of days covered (PDC) in the first year of treatment was calculated. Multivariable Cox and linear regressions assessed predictors associated with 5-ASA discontinuation and adherence, respectively. <h3>Results</h3> We identified 694 AYA initiated on oral 5-ASA treatment. The median time to 5-ASA discontinuation was 176 days (95% CI 153-204). A quarter of AYA stopped after a month of treatment and by a year 2 out of 3 individuals had discontinued. The proportion with continuous use of 5-ASA in the first year of treatment varied by age at initiation (10-14 years: 49%, 15-17 years: 52%, 18-24 years: 32% - Figure 1). The mean PDC was 73% (S.D. 0.31) in the first year of therapy and was lowest amongst individuals aged between 18 to 24 years, at 69% (S.D 0.32), compared to 81% (S.D 0.27) in 10 to 14 year olds and 79% amongst 15 to 17 year olds (S.D 0.30). Starting treatment between 18 and 24 years of age and socioeconomic deprivation increased the risk of discontinuation and lower adherence, while early corticosteroid use, a proxy marker of disease severity, was associated with a lower risk of discontinuation and better adherence. <h3>Conclusion</h3> AYA diagnosed with UC and initiated on oral 5-ASA medication are at risk early discontinuation and poor adherence. Clinicians should be vigilant regarding the higher risk following the first month of treatment, particularly in young adults and those living in deprived postcodes. Targeted interventions are needed to improve 5-ASA adherence among these high risk groups. <h3>Reference</h3> Spekhorst LM, <i>et al</i>. Adherence to oral maintenance treatment in adolescents with inflammatory bowel disease. <i>J. Pediatr. Gastroenterol. Nutr</i>. ( 2016).