Risk Factors For Treatment Discontinuation Research Articles

Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis

ObjectiveThere are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations. MethodsPatients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined. ResultsSix hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2–21.2) compared to double therapy (9.6 months; 95%CI: 7.03–12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P<0.0001 and at 12 months 3.2 vs. 3.5, P=0.0005). ConclusionPatients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant.

Sarcopenia is associated with chemoradiotherapy discontinuation and reduced progression-free survival in glioblastoma patients.

Sarcopenia may complicate treatment in cancer patients. Herein, we assessed whether sarcopenia measurements derived from radiation planning computed tomography (CT) were associated with complications and tumor progression during radiochemotherapy for glioblastoma. Consecutive patients undergoing radiotherapy planning for glioblastoma between 2010 and 2021 were analyzed. Retrocervical muscle cross-sectional area (CSA) was measured via threshold-based semi-automated radiation planning CT analysis. Patients in the lowest sex-specific quartile of muscle measurements were defined as sarcopenic. We abstracted treatment characteristics and tumor progression from the medical records and performed uni- and multivariable time-to-event analyses. We included 363 patients in our cohort (41.6% female, median age 63years, median time to progression 7.7months). Sarcopenic patients were less likely to receive chemotherapy (p < 0.001) and more likely to be treated with hypofractionated radiotherapy (p = 0.005). Despite abbreviated treatment, they more often discontinued radiotherapy (p = 0.023) and were more frequently prescribed corticosteroids (p = 0.014). After treatment, they were more often transferred to inpatient palliative care treatment (p = 0.035). Finally, progression-free survival was substantially shorter in sarcopenic patients in univariable (median 5.1vs. 8.4months, p < 0.001) and multivariable modeling (hazard ratio 0.61 [confidence interval 0.46-0.81], p = 0.001). Sarcopenia is astrong risk factor for treatment discontinuation and reduced progression-free survival in glioblastoma patients. We propose that sarcopenic patients should receive intensified supportive care during radiotherapy and during follow-up as well as expedited access to palliative care.

Ovarian Cancer in the Older Manitoban Population-Treatment Tolerance and Cancer-Related Outcomes: A Manitoba Ovarian Cancer Outcomes (MOCO) Group Study.

In Canada, individuals with gynecologic reproductive organs (ovaries, fallopian tubes, uterus) over the age of 70 comprise a large proportion of epithelial ovarian cancer patients. These patients often have co-morbidities, polypharmacy, or decreased functional status that may impact treatment initiation and tolerance. Despite this, there is limited evidence to guide treatment for older patients diagnosed with ovarian epithelial carcinoma. This is a retrospective study with data from Manitoba, Canada. The data were obtained from the Manitoba Ovarian Cancer Database, the Manitoba Cancer Registry, and electronic health records. All individuals with epithelial ovarian, fallopian tube, or peritoneal cancer diagnosed between 2009 and 2018 were identified. Patients aged > 70 at the time of diagnosis were included in the study cohort. Four hundred and forty individuals were included. The majority had advanced stage disease (56%). Moreover, 59% of patients received no chemotherapy. Of the patients who received chemotherapy, 20% received <2 cycles and 21% required a dose reduction due to toxicity. Univariable and multivariable analysis identified advanced stage (p < 0.001), treatment modality (p < 0.001), and advanced age at diagnosis (p < 0.001) with poorer overall survival. Our study demonstrated a high rate of chemotherapy dose reduction and discontinuation in the elderly epithelial ovarian cancer population. Further research is needed to identify risk factors for treatment discontinuation and intolerance in this population.

Risk Factors for Early Treatment Discontinuation Due to Toxicity Among Patients With Metastatic Castration-resistant Prostate Cancer Receiving Androgen Receptor-targeted Therapy.

Androgen receptor-targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity. We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC. One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P =0.016), rash (OR: 13.4, CI: [1.35-134.81]; P =0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P =0.019). Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden.

Occurrence and Risk Factors for Perioperative Treatment Discontinuation during Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU) Therapy in Symptomatic Uterine Fibroids-A Retrospective Case-Control Study.

The main aim of our study involves the analysis of reasons and risk factors for perioperative treatment discontinuation in patients with symptomatic uterine fibroids (UFs) who were qualified for magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) and in whom the procedure was discontinued. The presented research included 372 women who were primarily eligible for MR-HIFU, but the procedure was interrupted. The reasons and risk factors for treatment discontinuation were analyzed. A statistical comparison of two cohorts (patients in whom the treatment was discontinued and completed) was conducted based on epidemiological factors, UF characteristics and the implementation of uterotonics. The mean discontinuation rate was 18.28% (n = 68). The main reason was the malposition of the intestines (52.94% of all cases). The thermoablation of subserosal UFs was a statistically significant risk factor of perioperative treatment discontinuation (OR 4.62, CI 95% 2.04-10.56), while the therapy of intramural UFs considerably decreased the risk (OR 0.21, CI 95% 0.08-0.51). The volume of the targeted UF was negatively correlated with the risk of discontinuation (OR 0.991, CI 95% 0.986-0.996). Augmentation with oxytocin, but not misoprostol, during the procedure significantly decreased the risk of potential discontinuation (OR 0.15, CI 95% 0.045-0.387, p < 0.001). Although the discontinuation rate seems to be relatively low, further prospective randomized trials are needed to confirm our results. The establishment of particular eligibility criteria for the treatment is a crucial issue in this area. Resigning from the procedure in cases at a high risk of discontinuation might increase patient safety and shorten the time to introduce the most appropriate therapy.

Real-World Safety and Tolerability of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Interim Report of a Post-Marketing Surveillance in Japan.

Nintedanib is recommended for the treatment of idiopathic pulmonary fibrosis (IPF); however, treatment discontinuation due to adverse events (AEs) is common. A large-scale post-marketing surveillance study is investigating the real-world tolerability/safety of nintedanib in Japanese patients with IPF in routine clinical practice. Here, we report a 12-month interim analysis of this study. The study included Japanese patients with IPF who started nintedanib between 31 August 2015 and 25 December 2018. The primary outcome was the frequency of adverse drug reactions (ADRs), defined as AEs for which a causal relationship with nintedanib could not be excluded. The secondary outcome was change from baseline in forced vital capacity (FVC). Outcomes were analysed in patients who stopped ('discontinued' subgroup) and continued ('continued' subgroup) nintedanib after 12months. A multivariate analysis was performed to determine potential risk factors for treatment discontinuation. Of 5578 patients in the safety analysis set, 2795 (50.1%) discontinued nintedanib within 12months of treatment initiation. Overall, 3767 patients (67.5%) had ADRs, with 1356 (24.3%) discontinuing nintedanib because of an ADR. Among patients in the 'discontinued' subgroup (n = 2795), 1442 (51.6%) discontinued because of an ADR. The most common ADRs causing discontinuation within 3 and 12months were hepatic function abnormal (n = 137/730; 18.8%) and diarrhoea (n = 190/1442; 13.2%), respectively. At 12months, the decrease in FVC from baseline was smaller in the 'continued' versus the 'discontinued' subgroup (adjusted mean ± standard error change -104.4 ± 10.9ml vs. -311.2 ± 29.2ml). Stage III/IV IPF and FVC < 70% predicted at baseline were risk factors for early treatment discontinuation. About 50% of Japanese patients with IPF discontinued nintedanib within the first year of treatment, with worse lung function being associated with an increased risk of early treatment discontinuation. ClinicalTrials.gov: NCT02607722; European Union electronic register of Post-Authorisation Studies: EUPAS10891.

Real-World Effectiveness and Risk Factors for Discontinuation of Ustekinumab in Ulcerative Colitis

Introduction: Ustekinumab (UST) has been approved for the treatment of moderate-to-severe ulcerative colitis (UC). Real-world data showing the effectiveness and safety of UST are necessary to confirm the results of clinical trials for applicability in daily clinical practice. Although some studies have reported real-world evidence of UST, only few studies have confirmed its effectiveness in the real world. The aim of this study was to assess the short- and long-term effectiveness, durability, safety, and risk factors for discontinuation of UST in UC in clinical practice. Methods: This was a retrospective, single-center, observational study. From March 2020 to January 2023, all consecutive patients with active UC who were treated with UST at Nagoya University Hospital were included. The primary outcome was the clinical remission rate at weeks 2–8 and weeks 24–48. The secondary outcomes included clinical response, persistence of UST therapy, endoscopic changes during follow-up, risk factors for UST discontinuation, and occurrence of any adverse events. The clinical effectiveness was evaluated using the Lichtiger score. Results: A total of 31 patients were included in this study. The clinical remission rates were 9.7%, 29.0%, 54.8%, and 64.5% at weeks 2, 8, 24, and 48, respectively. Twelve (38.7%) patients discontinued UST during the follow-up period. The probability of continuing UST was 93.5%, 80.6%, 77%, and 70% at weeks 2, 8, 24, and 48, respectively. The major reason for discontinuation of UST was primary failure (75.0%). A high baseline C-reactive protein (CRP) level was a significant risk factor for the discontinuation of UST. No adverse events were observed in this study. Conclusion: UST is effective for patients with UC. High CRP levels were identified as a risk factor for UST discontinuation. The findings of this study would help clinicians to select appropriate treatment options for patients with UC by identifying the risk factors for treatment discontinuation.

Biological treatment interruption in inflammatory bowel disease: Motivation and predictive factors

BackgroundLoss-of-response and adverse events (AE) to biologics have been linked to HLA-DQA1*05 allele. However, the clinical factors or biologic used may influence treatment duration. Our objective was to evaluate the influence of clinical and therapeutic factors, along with HLA, in biological treatment discontinuation. MethodsA retrospective study of consecutive IBD patients treated with biologics between 2007 and 2011 was performed. Main outcome was treatment discontinuation due to primary non-response (PNR), secondary loss of response (SLR) or AE. HLA-DQA1 genotyping was done in all patients. Regression analyses were used to assess risk factors of treatment discontinuation. ResultsOne hundred fifty patients (61% male) with 312 biologic treatments were included. 147 (47%) were discontinued with a cumulative probability of 30%, 41% and 56% at 1, 2 and 5 years. The use of infliximab (p=0.006) and articular manifestations (p<0.05) were associated with treatment discontinuation. Considering cause of withdrawal, Ulcerative Colitis (UC) had a higher proportion of PNR (HR=4.99; 95% CI=1.71–14.63; p=0.003), SLR was higher if biologics had been indicated due to disease flare (HR=2.32; 95% CI=1.05–5.09; p=0.037) while AE were greater with infliximab (HR=2.46; 95% CI=1.48–4.08; p<0.001) or spondylitis (HR=2.46; 95% CI=1.78–6.89; p<0.001). According to the biological drug, HLA-DQA1*05 with adalimumab showed more SLR in cases with Crohn's disease (HR=3.49; 95% CI=1.39–8,78; p=0.008) or without concomitant immunomodulator (HR=2.8; 95% CI=1.1–6.93; p=0.026). ConclusionsHLA-DQ A1*05 was relevant in SLR of IBD patients treated with adalimumab without immunosupression. In patients treated with other biologics, clinical factors were more important for treatment interruption, mainly extensive UC or extraintestinal manifestations and having indicated the biologic for flare.

Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in France, Germany and Belgium

BackgroundLong-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients. We aim to assess risk factors of treatment discontinuation of patients on paliperidone palmitate and risperidone microsphere. Additionally, treatment discontinuation between patients with PP1M and PP3M was compared.MethodsThe IQVIA Longitudinal Prescription databases were used. Risk factors of treatment discontinuation were identified by a multilevel survival regression using Cox proportional hazards model. Kaplan Meier analyses were performed by identified significant risk factors.ResultsTwenty-five thousand three hundred sixty-one patients (France: 9,720; Germany: 14,461; Belgium: 1,180) were included. Over a one-year follow-up period, a significant lower treatment discontinuation was observed for patients newly initiated on paliperidone palmitate (53.8%) than those on risperidone microspheres (85.4%). Additionally, a significantly lower treatment discontinuation was found for ‘stable’ PP3M patients (19.2%) than ‘stable’ PP1M patients (37.1%). Patients were more likely to discontinue when drugs were prescribed by GP only (HR = 1.68, p < 0.001 vs. psychiatrist only) or if they were female (HR = 1.07, p < 0.001), whereas discontinuation decreased with age (31–50 years: HR = 0.95, p = 0.006 and > 50 years: HR = 0.91, p < 0.001 vs. 18–30 years).ConclusionsThis study demonstrates that patients stay significantly longer on treatment when initiated on paliperidone palmitate as compared to risperidone microspheres. It also indicated a higher treatment continuation of PP3M over PP1M. Treatment continuation is likely to be improved by empowering GPs with mental health knowledge and managing patients by a collaborative primary care-mental health model. Further research is needed to understand why females and younger patients have more treatment discontinuation.

Impact of reduced restrictions on buprenorphine prescribing during COVID-19 among patients in a community-based treatment program

BackgroundMedications such as buprenorphine are considered the gold standard for the treatment of opioid use disorders. This study aimed to determine whether less restrictive buprenorphine prescribing practices during the COVID-19 pandemic impacted retention in and adherence to buprenorphine among patients accessing treatment from 2018-2020 at a community-based syringe services program. MethodsIn this retrospective cohort study, we compared retention in treatment before and during the COVID-19 pandemic. Then, with relaxed restrictions acting as the intervention in a natural experiment, we conducted a sub-analysis of “continuity participants” who accessed treatment services both before and during the COVID-19 period. Records of 418 historical control patients treated with buprenorphine before COVID-19 were compared to 88 patients enrolled during COVID-19 (n=43 remote telemedicine and n=45 remote provider with patient on-site). Cox proportional hazards regressions were used to assess risk factors for treatment discontinuation. The sub-analysis used proportion of days covered (PDC) differences before and during COVID-19 (n=164) for a paired analysis in a nonparametric bootstrap test. ResultsThe risk of discontinuation was 71% lower in those accessing remote telemedicine during COVID-19 (HR=0.29; CI: 0.18, 0.47) and 51% lower in those accessing their remote provider onsite during COVID-19 (HR=0.49; CI:0.31, 0.77), compared to the historical control group. The average PDC did not significantly differ before and during COVID-19 (difference=2.4%; CI:-0.6%, 5.3%). ConclusionsThe risk of discontinuing treatment was lower in both COVID-19 treatment groups compared to historical controls. Less restrictive buprenorphine prescribing guidelines during COVID-19 led to improved retention in care over 6-months.

Durability of single tablet regimen for patients with HIV infection in Southern Taiwan: data from a real-world setting

BackgroundA single-tablet regimen (STR) has been associated with better drug adherence. However, the durability of different STRs was unknown in the real-world settings. Our aim was to investigate the durability of different initial STR regimens in antiretroviral-naive patients starting STR in southern Taiwan.MethodThis was a retrospective study of antiretroviral-naive patients that initiated first-line antiretroviral regimens with STRs between May 2016 and December 2017. The primary endpoint was time to virological failure. Secondary endpoints were STR discontinuation due to toxicity/intolerance. Durability was defined as time from the initiation until discontinuation/modification. Kaplan- Meier curves were plotted assessing time to virological suppression, treatment failure and discontinuation for the three STRs and Cox proportional hazards model was used to analyze the factors associated with time to viral suppression, treatment failure or discontinuation.ResultsTwo hundred and twenty-three patients were included: The median follow-up duration (IQR) was 73.9 (48–101.6) weeks, 25 patients (11%) experienced virological failure; the 48 weeks probability of treatment failure was 22.9% (16/70) for Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF), 24.1% (13/54) for Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) and 24.2% (24/99) for Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC) (p=0.16). Fifty-six patients (25%) discontinued their STRs owing to toxicity/intolerance. When compared to EFV/FTC/TDF, treatment with FTC/RPV/TDF (aHR 8.39, CI 1.98–35.58, p = 0.004) and ABC/DTG/3TC (aHR 8.40, CI 2.39–29.54, p=0.001) were more likely to have treatment failure. The predictors for treatment failure included age ≦ 30 years old (aHR 3.73, CI 1.25–11.17, p = 0.018), switch between different STR (aHR 2.3, CI 1.18–4.50, p = 0.001) and free of active syphilis infection (aHR 0.24, CI 0.08–0.73, p = 0.012). The risk factor for treatment discontinuation included younger age ≦ 30 years old (aHR 3.82, CI 1.21–12.37, p = 0.023), treatment with EFV/FTC/TDF (aHR 8.65, CI 2.64–28.39, p < 0.001) and free of active syphilis infection (aHR 0.16, CI 0.04–0.62, p = 0.006).ConclusionYounger age was associated with treatment failure and drug discontinuation. Active syphilis infection s/p treatment was associated with free from treatment failure and discontinuation. This probably driven by the more frequently sexual health education and counseling when patients had syphilis infection. Treatment with ABC/DTG/3TC was associated with higher risk of treatment failure. The STR durability was dependent on the drug toxicity/intolerance, age and syphilis infection.

Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in france, germany and belgium – a retrospective database study

IntroductionLong-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients.ObjectivesTo assess risk factors of treatment discontinuation in patients on paliperidone palmitate and risperidone microsphere. Additionally, treatment continuation between patients with PP1M and PP3M was compared.MethodsThe IQVIA Longitudinal Prescription databases were used. Risk factors of treatment discontinuation were identified by a multilevel survival regression using Cox proportional hazards model. Kaplan Meier analyses were performed by identified significant risk factors.Results25,361 patients (France: 9,720; Germany: 14,461; Belgium: 1,180) were included. Over a one-year follow-up period, a significant higher treatment continuation was observed for patients newly initiated on paliperidone palmitate (46.2%) than those initiated on risperidone microspheres (14.6%). Additionally, a significantly higher treatment continuation was found for ‘stable’ PP3M patients (81.8%) than ‘stable’ PP1M patients (62.9%). Patients were more likely to discontinue when drugs prescribed by GP only (HR = 1.68, p &lt; 0.001 vs. psychiatrist only) or being females (HR = 1.07, p &lt; 0.001), whereas discontinuation rate decreased with age (31-50 years: HR = 0.95, p = 0.006 and &gt; 50 years: HR = 0.91, p &lt; 0.001 vs. 18-30 years).ConclusionsPaliperidone palmitate was associated with a significantly higher treatment continuation than risperidone microspheres. Treatment continuation is likely to be improved by targeting young patients (18-30 years), empowering GPs with mental health knowledge and managing patients by a collaborative primary care-mental health model. Further research is needed to understand why females have more treatment discontinuation.DisclosureRui Cai, Flore Decuypere and Pierre Chevalier are IQVIA employees and served as paid consultants to Janssen during the conduct of this study. Antonie Wimmer, Pascal Guillon, Stefan Pype, Annabelle Godet, Valeria Timtschenko are Janssen employees.

Usage and adherence of antidementia drugs in a memory clinic cohort in Chongqing, Southwest China

AbstractBackgroundTo investigate the use and adherence of anti‐dementia drugs in elderly patients with dementia from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University.MethodPatients were recruited from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University between December 2010 and December 2018. The medical chart was reviewed, including diagnosis, dosage of antidementia medicine, neuropsychological testing scores, and the further questionnaires were conducted via face‐to‐face or telephone, included duration of treatment, types of anti‐dementia drugs, and reasons for treatment discontinuation.ResultThe data from 422 patients were analyzed retrospectively for this study. 315 were diagnosed with AD, 67 with MCI, and 40 with other types of dementia. From the 422 patients, 26.8% were treated with original donepezil, 11.6% with generic donepezil, 24.6% with memantine, 13.3% with huperzine A, and 23.7% with a combination of drugs. However, 73% of patients discontinued treatment within one year of initiation. Patients with less than nine years of education were more likely to discontinue treatment than patients with more than nine years of education. Patients with elevated PSMS scores had a high risk of discontinuation. Patients had a higher risk of discontinuation when they had received treatment for less than 36 months.ConclusionOverall treatment compliance is relatively poor in memory clinic in Chongqing. Our study demonstrates that high education, combined medication may lead to better treatment adherence in dementia care. However, poorer PSMS is a significant risk factor for treatment discontinuation.

Usage and adherence of antidementia drugs in a memory clinic cohort in Chongqing, Southwest China.

To investigate the use and adherence of antidementia drugs in elderly patients with dementia from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University. Patients were recruited from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University from December 2010 to December 2018. Medical charts were reviewed, including diagnosis, dosage of antidementia medicines, neuropsychological testing scores, and the further questionnaires were conducted via face-to-face or telephone, included duration of treatment, types of antidementia drugs, and reasons for treatment discontinuation. The data from 422 patients were analysed retrospectively for this study. Three hundred and fifteen were diagnosed with Alzheimer's disease (AD), 67 with mild cognitive impairment (MCI), and 40 with other types of dementia. From the 422 patients, 26.8% were treated with original donepezil (n = 113), 11.6% with generic donepezil (n = 49), 24.6% with memantine (n = 104), 13.3% with huperzine A (n = 56), and 23.7% with a combination of drugs (n = 100). However, 73% of patients discontinued treatment within 1 year of initiation. Patients treated for more than 36 months (37.8%) were more likely to choose combined medication, as compared with patients treated for less than 36 months. Patients with less than 9 years of education (odds ratio (OR): 2.394; 95% CI: 1.508-3.801) were more likely to discontinue treatment than patients with more than 9 years of education. Patients with elevated physical self-maintenance scale (PSMS) scores (OR: 1.195; 95% CI: 1.086-1.316) had a high risk of discontinuation. Overall treatment compliance is relatively poor in memory clinics in Chongqing. Our study demonstrates that higher education may lead to better treatment adherence in dementia care. Combination therapy may increase treatment time. However, poorer PSMS scores are a significant risk factor for treatment discontinuation.

A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study.

In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3days to 11.5months) due to poor tolerability (n = 163; 43.6%), disease activity (n = 95; 25.4%), adverse events (n = 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (n = 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (n = 107; 22.9%) than with oral DMT (n = 215; 16.4%), the Cox regression model revealed no significant between-group difference (p = 0.12). Female sex [hazard ratio (HR) = 1.39, p = 0.01] and previous exposure to ≥ 3 DMTs (HR = 1.71, p = 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.

Prior binge-drinking history promotes the positive affective valence of methamphetamine in mice

An alcohol use disorder is a major predisposing factor for methamphetamine (MA) abuse. Further, MA-alcohol co-abuse is a risk factor for treatment discontinuation and non-compliance in MA-dependent individuals. No effective treatment exists for MA addiction, let alone treatments directed at those suffering from MA-alcohol addiction co-morbidity. Thus, it is imperative that we develop high-throughput animal models to study the biobehavioral interactions between MA and alcohol of relevance to the etiology and treatment of co-abuse. To this end, we reported that a history of binge alcohol-drinking [5,10, 20 and 40% (v/v); 2 h/day for 10–14 days] reduces MA reinforcement and intake, but it augments MA-preference and intake when drug availability is behaviorally non-contingent. To reconcile this apparent discrepancy in findings, we employed a comparable 2-week binge-drinking paradigm as that employed in our previous studies followed by place-conditioning procedures (4 pairings of 0.25, 0.5, 1, 2 or 4 mg/kg MA, i.p.). This was meant to determine how a prior binge-drinking history impacts the affective valence of MA and sensitivity to MA-induced psychomotor-activation/sensitization. Prior binge-drinking history blunted spontaneous locomotor activity and shifted the MA dose-place-preference function upwards of water drinking controls. The potentiation of MA-conditioned reward by prior binge-drinking history was independent of any alcohol effects upon the locomotor-activating or –sensitizing effects of MA. Based on these results we propose that the reduced MA reinforcement reported previously by our group likely reflects a compensatory response to an increased sensitivity to MA’s positive subjective effects rather than increased sensitivity to the drug’s psychomotor-activating effects.

Risk Factors for Discontinuation of Treatment for Neovascular Age-Related Macular Degeneration

ABSTRACTPurpose: To investigate risk factors for treatment discontinuation for neovascular age-related macular degeneration (nAMD).Methods: Data from the Swedish Macula Register and the Skåne Healthcare Register are reported on the treatment received by 932 nAMD patients diagnosed 2013−2015. Treatment discontinuation is defined as having a termination visit or lacking a control or treatment visit during the period of 10−14 months after the diagnostic visit. The risk of treatment discontinuation during the first year is estimated using a Poisson model and a classification tree.Results: 503 eyes (50.9%) discontinued the treatment within the first year. Patients with visual acuity below 60 ETDRS letters (20/60 Snellen) at baseline, serious comorbidities, or treated at the university hospital have a 42% (95% CI 25−61%, P < 0.001), 27% (95% CI 13−43%, P = 0.001) and 30% (95% CI 15−46%, P < 0.001) increased risk to discontinue treatment compared with similar patients. Patients on ranibizumab therapy have a 45% (95% CI 28−63%, P < 0.001) increased risk for treatment discontinuation during year 1 compared with patients on aflibercept therapy. The classification tree also shows that patients on ranibizumab therapy and those with low VA at baseline are at a higher risk of terminating treatment.Conclusions: Almost half of the patients starting anti-VEGF therapy discontinue treatment during the first year. Patients with risk factors may require additional support to continue with the treatment. Aflibercept therapy could be an alternative to patients at risk of treatment discontinuation.

Predictors of early discontinuation of interferon-free direct antiviral agents in patients with hepatitis C virus and advanced liver fibrosis: results of a real-life cohort.

The aim of this study was to determine risk factors for premature treatment discontinuation among patients with hepatitis C and advanced fibrosis with advanced fibrosis treated with interferon (IFN)-free direct antiviral agents (DAA)-based therapy. We included all patients with chronic hepatitis C virus infection and advanced liver fibrosis in whom treatment was initiated with IFN-free DAA therapy at a university hospital from December 2015 through June 2016. We prospectively collected data from medical records using standardized questionnaires and evaluated them using Epi Info 7.1.2.0. The primary outcome was treatment interruption and associated factors. In total, 214 patients were included in this study; 180 patients were treated with sofosbuvir (SOF)+daclatasvir±ribavirin (RBV), 31 received SOF+simeprevir±RBV, and three were treated with SOF+RBV. Treatment discontinuation rate was 8.9% (19 patients) and cirrhotic decompensation was the main reason [8 (42.1%)]. Among patients with Child B or C cirrhosis (31), 10 (32.2%) prematurely interrupted treatment. The risk factors for treatment discontinuation in univariate analysis were older age (P=0.0252), higher comorbidity index (P=0.0078), higher model for end-stage liver disease (P<0.0001), higher fibrosis index based on the 4 factores (P=0.0122), and lower hemoglobin (P=0.0185) at baseline. Multivariate analysis showed that older age (odds ratio: 1.1, 95% confidence interval: 1.02-1.19) and higher model for end-stage liver disease (odds ratio: 1.27, 95% confidence interval: 1.03-1.56) were associated with premature treatment interruption. Older age and advanced liver disease were related to treatment interruption. Identification of risk factors associated with treatment discontinuation is important to recognize patients who should be followed up closely during treatment, ando those whom possibly may not benefit from immediate DAA treatment or should be followed up closely during treatment.

PIN3 - Predictors of Early Discontinuation of Interferon-Free Direct Antiviral Agents in Patients With HCV and Advanced Fibrosis: Results of A Real-Life Cohort

To determinate risk factors for premature treatment discontinuation among patients infected with HCV with advanced fibrosis treated with IFN-free direct antiviral agents (DAA)-based therapy. We included all patients with chronic HCV infection and advanced fibrosis who initiated treatment with IFN-free DAA therapy at an university hospital from December 2015 through June 2016. We prospectively collected data from medical records using standardized questionnaires and evaluated them using EpiInfo 7.1.2.0. Primary outcome was treatment interruption and factors associated. Of total, 214 patients were included in this study, 180 patients treated with sofosbuvir(SOF) + daclatasvir ± ribavirin(RBV), 31 received SOF + simeprevir ± RBV, and 3 treated with SOF+RBV. Treatment discontinuation rate was 8.9% (19), and cirrhotic decompensation was the main reason (8; 42.1%). Among patients with Child B or C cirrhosis (31), 10 (32.2%) prematurely interrupted treatment. Risk factors for treatment discontinuation in univariate analysis were higher age (p 0.0252), higher comorbidity index (p 0.0078), higher Model for end stage liver disease (MELD) (p<0.0001), higher FIB-4 (p 0.0122), and lower hemoglobin (p 0.0185) at baseline. Multivariate analysis demonstrated that higher age (OR 1.1, CI 1.02-1.19) and higher MELD (OR 1.27, CI 1.03-1.56) were associated with premature treatment interruption. Older age and advanced liver disease were related to treatment interruption. Identifying risk factors associated to treatment discontinuation is important to recognize patients that possibly would not benefit from immediate DAA treatment or should be followed up closely during treatment. This strategy could spare patients from risky situations such as worsening cirrhotic decompensation.

Risk Factors for Treatment Discontinuation Caused by Adverse Events When Using Telaprevir, Peginterferon, and Ribavirin to Treat Chronic Hepatitis C: A Real-World Retrospective Cohort Study.

In this study, a nationwide database was used to identify the risk factors for treatment discontinuation due to adverse events during telaprevir, peginterferon, and ribavirin (T/PR) treatment, and estimate the increase in the occurrence of adverse events when patients have multiple risk factors at the same time. The risk factors were identified using univariate logistic regression analysis, and a Cochran-Armitage trend test was used to analyze the correlation between the number of risk factors and treatment discontinuation due to adverse events. Of the 25989 individuals registered in the database, 1668 (age, mean±standard deviation (S.D.): 58.0±9.9) were included in the study. Of these, 188 (11.3%) discontinued T/PR therapy due to adverse events. In the univariate logistic regression analysis, sex, age, aspartate aminotransferase (AST) level, and platelet count were found to significantly affect the incidence of T/PR treatment discontinuation (p<0.05). Furthermore, the incidence of treatment discontinuation gradually increased from 4.6 to 27.2% as the number of risk factors increased from 0 to 4, and the Cochran-Armitage trend test showed a significant correlation (p<0.001). In conclusion, this study not only revealed the risk factors for treatment discontinuation but also showed that patients with multiple risk factors are more likely to discontinue treatment due to adverse events compared to patients with fewer risk factors.