Risk Of Treatment Discontinuation Research Articles

Sex influence on cancer immunotherapy efficacy and safety in advanced non-small cell lung cancer (NSCLC): A Canadian institution real-world experience.

e20618 Background: Males and females differ in innate and adaptive immune responses. This difference may also be reflected in their response to cancer immunotherapies. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced NSCLC, however the impact of sex on treatment outcomes in these patients remains unclear. The aim of this retrospective cohort study was to evaluate sex-related differences in immunotherapy outcome in a real-world population of NSCLC patients treated with ICIs. Methods: Demographics, clinical, pathological and treatment characteristics were assessed. Treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes including response rates, PFS, OS and all-cause treatment discontinuation (TD) in relation to sex. Results: 152 advanced NSCLC patients receiving first-line immunotherapy, either alone or in conjunction with chemotherapy, were included in the study cohort. Females were younger age, were more likely to be non-smokers, have non-squamous tumors and had a higher prevalence of pre-existing autoimmune diseases compared to males. Disease control (CR/PR/SD) was achieved in 65.8% of patients. Median PFS was 12.0 mo in females and 14.1 mo in males. Median OS for all patients was 15.8 mo; 16.1 and 15.7 mo in females and males respectively. No statistical differences based on gender were observed in PFS and OS (P = 0.767 and P = 0.657). In regression analysis older age and presence of liver metastases were independent poor prognostic factors. Gender was not an independent prognostic factor in PFS and OS. Notably, 44 or 28.9% patients developed symptomatic immune-related adverse events (ir-AEs) that led to TD (Table 1). ir-AE-related TD occurred at a significantly higher rate in females compared with males (Table 1; 38.2% vs 19.7%, RR = 1.90; 95% CI: 1.12 to 3.26; p = 0.018). GI toxicity, including hepatitis and colitis was predominantly observed in females, whereas pneumonitis was the most frequent ir-AE leading to TD in males. Conclusions: Despite no significant differences based on gender were observed in PFS and OS, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic ir-AEs and TD. This finding indicates that broad-based sex differences in this context could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.[Table: see text]

Effectiveness, durability and safety of dolutegravir and lamivudine versus bictegravir, emtricitabine and tenofovir alafenamide in a real-world cohort of HIV-infected adults.

Dolutegravir plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. The aim of this study was to analyze the effectiveness, durability, and safety of 2-DR compared to bictegravir/emtricitabine/tenofovir alafenamide (3-DR). This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) people living with HIV/AIDS (PLWH), who started 2-DR or 3-DR between 01 July 2018, and 31 January 2022. The primary endpoint was non-inferiority, at 24 and 48 weeks, of 2-DR vs 3-DR regarding the percentage of PLWH with viral load (VL)<50 and 200 copies/mL in TN (12% margin) and VL≥50 and 200 copies/mL in TE (4% margin). Durability of response and safety were also measured. 292 PLWH were included (39 TN and 253 TE). In TN PLWH, non-inferiority was not achieved at 24 weeks (17; 95% CI -17 to 51 p = 0.348). By week 48, all PLWH on 3-DR maintained VL<50 copies/mL compared to 70% of PLWH on 2-DR although without reaching statistical significance (-33; 95% CI -60 to -10 p = 0.289). Non-inferiority was not achieved in TE PLWH either at 24 (0.4; 95% CI -9 to 10 p = 1) or at 48 weeks (4.5; 95% CI -0.5 to 9 p = 0.132). In TN, the risk of treatment discontinuation was similar between groups (HR: 0.31, p = 0.07); similar rates were also found in TE (HR: 1.3, p = 0.38). TE PLWH on 2-DR showed a better safety profile compared to 3-DR (p = 0.017). Our results did not show non-inferiority in terms of virological effectiveness. Additionally, durability and safety of 2-DR were confirmed to be similar to 3-DR.

Dynamic Risk Prediction of Treatment Discontinuation Using Patient-Reported Outcomes Data in the Phase III NSABP B-35 Trial.

The dynamic prediction provided by partly conditional models offers valuable insights into the treatment discontinuation risks using PRO data collected over time from clinical trial participants. This tool may benefit healthcare professionals in identifying patients at high risk of premature treatment discontinuation and support interventions to prevent potential discontinuation.

One-Year Medication Adherence and Persistence in Rheumatoid Arthritis in Clinical Practice: A Retrospective Analysis of Upadacitinib, Adalimumab, Baricitinib, and Tofacitinib.

This study evaluated 12months adherence and persistence among Janus kinase inhibitors (upadacitinib, baricitinib, tofacitinib) and adalimumab, a tumor necrosis factor inhibitor (TNFi), in patients with rheumatoid arthritis (RA). This retrospective analysis used administrative claims data from the Merative™ MarketScan® Research Databases (2018-2022). Eligible adults had≥1 RA diagnosis before the index date,≥1 pharmacy claim for index medication, and≥12months of continuous insurance enrollment pre- and post-index. Adherence to treatment [defined as proportion of days covered (PDC)≥80%], risk of treatment discontinuation, and mean time to discontinuation were assessed during the 12months follow-up. Adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and 95% confidence intervals (CI) were reported. In total, 6317 patients were included (683 upadacitinib, 3732 adalimumab, 132 baricitinib, 1770 tofacitinib). Compared with upadacitinib, patients initiating adalimumab [aOR (95% CI): 0.82 (0.69, 0.96)], baricitinib [0.46 (0.31, 0.68)], and tofacitinib [0.74 (0.62, 0.88)] were significantly less likely to achieve PDC≥80%. Risk of treatment discontinuation was significantly higher in patients treated with adalimumab [aHR (95% CI): 1.14 (1.01, 1.29)], baricitinib [1.48 (1.16, 1.90)], and tofacitinib [1.22 (1.07, 1.38)] compared with upadacitinib. Mean time to discontinuation was 256 (upadacitinib), 249 (adalimumab), 221 (baricitinib), and 239 (tofacitinib) days. Similar results were observed in patients with prior TNFi use. Patients with RA, regardless of recent TNFi experience, initiating upadacitinib were significantly more likely to be adherent and less likely to discontinue therapy compared to adalimumab, baricitinib, and tofacitinib in the first 12months of treatment.

Pharmacogenomics in the Management of Pulmonary Arterial Hypertension: Current Perspectives.

Pulmonary arterial hypertension (PAH) is a rare disease with heterogeneous causes that can lead to right ventricular (RV) failure and death if left untreated. There are currently 10 medications representative of five unique pharmacologic classes that are approved for treatment. These have led to significant improvements in overall clinical outcome. However, substantial variability in dosing requirements and treatment response is evident, leading to suboptimal outcome for many patients. Furthermore, dosing is empiric and iterative and can lead to delays in meeting treatment goals and burdensome adverse effects. Pharmacogenomic (PGx) associations have been reported with certain PAH medications, such as treprostinil and bosentan, and can explain some of the variability in response. Relevant genes associated with treprostinil include CYP2C8, CYP2C9, CAMK2D, and PFAS. CYP2C8 and CYP2C9 are the genes encoding the major metabolizing liver enzymes for treprostinil, and reduced function variants (*2, *3) with CYP2C9 were associated with lower treatment persistence. Additionally, a higher CYP2C9 activity score was associated with a significantly less risk of treatment discontinuation. Other genes of interest that have been explored with treprostinil include CAMK2D, which is associated with right ventricular dysfunction and significantly higher dose requirements. Similarly, PFAS is associated with lower concentrations of cyclic adenosine monophosphate and significantly higher dose requirements. Genes of interest with the endothelin receptor antagonist (ERA) class include GNG2 and CYP2C9. A genetic variant in GNG2 (rs11157866) was linked to a significantly increased rate of clinical improvement with ERAs. The *2 variant with CYP2C9 (encoding for the major metabolizing enzyme for bosentan) was significantly associated with a higher risk for elevations in hepatic aminotransferases and liver injury. In summary, this article reviews the relevant pharmacogenes that have been associated to date with dosing and outcome among patients who received PAH medications.

Baricitinib retention rate: 'real-life' data from a mono-centric cohort of patients affected by rheumatoid arthritis.

The aim of this retrospective study was to evaluate baricitinib retention rate in patients affected by rheumatoid arthritis. Secondary aims were to compare the impact on treatment persistence of monotherapy and other variables such as systemic corticosteroid use, line of treatment, disease duration, sex, biomarkers positivity, and Herpes Zoster virus infection. Patients with Rheumatoid Arthritis undergoing baricitinib were consecutively enrolled. Rheumatoid Arthritis diagnosis was performed with 2010 ACR/EULAR classification criteria. The cohort's demographic, clinical and therapeutical data were retrospectively collected. The whole follow-up duration was 104 weeks. Ninety-five patients affected by rheumatoid arthritis and treated with baricitinib were consecutively enrolled. At the end of follow-up, the overall retention rate was 69.3%. No statistically significant difference in retention rate was observed between patients treated with baricitinib in monotherapy or in combination with methotrexate (p = 0.638) while patients undergoing a steroidal treatment showed a significantly reduced treatment retention (p = 0.028). Contrarily, patients treated with baricitinib as a first-line b/tsDMARD showed higher drug retention (p = 0.002) compared to further treatment lines. Steroid employment, steroid dosage and previous treatment with bDMARDs correlated with risk of treatment discontinuation and at univariate analysis (p = 0.028, p < 0.001, and p = 0.002 respectively). Multivariate analysis confirmed significance for higher steroid dosage and previous treatment with bDMARDs (p = 0.002 and p = 0.046). No adverse events such as deep venous thrombosis, pulmonary embolism or tubercular infection/reactivation were reported during the study observation. Our data show a good baricitinib retention rate after 12 and 24 months of observation (75.1 and 69.3%, respectively). In our cohort, concomitant treatment with methotrexate did not influence treatment persistence while retention was reduced in patients undergoing a steroidal treatment and/or in multi-failure subjects.

Cardiometabolic risk reductions in patients with type 2 diabetes mellitus newly treated with a sodium-glucose cotransporter 2 inhibitor versus a dipeptidyl peptidase-4 inhibitor: A real-world administrative database study in Japan.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown beneficial effects on cardiometabolic risk factors (hemoglobin A1c, body mass index, systolic blood pressure) in patients with type 2 diabetes mellitus. We compared combined cardiometabolic effects of SGLT2i on hemoglobin A1c, body mass index and systolic blood pressure versus dipeptidyl peptidase-4 inhibitors (DPP4i) in Japanese patients with type 2 diabetes mellitus. This Japanese retrospective cohort study used the JMDC claims database. Patients newly treated with an SGLT2i (n=18,936) or DPP4i (n=55,484) were enrolled (January 2015-March 2020) and matched 1:1 using the propensity score. The primary end-point was the proportion of patients achieving a composite outcome (i.e., simultaneous absolute/percent reduction in hemoglobin A1c ≥0.5%, body mass index ≥3% and systolic blood pressure ≥2 mmHg) 1 year after first SGLT2i or DPP4i prescription; Mantel-Haenszel common risk difference and its 95% confidence interval were estimated. Other end-points included treatment persistence, with the associated hazard ratio calculated using the Cox proportional hazards model. After matching, patient characteristics were balanced (7,302 patients each). Theproportion of patients achieving the composite outcome was significantly greater in patients receiving an SGLT2i than those receiving a DPP4i (31.0% [1,279/4,120] vs 12.9% [524/4,070], risk difference 18.6%, 95% confidence interval 16.3, 20.9, P < 0.001). Risk of treatment discontinuation was significantly lower in the SGLT2i group than in the DPP4i group (hazard ratio 0.85, 95% confidence interval 0.81, 0.90, P < 0.001). In the present study, SGLT2i showed favorable cardiometabolic risk reduction and longer treatment persistence than DPP4i in Japanese patients with type 2 diabetes mellitus.

External validation of a clinical prediction model in multiple sclerosis

Background: Timely initiation of disease modifying therapy is crucial for managing multiple sclerosis (MS). Objective: We aimed to validate a previously published predictive model of individual treatment response using a non-overlapping cohort from the Middle East. Methods: We interrogated the MSBase registry for patients who were not included in the initial model development. These patients had relapsing MS or clinically isolated syndrome, a recorded date of disease onset, disability and dates of disease modifying therapy, with sufficient follow-up pre- and post-baseline. Baseline was the visit at which a new disease modifying therapy was initiated, and which served as the start of the predicted period. The original models were used to translate clinical information into three principal components and to predict probability of relapses, disability worsening or improvement, conversion to secondary progressive MS and treatment discontinuation as well as changes in the area under disability-time curve (ΔAUC). Prediction accuracy was assessed using the criteria published previously. Results: The models performed well for predicting the risk of disability worsening and improvement (accuracy: 81%–96%) and performed moderately well for predicting the risk of relapses (accuracy: 73%–91%). The predictions for ΔAUC and risk of treatment discontinuation were suboptimal (accuracy < 44%). Accuracy for predicting the risk of conversion to secondary progressive MS ranged from 50% to 98%. Conclusion: The previously published models are generalisable to patients with a broad range of baseline characteristics in different geographic regions.

Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease.

To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD). A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes. Eighty-seven patients [Crohn's disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations ( P = 0.018) and in those who were nonnaïve to anti-TNF-α ( P = 0.027). This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.

Time-of-day infusion of immunotherapy may impact outcomes in advanced non-small cell lung cancer patients (NSCLC).

e21126 Background: Circadian rhythms have shown direct impact on toxicity and efficacy of anticancer treatments. Adaptive immune responses related to (or associated with) check point inhibitor (CPI) administration may have lower intensity later in the day. Notably, emerging evidence suggests that the time-of-day administration of different immunotherapies could have survival implications in different tumor types. Methods: We extracted de-identified data from curated the Real-World database of the Oncoclínicas Group, including 21 community-oncology practices in Brazil with EHR information on time-of-day administration of CPI in patients with advanced NSCLC. Only patients treated with single-agent CPIs with palliative intent (Nivolumab, Pembrolizumab or Atezolizumab) from Jan 2018 through Dec 2021 were analyzed. The primary endpoint was a comparative analysis of the median Time to Treatment Discontinuation (TTD) of CPI stratified according to time-of-day administration using a propensity-score (PS) matching model. On the basis of previous reports, we selected the cutoff of 20% of CPI doses administered after 4:00 pm as the late-day subgroup. Variables included in PS matching were: age (&lt; 60, 60+); line of therapy (1st, 2ndor beyond); gender (male, female), and CPI agent (Pembrolizumab vs. others). Results: From a total of 1,603 patients with advanced NSCLC treated at Oncoclínicas during the study period, 508 received CPI as per inclusion criteria. Median age was 73 years (36-94), 66% were male, 63% received CPI in the 1stline setting, 50% with Pembrolizumab. Overall, 219 CPI infusions (15%) occurred after 4:00 pm and 9% of the patients (n = 43) qualified as late-day infusion subgroup (more than 20% of infusions after 4pm). Median TTD was 4.9 months (CI 95%, 2.83-13.5) in these patients. In the PS matched population with early-day infusions (2:1, n = 86), median TTD was 14 months (CI 95%, 8.87-23.4). Overall, with 73 events in 129 patients, we found a significantly increased risk of treatment discontinuation in the late-day subgroup (HR 1.61, CI95% 1.0-2.6, p = 0.05). With only 33 death events and median follow-up of 11 months, median overall survival was not reached in late-day or early-day subgroups (HR 1.25, CI95% 0.6-2.6, p = 0.5). Conclusions: This preliminary and exploratory real-world data analysis suggests that the time-of-day administration of CPI in patients with advanced NSCLC could have a meaningful impact on patient outcomes, in line with studies conducted in melanoma. This simple and inexpensive intervention merits further exploration in prospective controlled clinical trials.

Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study

This multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) including baricitinib (BAR) and tofacitinib (TOF) in patients with RA. Patients were as follows; females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories. The drug retention was evaluated at 24 months using the Kaplan–Meier method and multivariate Cox proportional hazards modelling adjusted by confounders. Discontinuation rates for the corresponding reasons were as follows; ineffectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior history of anti-interleukin-6 receptor antibody (aIL-6R) ineffectiveness significantly increased the risk of treatment discontinuation due to ineffectiveness (p = 0.020). Aging (≥ 75 years) (p = 0.028), usage of PSL ≥ 5 mg/day (p = 0.017) and female sex (p = 0.041) significantly increased the risk of treatment discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, difference of JAKi, and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.

Effectiveness, Durability, and Safety of Dolutegravir and Lamivudine Versus Dolutegravir, Lamivudine, and Abacavir in a Real-Life Cohort of HIV-Infected Adults.

Dolutegravir (DTG) plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. To analyze the effectiveness, durability, and safety of 2-DR compared with DTG plus abacavir/lamivudine (3-DR). This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) patients who started 2-DR or 3-DR between July 1, 2018, and November 30, 2020. The primary end point was noninferiority, at 24 and 48 weeks, of 2-DR versus 3-DR regarding the percentage of patients with viral load (VL)≥50 and 200 copies/mL in TN (4% margin) and VL<50 and 200 copies/mL in TE (margin 12%). Durability of response, and safety were also measured. 242 patients were included (53 TN and 189 TE). Two TN patients on 2-DR had VL≥50 copies/mL and 1 had VL≥200 copies/mL at week 24. In TE patients on 2-DR, 90.2% achieved VL<200 copies/mL at week 24 (difference: 3.8%; 95% CI = -6.3% to 14%) and 91.8% at week 48 (difference: 0.06%; 95% CI = -9% to 10%), meeting noninferiority criteria. Among the 53 TN patients, only 1 VF was observed in 2-DR. In TN patients, the risk of treatment discontinuation was similar between groups (hazard ratio [HR] = 0.37; P = 0.15); similar rates were also found in TE patients (HR = 0.94; P = 0.85). TE patients on 2-DR showed a better safety profile compared with 3-DR patients (P<0.001). Our results did not show noninferiority in terms of virological effectiveness. Nevertheless, all effectiveness measures support the use of 2-DR in a real-life cohort of TN and TE. Additionally, durability and safety of 2-DR were confirmed to be similar to that of 3-DR.

Telehealth Utilization Is Associated with Lower Risk of Discontinuation of Buprenorphine: a Retrospective Cohort Study of US Veterans.

ObjectiveTreatment for opioid use disorder (OUD) may include a combination of pharmacotherapies (such as buprenorphine) with counseling services if clinically indicated. Medication management or engagement with in-person counseling services may be hindered by logistical and financial barriers. Telehealth may provide an alternative mechanism for continued engagement. This study aimed to evaluate the association between telehealth encounters and time to discontinuation of buprenorphine treatment when compared to traditional in-person visits and to evaluate potential effect modification by rural-urban designation and in-person and telehealth combination treatment.MethodsA retrospective cohort study of Veterans diagnosed with OUD and treated with buprenorphine across all facilities within the Veterans Health Administration (VHA) between 2008 and 2017. Exposures were telehealth and in-person encounters for substance use disorder (SUD) and mental health, treated as time-varying covariates. The primary outcome was treatment discontinuation, evaluated as 14 days of absence of medication from initiation through 1 year.ResultsCompared to in-person encounters, treatment discontinuation was lower for telehealth for SUD (aHR: 0.69; 95%CI: 0.60, 0.78) and mental health (aHR: 0.69; 95%CI: 0.62, 0.76). There was no evidence of effect modification by rural-urban designation. Risk of treatment discontinuation appeared to be lower among those with telehealth only compared to in-person only for both SUD (aHR: 0.48, 95%CI: 0.37, 0.62) and for mental health (aHR: 0.46; 95%CI: 0.33, 0.65).ConclusionsAs telehealth demonstrated improved treatment retention compared to in-person visits, it may be a suitable option for engagement for patients in OUD management. Efforts to expand services may improve treatment retention and health outcomes for VHA and other health care systems.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06969-1.

P533 Adalimumab 80mg every other week in inflammatory bowel disease: Treatment intensification outcomes in real life clinical practice

Abstract Background Adalimumab (ADA) intensification is recommended for inadequate or loss of response in inflammatory bowel disease (IBD) patients. A new presentation of ADA 80mg administered every other week (eow) has been approved as an alternative to ADA 40mg every week (ew). Data regarding impact of ADA 80mg eow in clinical practice is still scarce. The aim of this study was to assess long-term durability, safety and cost-effectiveness of treatment with ADA 80mg eow in patients with IBD. Methods A retrospective cohort study in a tertiary hospital that included all IBD patients under intensified maintenance therapy with ADA 80mg eow was performed. Durability was calculated considering the time from the first dose to treatment withdrawn or to the end of follow-up. Biological remission (BR) was defined as CR together with fecal calprotectin (FC) &amp;lt;250µg/g and C-reactive protein (CRP) &amp;lt;5mg/dl. Economic impact of ADA 80mg eow was estimated considering current price of both ADA 40mg and ADA 80mg pens at our centre. Results Sixty-three patients (52 CD and 11 CU) were included; median age 47 (IQR 39–59), 54% male; median duration of the disease before ADA of 11 years (IQR 6–20); 30% were active smokers. Among CD patients, 56% had ileal disease, 17% colonic and 27% ileocolonic. The inflammatory behavior was the most frequent (52%) and 31% had perianal disease. In UC, 55% had extensive colitis. 44 patients (70%) were bio-naïve and 36 (57%) received immunosuppressants at baseline. At the time of escalation, 48 patients (76%) were symptomatic. After intensification, 52 (83%) patients (CD 42 and UC 10) achieved CR and 46 (73%) BR. The changes in the levels of FC, CRP and ADA were significant (p &amp;lt;0.001) (Graphs 1–3). 22 patients (35%) discontinued treatment after a median of 6.5 (IQR 5–10) months due to: 11 no clinical response (50%), 4 loss of response (18%), 3 adverse events (14%) (psoriasis) and 4 endoscopic progression (18%). 44 patients (70%) remained under treatment and in CR (median follow-up 17 months, IQR 13–24) (Graph 4) and with a median ADA levels of 10.46 mg/l (IQR 7.34–15.25). Use of ADA 80 eow regimen saved 223500€ in patients who maintained treatment. In the multivariate analysis, being in CR when intensifying reduced the risk of treatment discontinuation by 87% (HR 0.13, 95%CI 0.02–0.99; p&amp;lt;0.001), having reached BR by 99.5% (HR 0.05, 95%CI 0.02–0.14; p &amp;lt;0.001) and having ADA levels ≥5 mg/l after intensification by 68% (HR 0.32, 95%CI 0.13–0.75; p = 0.02). Smoking habit was associated with treatment withdrawn (HR 1.74, 95%CI 1.02–2.96; p=0.04). Conclusion ADA intensification to 80mg eow in IBD patients is safe, effective and may reduce costs in real life clinical practice. Early intensification, even in CR, may enhance ADA treatment durability.

Predictors of long-acting injectable antipsychotic treatment discontinuation in outpatients with schizophrenia: relevance of the Drug Attitude Inventory-10.

Given the importance of patients' subjective experience and attitudes in the management of severe mental illness, the present study evaluated their potential role as predictors of future continuation of long-acting injectable antipsychotic maintenance treatment (LAI-AMT) in clinically stable outpatients with schizophrenia switching from an oral therapy. Retrospective data from 59 subjects receiving LAI-AMT for at least 6 months were collected. Patients who continued LAI treatment (n = 32) were compared to those who discontinued it (n = 27), assessing baseline socio-demographic and clinical characteristics, psychopathological features (Positive And Negative Syndrome Scale, Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale) and patient-reported experience of treatment through Drug Attitude Inventory 10-item (DAI-10) and Subjective Well-being under Neuroleptics short form. Binary logistic and Cox regression analyses explored the predictive role of the mentioned variables on treatment discontinuation. The Kaplan-Meier estimator compared dropout from LAI treatment in subsamples with different characteristics. Unemployment and lower baseline DAI-10 scores predicted LAI-AMT discontinuation. No major differences were detected in other socio-demographic, clinical or psychometric indexes. When switching from oral to LAI-AMT, the preliminary assessment of attitude towards drug might be clinically relevant, allowing the identification of patients at risk for treatment discontinuation.

Analysis of treatment adherence and cost among patients with epilepsy: a four\u2010year retrospective cohort study in Pakistan

BackgroundThe adherence pattern of antiepileptic drugs (AEDs) among patients with epilepsy is relatively lower in the United States and different European countries. However, adherence and cost analysis of AEDs in Asian countries have not been thoroughly studied. Therefore, the present study aimed to analyze the cost and adherence of AEDs and its associated factors in patients followed in Pakistan.MethodsData from prescriptions collected from patients with epilepsy who have visited the Outpatient Department (OPD) of different tertiary care hospitals at the cosmopolitan city of Karachi, Pakistan from December 2015 to November 2019. The mean follow-up period for each participant was about 22 months. Pairwise comparisons from Cox regression/hazard ratios were used to assess the predictors of adherence. Direct costs of AEDs were calculated and presented as the annual cost of drugs.ResultsA total of 11,490 patients were included in this study, 51.2 % were male and 48.8 % were female with a mean age of 45.2 ± 15.8 y. Levetiracetam was found as the most prescribing AED in all study participants (32.9 %). Of them, 49.1 % of patients continued their initial recommended treatment. However, 31.3 % of patients have discontinued the therapy, while, 19.6 % were switched to other AED. Adherence with initial treatment was more profound in male (57.4 %) patients, compared to female with a mean age of 44.2 years. Lamotrigine users (60.6 %) showed a higher tendency to retain on initially prescribed drugs. The total cost of epilepsy treatment in the entire study cohort was 153280.5 PKR ($941.9). By applying the Cox regression analysis, it can be observed that the patients with increasing age (OR, 2.04), migraine (OR, 2.21), psychiatric disorders (OR, 4.28), other comorbidities (OR, 1.52) and users of other than top five prescribing AEDs (2.35) were at higher risk of treatment discontinuation. However, levetiracetam (OR, 0.69), valproic acid (OR, 0.52), carbamazepine (OR, 0.81), lamotrigine (OR, 0.80) or lacosamide (OR, 0.65) users have more chances to continue their initial therapy.ConclusionsSimilar to western countries, the majority of patients with epilepsy exhibited low adherence with AEDs. Various associated factors for improving adherence were identified in this study.

Cost effectiveness of buprenorphine vs. methadone for pregnant people with opioid use disorder

Objective To assess the cost effectiveness of buprenorphine versus methadone in the management of opioid use disorder (OUD) during pregnancy. Methods We designed a decision-analytic model to evaluate the costs and outcomes associated with buprenorphine compared to methadone for pregnant people with OUD. We used a theoretical cohort of 22,400 pregnant people, which is an estimation of pregnancies affected by OUD per year in the United States. Outcomes included maternal retention in maintenance treatment, neonatal opioid withdrawal syndrome, preterm birth, fetal growth restriction, cerebral palsy, and maternal overdose in addition to cost and quality-adjusted life-years (QALYs). We used a willingness-to-pay threshold of $100,000/QALY. All model inputs were derived from the literature and varied in sensitivity analyses to assess the robustness of our baseline inputs. Results In our theoretical cohort, treatment of OUD with buprenorphine during pregnancy resulted in 2413 fewer cases of neonatal opioid withdrawal syndrome, 1089 fewer preterm births, 299 fewer cases of fetal growth restriction, 32 fewer stillbirths, and 13 fewer cases of cerebral palsy compared to methadone treatment. Despite lower rates of retention, buprenorphine treatment saved nearly 123 million healthcare dollars and resulted in 558 additional QALYs, making it the dominant strategy compared to methadone treatment. Our findings were robust over a wide range of assumptions. Conclusion Our data suggest that buprenorphine should be considered a cost effective treatment option for OUD in pregnancy, as it is associated with improved neonatal outcomes compared to methadone despite the risk of treatment discontinuation.

Efficacy and Safety of Ixazomib Induction and Maintenance in Newly Diagnosed Multiple Myeloma Patients According to the IMWG Frailty Score: A Post-Hoc Analysis of the EMN10-Unito Trial

Efficacy and Safety of Ixazomib Induction and Maintenance in Newly Diagnosed Multiple Myeloma Patients According to the IMWG Frailty Score: A Post-Hoc Analysis of the EMN10-Unito Trial

Buprenorphine Versus Methadone in Pregnant Women With Opioid Use Disorder: A Cost-Effectiveness Analysis [06E

INTRODUCTION: Opioid use disorder (OUD) during pregnancy has increased more than fourfold since 1999. Methadone is the longstanding treatment of choice for OUD in pregnancy, but recent data demonstrate benefits of buprenorphine, as it is associated with improved neonatal outcomes despite increased drug cost and rates of discontinuation of therapy. This model compares cost-effectiveness of buprenorphine versus methadone in management of OUD during pregnancy. METHODS: We used a theoretical cohort of 22,400 pregnant women to approximate the number of pregnancies affected by OUD per year in the United States. Outcomes included maternal retention in maintenance treatment, maternal overdose, neonatal abstinence syndrome, preterm birth, intrauterine growth restriction, and cerebral palsy in addition to cost and quality-adjusted life-years. The cost-effectiveness threshold was set at $100,000/QALY. Model inputs were derived from the literature and varied in sensitivity analyses to assess robustness of the model. RESULTS: Despite lower rates of retention and higher associated overdoses, buprenorphine treatment during pregnancy saved over $102 million healthcare dollars and 563 QALYs, making it the dominant strategy over methadone treatment. In our cohort, buprenorphine treatment resulted in 2,886 fewer cases of NAS, 1,006 fewer preterm births, 299 fewer cases of IUGR, 32 fewer stillbirths, and 12 fewer cases of CP. Sensitivity analyses showed that our results were robust over a wide range of assumptions. CONCLUSION: Buprenorphine treatment should be considered a first-line option for opioid dependence in pregnancy, as it leads to improved neonatal outcomes compared to methadone despite increased drug cost and risk of treatment discontinuation.

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