Treatment Discontinuation In Patients Research Articles

C-Peptide and BMi predict anti-hyperglycemic treatment lines in breast cancer patients treated with Alpelisib.

Alpelisib is a PI3K (Phosphoinositide 3-kinases) inhibitor used for breast cancer which develops hyperglycemia based on its action on glucose metabolism regulation. This study aims to identify potential risk factors predicting hyperglycemia development and the need for multiple treatments for hyperglycemia in patients receiving Alpelisib. Fourteen women diagnosed with metastatic hormone receptor-positive breast cancer carrying PI3K mutations who initiated treatment with Alpelisib were monitored through consultations in the Oncology and Endocrinology departments. Non-parametric ROC curves were generated to assess the need for three or more antidiabetic medications to achieve glycemic control. The study population had a median age of 64 years (range:48-69) with a median body mass index (BMI) of 26.6 kg/m2 (range: 22.9-29.4). Overweight was observed in 35.7% of the participants and obesity in 21.4%. Fifty percent of the participants had prediabetes, and 85.7% developed hyperglycemia requiring pharmacological treatment, although none of them needed to discontinue treatment for this reason. Baseline C-peptide levels and BMI were associated with the number of antidiabetic drugs used (Spearman's Rho 0.553, p = 0.040; Spearman's Rho 0.581, p = 0.030, respectively). ROC curve analysis showed and area under the curve (AUC) of 0.819 for the variable risk profile (defined as baseline C-peptide >10.5 ng/ml and BMI > 27 kg/m2), whereas AUC values were 0.556 and 0.514 for HbA1c and baseline glucose, respectively, (p = 0.012). A joint follow-up by an Oncology department and a Diabetes Unit can prevent treatment discontinuation in patients under Alpelisib therapy. Baseline BMI and plasma C-peptide levels can predict an increased need for anti-hyperglycemic treatment.

Treatment Discontinuation in Patients with Psoriasis Treated with Biologics: A Retrospective Analysis of German Health Claims Data.

Plaque psoriasis is a common, often debilitating, chronic autoimmune inflammatory skin disease. Moderate-to-severe forms of psoriasis can be treated with biologics such as anti-interleukin and anti-tumor necrosis factor antibodies. We aimed to investigate treatment discontinuation among patients with psoriasis who initiated biologic treatment. We conducted a retrospective, non-interventional cohort study based on anonymized claims data from the German statutory health insurance which covered the years from 2016 to 2021. We included adult patients with psoriasis who initiated biologic treatment in drug-specific cohorts. Over a 365-day follow-up period, we assessed the frequencies and the time until treatment discontinuation for different biologics. Differences in discontinuation rates were compared using a multivariate Cox proportional hazards model. A total of 2565 patients with psoriasis who initiated treatment with secukinumab (n = 612), adalimumab (n = 454), guselkumab (n = 354), ixekizumab (n = 259), ustekinumab (n = 241), tildrakizumab (n = 205), brodalumab (n = 166), risankizumab (n = 145), etanercept (n = 91), certolizumab (n = 29), and infliximab (n = 9) were included. A total of 1290 patients (50.29%) discontinued treatment during the follow-up period, ranging from 30.34% (risankizumab) to 69.23% (etanercept). Median time until discontinuation of treatment ranged from 102days (etanercept) to 208days (risankizumab). Once the biologic treatment was discontinued, 45.05% of patients restarted the treatment with the same agent, 23.10% of patients switched to another biologic, and 31.86% received no further biologic agent. Compared to patients treated with risankizumab, the treatment discontinuation rate was significantly higher (p < 0.05) in patients treated with the other biologics except ustekinumab (p = 0.12). Further research should explore reasons leading to treatment discontinuation in order to support treatment choices for patients with moderate-to-severe psoriasis.

The efficacy and tolerability of bortezomib, thalidomide, and dexamethasone induction therapy with a thalidomide dose step-up strategy in patients with newly diagnosed multiple myeloma: A prospective observational study.

Thalidomide-containing regimens cause adverse events (AEs) that may require a reduction in treatment intensity or even treatment discontinuation in patients with multiple myeloma. As thalidomide toxicity is dose-dependent, identifying the most appropriate dose for each patient is essential. This study aimed to investigate the effects of a thalidomide dose step-up strategy on treatment response and progression-free survival (PFS). This prospective observational study included 93 patients with newly diagnosed multiple myeloma (NDMM) who received bortezomib, thalidomide, and dexamethasone (VTD). The present study assessed the incidence of thalidomide dose reduction and discontinuation, the overall dose intensity, and their effects on therapeutic efficacy. Furthermore, this study used Cox proportional hazard models to analyze the factors contributing to thalidomide intolerability. The results showed the overall response rates in all patients and the evaluable patients were 78.5% and 98.7%, respectively. The median PFS in the study cohort was not reached. The most common thalidomide-related AEs were constipation (32.3%) and skin rash (23.7%), resulting in dose reduction and discontinuation rates of 22.6% and 21.5%, respectively. The responders had a significantly higher average thalidomide dose intensity than the nonresponders (88.6% vs. 42.9%, p < .001). The thalidomide dose step-up approach is a viable option for patients with NDMM receiving VTD induction therapy with satisfactory efficacy and tolerability. However, thalidomide intolerance may lead to dose reduction or discontinuation due to unpredictable AEs, leading to lower dose intensity and potentially inferior treatment outcomes. In addition to a dose step-up strategy, optimal supportive care is critical for patients with multiple myeloma receiving VTD induction therapy.

Imaging to predict early relapses after treatment discontinuation in patients with large vessel giant cell arteritis – A cohort study

ObjectivesTo investigate the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in predicting relapse after treatment discontinuation in patients with large-vessel giant cell arteritis (LV-GCA). MethodsThis study included patients with LV-GCA whose treatment was discontinued between 2018 and 2023. All patients underwent PET/CT and/or MRI at the time of treatment discontinuation in clinical remission. Qualitative and quantitative PET/CT scores, by measuring standardized uptake values (SUV), and semiquantitative MRI scores of the aorta and supraaortic vessels were compared between patients who relapsed within 4 months after treatment discontinuation and those who did not. ResultsForty patients were included (median age 67.4 years, interquartile range (IQR) 60.8–74.0; 77.5 % females). Eleven patients (27.5 %) relapsed after treatment discontinuation (time to relapse 1.9 months, IQR 1.4–3.3). Patients who relapsed were comparable to those who remained in remission with respect to the presence of active vasculitis on MRI and/or PET/CT (54.5% vs. 58.6 %, p = 1.0), the number of segments with vasculitic findings on MRI (0, IQR 0.0–1.5, vs. 2, IQR 0.0–3.0, p = 0.221) or the highest SUV artery/liver ratio on PET/CT (1.5, IQR 1.4–1.6, vs. 1.3, IQR 1.2–1.6, p = 0.505). The median number of vasculitic segments on PET/CT was 2.5 (IQR 0.5–4.5) in those with vs. 0 (IQR 0.0–1.5, p = 0.085) in those without relapse, and the PET/CT scores 4.5 (IQR 0.75–8.25) vs. 0 (IQR 0.0–3.0, p = 0.172). ConclusionPET/CT or MRI at treatment stop did not predict relapse and may not be suited to guide treatment decisions in patients with LV-GCA in remission.

Safety outcomes of salbutamol: A systematic review and meta-analysis.

Salbutamol has been used to alleviate bronchospasm in airway disease for decades, while its potential risks have not been systematically investigated yet. The risk of any potential adverse events (AEs) in patients treated with salbutamol was assessed through systematic review and meta-analysis. A systematic search of the literature was conducted, using EMBASE, PubMed and Cochrane library, until 3 April 2023. Once the AE incidence was evaluated, randomized controlled trials (RCTs) were eligible for review. The endpoints included the incidence of total AEs, severe AEs, treatment discontinuation and specific AEs. The pooled AEs incidence was analysed via random-effects model in a single-arm meta-analysis. A subgroup study was carried out to examine whether the pooled incidence of AE differed by indications or formulations. Of the 8912 studies that were identified, 58 RCTs met the inclusion criteria and involved 12 961 participants. The analysis showed the pooled incidences of total AEs, severe AEs and treatment discontinuation in patients treated with salbutamol were 34%, 2% and 3%, respectively. Subgroup analysis indicated that premature labour users and intravenous salbutamol users were more likely associated with total AEs. The most frequently observed specific AEs were palpitations or tachycardia. This meta-analysis indicated that salbutamol was associated with a very common risk of palpitations or tachycardia. Clinical vigilance and research efforts are needed to optimize the safe use of salbutamol.

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 Duration of Use and Dosing Frequency of Daratumumab in Patients With Multiple Myeloma in the United States

Daratumumab (DARA) is an anti-CD38 monoclonal antibody approved as a combination therapy for newly diagnosed multiple myeloma (MM) and as monotherapy and combination therapy for relapsed or refractory MM cases. We assessed the length of DARA use across lines of therapy and the probabilities of treatment discontinuation in patients with MM in the real-world. We used the deidentified Clinformatics Data Mart database from Optum to identify patients with MM (n=2124) who received DARA-containing treatment between November 1, 2015 and March 31, 2021 in the United States. Patients were excluded if they had received a stem cell transplant. The duration of DARA use was defined as the time interval between the first initiation and discontinuation of DARA as a time-to-event outcome using the Kaplan-Meier method. A gap of more than 60 days between 2 consequent DARA claim dates was defined as DARA discontinuation. The median duration of continuous DARA use was 16.6 months. By 24 months, 33.1% of patients remained on DARA treatment. In a subgroup analysis of patients with 12 months or more continuous insurance coverage (n=1246), the median length of DARA use was 24.7 months; by 24 months, 51.8% remained on DARA treatment. The dose adherence ratios (observed DARA doses relative to the label) were close to 1.0, particularly among patients with longer follow-up, indicating that real-world DARA dosing frequency was similar to that on the approved label. In summary, this real-world analysis reported that the median duration of continuous DARA use is 16.6 months, with high dosing adherence in patients who have MM.

Standardized tapering off subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy.

Attempting discontinuation of treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is recommended. However, there is no evidence based regimen for tapering off subcutaneous immunoglobulin (SCIG). This trial investigated stepwise tapering off SCIG to detect remission and the lowest effective dosage. During tapering off, frequent vs less frequent clinical evaluation was compared. Patients with CIDP receiving a stable SCIG dosage followed a standardized tapering off regimen: 90%, 75%, 50%, 25% and 0% of the initial dose every 12th week, pending no deterioration occurred. In case of relapse during tapering off, the lowest effective dose was identified. Treatment with SCIG was registered for two years after participation. Disability score and grip strength were primary parameters. Participants were randomized to clinical evaluation every 6th week (frequent) or 12th week (less frequent). Fifty-five patients were included of which thirty-five relapsed. Twenty patients (36%) were able to discontinue treatment without relapse. In relapsing patients, median dosage could be reduced by 10% (range, 0-75). After two years, 18 of 20 patients were still in remission without treatment. Frequent clinical evaluation did not detect deterioration more frequently than less frequent evaluation; RR 0.5 (95% CI, 0.2-1.2) (p = 0.17). In stable CIDP patients, SCIG could be completely tapered off in 36% of the patients and only in 10% of these patients relapse occurred during the following two years. More frequent evaluation was not superior to detect deterioration.

POSTER: CML-250 The Prognostic Factors of Late Molecular Relapses after Treatment Discontinuation in Patients With Chronic Myeloid Leukemia

POSTER: CML-250 The Prognostic Factors of Late Molecular Relapses after Treatment Discontinuation in Patients With Chronic Myeloid Leukemia

CML-250 The Prognostic Factors of Late Molecular Relapses after Treatment Discontinuation in Patients With Chronic Myeloid Leukemia

CML-250 The Prognostic Factors of Late Molecular Relapses after Treatment Discontinuation in Patients With Chronic Myeloid Leukemia

LB1681 Risk of merkel cell carcinoma progression after treatment discontinuation in patients with an objective response to anti-PD-(L)1 immunotherapy

LB1681 Risk of merkel cell carcinoma progression after treatment discontinuation in patients with an objective response to anti-PD-(L)1 immunotherapy

LAI antipsychotics offer little advantage for continuation of treatment

Long‐acting injectable (LAI) antipsychotics resulted in no significant advantage over oral medications in increasing the time to treatment discontinuation in patients with schizophrenia, an open‐label trial has found. Efficacy outcomes improved substantially in both the LAI and oral antipsychotic groups, study investigators reported. Results were published online Jan. 27, 2023, in Lancet Psychiatry.

Tapinarof for psoriasis and atopic dermatitis: 15 years of clinical research.

Tapinarof is a topical, aryl-hydrocarbon receptor agonist that has recently received FDA-approval for the treatment of psoriasis. This novel therapeutic has also been shown to be effective for atopic dermatitis and is currently in phase 3 for this indication. Beyond good efficacy and fast onset of action in patients with psoriasis, the clinical response to tapinarof is notable for durable remission or near remission, maintained for an average of 130 days beyond treatment discontinuation in patients with psoriasis in phase 3 studies. Tapinarof is usually well tolerated but can induce a follicular inflammatory reaction and dermatitis in some patients. This narrative review covers the historical development of this molecule, safety and efficacy data from clinical trials conducted with various topical formulations, and practical considerations derived from our 15 years of clinical trial experience with the drug.

Attrition and Withdrawal Amongst Patients with Multiple Myeloma Participating in Randomized Clinical Trials: A Systematic Review

Introduction: In clinical trials, and in the real-world, patients with multiple myeloma (MM) discontinue treatment for a variety of reasons including death, disease progression, and toxicity of treatments. Patients may also discontinue trial treatment due to the other reasons such as a physician withdrawing the patient from the trial, or patient deciding to withdraw. The proportion of patients discontinuing treatment for each of these reasons has not previously been reported for MM randomized controlled trials (RCTs). Furthermore, a large number of patients withdrawing from one arm of a trial may raise concern for informative censoring and biased data. To date, there is no prior study evaluating MM RCTs analyzing trial discontinuation and attrition. Due to this, we aimed to assess reasons for discontinuing treatment amongst participants in trials, imbalances in attrition between trial arms, and the practice of reporting this data through a systematic review of all MM RCTs published between 2015-2020. Methods: Three databases were searched (MEDLINE/PubMed, Embase, and Cochrane Registry of Controlled Trials) for all RCTs in MM from 2015 to 2020. Studies reported as abstracts (without full manuscript available for review), or those that assessed purely supportive care strategies were excluded. We collected documentation of patient discontinuation and reasons for discontinuation in intervention arms, control arms, and in total. As discontinuation due to progression, toxicity and death is expected, we aimed to quantify and assess for rates of discontinuation due to other reasons beside these, such as patient withdrawal or physician decision to withdraw patient. Trials in which the absolute difference in discontinuation rate for these "other” reasons was greater than 5% between the intervention and control arms were thus determined to be outliers. Trials were also assessed for concordance to recommendations outlined by CONSORT guidelines for RCTs. Results: A total 47 RCTs were analyzed that met our inclusion criteria. Table 1 lists characteristics of included studies. Primary endpoint was progression free survival in 33 (70.2%) of these studies and overall survival in 4 (8.5%) studies. In these RCTs, a total of 21,985 patients were randomized to treatment. A total of 10,572 (48.1%) patients had discontinued the RCT by time of primary endpoint ascertainment. The causes of discontinuation in decreasing order of frequency included disease progression (n=4,893; average rate per study (ARPS)=26.4%); toxicity (n=2,691; ARPS=11.7%); patient or physician withdrawal in absence of toxicity/progression/death (n=1,136; ARPS=7.3%) and death (n=527; ARPS=2.6%). A total of 21,540 (98.4%) patients were included in primary endpoint analyses with 45 of 47 trials citing the use of intention to treat analysis. In regard to withdrawal due to reasons other than toxicity, progression or death, a total of 13 (27.7%) of the RCTs were outliers as defined in methods. Amongst these 13 RCTs, attrition was higher in control arm in 10 trials, and higher in intervention arm in 3 trials. Outliers were more commonly found in trials that met their primary endpoint compared to those that did not (10 vs 3 trials, respectively). In the 10 trials meeting their primary endpoint, attrition rate was higher in 8 trials in control arm, and 2 in intervention arm. Although a minority [19 (40.4%)] of trials followed the full recommended guidelines for RCT reporting, the majority 45 (95.7%) of the trials included a CONSORT diagram. Conclusion: Our analysis demonstrates that although disease progression is the most common reason for discontinuation of treatment in patients with MM on RCT's, over 10% of patients discontinue treatment due to toxicity prior to disease progression or death. Furthermore, 27.7% of trials showed substantial imbalances between the control and intervention arms in the number of patients withdrawn for reasons other than progression, toxicity, or death. This raises concern for informative censoring and bias in results and emphasizes the importance of detailed characterization of reasons for withdrawal in MM RCTs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and Safety of Bosutinib Vs Imatinib By Charlson Comorbidity Index in Newly Diagnosed Patients with Chronic Myeloid Leukemia

Introduction: The efficacy and safety of bosutinib (BOS) vs imatinib (IMA) in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) was assessed in the phase 3 BFORE trial (NCT02130557) after 5 years of follow-up (Brümmendorfet al., J Clin Oncol, 2022). Here we analyze the impact of comorbidities on efficacy and safety, reporting the results by Charlson Comorbidity Index (CCI) score. Methods: Patients with newly diagnosed CP CML were randomized 1:1 to receive BOS or IMA (starting dose: 400 mg QD). Outcomes were assessed after 5 years (240 weeks) of follow-up (database lock: June 12, 2020) according to the CCI score without the age component (mCCI). Patients were grouped by mCCI scores of 2 (BOS, n=195; IMA, n=196 [2 untreated]) and >2 (BOS, n=73; IMA, n=72 [1 untreated]). Efficacy was assessed in all randomized patients (intent-to-treat population) and safety in patients who received >1 dose of study medication (safety population). Results: In patients with mCCI 2 and >2, the median treatment duration was 55.1 and 53.4 months with BOS vs 55.0 and 55.1 months with IMA; respective median (range) dose intensity was 396.4 (39−583) and 367.2 (74−573) mg/day with BOS vs 400.0 (240−765) and 400.0 (189−754) mg/day with IMA. Permanent treatment discontinuations in patients with mCCI 2 and >2, respectively, were reported in 36.4% and 50.7% of patients with BOS vs 45.4% and 32.4% of patients with IMA. The most common primary reasons for permanent discontinuation were adverse events (AEs) in the BOS arm (BOS: mCCI 2, 21.0%; mCCI >2, 35.6%; IMA: mCCI 2, 13.9%; mCCI >2, 8.5%) and lack of efficacy (suboptimal response, treatment failure, or disease progression) in the IMA arm (BOS: mCCI 2, 6.7%; mCCI >2, 2.7%; IMA: mCCI 2, 20.6%; mCCI >2, 9.9%). In both treatment arms, the majority of permanent discontinuations due to AEs occurred in year 1 (BOS: mCCI 2, 11.3%; mCCI >2, 20.5%; IMA: mCCI 2, 7.7%; mCCI >2, 5.6%). Among patients with mCCI 2 and >2, respectively, the proportion who achieved an early molecular response (BCR::ABL1 ≤10% at 3 months) was 79.4% and 83.8% with BOS vs 56.5% and 71.0% with IMA (Table 1). Cumulative response rates according to mCCI score and treatment arm are shown in the Table 1. There were 14 deaths during the study period in both the BOS- (mCCI 2, n=7; mCCI >2, n=7) and IMA (mCCI 2, n=9; mCCI >2, n=5) arms; 3 and 4 deaths, respectively, were assessed by investigators as CML-related (all in patients with mCCI 2). Treatment-emergent AEs (TEAEs) occurred in ≥98.5% of patients in each treatment arm and across CCI subgroups. In patient with CCI 2 and >2, respectively, the most common (≥30% in either subgroup) TEAEs with BOS were diarrhea (79.5% and 63.0%), thrombocytopenia (37.4% and 31.5%), nausea (35.9% and 41.1%), increased alanine aminotransferase ([ALT] 34.4% and 31.5%), and fatigue (17.9% and 30.1%). Most common TEAEs with IMA were diarrhea (37.1% and 49.3%), nausea (41.2% and 45.1%), muscle spasms (33.0% and 23.9%), and anemia (17.5% and 36.6%). Among patients with CCI 2 and >2, respectively, grade 3/4 TEAEs were observed in 69.2% and 84.9% with BOS vs 55.2% and 62.0% with IMA. The most frequently reported grade 3/4 TEAEs are shown in Table 2. TEAEs resulting in death in the BOS arm (n=3) were acute cardiac failure, myocardial ischemia, and renal failure (all in patients with CCI >2). TEAEs leading to death in the IMA arm (n=4) were sepsis and CML in patients with CCI 2, and pneumonia and cerebrovascular accident in patients with CCI >2. Conclusions: After 5 years of follow-up in the BFORE study, a substantial proportion of patients across mCCI scores achieved molecular responses with BOS or IMA. In the BOS arm, there was a trend toward a higher rate (>10% difference) of MR4 in patients with CCI 2 vs CCI >2, with a similar proportion of patients achieving MMR and MR4.5 in both subgroups. Molecular response rates by 60 months were higher with BOS vs IMA in patients with CCI 2 and similar in patients with CCI >2. Safety data were consistent with the known safety profiles of BOS and IMA. Discontinuations due to AEs were higher (>10% difference) in patients with CCI >2 in the bosutinib arm and similar across CCI groups in the imatinib arm. However, in both treatment arms, there were no relevant differences in the frequency of TEAEs across the most commonly occurring AEs between patients with CCI 2 and CCI >2. These results support the use of 400 mg once daily BOS in patients with newly diagnosed CP CML irrespective of baseline comorbidities. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cost-Effectiveness of Triple Therapy with Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate versus Dual Therapies in Moderate-to-Very Severe Chronic Obstructive Pulmonary Disease: United Kingdom Analysis Using the ETHOS Study

In the 52-week ETHOS study (NCT02465567), fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) reduced moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations versus fixed-dose long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) or inhaled corticosteroid (ICS)/LABA dual therapies. Here, ETHOS data were used to estimate the long-term cost-effectiveness of BGF versus LAMA/LABA and ICS/LABA dual therapies in the United Kingdom. Costs, exacerbations, quality-adjusted life-years (QALYs), and LYs were extrapolated using a Markov model that considered disease severity progression, risk of moderate and severe exacerbations, adverse events, and treatment discontinuation in patients with moderate-to-very severe COPD receiving BGF 320/14.4/10 µg, the LAMA/LABA glycopyrronium/formoterol fumarate dihydrate 14.4/10 µg (GFF), or the ICS/LABA budesonide/formoterol fumarate dihydrate 320/10 µg (BFF). Utilities for COPD severity states were estimated using EuroQol 5-dimension 5-level data from ETHOS. Exacerbation disutilities were sourced from published literature. Healthcare resource utilization was based on ETHOS data, published literature, key external experts' input, and informed assumptions. Unit costs came from the UK National Health Service Schedule of Reference Costs, Unit Costs of Health and Social Care from the Personal Social Services Research Unit, and published literature. A lifetime horizon was considered, with costs, QALYs, and LYs discounted at 3.5% per annum. The incremental cost-utility ratio (ICUR; per QALY gained) was £9901 for BGF versus GFF and £2164 for BGF versus BFF. The probability of treatments being cost-effective at the conventional UK-adopted willingness-to-pay threshold of ICUR <£20,000 was 85.1% for BGF, 14.3% for GFF, and 0.6% for BFF. Based on ETHOS data, BGF was demonstrated to be cost-effective versus LAMA/LABA and ICS/LABA dual therapies at the conventional UK-adopted willingness-to-pay threshold (ICUR <£20,000). The main cost-effectiveness driver for BGF versus LAMA/LABA and ICS/LABA therapies was reduction in rate of exacerbations, which reduced costs and preserved quality of life.

Multicentre study on rates and reasons for treatment discontinuation in patients with remaining cryopreserved embryos

Research questionWhat is the discontinuation rate among patients with remaining cryopreserved embryos in Belgium and what are the reasons for discontinuation? DesignMulticentre, cross-sectional study across 11 Belgian fertility clinics. Patients were eligible (n = 1917) if they had previously undergone an unsuccessful fresh embryo transfer (fresh group) or frozen embryo transfer (FET) (in-between group) and did not start a subsequent FET cycle within 1 year despite having remaining cryopreserved embryos. The denominator was all patients with embryos cryopreserved during the same period (2012–2017) (n = 21,329). Data were collected through an online anonymous questionnaire. ResultsThe discontinuation rate for patients with remaining cryopreserved embryos was 9% (1917/21329). For the final analysis, 304 completed questionnaires were included. The most important reasons for discontinuing FET cycles were psychological (50%) and physical (43%) burden, effect on work (29%), woman's age (25%) and effect on the relationship (25%). In 69% of cases, the patient themselves made the decision to delay FET treatment. In 16% of respondents, the decision to delay FET was determined by external factors: treating physician (9%), social environment (4%), close family (3%) and society (3%). Suggested improvements were psychological support before (41%), during (51%) and after (51%) treatment, as well as lifestyle counselling (44%) and receiving digital information (43%). ConclusionsThe discontinuation rate is remarkably high in patients with remaining cryopreserved embryos who have a good prognosis. Respondents stressed the need to improve the integration of psychological and patient-tailored care into daily assisted reproductive technology practice.

FINANCIAL IMPACT OF IMATINIB DISCONTINUATION IN BRAZIL – A PHARMACOECONOMIC STUDY IN CHRONIC MYELOID LEUKEMIA OF A PRIVATE INSTITUTION

Recent studies showed that tyrosine kinase inhibitors (TKI) treatment could be safely discontinued in a selected group of chronic phase (CP) chronic myeloid leukemia (CML) patients that achieved deep molecular response (DMR), making treatment-free remission (TFR) a new goal of therapy. The discontinuation of treatment in patients with sustained molecular response to MR4 or MR4.5, a practice that has been performed in other countries is not feasible in Brazil outside clinical trials because of the lack of coverage for performing RQ-PCR as recommended by the international guidelines. For all these aspects, it seemed essential to us to analyze the financial impact of TKI discontinuation, following strict monitoring criteria, and perform a projection of economic costs in a population of CML patients treated in first-line with imatinib eligible for discontinuation. To demonstrate the feasibility of coverage of Q-PCR to perform discontinuation of imatinib treatment on eligible patients [ treatment free-response (TFR)] in Brazil based on the financial impact. From 2020 -2021, 20 eligible patients from a single private institution in Brazil were invited to participate in a single-arm trial of Imatinib discontinuation (DIP). After discontinuation, patients were monitored by RT- PCR monthly in the first year, every two months in the second year, and every three months after the third year. Criteria for Imatinib re-initiation were the same of the Euro-Ski trial. Considering that US$ 1.00 are R$ 5.3 (Brazilian currency- March /2022) for Branded Imatinib – 400 mg/d, the monthly cost has been estimated at R$ 16,933.90 or US$ 3,95.07 and the generic imatinib- 400mg/d monthly R$ 13,048.90 or US$ 2,462.05 (CEMED- March/2022). The unitary value for the Q-PCR exam has been estimated, with a large price range at R$ 1,311.25 (R$790.00 to R$ 2,159.00) or US$ 247.40. Of 26 patients, 20 consent to discontinuation of imatinib. Twelve patients (60%) presented MR4. Median time diagnosis to discontinuation of imatinib 8.5 (4.6-15.5) years. Twelve (60%) patients sustained TFR. During the follow-up, 244 RQ-PCR were performed. The cumulative time without treatment was 224.5 months. The costs with Q-PCR were R$ 319,945.00 or US$ 60,366.98 (244 exams during follow-up (median time 14,4 months). The average time of months without treatment was 224.5 months. The cost of treatment without discontinuation would be R$ 4,131,871.60 or US$ 779,598.41 (Branded Imatinib) or R$ 2,929,478.05 or US$ 552,731.70 (imatinib copies). The saving on median time of follow-up (14.4 months) were R$ 3,811,926.60 or US$ 719,231.43 (Branded Imatinib) or R$ 2,609,533.05 or US$ 492,364.72 (imatinib copies). Considering the methodology of Cost-Utility, the saving resulting from the discontinuation of treatment for 20 patients for 14.4 months despite the loss of MR of 40 % of patients were R$ 3,811,926.60 or US$ 719,231.43 (Branded Imatinib) or R$ 2,609,533.05 or US$ 492,364.72 (imatinib copies). The results show that if Q-PCR tests were available in clinical practice, within pre-established protocols, there would be equalization and adequacy with the international monitoring guidelines, and discontinuation protocols could be feasible in clinical practice. The possibility of discontinuation would have a huge financial impact on the Brazilian Health System, resulting in the economic viability of treating hundreds of patients and performing thousands of Q-PCR exams, creating a rational and balanced model of clinical efficacy coupled with basic sustainability premises of modern oncology.

TREATMENT-FREE REMISSION IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA: MANAGEMENT APPROACHES

The study objective was to analyze the short- and long-term results of treatment discontinuation in patients with chronic myeloid leukemia (CML) and complete molecular response (CMR). This prospective study enrolled 22 patients (pts) with chronic phase of CML, managed at the Oncologic Institute from Moldova between 2017–2022. The age range was 29–73 years. The male/female ratio was 1:1.2. The real-time quantitative PCR revealed the wide range of BCR-ABL p210 transcript: 21.84–100% IS. In 7 (31.8%) pts the rate of BCR-ABL p210-positive cells was less than 50%. CMR was achieved in 15 (68.2%) pts after imatinib therapy and in 7 (31.8%) pts after the 2nd generation of TKIs. The therapy with TKIs was stopped due to the different reasons in all patients after the CMR was obtained. Two (9.1%) pts stopped the TKIs treatment due to the pregnancy. The molecular relapse occurred in 6 (27.3%) pts, including one pregnant female. All relapsed pts had the initial BCR-ABL p210 transcript expression > 50%. The CMR span ranged between 2.5-26 months in relapsed pts. The range of BCR-ABL p210 transcript in the relapsed pts was 0.002-0.56%. These pts achieved the 2nd CMR after restarting TKIs treatment. All pts are alive, with the ECOG score of 0-1. TKIs discontinuation may be considered an option in CML patients with CMR, especially in those with the initially low BCR-ABL p210 transcript expression. The 2nd CMR may be obtained after restarting the TKIs treatment in pts with minor molecular relapse.

Reasons and Determinants of BoNT-A Treatment Discontinuation in Patients Living with Spasticity: A 10-Year Retrospective Analysis.

Background: The present study aimed to evaluate the reasons and determinants of BoNT-A discontinuation in patients with stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. Methods: It is a retrospective study of 56 discontinuer patients treated with botulinum toxin between January 2011 and December 2021. Discontinuation rates and their predictors were estimated using Kaplan–Meier, Log rank test, and Cox’s regression method of analyses. Results: The mean age was 56.54 years, 53.57% were affected by post-stroke spasticity, 17.86% by spinal cord injury, 12.5% and 16.07% by traumatic brain injury and multiple sclerosis, respectively. The median discontinuation time was 5 months. The main reason for discontinuation were logistic problems (37%) and orthopedic surgeries or intrathecal baclofen (27%). Discontinuers were more likely to have severe spasticity (R = 1.785), have no pain (HR = 1.320), no access to rehabilitation services (HR = 1.402), and have cognitive impairment (HR = 1.403). Conclusions: The main reasons for discontinuation are related to logistic issues (due to distance or the absence of an adequate caregiver) and surgical interventions for spasticity, including intrathecal baclofen. It is crucial to identify possible predictors of discontinuation to improve the effectiveness of a multidisciplinary management. The study confirms the crucial role of rehabilitation and caregivers in achieving better long-term outcomes.