Drugs In Adult Patients Research Articles

Mental health and use of psychotropic prescription drugs in adult patients with primary immune thrombocytopenia: a nationwide population-based cohort study.

Patients with primary immune thrombocytopenia (ITP) suffer from reduced survival and quality of life, but the underlying reasons for this are largely undescribed. Mental health and the use of psychotropic drugs in ITP is unknown. We investigated the risk of hospital-registered mental health events including fatigue and the use of psychotropic drugs in adult patients with ITP compared with the general population, using nationwide registry-data. We identified 3,749 patients with ITP and 149,849 age- and sex-matched general population comparators in the Danish Health Registries in the period 1997-2016. The median age was 60 years (interquartile range [IQR], 40-73) and 53% were women. We followed the individuals for incident mental health events and estimated the use of psychotropic drugs over calendar-years and in temporal relation to diagnosis of ITP. The first year cumulative incidence of any mental health event was 2.3% (95% confidence interval [CI]: 1.9-2.9) in patients and 0.7% (95% CI: 0.6-0.7) in comparators, yielding an adjusted cause-specific hazard ratio (csHR) of 3.57 (95% CI: 2.84-4.50). The corresponding estimates for depression were 1.2% (95% CI: 0.9-1.6) and 0.3% (0.3-0.4) respectively, with an adjusted csHR of 3.53 (95% CI: 2.56-4.85). We found similar findings for anxiety and fatigue, but risks generally diminished after 1-5 years. The use of opioids, antidepressants, and benzodiazepines increased in temporal relation to diagnosis of ITP. The risk of mental health events and the use of psychotropic drugs is higher in adult patients with ITP compared with the general population, and has a temporal relation to diagnosis of ITP emphasizing that mental health in ITP is a concern.

Impact of using novel antitumor drugs in adult patients with locally advanced or metastatic urothelial carcinoma on reducing cancer mortality in Russia

Background. Standard first-line therapy options for patients with locally advanced or metastatic urothelial carcinoma (UC) is platinum-based chemotherapy. Currently, patients also have access to immune checkpoint inhibitors (ICIs) such as pembrolizumab, nivolumab, and atezolizumab, along with avelumab, which, unlike other drugs in this class, can be used as maintenance therapy after first-line platinum-based chemotherapy.Aim. To evaluate the effects of using ICIs in treating adult patients with locally advanced or metastatic UC on reducing overall and one-year cancer mortality in Russia.Materials and methods. A mathematical model based on overall survival and progression-free survival data from clinical trials has been proposed. This model describes duration of therapy and treatment outcomes for cases of treatment without ICIs (routine clinical practice); with pembrolizumab, nivolumab, and atezolizumab in first and second-line therapy according to real-life clinical practice (current practice); and with avelumab as maintenance therapy after platinum-based chemotherapy (proposed practice) over a 3-year period. The model was used to estimate the number of lives saved and healthcare system costs when transitioning from historical to current practice, and from current to proposed practice over a three-year horizon, considering the number of locally advanced or metastatic UC patients who may start platinum-based therapy annually in Russia.Results. Annually, up to 4,182 patients with locally advanced or metastatic UC in Russia can start platinum-based chemotherapy. Compared to historical practice, the use of pembrolizumab, nivolumab, and atezolizumab in the first and second lines of therapy in accordance with the routine clinical practice allows to reduce mortality from malignant neoplasms by 553 cases over a 3-year horizon. Over the same period, avelumab-based treatment would additionally save 2,506 lives. Moreover, the cost of saving one life with the use of avelumab amounts to 6.0 million rubles, which is 9 % lower than the cost of saving one life with the use of other ICIs (6.6 million rubles).Conclusion. The use of avelumab as maintenance therapy after platinum-based chemotherapy in the 1st line in patients with locally advanced or metastatic UC has a significant and quantifiable impact on reducing cancer-related mortality in Russia.

The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate-Severe Crohn's Disease: A Systematic Review.

Conventional therapy is the most commonly used treatment for Crohn's disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of biologic drugs in adult patients diagnosed with moderate-severe CD. An intensive search was performed in PubMed, Web of Science and Medline to collect phase 2 or 3 clinical trials published between 2018 and 2023 that were randomized, placebo-controlled and double-blind trials analyzing the efficacy and safety of biologic drugs in adult patients diagnosed with CD. This systematic review was conducted according to the PRISMA statement. Thirteen clinical trials evaluating eight biologic drugs were included. Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate-severe CD in adult patients with an inadequate response or intolerance to conventional therapy.

Predictors of adverse effects to antiseizure drugs in adult patients with epilepsy from Colombia: A case–control study

IntroductionAdverse drug reactions (ADRs) to antiseizure therapy can worsen the quality of life, reduce adherence, and potentially lead to treatment discontinuation and uncontrolled seizures. ObjectivesThe aim of the study was to develop a prognostic model for ADRs to antiseizure therapy in adult patients with epilepsy from Colombia. MethodsThis case–control study included adult patients with epilepsy, who were separated into two groups: one group with ADRs to antiseizure therapy (cases), as determined by a complete evaluation conducted by an epileptologist, and another group without ADRs (controls). Variables were analyzed to identify statistical differences between the two groups and were then selected to construct a prognostic model using logistic regression. The Bonferroni method was applied for multiple comparisons. ResultsThree hundred fifty-four patients with epilepsy were studied. One hundred and fifty (42%) patients had ADRs and 204 (57%) patients did not have ADs. A total of 362 ADRs were reported, with a third of them being general symptoms and most frequently occurring with older-generation antiseizure drugs (58%). Female sex, drug-resistant epilepsy, LEV, and CZP were risk factors, whereras the presence of tumoral etiology, absence of seizure triggers, and VPA were identified as protective factors. A prognostic model was constructed using previously reported risk factors for ADRs to antiseizure therapy and other variables available in this population study. In the multivariable analysis, the number of previously used antiseizure drugs (1, 2, or ≥3), TPM, CZP, LEV, PHT, and female sex were predictors of ADRs. The corrected p-values were estimated by the Bonferroni method; however, not all the variables achieved statistical significance with this adjustment. ConclusionsIn adult patients with epilepsy from Colombia, we found that the number of previously used antiseizure drugs, TPM, CZP, LEV, PHT, and female sex were predictive factors for ADRs to antiseizure therapy.

Combining thrombopoietin receptor agonists with immunosuppressive drugs in adult patients with multirefractory immune thrombocytopenia, an update on the French experience.

Combining drugs could be an effective option for treating multirefractory ITP, that is, patients not responding to rituximab, thrombopoietin receptor agonists (TPO-RA) and splenectomy. We conducted a retrospective, multicenter, observational study including multirefractory ITP patients who received a combination of a TPO-RA and an immunosuppressive drug. We included 39 patients (67% women, median age 59 years [range 21-96]), with a median ITP duration of 57 months [3-393] and a median platelet count at initiation of 10 × 109 /L [1-35]. The combination regimen was given for a median duration of 12 months [1-103] and included eltrombopag (51%) or romiplostim (49%), associated with mycophenolate mofetil (54%), azathioprine (36%), cyclophosphamide (5%), cyclosporin (3%) or everolimus (3%). Overall, 30 patients (77%) achieved at least a response (platelet count ≥30 × 109 /L and at least doubling baseline during at least 3 months), including 24 complete responses (platelet count >100 × 109 /L during at least 3 months) with a median time to response of 30 days [7-270] and a median duration of response of 15 months [4-63]. Severe adverse event related to ITP treatment was observed in 31%. In conclusion, this study confirms that some patients with multirefractory ITP can achieve long lasting response with this combination.

A non-inferiority randomized phase III trial of standard immunotherapy by checkpoint inhibitors vs. reduced dose intensity in responding patients with metastatic cancer: the MOIO protocol study

BackgroundImmunotherapy (IO) has become a standard of care for treating various types of metastatic cancers and has significantly improved clinical outcome. With the exception of metastatic melanoma in complete response for which treatment can be stopped at 6 months, these treatments are currently administered until either disease progression for some IO, 2 years for others, or unacceptable toxicity. However, a growing number of studies are reporting maintenance of response despite discontinuation of therapy. There is currently no evidence of a dose effect of IO in pharmacokinetic studies. Maintaining efficacy despite a reduction in treatment intensity by decreasing the frequency of administration in patients with highly selected metastatic cancer, is the hypothesis evaluated in the MOIO study.Method/designThis non-inferiority, randomized phase III study aims to compare the standard regimen to a 3 monthly regimen of variousIO drugs in adult patients with metastatic cancer in partial (PR) or complete response (CR) after 6 months of standard IO dosing (except melanoma in CR). This is a French national study conducted in 36 centers. The main objective is to demonstrate that the efficacy of a three-monthly administration is not unacceptably less efficacious than a standard administration. Secondary objectives are cost-effectiveness, quality of life (QOL), anxiety, fear of relapse, response rate, overall survival and toxicity.After 6 months of standard IO, patients with partial or complete response will be randomized 1:1 between standard IO or a reduced intensity dose of IO, administered every 3 months. The randomization will be stratified on therapy line,, tumor type, IO type and response status. The primary endpoint is the hazard ratio of progression-free survival. With a planned study duration of 6 years, including 36 months enrolment time, 646 patients are planned to demonstrate with a statistical level of evidence of 5% that the reduced IO regimen is non-inferior to the standard IO regimen, with a relative non-inferiority margin set at 1.3.DiscussionShould the hypothesis of non-inferiority with an IO reduced dose intensity be validated, alternate scheduling could preserve efficacy while being cost-effective and allowing a reduction of the toxicity, with an increase in patient’s QOL.Trial registrationNCT05078047.

Efficacy of targeted drugs for the treatment of adults with moderate-to-severe plaque psoriasis in the Russian Federation: a systematic literature review update

Background. A systematic literature review helps to identify the main treatment options, and evidence synthesis supports decision-making by comparing clinical efficacy of different treatments. Nowadays new drugs and clinical trials emerge rapidly, so previous network meta-analyses might need to be updated.Objective: to update the existing systematic review and network meta-analysis comparing efficacy of targeted drugs in adult patients with moderate-to-severe plaque psoriasis by adding randomized clinical trials (RCTs) on a new interleukin (IL) 23 inhibitor registered in the Russian Federation – risankizumab, and other RCTs published after 2019; to reassess the Psoriasis Area and Severity Index (PASI) 75/90 numbers of patients needed to treat to achieve clinical response to therapy and the costs per responder for 12–16 weeks and 1 year of therapy.Material and methods. We updated our systematic literature search in the PubMed/MEDLINE and Embase databases. Evidence synthesis included RCTs evaluating the efficacy of adalimumab (ADA), infliximab (INF), etanercept (ETN), certolizumab pegol (CZP), ixekizumab (IXE), netakimab (NTK), secukinumab (SEC), risankizumab (RIS), guselkumab (GUS), ustekinumab (UST), tofacitinib (TOFA), and apremilast (APR) after 12 weeks of therapy. The Bayesian meta-analyses with meta-regression models were performed in order to account for high heterogeneity in patient characteristics and significant differences in the placebo response rates. The considered drugs were ranked based on values of surface under the cumulative ranking curve (SUCRA). Additionally, drug class analyses were carried out.Results. Twenty three new RCTs were added to the network. IL-23 inhibitor RIS, recently approved in the Russian Federation, has joined the group of the most efficacious drugs, such as IL-17 inhibitors NTK and IXE, as well as IL-23 inhibitor GUS. In terms of PASI 75, RIS and IXE showed superiority compared to all tumor necrosis factor alpha (TNFα) inhibitors (INF, ADA, ETN), small molecules (TOFA and APR), and IL-12/23 inhibitor UST, while NTK and GUS were characterized by comparable efficacy with INF and outperformed the remaining drugs. There were no statistically significant differences in efficacy between all the TNFα inhibitors. GUS, IXE, INF, NTK, RIS and SEC demonstrated that no more than 2 patients need to be treated to achieve one PASI 75 response, and no more than 3 need to be treated for one PASI 90 response (according to the upper limit of 95% credible interval). Same as in the previously published study, NTK showed the lowest costs per responder for both 12-week and 1-year periods.Conclusion. The addition of head-to-head trials and increased statistical power of the network revealed previously unidentified significant differences between treatment options for moderate-to-severe plaque psoriasis.

Factors Influencing the Withdrawal of Antiepileptic Drugs in Adult Patients with Symptomatic Seizures Secondary to Neuronal Surface Antibodies-Associated Autoimmune Encephalitis

PurposeThis retrospective study aimed to investigate the relationship between clinical characteristics, seizure outcomes, and the potential factors influencing the withdrawal of antiepileptic drugs (AEDs) in adult patients with symptomatic seizures secondary to neuronal surface antibody (NSAb)-associated autoimmune encephalitis (AE).Patients and MethodsEighty-one patients (age ≥18 years) diagnosed with NSAb-associated AE were included in this retrospective study. After at least 1 year of follow-up, clinical details, magnetic resonance imaging (MRI) findings, electroencephalography (EEG) data, cerebrospinal fluid parameters, and the therapeutic outcomes were analyzed. Patients who needed long-term AEDs to control seizures were divided into two groups (withdrawal ≤1 year and withdrawal >1 year). Multivariable logistic regression analysis was performed to identify the risk factors affecting the AEDs’ withdrawal in patients with seizures secondary to NSAb-associated AE.ResultsDuring the 12-month follow-up after AEDs’ withdrawal, 28 (44.4%) patients among the 63 patients who needed long-term AEDs stopped AEDs within 1 year, while 35 (55.6%) patients continued AEDs treatment. Multivariable logistic regression analysis showed that delayed immunotherapy, status epilepticus (SE), and elevated intrathecal Immunoglobulin G synthesis rate of 24 hours (24-h intrathecal IgG) were independent risk factors for delayed withdrawal in patients with seizure secondary to NSAb-associated AE (odds ratios: 1.129, 6.497, 3.415, P<0.05). The receiver operating characteristics (ROC) curve analysis showed that the area under the curve (AUC) of delayed immunotherapy, SE, and elevated 24-h intrathecal IgG was 0.816 (95% CI=0.711–0.921, P<0.001).ConclusionDelayed immunotherapy, status epilepticus and elevated 24-hour intrathecal IgG synthesis rate are the factors that may influence the decision to delay AEDs’ withdrawal.

Hyperprolactinemia in Adults Treated With Anti-psychotic Drugs Attending Tertiary Hospitals in Oman: An Observational Study.

Introduction: Hyperprolactinemia is a common side effect associated with the use of anti-psychotic medications. This study aimed at exploring the rate of hyperprolactinemia induced by anti-psychotic drugs in adult patients admitted to Sultan Qaboos University Hospital (SQUH) and Al Masarra hospital (AMH). Additionally, factors associated with higher prolactin levels in anti-psychotic patients were explored.Methods: Bespoke XL sheets on age, gender, region (place of stay), BMI, diagnosis, type of drugs, dose, symptoms, and prolactin levels were recorded from the existing health information system. All adult patients who were on anti-psychotic medication between January 2016 and June 2019 were included. Patients diagnosed with pre-existing endocrine conditions, pregnant females, and those with high prolactin levels at baseline were excluded.Results: A total of 1103 cases were included in this study of which 34.1% were from the SQUH vs 65.9% from AMH. The mean (SD) age of the study population was 35.6 (12.1), 56.7% were females and 58.7% cases were from Muscat. The common diagnoses were schizophrenia (59.3%) and bipolar affective disorder (14.7%). High prolactin levels existed in 68.3% of the cases from which 59.6% were treated with atypical anti-psychotic drugs. The proportion of cases with high prolactin levels in AMH was significantly different (higher) compared to cases in SQUH (76.9% vs 51.6%, P<0.001).The most common symptoms were painful breasts (55.2%), galactorrhoea (10.5%), amenorrhea (14.3%) and irregular periods (20.0%). Type of drugs used [haloperidol (typical) vs risperidone (atypical) anti-psychotics (P<0.001)], older vs younger age (P=0.03), and presence vs absence of symptoms (P<0.001) were predictors for the high prolactin levels.Conclusion: Similar to evidence from the west, results from this study showed a high rate of hyperprolactinemia in adults treated with anti-psychotics. More work is required to standardize anti-psychotic management and monitoring guidelines for psychotic patients across all psychiatric hospitals in Oman.

POSC283 Number Needed to Treat and Incremental Costs per Responder for Biologics and Targeted Synthetic Drugs in Adult Patients with Active Psoriatic Arthritis in the Russian Federation

Psoriatic arthritis (PsA) is an autoimmune disease – a rare form of inflammatory arthritis with variety of symptoms, which imposes a considerable economic burden to patients and society. A growing range of new medicines is extremely helpful in controlling condition. However, the costs of therapy remain substantial.

Impact of the timing of tumor assessments on median progression-free survival in clinical trials in advanced cancer patients

BackgroundSurvival-based surrogate endpoints such as progression-free survival (PFS) are commonly used in oncology clinical trials. The evaluation-time bias in the assessment of median disease progression in randomized trials has been suggested by several simulation studies, but never demonstrated in the clinic. We aimed to demonstrate the existence of potential evaluation-time bias by assessing the impact of the timing of tumor assessments on median PFS from control arms without any active treatment of randomized controlled trials involving advanced cancer patients.Materials and methodsA systematic literature search of English language publications from 1 January 2000 to 7 January 2021 was performed using MEDLINE (PubMed). Eligible trials for our meta-analysis included all randomized clinical trials evaluating anticancer drugs in adult patients with advanced cancers with a control arm without any anticancer drug consisting of best supportive care with or without a placebo. We performed a meta-regression analysis to analyze the correlation between the timing of the first tumor assessment and median PFS in patients randomized in the control arms without any active treatment.ResultsOf 3551 studies screened, 97 eligible trials were retrieved involving 36 747 patients, including 14 229 patients randomized into the control arms. A later first tumor assessment correlated with a prolonged median PFS (R2 = 0.44, P < 10−5).ConclusionsOur results confirm the existence of potential evaluation-time bias in clinical research that had been suggested by simulation studies. The timing of tumor assessments should be kept the same in precision medicine trials using the PFS ratio as an efficacy endpoint.

A prospective, randomized and double blinded clinical comparative study to evaluate dexmedetomidine and nitro-glycerine for controlled hypotensive anaesthesia elective spine surgeries

Aim: To compare the efficacy of and safety of dexmeditomidine versus nitroglycerine during hypotensive anaesthesia induced by either drug in adult patients posted for elective spine surgeries. Material and Methods: This was a prospective, randomized, and double blinded clinical comparative study conducted in the Department of Anaesthesiology, ESIC Medical College, Sanath Nagar, Hyderabad, Telangana, India for the period of 1 year. 100 participants belonging to ASA class I or II between 20 and 55 years of age scheduled for elective spine surgeries were include in this study. The study drug dexmeditomidine was given to group DX in the dose of 1 micro gram/kg body weight in a 600 seconds infusion before induction diluted to 10 ml with normal saline followed by maintenance dose at infusion rate of 0.2- 0.7 microgm/kg. The group NG received 10 ml plain normal saline over 600 seconds before induction followed by maintenance dose of nitroglycerine at an infusion rate of 0.5-10 microgm/kg/min. different parameter were compared in both the groups.

Risks and benefits of anticancer drugs in advanced cancer patients: A systematic review and meta-analysis.

Background: Randomized clinical trials (RCTs) of anticancer drugs without active comparators in patients who have exhausted standard of care treatment options are debated. We aimed to quantify the safety and the efficacy of anticancer drugs in advanced cancer patients who have exhausted standard of care treatments from RCTs without active comparators.Methods: This systematic review and meta-analysis was conducted according to preferred reporting Items for systematic review and Meta-Analyses (PRISMA) guidelines (CRD42021243968). A systematic literature search of English language publications from January 1, 2000, to January 7, 2021, was performed using MEDLINE (PubMed). Eligible trials included all RCTs evaluating anticancer drugs in adult patients with advanced solid tumors with a control arm without any anticancer drug consisting of best supportive care with or without a placebo. RCTs performed in the adjuvant, neoadjuvant or maintenance settings were excluded, as were clinical trials evaluating anticancer drugs in combination with radiotherapy. Two authors (C.M.B. and E.C.) independently reviewed the studies for inclusion. Data from published reports were extracted by investigators, and random-effects meta-analysis was performed to estimate the overall hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS). Correlations between severe toxicity and efficacy was assessed using R2 measures.Findings: Of 3551 studies screened, 128 eligible trials were found involving 47,432 patients. The HRs for PFS and OS were 0·58 [95%CI: 0·53–0·63] and 0·82 [95%CI: 0·78–0·85]. The absolute benefits however were limited with PFS and OS gains of 2·1 and 0·5 months. The absolute excesses in all grade, severe grade III, IV and V (death) adverse events between the two arms were +13·9%, 10·2%, and +0·5%. A weak correlation was measured between the excess of severe toxicity and efficacy (all R² < 0·2).Interpretation: Anticancer drugs evaluated in RCTs against no active treatment benefited trial participants. Severe toxicity did not significantly correlate with efficacy.FundingNone.

Analysis Of The Effect Of Age On Medication Adherence With Oral Antidiabetes And Oral Antihypertension Drugs Using Pill Count Method

Compliance with taking medication is a problematic patients who get polypharmacy prescribing, this is because of the many drugs that must be consumed. As a result of the consumption of many drugs that cause sufferers of degenerative diseases are not compliant to take medication and health awareness decreases. This is not only experienced in elderly and geriatric patients but in adulthood also experience non-compliance with taking medication due to the many activities, lazy to take medication and also forget. This study was conducted to analyze the effect of age on adherence to taking oral antidiabetic drugs and oral antihypertensive drugs using the pill count method at the Regional Hospital of South Surabaya. The Pill Count method was chosen in this study with the aim of analyzing patient compliance in taking medication by calculating the remaining drug based on the rules of use and dosage when the patient returns to control. In addition, this study also aims to determine the effect of age on patient compliance in taking oral antidiabetic drugs and oral antihypertensive drugs. This research is descriptive observational with prospective data collection. Data analysis used descriptive and continued with statistical analysis using Chi-Square. The results of this study that adherence to take medication for elderly patients who received oral antidiabetic drug therapy obtained as much as 96.7% and 90% in adult patients. Compliance to oral antihypertension drugs in adult patients are 90% and 83.3% in elderly patients. Age does not effect compliance patients with Chi-Square analysis with p value = 0,301 and 0,448 &gt; 0.05.

Risks and Benefits of Anticancer Drugs in Advanced Cancer Patients: A Systematic Review and Meta-Analysis

Background: Randomized clinical trials of anticancer drugs without active comparators are debated. The overall assessment of the trade-off between safety and efficacy would help to properly inform patients eligible for randomized clinical trials without active comparators. We aimed to quantify the safety and the efficacy of anticancer drugs in advanced cancer patients from randomized clinical trials without active comparators. Methods: This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A systematic literature search of English language publications from January 1, 2000, through January 7, 2021, was performed using MEDLINE (PubMed). Eligible trials included all randomized clinical trials evaluating anticancer drugs in adult patients with advanced cancers with a control arm without any anticancer drug consisting of BSC with or without a placebo. Clinical trials performed in the adjuvant, neoadjuvant or maintenance settings were excluded, as were clinical trials evaluating anticancer drugs in combination with radiotherapy. Two authors (C.M.B. and E.C.) independently reviewed the studies for inclusion. Data from published reports were extracted by investigators, and random-effects meta-analysis was performed to estimate the overall hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS). Findings: Of 3,551 studies screened, 128 eligible trials were found involving 47,432 patients. The HRs for PFS and OS were 0•58 [95%CI: 0•53–0•63] and 0•82 [95%CI: 0•78–0•85]. The absolute excesses in all grade, severe grade III-IV, and grade V (death) adverse events between the two arms were +13•9%, 10•2%, and +0•5%. A weak correlation was measured between the excess of severe toxicity and efficacy. Interpretation: Anticancer drugs evaluated in randomized clinical trials against no active treatment benefited trial participants. Severe toxicity did not significantly correlate with efficacy. Funding: None Declaration of Interest: None

Cost-effectiveness study of treatment with biologic disease-modifying antirheumatic drugs in adult patients with active ankylosing spondylitis

Objective: to conduct a cost-effectiveness study of major biologic disease-modifying antirheumatic drugs (bDMARDs) used for the treatment of ankylosing spondylitis (AS) in Russian health care system with the focus on the new effective drug netakimab (NTK).Patients and methods. Based on the available meta-analysis, a Markov model for therapy was constructed using reference drugs. Then, based on the simulation results, a Cost-Effectiveness Analysis (CEA) and a Budget Impact Analysis (BIA) were carried out. The robustness of the result has been confirmed by several sensitivity analyzes.Results and discussion. NTK showed an advantage in CEA, including the cases when the direct costs of therapy were lower for the reference drug (which shows the greater efficacy of NTK). According to the BIA, the extension of NTK administration in naive patients was consistently associated with a decrease in the budgetary burden. Sensitivity analyzes confirmed the robustness of the result.Conclusion. NTK has clinical and economic advantage in the treatment of AS, it is attractive in terms of both patient's and health care benefit in general. More extensive use of NTK can save more than 5 billion RUB.

Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients

Background - Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose - The new drugs change the progression of SMA with neonatal and childhood onset. Increasing amount of data are available about the effects of these drugs in adult patients with SMA. In this article, we summarize the available data of new SMA therapies in adult patients. Methods - Members of the Executive Committee of the Hungarian Clinical Neurogenetic Society surveyed the literature for palliative treatments, randomized controlled trials, and retrospective and prospective studies using disease modifying therapies in adult patients with SMA. Patients - We evaluated the outcomes of studies focused on treatments of adult patients mainly with SMA II and III. In this paper, we present our consensus statement in nine points covering palliative care, technical, medical and safety considerations, patient selection, and long-term monitoring of adult patients with SMA. This consensus statement aims to support the most efficient management of adult patients with SMA, and provides information about treatment efficacy and safety to be considered during personalized therapy. It also highlights open questions needed to be answered in future. Using this recommendation in clinical practice can result in optimization of therapy.

Adherence to biologic disease-modifying antirheumatic drugs in adult patients with rheumatic diseases

The emergence of biologics has revolutionized the management of refractory rheumatic diseases (RD) by improving clinical outcomes. Unfortunately, the impact of non-adherence to the emerging therapy can limit their potential benefit. The objective of our study was to evaluate biologics' adherence in Tunisian patients with RD and to assess the determinants of non-adherence. We conducted a cross-sectional study involving patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated with bDMARDs (biologic disease-modifying antirheumatic drugs) for at least three months. Socio-demographic, clinical and biological data were collected. Biologic adherence was assessed using the compliance questionnaire for rheumatology (CQR). One hundred patients with RD (45 RA and 55 SpA) were collected. Non-adherence to bDMARDs was found in 70% of cases. In univariate analysis, non-adherence to bDMARDs was statistically related to the absence of coxitis (P=0.003), to a low ASDAS-CRP (ankylosing spondylitis disease activity score) prior to the initiation of the bDMARDs (P=0.01), to a rate of administration of bDMARDs less than one injection per month (P=0.01), to the subcutaneous delivery route (P=0.02) as well as to non-adherence to csDMARDs (conventional disease-modifying antirheumatic drugs) (P=0.001). In multivariate analysis, the predictors of non-adherence were the absence of coxitis (OR=6.01; IC 95% [1.88-19.12]; P=0.002], and a rate of administration of bDMARDs less than one injection per month (OR=8.79; IC 95% [2.13-36.22]; P=0.003). This work has revealed the low rate of adherence to biological treatments in Tunisian patient with RD. Predictors of poor adherence were the absence of coxitis and a rate of administration of bDMARDs less than one injection per month. Detection of these factors could help us to adapt our strategies to improve adherence that are essentially based on therapeutic education program.

Comparative clinical and economic analysis of using cabozantinib as second-line therapy for adult patients with advanced renal cell carcinoma

Background. Currently there exists a wide range of advanced renal cell carcinoma (RCC) treatment schemes, among them cabozantinib, registered in Russia in 2019, was approved as a second-line therapy in both foreign and domestic guidelines. Objective: to conduct a comparative clinical and economic analysis of cabozantinib and alternative drugs in adult patients with advanced RCC after previous systemic therapy. Materials and methods. A literature review was conducted on clinical efficacy and safety of various second-line therapy drugs for advanced RCC in the available databases. The foreign partitioned survival model, reflecting the development of widespread RCC when using 4 different second-line therapy drugs (cabosantinib, nivolumab, axitinib and everolimus), was adapted considering 3 consecutive mutually exclusive conditions (before progression, after progression, death). Pharmacoeconomic analysis included “cost-effectiveness” and “cost-utility” analysis. We estimated direct medical costs for second- and third-line therapy and maintenance therapy (outpatient monitoring and palliative care). To estimate drug costs we used prices from the State Register of maximum selling prices, for cabozanthinib — price presented by the manufacturer. Costs of maintenance therapy were estimated based on the normal standardfor financial costs in accordance with the Program of state guarantees for 2020. Results. Efficacy analysis based on the partitioned survival model showed the highest rates of life-years gained (3.18 life-years-gained (LYG)) and quality adjusted life-years (1.87quality adjusted life-years (QALY)) for cabozanthinib compared with nivolumab (2.53 LYG and 1.6 QALY), axitinib and everolimus (2.21 LYG and 1.31 QALY). Total costs for advanced RCC patients when treated with cabozanthinib were 4.3 million rubles, which is 5 % less than when using nivolumab (4.5 million rubles). Total costs for axitinib were 2.1 million rubles, while its effectiveness was lower compared with the cabozanthinib one. Costs of 1 life-year saved for cabozantinib were 1.4 million rubles, which is 25 % less compared to those for nivolumab. Costs of 1 quality-life year saved when using cabozantinib amounted 2.3 million rubles, which is 19 % less than those for nivolumab. Conclusion. The study results showed that using cabozantinib to treat advanced RCC after previous systemic treatment is both clinically and cost-effective for adult patients with advanced RCC in the Russian Federation.

Associations between safety and tolerability and reporting of health-related quality of life in phase III randomized trials in common solid tumors.

e19206 Background: Anti-cancer drugs are approved typically on the basis of efficacy and safety as evaluated in phase III randomized trials (RCTs). Health related quality of life (HRQoL) is a direct measure of patient benefit from drugs. Despite this, HRQoL is not reported universally for all anti-cancer drugs. Here we explore associations with reporting of HRQoL data in phase III RCTs in common solid tumors. Methods: We searched ClinicalTrials.gov to identify phase III oncology RCTs evaluating new drugs in adult patients with breast, colorectal, lung, or prostate cancers. We included all completed or active trials that completed accrual between January 1, 2005 and October 31, 2016. Data were extracted from published trials including HRQoL data and toxicity data on toxic death, treatment discontinuation and commonly reported grade 3 or 4 adverse events (AEs). Then, we explored associations between these safety and tolerability measures and the odds of reporting HRQoL data and whether HRQoL were favourable or not. Analysis comprised logistic regression and was performed in SPSS version 25. Results: A total of 377 phase III RCTs were initially identified. After excluding ineligible studies, a total of 143 studies were analysed. All trials (100%) were in the metastatic setting with 79 (55%) being positive trials. 40 (28%) were breast cancer trials, 38 (26%) were focused on evaluating chemotherapy, and 128 (90%) of trials were industry sponsored. 84 (59%) trials reported measuring HRQoL data, however of these, only 47 (56%) reported HRQoL data. In 14 (30%) HRQoL was improved with experimental therapy. There was no association between treatment related death (OR 1.25, 95%CI 0.74-2.12, p = 0.398) or treatment discontinuation (OR 1.12, 95%CI 0.73-1.72, p = 0.61) with reporting of HRQoL data. Associations with grade 3 or 4 AEs are shown in the Table. Conclusions: HRQoL is reported for only around a half of RCTs that collect such data. Reporting of HRQoL is not associated with safety and tolerability of anti-cancer drugs. [Table: see text]