Search

This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with deprescribing intervention trials (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with medication cessation trials (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with deprescribing intervention trials. Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of medication cessation trials, a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.

Abstract Introduction This analysis of two Japanese clinical trials evaluated efficacy and safety after galcanezumab (GMB) discontinuation in patients with episodic migraine (EM) and chronic migraine (CM). Methods Data were from a 6-month, randomized, double-blind, placebo [PBO]-controlled primary trial (patients with EM) and a 12-month open-label extension trial (patients with EM/CM). Patients received 6 months’ (primary) or 12/18 months’ (extension) treatment with GMB 120 mg (GMB120) plus 240-mg loading dose or 240 mg (GMB240) with 4 months’ post-treatment follow-up. Efficacy was assessed as number of monthly migraine headache days during post-treatment. Safety was assessed via post-treatment-emergent adverse events (PTEAEs). Results The analysis population included 186 patients from the primary trial (PBO N = 93; GMB120 N = 45; GMB240 N = 48), 220 patients with EM from the extension trial (PBO/GMB120 N = 57; PBO/GMB240 N = 55; GMB120/GMB120 N = 55; GMB240/GMB240 N = 53), and 55 patients with CM (GMB120 N = 28; GMB240 N = 27). In patients with EM receiving 6 months’ GMB120, mean standard deviation (SD) monthly migraine headache days increased from 5.69 (4.64) at treatment end to 6.24 (4.37) at end of follow-up but did not return to pre-treatment levels (8.80 [2.96]). In the extension trial, mean monthly migraine headache days in patients with EM receiving GMB120 were 4.13 (3.85) after 12 months and 4.45 (3.78) at end of follow-up, and 3.59 (3.48) after 18 months and 3.91 (3.57) at end of follow-up. Monthly migraine headache days in patients with CM (12 months’ GMB120) were 10.71 (4.61) at treatment end and 11.17 (5.64) at end of follow-up (pre-treatment 20.15 [4.65]). Similar results were seen for patients receiving GMB240. The most observed PTEAE after GMB discontinuation was nasopharyngitis. Conclusion Galcanezumab exhibited post-treatment efficacy for up to 4 months in Japanese patients with EM and with CM. No unexpected safety signals were observed. Clinical Trial Registration ClinicalTrials.gov, NCT02959177 and NCT02959190.

Introduction: This analysis of two Japanese clinical trials evaluated efficacy and safety after galcanezumab (GMB) discontinuation in patients with episodic migraine (EM) and chronic migraine (CM). Methods: Data were from a 6-month, randomized, double-blind, placebo [PBO]-controlled primary trial (patients with EM) and a 12-month open-label extension trial (patients with EM/CM). Patients received 6 months' (primary) or 12/18 months' (extension) treatment with GMB 120 mg (GMB120) plus 240-mg loading dose or 240 mg (GMB240) with 4 months' post-treatment follow-up. Efficacy was assessed as number of monthly migraine headache days during post-treatment. Safety was assessed via post-treatment-emergent adverse events (PTEAEs). Results: The analysis population included 186 patients from the primary trial (PBO N = 93; GMB120 N = 45; GMB240 N = 48), 220 patients with EM from the extension trial (PBO/GMB120 N = 57; PBO/GMB240 N = 55; GMB120/GMB120 N = 55; GMB240/GMB240 N = 53), and 55 patients with CM (GMB120 N = 28; GMB240 N = 27). In patients with EM receiving 6 months' GMB120, mean standard deviation (SD) monthly migraine headache days increased from 5.69 (4.64) at treatment end to 6.24 (4.37) at end of follow-up but did not return to pre-treatment levels (8.80 [2.96]). In the extension trial, mean monthly migraine headache days in patients with EM receiving GMB120 were 4.13 (3.85) after 12 months and 4.45 (3.78) at end of follow-up, and 3.59 (3.48) after 18 months and 3.91 (3.57) at end of follow-up. Monthly migraine headache days in patients with CM (12 months' GMB120) were 10.71 (4.61) at treatment end and 11.17 (5.64) at end of follow-up (pre-treatment 20.15 [4.65]). Similar results were seen for patients receiving GMB240. The most observed PTEAE after GMB discontinuation was nasopharyngitis. Conclusion: Galcanezumab exhibited post-treatment efficacy for up to 4 months in Japanese patients with EM and with CM. No unexpected safety signals were observed. Clinical Trial Registration: ClinicalTrials.gov, NCT02959177 and NCT02959190. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite the contradicting recommendations. There is a need to inform the scientific community regarding first-line pain control among patients with PPDN. This meta-analysis assessed pregabalin and amitriptyline effects on PPDN. PATIENTS AND METHODS: We searched PubMed, MEDLINE, Cochrane Library, EBSCO, and Google Scholar; the terms used were amitriptyline, pregabalin, painful diabetic neuropathy, antidepressant, gabapentinoids, quality of life, and adverse events. Boolean operators like AND, and OR were used. Six hundred and thirty-one studies were retrieved, and 37 full texts were screened. However, only six randomized controlled trials fulfilled the inclusion and exclusion criteria. RESULTS: No significant statistical differences between amitriptyline and pregabalin regarding pain score and significant pain reduction (odd ratio, -0.82, 95% CI, -2.21-0.58, and odd ratio, 1.16, 95% CI, 0.76-1.76 respectively). Quality of life, total adverse events, and drug discontinuation were not different between the two drugs (odd ratio, 0.89, 95% CI, -2.11-3.89, odd ratio, 0.98, 95% CI, 0.52-1.85, and odd ratio, 0.51, 95% CI, 0.08-3.15, respectively). CONCLUSIONS: No significant statistical differences between amitriptyline and pregabalin regarding their effects on pain and quality of life. The drugs showed similar total adverse events and drug withdrawal. Further larger real-world studies are needed. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of antidiabetic agents known to exert cardioprotective, renoprotective, and hypoglycemic effects. However, these agents have been associated with adverse effects, such as genital infection, volume depletion, hypoglycemia, and diabetic ketoacidosis, resulting in drug discontinuation. Herein, we aimed to determine the reasons for discontinuing treatment with SGLT2is among Japanese patients with diabetes. This retrospective cohort study enrolled 766 patients with diabetes who had initiated SGLT2is between January 2014 and September 2021. The follow-up period was 2 years from the initiation of the SGLT2is. Overall, 97 patients (12.7%) discontinued the SGLT2is during the follow-up period. The most common reasons for discontinuing the SGLT2is were frequent urination (19.6%), followed by genital infection (11.3%), improved glycemic control (10.6%), and renal dysfunction (8.2%). A comparison of the characteristics between the continuation and the discontinuation group was conducted, excluding those who discontinued the SGLT2is because of improved glycemic control. The patients in the discontinuation group (68 [55–75] years) were older than those in the continuation group (64 [53–71] years; p = 0.003). Importantly, we found no significant association between diabetes duration, diabetic control, renal function, or complications of diabetes in both groups. This real-world study revealed that frequent urination was the most common reason underlying SGLT2i discontinuation among Japanese patients with diabetes. To avoid discontinuation, precautions against various factors that may cause frequent urination must be implemented. [ABSTRACT FROM AUTHOR]

Abstract Background Trials evaluating drug discontinuation (drug discontinuation trials, DDTs) show a broad methodological spectrum. There are several specific methodological aspects in drug discontinuation trials (e.g., determination of research question; configuration of intervention; definition of outcomes). To verify this specifies, we did a scoping review about the study designs of drug discontinuation trials. Methods A systematic literature search in Medline (PubMed), The Cochrane Library, EMBASE, CINAHL, Web of Science, and PsycINFO was performed. In a two-step selection process, we identified DDTs, which evaluate the discontinuation of one or more long-term medication as the investigated intervention, by two independent reviewers. Besides bibliographic data, we extracted several parameters to describe the used study design of the included DDTs: motivation for DDT, initially treatment aim of the discontinued medication, study design, methods of discontinuation, follow-up times, number of study participants, and outcome parameter. Results Out of 12,132 records, we included 581 DDTs. The most common motivation for doing a DDT were expected side effects (48.8%), the motivation of proving the efficacy of medication (21.6%), or doubts on the expected benefit of the used medication (13.8%). The majority of the discontinued medication was initially prescribed to improve the prognosis of a chronic disease (60.4%) or to relieve symptoms (31%). The study designs of the trials showed a broad methodological spectrum. The minority of the drug discontinuation trials were randomized controlled trials (34%). Conclusion The results of this scoping review illustrates the need for an evidence-based methodological standard for planning and conducting drug discontinuation trials.

Purpose: To investigate the longitudinal effect of using and discontinuing central nervous system (CNS) medications on cognitive performance. Methods: Using longitudinal cognitive data from population representative adults aged 25–100 years (N = 2188) from four test waves 5 years apart, we investigated both the link between use of CNS medications (opioids, anxiolytics, hypnotics and sedatives) on cognitive task performance (episodic memory, semantic memory, visuospatial ability) across 15 years, and the effect of discontinuing these medications in linear mixed effects models. Results: We found that opioid use was associated with decline in visuospatial ability whereas using anxiolytics, hypnotics and sedatives was not associated with cognitive decline over 15 years. A link between drug discontinuation and cognitive improvement was seen for opioids as well as for anxiolytics, hypnotics and sedatives. Conclusions: Although our results may be confounded by subjacent conditions, they suggest that long‐term use of CNS medications may have domain‐specific negative effects on cognitive performance over time, whereas the discontinuation of these medications may partly reverse these effects. These results open up for future studies that address subjacent conditions on cognition to develop a more complete understanding of the cognitive effects of CNS medications. [ABSTRACT FROM AUTHOR]

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer.

Background: Trials evaluating drug discontinuation (drug discontinuation trials, DDTs) show a broad methodological spectrum. There are several specific methodological aspects in drug discontinuation trials (e.g., determination of research question; configuration of intervention; definition of outcomes). To verify this specifies, we did a scoping review about the study designs of drug discontinuation trials. Methods: A systematic literature search in Medline (PubMed), The Cochrane Library, EMBASE, CINAHL, Web of Science, and PsycINFO was performed. In a two-step selection process, we identified DDTs, which evaluate the discontinuation of one or more long-term medication as the investigated intervention, by two independent reviewers. Besides bibliographic data, we extracted several parameters to describe the used study design of the included DDTs: motivation for DDT, initially treatment aim of the discontinued medication, study design, methods of discontinuation, follow-up times, number of study participants, and outcome parameter. Results: Out of 12,132 records, we included 581 DDTs. The most common motivation for doing a DDT were expected side effects (48.8%), the motivation of proving the efficacy of medication (21.6%), or doubts on the expected benefit of the used medication (13.8%). The majority of the discontinued medication was initially prescribed to improve the prognosis of a chronic disease (60.4%) or to relieve symptoms (31%). The study designs of the trials showed a broad methodological spectrum. The minority of the drug discontinuation trials were randomized controlled trials (34%). Conclusion: The results of this scoping review illustrates the need for an evidence-based methodological standard for planning and conducting drug discontinuation trials. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of antidiabetic agents known to exert cardioprotective, renoprotective, and hypoglycemic effects. However, these agents have been associated with adverse effects, such as genital infection, volume depletion, hypoglycemia, and diabetic ketoacidosis, resulting in drug discontinuation. Herein, we aimed to determine the reasons for discontinuing treatment with SGLT2is among Japanese patients with diabetes. This retrospective cohort study enrolled 766 patients with diabetes who had initiated SGLT2is between January 2014 and September 2021. The follow-up period was 2 years from the initiation of the SGLT2is. Overall, 97 patients (12.7%) discontinued the SGLT2is during the follow-up period. The most common reasons for discontinuing the SGLT2is were frequent urination (19.6%), followed by genital infection (11.3%), improved glycemic control (10.6%), and renal dysfunction (8.2%). A comparison of the characteristics between the continuation and the discontinuation group was conducted, excluding those who discontinued the SGLT2is because of improved glycemic control. The patients in the discontinuation group (68 [55–75] years) were older than those in the continuation group (64 [53–71] years; p = 0.003). Importantly, we found no significant association between diabetes duration, diabetic control, renal function, or complications of diabetes in both groups. This real-world study revealed that frequent urination was the most common reason underlying SGLT2i discontinuation among Japanese patients with diabetes. To avoid discontinuation, precautions against various factors that may cause frequent urination must be implemented.

Background and purpose: Treatment of rheumatic diseases depends on proper use of medications. The aim of this study was to evaluate the frequency and reasons for discontinuation of drugs in these patients. Materials and methods: A cross-sectional study was performed in patients with inflammatory rheumatic diseases in Sari, Iran 2020-2021 to investigate the frequency and reasons for discontinuation of drugs. Statistical analysis was performed using SPSS V20 and descriptive statistical methods were used to determine the frequency of drug discontinuation and its causes. Results: The participants (n=251) included 197 patients with rheumatoid arthritis, 31 with systemic lupus, 16 with ankylosing spondylitis, and 7 patients with psoriatic arthritis. The mean age of patients was 52.36±13.4 and mean duration of illness was 8.35±7.31 years. Drug discontinuation was seen in 73 patients (85 cases). The most common reason for drug discontinuation was drug side effects (55.4%). Drug shortage, transient improvement of symptoms, ineffectiveness of the drug, and fear of developing COVID 19 were some of the reasons for discontinuation of drug. Conclusion: The most common cause of discontinuation of treatment was drug side effects, but in about one third of cases, there are factors that could be corrected to help preventing drug discontinuation and non-adherence to treatment.

Aims To search for sequence variants associated with ACEi discontinuation and to test their association with ACEi-associated adverse drug reactions (ADRs). Methods and results A genome-wide association study (GWAS) on ACEi discontinuation was conducted, including 33 959 ACEi-discontinuers and 44 041 controls. Cases were defined as persons who switched from an ACEi treatment to an angiotensin receptor blocker. Controls were defined as persons who continued ACEi treatment for at least 1 year. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed for ACEi discontinuation risk by mixed model regression analysis. Summary statistics from the individual cohorts were meta-analyzed with a fixed-effects model. To test for association with specific ACEi-associated ADRs, any genome-wide significant (P < 5 × 10-8) ACEi discontinuation variants was tested for association with ACEi-associated cough and angioedema. A polygenetic risk score (PRS) based on ACEi discontinuation GWAS data was constructed and tested for association with ACEi-associated cough and angioedema in two population-based samples. In total, seven genetic genome-wide loci were identified, of which six were previously unreported. The strongest association with ACEi discontinuation was at 20q13.3 (NTSR1 ; OR: 1.21; 95% CI: 1.17–1.24; P = 2.1 × 10–34). Five of seven lead variants were associated with ACEi-associated cough, whereas none were associated with ACEi-associated angioedema. The ACEi discontinuation PRS was associated with ACEi-associated cough in a dose–response manner but not with ACEi-associated angioedema. ACEi discontinuation was genetically correlated with important causes for cough, including gastro-esophageal reflux disease, allergic rhinitis, hay fever, and asthma, which indicates partly shared genetic underpinning between these traits. Conclusion This study showed the advantage of using prescription patterns to discover genetic links with ADRs. In total, seven genetic loci that associated with ACEi discontinuation were identified. There was evidence of a strong association between our ADR phenotype and ACEi-associated cough. Taken together, these findings increase insight into the pathophysiological processes that underlie ACEi-associated ADRs. [ABSTRACT FROM AUTHOR]

Background and purpose: Preventing relapse by immunosuppressants (ISs) is critical for the prognosis of neuromyelitis optica spectrum disorder (NMOSD); however, the optimal duration of IS treatment is still under discussion. The objective was to explore the optimal duration of IS treatment and the risk of IS discontinuation for NMOSD. Method: This cohort study was conducted at a major neurological center that housed the largest NMOSD database in South China. Eligible participants were patients with NMOSD undergoing IS treatment. The main outcome measures were changes in relapse risk based on IS treatment duration, clinical outcomes and predictors of relapse following IS discontinuation. Results: In total, 343 patients were included in this study. The duration of IS treatment was strongly associated with a decrease in relapse risk (hazard ratio [HR] 0.53, p < 0.001). Continuous IS treatment resulted in decreased relapse HRs within 5 years of receiving IS medication, with a mild rebound starting at 5 years. Rituximab reduced the risk of NMOSD relapse to approximately zero within 3 years. The rate of relapse after IS withdrawal was high (77.5%). As opposed to other ISs, a delayed relapse following rituximab withdrawal was observed in this study. Longitudinal extensive transverse myelitis (HR = 2.023, p = 0.006) was associated with a higher risk of relapse after IS discontinuation. Conclusions: Long‐term IS medication for NMOSD is generally suitable. Patients with longitudinal extensive transverse myelitis had a higher risk of relapse after IS discontinuation. Future studies should explore individualized strategies of rituximab maintenance treatment. [ABSTRACT FROM AUTHOR]

Background: Monotherapy, age, and side effects are significant risk factors for the discontinuation of antiglaucoma therapy. Long-term therapy persistence is crucial for slowing disease progression and preventing irreversible blindness. Therefore, it is essential to identify patients at higher risk of discontinuation. In this study, we aimed to evaluate the real-world persistence of antiglaucoma therapy in patients diagnosed with glaucoma in the primary healthcare units of the Lisbon and Tagus Valley regions., Methods: We conducted a retrospective longitudinal study by collecting data from the prescription records of new antiglaucoma drug users diagnosed with glaucoma between 2012 and 2013 in the Primary Health Care Units of the Lisbon and Tagus Valley Region. These patients were followed over 3 years. Therapy persistence was measured as the proportion of patients remaining on any antiglaucoma drug, regardless of any modifications or switching of drugs over time. Persistence was assessed at three time points: the end of the first, second, and third years of the observation period., Results: A total of 2138 patients treated using new antiglaucoma drugs (867 [40.6%] male patients; 1271 [59.4%] female patients) were included in the study. Over the observation period, the overall persistence rate decreased from 91.9% (n = 1965) in the first year to 67.3% (n = 1439) in the third year. Older patients (≥ 65 years) showed higher persistence rates, although there was a decrease over the 3-year follow-up period (from 1481 [92.7%] to 1124 [70.4%]). Additionally, participants initially treated with monotherapy showed higher persistence rates, ranging from 92.4% (n = 1186) in the first year to 70.2% (n = 901) in the third year., Conclusions: The findings highlight the importance of patient follow-up over time, as almost one in three new antiglaucoma therapy users completely discontinued treatment, potentially risking disease progression. This could be mitigated with proper use of these drugs. Further studies should utilize recent health information systems to explore the impact of medication adherence and persistence on the functional and structural outcomes in patients with glaucoma., Competing Interests: None., (© Author(s).)

Background and purpose: Treatment of rheumatic diseases depends on proper use of medications. The aim of this study was to evaluate the frequency and reasons for discontinuation of drugs in these patients. Materials and methods: A cross-sectional study was performed in patients with inflammatory rheumatic diseases in Sari, Iran 2020-2021 to investigate the frequency and reasons for discontinuation of drugs. Statistical analysis was performed using SPSS V20 and descriptive statistical methods were used to determine the frequency of drug discontinuation and its causes. Results: The participants (n=251) included 197 patients with rheumatoid arthritis, 31 with systemic lupus, 16 with ankylosing spondylitis, and 7 patients with psoriatic arthritis. The mean age of patients was 52.36±13.4 and mean duration of illness was 8.35±7.31 years. Drug discontinuation was seen in 73 patients (85 cases). The most common reason for drug discontinuation was drug side effects (55.4%). Drug shortage, transient improvement of symptoms, ineffectiveness of the drug, and fear of developing COVID 19 were some of the reasons for discontinuation of drug. Conclusion: The most common cause of discontinuation of treatment was drug side effects, but in about one third of cases, there are factors that could be corrected to help preventing drug discontinuation and non-adherence to treatment. [ABSTRACT FROM AUTHOR]

Purpose: Alpelisib is a phosphoinositide-3-kinase inhibitor approved for hormone-receptor-positive, PIK3CA-mutated metastatic breast cancer. However, length of drug exposure, maximum-tolerated dose, and therefore clinical response can vary significantly outside of the trial setting. This study evaluates our center's "real world" experience with alpelisib and focuses on duration of therapy and factors associated with cancer progression. Methods: Patients receiving alpelisib at our center between 2019 and 2021 were identified. We evaluated duration of alpelisib therapy and the causative reasons for drug discontinuation. The association of drug duration and dose with subsequent cancer progression were assessed, along with the association between hyperglycemia during alpelisib therapy and cancer progression. Results: Sixty-two women prescribed alpelisib were included (mean age 61 years). Disease progression was the most common reason for drug discontinuation, while discontinuation within 30 days was primarily attributed to adverse events (AEs). Among those who progressed, median time to progression was longer in those on alpelisib for > 90 days compared with those on alpelisib for ≤ 90 days (187 vs. 77 days, p < 0.001). At 200 days, freedom from progression was greater for those on alpelisib for > 90 days compared to those receiving therapy for ≤ 90 days (59% vs. 19%, p = 0.001). Median blood glucose as a continuous variable was associated with disease progression (HR 1.01, 95% CI 1.00–1.02, p = 0.02). Conclusion: While progression of disease is the largest contributor to alpelisib discontinuation, AEs are the leading cause for early drug cessation. Shorter alpelisib exposure is associated with greater cancer progression. Further studies are needed to determine the impact of sustained hyperglycemia on cancer progression. [ABSTRACT FROM AUTHOR]

Objectives Whether immunosuppressive therapy may be safely withdrawn in lupus nephritis (LN) is still unclear. We assessed rate and predictors of flare after IS withdrawal in patients with LN in remission. Methods Patients with biopsy-proven LN treated with immunosuppressants (IS) between 1980 and 2020 were considered. Remission was defined as normal serum creatinine, proteinuria <0.5 g/24 h, inactive urine sediment, and no extra-renal SLE activity on stable immunosuppressive and/or antimalarial therapy and/or prednisone ≤5mg/day. IS discontinuation was defined as the complete withdrawal of immunosuppressive therapy, flares according to SLEDAI Flare Index. Predictors of flare were analysed by multivariate logistic regression analysis. Results Among 513 SLE patients included in our database, 270 had LN. Of them, 238 underwent renal biopsy and were treated with IS. Eighty-three patients (34.8%) discontinued IS, 46 (30) months after remission achievement. During a mean (s. d.) follow-up of 116.5 (78) months, 19 patients (22.9%) developed a flare (8/19 renal) and were re-treated; 14/19 (73.7%) re-achieved remission after restarting therapy. Patients treated with IS therapy for at least 3 years after remission achievement had the lowest risk of relapse (OR 0.284, 95% CI: 0.093, 0.867; P = 0.023). At multivariate analysis, antimalarial maintenance therapy (OR 0.194, 95% CI: 0.038, 0.978; P = 0.047), age at IS discontinuation (OR 0.93, 95% CI: 0.868, 0.997; P = 0.040), remission duration >3 years before IS discontinuation (OR 0.231, 95% CI: 0.058, 0.920; P = 0.038) were protective against disease flares. Conclusions Withdrawal of IS is feasible in LN patients in remission for at least 3 years and on antimalarial therapy. Patients who experience flares can re-achieve remission with an appropriate treatment. [ABSTRACT FROM AUTHOR]

Amaç: İnflamatuar romatizmal hastalıklar her yaşta görülebilen remisyon ve alevlenmelerle seyreden kronik hastalıklardır. Bu anket çalışması, hastaların tedavilerini kesmelerine etki eden faktörleri araştırmak ve hangi tedavi yöntemlerini seçtiklerini belirlemek amacıyla düzenlenmiştir.Gereç ve Yöntem: Bu çalışma Ocak 2019-Aralık 2019 arasında Romatoloji Bilim Dalında yapıldı. Çalışmaya 18 yaş üzeri hayatının bir döneminde tedavisini kesen 150 hasta alındı. Çalışmaya romatoid artrit, ankilozan spondilit, bağ doku hastalığı tanısı olan hastalar dahil edildi. Bulgular: Kliniğimizde değerlendirilen 150 hastanın 101 tanesi kadın, 49 tanesi erkekti. Hastaların yaş ortalaması 46 olarak bulundu. Hastaların tanılarına göre değerlendirildiğinde romatoid artrit %50, ankilozan spondilit %19,3, bağ doku hastalığı %14, diğerleri %16 bulundu. Hastaların tedaviyi kesme nedeni en sık ilaç ilaç yan etkisi %32,7 olup diğerleri sosyal güvenlik sorunları %23,3, hastalığın iyileştiğini düşünme %16, tedaviye inanmama %12,7, hamilelik %6, görsel medya %3, tamamlayıcı ve alternatif tıb (TAT) %6, diğerleri %2 olarak bulundu. Hastaların eğitim düzeyi, yaşadığı yer, tanı farklılıkları ile medikal tedaviyi kesme ilişkisi bulunmadı. Tedaviyi kesen hastaların %80,6’sı hiçbir ilaç almadığı %19,4’ü TAT yöntemlerine başvurduğu bulundu. En sık kullanılan TAT yöntemi %68 bitkisel yöntemdi.Medikal tedaviyi kesen hastalarda alternatif tedavi seçimi ile eğitim, yaşadığı yer arasında ilişki bulunmadı. Medikal tedaviyi kesen romatoid artrit hastalarında %72, ankilozan spondilit hastalarında %65,5, bağ doku hastalığında %57,1 oranında ilk 6 ay içinde hastalık alevlenmesi gözlendi. Tartışma-Sonuç: İnflamatuar romatizmal hastalarında hayatının bir döneminde tıbbi tedaviyi bırakarak takip dışı kaldığı gözlenmiştir. Bu nedenle hastalar medikal tedavinin sürekli olması gerektiği ve ilaçların hastalık üzerinde etkileri konusunda bilgilendirilmelidir. Medikal tedaviyi kesen hastaların ilk 6 ayda hastalık alevlenmesi nedeniyle medikal tedaviye başladığı gözlenmiştir.

Objectives:This study aims to investigate the remission and relapse in patients with epilepsy after the withdrawal of AEDs due to seizure-free, and to review the criteria for withdrawal of AEDs.Methods:The records of 105 patients who were followed up regularly in our epilepsy outpatient clinic and were planned to be discontinued due to seizurefree were analyzed retrospectively in this study. Seventeen patients were excluded from this study because they did not meet the criteria. The sociodemographic and clinical features of the patients, the duration of the seizure, and the EEG findings before and after the drug discontinuation were recorded.Results:In this study, 46 (52.3%) patients were female and 42 (47.7%) were male. Mean age was 28.8±12.3 (10–63). Seventy-one patients (80.7%) were in complete remission at least one year after drug treatment. Seventeen patients (19.3%) had seizure recurrence. Four (23.5%) patients had recurrent seizures in the first 12 months, with 14 (82.4%) patients in the first three months. It was observed that the age of onset of epilepsy and the age of onset of AED were higher in patients with seizure recurrence, and this difference was statistically significant (p=0.036, p=0.005). EEG examinations performed after discontinuation of the drug showed that the rate of recurrence of patients with pathological findings increased (p

Background: Angiotensin receptor neprilysin inhibitor (ARNI) reduces morbidity and mortality in patients of heart failure with reduced ejection fraction (HFrEF). However, the use of ARNI in real-world practice is limited by safety issues, especially in acute decompensated heart failure (ADHF) patients. Methods and Results: Forty-seven hospitalized ADHF inpatients and 53 chronic compensated heart failure (CCHF) outpatients were enrolled in the study. ARNI was initiated and aimed to be up-titrated to a target dose of 97 mg of sacubitril with 103 mg of valsartan twice daily. Efficacy endpoints were New York Heart Association functional class, 6-min walk distance (6MWD), change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels and left ventricular ejection fraction (LVEF) from baseline with follow-up at 1 month, 6 months, and 2 years. Safety endpoints were the rates of worsening serum creatinine, hyperkalemia, symptomatic hypotension, angioedema, and need for drug discontinuation. Cumulative adverse drug effect was observed in 42.6% and 13.2% patients of ADHF and CCHF groups, respectively. The most common side-effect was symptomatic hypotension that occurred in 10 (21.3%) patients of ADHF group and 3 (5.7%) patients of CCHF group. Drug discontinuation rate was 19.1% in ADHF group and 3.8% in CCHF group. Significant improvement was seen in both the groups with respect to 6 MWD, functional class, change in NT-pro BNP levels and LVEF. At 2-year follow-up, 3 (6.4%) deaths occurred in ADHF group while none was reported from CCHF group. Conclusion: ARNI results in a significant clinical, biochemical, and functional improvement in HFrEF patients but at the cost of worsening renal function and hypotension especially in ADHF setting.

Abstract Introduction The current study sought to compare the treatment continuation rates of asenapine and brexpiprazole while specifically investigating the factors influencing this index and the clinical efficacy of brexpiprazole. Methods Retrospective study on patients with schizophrenia who were prescribed either asenapine (n = 73) or brexpiprazole (n = 136), as part of their routine medical care. Results The treatment continuation rates for asenapine and brexpiprazole were 19.0% and 38.6% at 52 weeks, with that of brexpiprazole found to be significantly higher than that of asenapine (p = .002). Moreover, age was found to be a significant factor affecting the treatment continuation rate for brexpiprazole (p = .03). Additionally, patients with a longer continuation duration had significantly lower Clinical Global Impression‐Severity of Illness (CGI‐S) scale scores compared to those who discontinued early (p = .04). The continuation rate was also significantly higher for those who began using the drug as outpatients compared to those first administered the drug as inpatients (p = .04). Furthermore, disease duration, CGI‐S scale, and continuation duration significantly affected the clinical efficacy of brexipiprazole (p

Maintenance treatment with antipsychotics remains the key principle in the long-term management of psychotic disorders. For some patients, it means life-long use of medication. Continuous drug administration helps to prevent relapses, maintain remission, and achieve functional recovery. Moreover, epidemiological data suggest that antipsychotic treatment significantly reduces mortality rates of schizophrenia patients. On the other hand, some authors argue that antipsychotic drugs may lose its efficacy over time, their long-term exposure results in more harm than benefit. Especially elderly patients are more sensitive to side effects. Several studies which followed-up patient cohorts over the span of several decades found that there are schizophrenia patients who can achieve good functional outcome and full recovery without antipsychotic treatment. Therefore, it is paramount to identify those individuals, particularly among elderly psychotic patients, who can thrive and benefit from timely antipsychotic discontinuation.

Introduction: The current study sought to compare the treatment continuation rates of asenapine and brexpiprazole while specifically investigating the factors influencing this index and the clinical efficacy of brexpiprazole. Methods: Retrospective study on patients with schizophrenia who were prescribed either asenapine (n = 73) or brexpiprazole (n = 136), as part of their routine medical care. Results: The treatment continuation rates for asenapine and brexpiprazole were 19.0% and 38.6% at 52 weeks, with that of brexpiprazole found to be significantly higher than that of asenapine (p =.002). Moreover, age was found to be a significant factor affecting the treatment continuation rate for brexpiprazole (p =.03). Additionally, patients with a longer continuation duration had significantly lower Clinical Global Impression‐Severity of Illness (CGI‐S) scale scores compared to those who discontinued early (p =.04). The continuation rate was also significantly higher for those who began using the drug as outpatients compared to those first administered the drug as inpatients (p =.04). Furthermore, disease duration, CGI‐S scale, and continuation duration significantly affected the clinical efficacy of brexipiprazole (p <.05 for all). Conclusions: The continuation rate for brexpiprazole increases as the age of the patient increases, as disease severity decreases, and if the patient first uses the drug as an outpatient. Shorter disease duration and longer drug administration may lead to improved clinical efficacy. These results suggest that brexpiprazole is an effective treatment option for maintenance therapy of schizophrenia. [ABSTRACT FROM AUTHOR]

Uptake and retention for opioid agonist treatment (OAT) remains low. Novel extended-release formulations may improve OAT accessibility by reducing the frequency of healthcare visits. Our aim was to examine uptake, characteristics, treatment patterns and retention of individuals initiating extended-release subcutaneous buprenorphine (BUP-ER), a monthly injectable OAT. We conducted a population-based cohort study among adults aged 18+ initiated on BUP-ER between February 3, 2020 and March 31, 2022 in Ontario, Canada. Using administrative health data, we defined continuous BUP-ER use based on repeat injections within a 56-day period and used Kaplan-Meier curves to estimate time on treatment. Among new BUP-ER recipients, we described individual and prescriber characteristics, healthcare utilization and treatment patterns. 2366 individuals initiated BUP-ER. The median time to BUP-ER discontinuation was 183 days (interquartile range: 66–428 days) and 52.0% of individuals were co-prescribed buprenorphine/naloxone at least once throughout the period of BUP-ER receipt. Among individuals who initiated on a dose of 300 mg BUP-ER and had three or more injections, 18.8% continued to receive only 300 mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100 mg (N=341 of 1194) had a subsequent dose increase to 300 mg. On average, people initiating BUP-ER discontinue within the first 6 months of treatment. While BUP-ER is likely providing an important OAT option, the high occurrence of discontinuation, supplementation with buprenorphine/naloxone, and frequent dose increases suggest inadequacy of current dosing recommendations among a proportion of individuals. • On average, time to extended-release subcutaneous buprenorphine discontinuation was 183 days. • Half of new recipients were co-prescribed buprenorphine/naloxone while on treatment. • Almost 1 in 5 people were sustained on a high dose of subcutaneous buprenorphine. • Return to a high dose of subcutaneous buprenorphine was also common (28.6%). [ABSTRACT FROM AUTHOR]

Abstract Introduction Patient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation. Methods ROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up). Results A total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation. Conclusions Study drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. ClinicalTrials.gov NCT00403767. Funding The ROCKET AF trial was funded by Johnson & Johnson and Bayer.

Background: Angiotensin receptor neprilysin inhibitor (ARNI) reduces morbidity and mortality in patients of heart failure with reduced ejection fraction (HFrEF). However, the use of ARNI in real-world practice is limited by safety issues, especially in acute decompensated heart failure (ADHF) patients. Methods and Results: Forty-seven hospitalized ADHF inpatients and 53 chronic compensated heart failure (CCHF) outpatients were enrolled in the study. ARNI was initiated and aimed to be up-titrated to a target dose of 97 mg of sacubitril with 103 mg of valsartan twice daily. Efficacy endpoints were New York Heart Association functional class, 6-min walk distance (6MWD), change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels and left ventricular ejection fraction (LVEF) from baseline with follow-up at 1 month, 6 months, and 2 years. Safety endpoints were the rates of worsening serum creatinine, hyperkalemia, symptomatic hypotension, angioedema, and need for drug discontinuation. Cumulative adverse drug effect was observed in 42.6% and 13.2% patients of ADHF and CCHF groups, respectively. The most common side-effect was symptomatic hypotension that occurred in 10 (21.3%) patients of ADHF group and 3 (5.7%) patients of CCHF group. Drug discontinuation rate was 19.1% in ADHF group and 3.8% in CCHF group. Significant improvement was seen in both the groups with respect to 6 MWD, functional class, change in NT-pro BNP levels and LVEF. At 2-year follow-up, 3 (6.4%) deaths occurred in ADHF group while none was reported from CCHF group. Conclusion: ARNI results in a significant clinical, biochemical, and functional improvement in HFrEF patients but at the cost of worsening renal function and hypotension especially in ADHF setting. [ABSTRACT FROM AUTHOR]

Objectives: Adrenocortical scintigraphy for patients with primary aldosteronism (PA) without discontinuation or modification of antihypertensive medications is of concern because of drug interference with the renin–angiotensin–aldosterone system. We report the surgical outcomes of patients with PA lateralized with adrenocortical scintigraphy without drug discontinuation or modification. Materials and Methods: We retrospectively reviewed 34 patients with PA with computed tomography (CT)-documented adrenal tumors who had undergoing subsequent I-131-6 β-iodomethyl-norcholesterol (NP-59) single photon emission CT (SPECT)/CT followed by unilateral adrenalectomy according to the results of NP-59 uptake between May 2005 and December 2014. All enrolled patients underwent standard confirmatory tests and lateralization with NP-59 SPECT/CT without discontinuation of existing antihypertensive medications, including spironolactone. The pathological findings, hypertension outcomes, and biochemical changes were reported. The accuracy of NP-59 SPECT/CT without drug discontinuation or modification was also evaluated. Results: None of the 34 enrolled patients (M:F = 16:18) had complications such as a hypertensive crisis, life-threatening hypokalemic event, or cardiac arrhythmia. Pathology disclosed 31 (91%) adenomas and three cases of hyperplasia. Hypertension cure and improvement were observed in 12 (35%) and 18 (53%) patients, respectively. All of the 30 patients (100%) without postoperative use of beta-blockers and with an available postoperative aldosterone/renin ratio achieved a biochemical cure. The positive predictive values of NP-59 SPECT/CT were 91%, 88%, and 100% for the pathological findings, hypertension outcomes, and biochemical changes, respectively. Conclusion: Noninvasive NP-59 SPECT/CT without discontinuation or modification of antihypertensive medications not only provided accurate lateralization and safety but also resulted in a high improvement rate for PA-associated hypertension.

Purpose To analyse the drug use pattern in women with psoriasis before, during and after pregnancy. Methods: All children born (2009‐2016) in a central Italian region (Lazio) to mothers with a diagnosis of psoriasis were identified. Drug use patterns (biologicals, systemic, and topical), and discontinuation and switching of drug therapies before, during, and after pregnancy were studied. Findings were compared with data from a population exposed to similar drug therapies (eg, antirheumatic drugs). Results: Among 3499 deliveries by women affected by psoriasis, 1876 (53.6%) were diagnosed with this condition before the Last Menstrual Period (LMP). Of these, 525 (27.9%) had at least one drug prescription for psoriasis therapy during 6 months before LMP. For each class of drugs considered, there was a general decrease in its use during pregnancy. Considering the two trimesters preceding LMP and the three trimesters of pregnancy, the following percentages of prescriptions were observed: from 10.5% to 0% for biologicals, 7.2% to 2.5% for the conventional systemic drugs, and 51.1% to 9.4% for the topical treatments. After delivery, previous treatments were resumed. Similar results were observed for rheumatoid arthritis, a chronic condition. Conclusions: Majority of drugs come with warnings regarding potential embryo‐fetotoxicity, which might play a role in the decision to continue treatments during pregnancy. According to our study pregnancy appears to have a significant influence on drug prescriptions of different pharmacological treatments for psoriasis. [ABSTRACT FROM AUTHOR]

Objectives Patients with SLE are often exposed to prolonged immunosuppression since few data on flare recurrence in remitted patients who discontinued immunosuppressants are available. We aimed to assess the rate and predictors of flare after immunosuppressant withdrawal in SLE patients in remission. Methods SLE patients diagnosed between 1990 and 2018 (according to the ACR criteria), ever treated with immunosuppressants and currently in follow-up were considered. Immunosuppressant discontinuation was defined as complete withdrawal of any immunosuppressive drug. Reasons for discontinuation were remission, defined as clinical SLEDAI-2K = 0 on a stable immunosuppressive and/or antimalarial therapy and/or on prednisone ⩽5 mg/day, or poor adherence/intolerance. Flares were defined according to the SLEDAI Flare Index. Predictors of a subsequent flare were analysed by multivariate logistic regression. Results There were 319 eligible patients out of 456 (69.9%). Of the 319 patients, 139 (43.5%) discontinued immunosuppressants, 105 (75.5%) due to remission, 34 (24.5%) due to poor adherence/intolerance. The mean (s. d.) follow-up time after immunosuppressant withdrawal was 91 (71) months (range 6–372). Among the patients who discontinued immunosuppressants, 26/105 remitted (24.7%) and 23/34 unremitted patients (67.6%) experienced a flare (P < 0.001) after a median (range) follow-up of 57 (6–264) and 8 months (1–72), respectively (P = 0.009). In patients who discontinued immunosuppressants due to remission, maintenance therapy with antimalarials (OR 0.243, 95% CI 0.070, 0.842) and the duration of remission at immunosuppressant discontinuation (OR 0.870, 0.824–0.996) were independent protective factors against disease flare. Conclusion SLE flares are not uncommon after immunosuppressant discontinuation, even in remitted patients; however, antimalarial therapy and durable remission can significantly reduce the risk of flare. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the remission and relapse in patients with epilepsy after the withdrawal of AEDs due to seizure-free, and to review the criteria for withdrawal of AEDs. Methods: The records of 105 patients who were followed up regularly in our epilepsy outpatient clinic and were planned to be discontinued due to seizurefree were analyzed retrospectively in this study. Seventeen patients were excluded from this study because they did not meet the criteria. The sociodemographic and clinical features of the patients, the duration of the seizure, and the EEG findings before and after the drug discontinuation were recorded. Results: In this study, 46 (52.3%) patients were female and 42 (47.7%) were male. Mean age was 28.8±12.3 (10–63). Seventy-one patients (80.7%) were in complete remission at least one year after drug treatment. Seventeen patients (19.3%) had seizure recurrence. Four (23.5%) patients had recurrent seizures in the first 12 months, with 14 (82.4%) patients in the first three months. It was observed that the age of onset of epilepsy and the age of onset of AED were higher in patients with seizure recurrence, and this difference was statistically significant (p=0.036, p=0.005). EEG examinations performed after discontinuation of the drug showed that the rate of recurrence of patients with pathological findings increased (p<0.001). Conclusion: Although epilepsy is a chronic disease, it is noted that some patients have survived the period of seizure in clinical follow-up and can continue their life without medication and seizure. It is important to recognize these patients and to stop treatment in appropriate patients for the quality of life of them. The possibility of relapse is highest during the first year after discontinuation of AED treatment. Close follow-up of the patients in the first year is important. [ABSTRACT FROM AUTHOR]

• Glucocorticoids (GCs) have served as the cornerstone in the management of lupus nephritis (LN). • GC discontinuation in LN patients with complete remission and a stable treatment regimen for at least 5 years was feasible. • NS at disease onset was an independent risk factor to predict unachievable GC withdrawal. To evaluate the proportion of patients successfully withdrawn from glucocorticoids (GC) in a longitudinal cohort of patients with lupus nephritis over a period of 20 years, clinical and pathological predictors of patients with GC withdrawal and renal outcomes after GC withdrawal were further explored. Patients with successful GC withdrawal were identified for the cohort, and the following data were collected: demographic characteristics, clinical manifestations, pathological findings at disease onset, flares, and renal outcomes subsequent to GC withdrawal. There were 365 patients with lupus nephritis included with a median follow-up of 109.5 (83.5,165.3) months in our cohort. A total of 21 patients (5.8 %) achieved successful GC discontinuation, with a median duration of 7.5 (3,10) years necessary for GC withdrawal. The average duration of GC reduction from 7.5 mg/d to complete withdrawal lasted for approximately 25 months (18,30). Patients in the GC-withdrawal group had a lower prevalence of nephrotic syndrome (NS) at onset (28.5 % vs. 47.3 %, P = 0.035), a higher prevalence of positive anti–double-stranded DNA (anti-dsDNA) antibody (85.7 % vs. 61.6 %, P = 0.028) and more severe endocapillary hypercellularity in the renal histopathology evaluations (3(2.5,3) vs. 3(2,3), P = 0.022). NS at disease onset was an independent risk factor to predict unachievable GC withdrawal (OR 0.296, 95 % CI (0.104,0.842), P = 0.022) by multivariate analysis. With a median follow-up of 34 (20,42) months, none of these patients had flares after GC withdrawal. The discontinuation of GC therapy in LN patients with complete remission and a stable treatment regimen for at least 5 years was feasible without an increased risk of flares, ESKD or death. Low-dose GC withdrawal necessitates a prolonged duration of time and meticulous monitoring. [ABSTRACT FROM AUTHOR]

Background: In patients with idiopathic pulmonary fibrosis (IPF), continuing treatment with antifibrotic agents is crucial to decrease the reduction of forced vital capacity and mortality rate. However, predictive factors for the discontinuation of antifibrotic agents are unknown. This study aims to investigate the clinical characteristics and predictive factors for the discontinuation of antifibrotic agents in patients with IPF. Methods: This was a double-center retrospective study that enrolled patients with IPF treated with pirfenidone or nintedanib between 2009 and 2017. We compared clinical parameters between the medication-continuing group and the discontinued group. The predictive factors were determined using Cox proportional hazards analyses. Results: A total of 66 subjects were included: 43 received pirfenidone and 23 received nintedanib. At 1 year, 23 of 66 patients had discontinued due to adverse events (n = 12), disease progression (n = 9), or death (n = 2). The characteristics of the discontinuation group were poor performance status (PS) and delay from diagnosis to treatment. In the receiver operating characteristic (ROC) analysis associated with the discontinuation of antifibrotic agents, PS was the highest area under the ROC curve (AUC) value (cut-off value, 2; AUC, 0.83; specificity, 63%; sensitivity, 87%). This finding was consistent even when analyzing, except for examples of death and adjusting for the type of antifibrotic agent. The treatment persistence rate by PS was PS 0–1 = 90%, PS 2 = 65%, and PS 3 = 19%. Analysis of the relationship between PS and administration period of antifibrotic agents revealed that delays from diagnosis to treatment led to worsening of dyspnea, a decline in lung function, and deterioration of PS. Conclusions: PS may be informative for predicting discontinuation of medication. Our data reinforced the importance of early initiation of antifibrotic treatment, and we suggest PS should be used as a guide for starting antifibrotic agents in everyday practice. The reviews of this paper are available via the supplementary material section. [ABSTRACT FROM AUTHOR]

Several antiresorptive drugs, like bisphosphonates and denosumab, are currently available for the treatment of osteoporosis due to their evidenced efficacy in reducing fracture risk at mid-term. Osteoanabolic therapies, like teriparatide, whose treatment duration is limited to 2 years, have also shown efficacy in the reduction of fracture risk. However, depending on the severity of osteoporosis and the presence of other associated risk factors for fracture, some patients may require long-term treatment to preserve optimal bone strength and minimize bone fracture risk. Given the limited duration of some treatments, the fact that most of the antiresorptive drugs have not been assessed beyond 10 years, and the known long-term safety issues of these drugs, including atypical femoral fractures or osteonecrosis of the jaw, the long-term management of these patients may require an approach based on drug discontinuation and/or switching. In this regard, interest in sequential osteoporosis therapy, wherein drugs are initiated and discontinued over time, has grown in recent years, although the establishment of an optimal and individualized order of therapies remains controversial. This review reports the currently available clinical evidence on the discontinuation effects of different anti-osteoporotic drugs, as well as the clinical outcomes of the different sequential treatment regimens. The objective of this article is to present up-to-date practical knowledge on this area in order to provide guidance to the clinicians involved in the management of patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Introduction: Continuous usage of direct oral anticoagulants (DOACs) among nonvalvular atrial fibrillation (NVAF) patients is essential to maintain stroke prevention. We examined switching and discontinuation rates for the three most frequently initiated DOACs in NVAF patients in the USA.Methods: Patients who initiated apixaban, rivaroxaban, or dabigatran (index event/date) were identified from the Pharmetrics Plus claims database (Jan 1, 2013-Sep 30, 2016, includes patients with commercial and Medicare coverage) and grouped into cohorts by index DOAC. Patients were required to have a diagnosis of NVAF and continuous health plan enrollment for 12 months prior to the index date (baseline period) and at least 3 months during the follow-up period. Drug switching rates to any other DOAC or warfarin and index DOAC discontinuation rate were evaluated separately with descriptive statistics, Kaplan-Meier analysis, and multivariable Cox regression analysis.Results: Of the NVAF study population (n = 41,864), 37% initiated apixaban (n = 15,352; mean age 62 years), 51% initiated rivaroxaban (n = 21,250; mean age 61 years), and 13% initiated dabigatran (n = 5262; mean age 61 years). During the follow-up period, the unadjusted drug switching rates of patients treated with apixaban, rivaroxaban, and dabigatran were 3.6%, 6.3%, and 11.1%, respectively (p < 0.001 across the three cohorts); while the index DOAC discontinuation rates were 52.8%, 60.3%, and 62.9%, respectively (p < 0.001). After we controlled for differences in patient characteristics, patients treated with rivaroxaban (HR 1.8; 95% CI 1.6-2.0; p < 0.001) and dabigatran (HR 3.4; 95% CI 3.0-3.8, p < 0.001) had a significantly greater likelihood for drug switching than patients treated with apixaban. Also, both rivaroxaban (HR 1.1; 95% CI 1.1-1.2, p < 0.001) and dabigatran (HR 1.3; 95% CI 1.2-1.3, p < 0.001) treated patients were more likely to discontinue treatment.Conclusion: In the real-world setting, patients with NVAF newly treated with apixaban were less likely to switch or discontinue treatment compared to patients treated with rivaroxaban or dabigatran.Funding: Pfizer and Bristol-Myers Squibb. [ABSTRACT FROM AUTHOR]

We compared the risks of switching to another oral anticoagulant (OAC) and discontinuation of direct oral anticoagulants (DOACs) among elderly patients with nonvalvular atrial fibrillation (NVAF) who were prescribed rivaroxaban or dabigatran versus apixaban. Patients (-65 years of age) with NVAF prescribed DOACs (January 1, 2013 to September 30, 2017) were identified from the Humana research database and grouped into DOAC cohorts. Cox regression analyses were used to evaluate whether the risk for switching to another OAC or discontinuing index DOACs differed among cohorts. Of the study population (N = 38 250), 55.9% were prescribed apixaban (mean age: 78.6 years; 49.8% female), 37.3% rivaroxaban (mean age: 77.4 years; 46.7% female), and 6.8% dabigatran (mean age: 77.0 years; 44.0% female). Compared to patients prescribed apixaban, patients prescribed rivaroxaban (hazard ratio [HR]: 2.08; 95% confidence interval [CI], 1.92-2.25; P < .001) or dabigatran (HR: 3.74; 95% CI, 3.35-4.18, P < .001) had a significantly higher risk of switching to another OAC during the follow-up; compared to patients prescribed apixaban, the risks of discontinuation were also higher for patients treated with rivaroxaban (HR: 1.10; 95% CI, 1.07-1.13, P < .001) or dabigatran (HR: 1.29; 95% CI, 1.23-1.35, P < .001). [ABSTRACT FROM AUTHOR]

Background: Although it is a truism that drugs benefit patients only when taken, surprisingly little is known about real-world drug-use persistence and discontinuation, even for expensive biologic drugs., Methods: We used longitudinal self-reported drug-use data from the inflammatory bowel disease (IBD) Partners registry of people with IBD to construct Kaplan-Meier drug-use persistency graphs for biologic drug-use spans that started between 2017 and 2022., Results: We examined 2034 drug-use spans for 1594 survey participants. Most of the biologic drugs had a 75%+ persistency rate around the one-year mark and 60%+ persistency at the 3-year mark. The overall persistency and the differences in persistency between drugs were aligned with published literature., Conclusions: This analysis demonstrates the feasibility of collecting IBD-specific patient-reported drug persistency data via a voluntary patient registry. Patient-reported persistency provides real-world drug persistency data and the patient's perspectives as to why they discontinued use of the drug-a combination of data and perspective that is not available from any other real-world medical record, claim, and pharmacy data source that are valuable to physician, patients, payers, healthcare policymakers, and health technology assessment organizations., Competing Interests: The authors have no financial or commercial interests to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Objectives: Adrenocortical scintigraphy for patients with primary aldosteronism (PA) without discontinuation or modification of antihypertensive medications is of concern because of drug interference with the renin–angiotensin–aldosterone system. We report the surgical outcomes of patients with PA lateralized with adrenocortical scintigraphy without drug discontinuation or modification. Materials and Methods: We retrospectively reviewed 34 patients with PA with computed tomography (CT)-documented adrenal tumors who had undergoing subsequent I-131-6 β-iodomethyl-norcholesterol (NP-59) single photon emission CT (SPECT)/CT followed by unilateral adrenalectomy according to the results of NP-59 uptake between May 2005 and December 2014. All enrolled patients underwent standard confirmatory tests and lateralization with NP-59 SPECT/CT without discontinuation of existing antihypertensive medications, including spironolactone. The pathological findings, hypertension outcomes, and biochemical changes were reported. The accuracy of NP-59 SPECT/CT without drug discontinuation or modification was also evaluated. Results: None of the 34 enrolled patients (M:F = 16:18) had complications such as a hypertensive crisis, life-threatening hypokalemic event, or cardiac arrhythmia. Pathology disclosed 31 (91%) adenomas and three cases of hyperplasia. Hypertension cure and improvement were observed in 12 (35%) and 18 (53%) patients, respectively. All of the 30 patients (100%) without postoperative use of beta-blockers and with an available postoperative aldosterone/renin ratio achieved a biochemical cure. The positive predictive values of NP-59 SPECT/CT were 91%, 88%, and 100% for the pathological findings, hypertension outcomes, and biochemical changes, respectively. Conclusion: Noninvasive NP-59 SPECT/CT without discontinuation or modification of antihypertensive medications not only provided accurate lateralization and safety but also resulted in a high improvement rate for PA-associated hypertension. [ABSTRACT FROM AUTHOR]

Background: The dose of tenofovir alafenamide is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate (TDF). In this study, we aim to quantify the effect of cobicistat (COBI) both on tenofovir concentrations and TDF durability in real life setting. Methods: HIV-positive patients receiving TDF-containing antiretroviral therapies with at least 1 assessment of tenofovir plasma trough concentrations were included in the study. Univariate and multivariate regression analyses were performed considering tenofovir concentration as the dependent variable and clinical characteristics as independent covariates. Subsequently, survival and Cox analyses were performed considering as the primary outcome TDF discontinuation for any reasons. Results: Patients were given TDF with protease inhibitors/ritonavir (n = 212), non-nucleoside reverse transcriptase inhibitors (n = 176), integrase inhibitors (dolutegravir or raltegravir, n = 46), or with elvitegravir/COBI (ELV/COBI) (n = 76). By multivariate analysis, concomitant antiretroviral therapies resulted significantly associated with tenofovir levels, with the highest drug concentrations measured in patients given ELV/COBI. By survival analysis, we found that patients given TDF with ELV/COBI had the lowest rate of drug durability. Overall, these patients had a 2.3-fold increased risk to experience TDF discontinuation. Conclusions: Coadministration with COBI resulted in significantly higher tenofovir concentrations and higher TDF discontinuation compared with other antiretroviral regimens. Accordingly, the possibility that the lack of proper dose adjustment for TDF when given with COBI might have biased the safety comparisons with tenofovir alafenamide during registrative trials cannot be ruled out. [ABSTRACT FROM AUTHOR]

The authors compared the effectiveness of thiazide diuretic (TD), angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB) monotherapies for the treatment of nondiabetic hypertension using MarketScan Databases 2010-2014. Multivariable Cox regression models assessed whether the addition of a new antihypertensive drug, treatment discontinuation, or switch and major cardiovascular or cerebrovascular events varied across groups. A total of 565 009 patients started monotherapy with ACEIs (43.6%), CCBs (23.6%), TDs (18.8%), or ARBs (14.0%). Patients who took TDs had a higher risk for either drug addition or discontinuation than patients who took ACEIs (hazard ratio [HR], 0.69 [95% CI, 0.68-0.70] vs HR, 0.81 [95% CI, 0.80-0.81]), ARBs (HR, 0.67 [95% CI, 0.66-0.68] vs HR, 0.66 [95% CI, 0.65-0.67]), and CCBs (HR, 0.85 [95% CI, 0.84-0.87] vs HR, 0.94 [95% CI, 0.93-0.95]). Conversely, patients who took TDs experienced a lower risk of clinical events compared with patients who took ACEIs (HR, 1.24 [95% CI, 1.15-1.33]), ARBs (HR, 1.28 [95% CI, 1.18-1.39]), and CCBs (HR, 1.35 [95% CI, 1.25-1.46]). Our results provide a strong rationale for choosing TDs as first-line monotherapy for the control of hypertension. [ABSTRACT FROM AUTHOR]