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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).)

Competing Interests: Conflicts of interest Dr Enos has previously served as a consultant on an advisory board for UCB and Amgen, is an investigator for Amgen and Castle Biosciences, and has previously received research funding from the ASA/Arcutis Biotherapeutics. Authors McLean, Sima, and Eckmann are employed by CorEvitas, LLC. Dr Van Voorhees has received grant/research support from Celgene, Lilly, and AbbVie and is a consultant for Amgen, Boehringer Ingelheim, BMS, UCB, and Novartis. Dr Yi and Vera have no conflicts of interest to declare.

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., (© 2024. The Author(s).)

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., (© 2024 Nuša Japelj et al., published by Sciendo.)

Background: 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., Methods: 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., Results: 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 300mg BUP-ER and had three or more injections, 18.8% continued to receive only 300mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100mg (N=341 of 1194) had a subsequent dose increase to 300mg., Conclusions: 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., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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: 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.)

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., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

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., (© 2023. The Author(s).)

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., Competing Interests: Conflict of interest: The authors who are affiliated with deCODE genetics/Amgen Inc. declare competing financial interests as employees. C.T.P. reports grants from Bayer and grants from Novo Nordisk, outside the submitted work. L.K. reports personal fees and speakers honorarium for Novartis, AstraZeneca, and Boehringer, outside the submitted work. H.B. receives lecture fees from Bristol-Myers Squibb, Merch Sharp and Dohme. S.B. is a board member for Proscion A/S and Intomics A/S. All other authors declare that there is no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 &lt; 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., (© 2022 European Academy of Neurology.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale & Objective: Clinical trial data have demonstrated the efficacy of etelcalcetide for reducing parathyroid hormone (PTH) levels in hemodialysis (HD) patients. We provide a real-world summary of etelcalcetide utilization, dosing, effectiveness, and discontinuation since its US introduction in April 2017., Study Design: New-user design within prospective cohort., Setting & Participants: 2,596 new users of etelcalcetide from April 2017 through August 2019 in a national sample of adult maintenance HD patients in the US Dialysis Outcomes and Practice Patterns Study (DOPPS)., Predictors: Baseline PTH, prior cinacalcet use, initial etelcalcetide dose., Outcome: Trajectories of etelcalcetide dose, chronic kidney disease-mineral and bone disease (CKD-MBD) medications, and levels of PTH, serum calcium, and phosphorus in the 12 months after etelcalcetide initiation., Analytical Approach: Cumulative incidence methods for etelcalcetide discontinuation and linear generalized estimating equations for trajectory analyses., Results: By August 2019, etelcalcetide prescriptions increased to 6% of HD patients from their first use in April 2017. Starting etelcalcetide dose was 15 mg/wk in 70% of patients and 7.5 mg/wk in 27% of patients; 49% of new users were prescribed cinacalcet in the prior 3 months. Etelcalcetide discontinuation was 9%, 17%, and 27% by 3, 6, and 12 months after initiation. One year after etelcalcetide initiation, mean PTH levels declined by 40%, from 948 to 566 pg/mL, and the proportion of patients with PTH within target (150-599 pg/mL) increased from 33% to 64% overall, from 0 to 60% among patients with baseline PTH ≥ 600 pg/mL, and from 30% to 63% among patients with prior cinacalcet use. The proportion of patients with serum phosphorus > 5.5 mg/dL decreased from 55% to 45%, while the prevalence of albumin-corrected serum calcium < 7.5 mg/dL remained at 1%-2%. There were increases in use of active vitamin D (from 77% to 87%) and calcium-based phosphate binders (from 41% to 50%) in the 12 months after etelcalcetide initiation., Limitations: Data are unavailable for provider dosing protocols, dose holds, or reasons for discontinuation., Conclusions: In the 12 months after etelcalcetide initiation, patients had large and sustained reductions in PTH levels. These results support the utility of etelcalcetide as an effective therapy to achieve the KDIGO-recommended guidelines for CKD-MBD markers in HD patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Due to the increasing concerns about polypharmacy, there is a growing need for clinical recommendations for drug discontinuation. This requires studies investigating the process on several levels. This paper addresses the methodological problems of drug discontinuation trials (DDTs). To that end, we offer a new typology of research aims and corresponding methodological recommendations for trials evaluating drug discontinuation., Study Design and Setting: Multi-stage development process, including literature search and expert panels., Results: Clinical trials are only required in cases of scientific uncertainty. We identified three situations of uncertainty associated with drug discontinuation from which we derived three study types: 1) Uncertainty regarding the effectiveness and/or safety of a drug; 2) Uncertainty regarding the procedure of discontinuing a previously taken drug; 3) Uncertainty regarding the effectiveness of complex strategies used to discontinue one or more drugs. We developed specific methodological recommendations for each study type., Conclusion: We offer a comprehensive definition of research aims, study designs, and methodological recommendations regarding DDTs. The typology we propose can help investigators clarify their research aims and study design. The type-specific methodological recommendation should improve the quality of future drug discontinuation trials., (Copyright © 2021. Published by Elsevier Inc.)

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., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: The use of trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia (PcP) prophylaxis is often discontinued owing to adverse drug reactions. Half-dosage of TMP-SMX (40/200 mg daily) is considered more tolerable than the conventional dosage (80/400 mg daily). However, patient background characteristics that are associated with the discontinuation of TMP-SMX prophylaxis and suitable for reduced dosage remain unclear. In this study, we aimed to identify the risk factors for the discontinuation of and efficacy of different doses of TMP-SMX prophylaxis in patients with creatinine clearance higher than 30 mL/min., Methods: We retrospectively evaluated 318 immunocompromised non-human immunodeficiency virus (HIV)-infected patients (194 men and 124 women; median age, 68.5 [interquartile range, 59-75] years) who underwent TMP-SMX therapy as a primary PcP prophylaxis between July 2014 and August 2019. The patients were segregated into two groups on the basis of dosage: single-strength (SS; n = 244) and half-strength (HS; n = 74) groups. We evaluated PcP occurrence, TMP-SMX discontinuation rate, and discontinuation-related risk factors in these groups., Results: PcP did not occur in either group. The univariate and multivariate Cox proportional hazards models revealed that the SS dosage and renal function (e.g. serum creatinine and creatinine clearance) were independently associated with prophylaxis discontinuation. At 24 weeks, the HS group presented significantly lower discontinuation rates than the SS group (P = 0.019, log-rank test). In the SS group, patients with mild renal impairment (e.g. serum creatinine ≥0.78 mg/dL or creatinine clearance ≤64.26 mL/min) presented significantly higher TMP-SMX discontinuation rates than those without such an impairment (P < 0.05, log-rank test with Bonferroni correction). This difference was not significant in the HS group., Conclusion: Mild renal impairment might increase the risk of discontinuation of conventional TMP-SMX prophylaxis. In patients with a mild renal impairment, the HS dosage may improve tolerability while maintaining prophylactic efficacy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The discovery of the tyrosine kinase inhibitor (TKI) imatinib in the early 2000's revolutionized the treatment and prognosis of patients with chronic myeloid leukemia (CML) [Hochhaus et al. in N Engl J Med 376:917-927, 2017]. The treatment of patients with CML has changed dramatically since the approval of imatinib and other TKIs. Before the TKI era, newly diagnosed patients would undergo HLA typing to try to identify a well-matched donor, and then proceed quickly to allogeneic hematopoietic cell transplantation (HCT). With the introduction of imatinib followed a few years later by dasatinib, nilotinib, then bosutinib, treatment approaches changed in a dramatic way. Transplantation is no longer an upfront treatment option for newly diagnosed CML patients, and in fact, it is very rarely used in the management of a patient with CML currently. The management of CML patients has been a model of personalized medicine or targeted therapy that is being emulated in the treatment of many other hematologic malignancies and solid tumors such as lung cancer [Soverini et al. in Mol Cancer 17:49, 2018]. The Philadelphia Chromosome (Ph) which leads to the formation of the BCR-ABL fusion gene and its product the BCR-ABL protein is the cause of CML. With effective targeting of this protein with the available TKIs, the disease is completely controllable if not curable for most patients. Life expectancy for patients with CML is essentially normal. Quality of life becomes an important goal including the potential for pregnancy, and ultimately the chance to discontinue all TKI therapy permanently. The three cases outlined below serve to highlight some of the important issues in the management of patients with CML in the post-TKI era., (© 2021. Springer Nature Switzerland AG.)

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., (© 2020 John Wiley & Sons Ltd.)

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

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.

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.

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).

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.

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., Competing Interests: There is no conflict of interest.

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., (©2017 Wiley Periodicals, Inc.)

Purpose: The goal of this study was to investigate the effect of siponimod treatment re-initiation on the initial negative chronotropic effects and cardiac rhythm after variable drug discontinuation periods., Methods: This partially double-blind, randomized, placebo-controlled study was conducted in healthy subjects. Siponimod doses (0.5-4.0 mg) and placebo were evaluated in combination with drug discontinuation periods ranging from 48 to 192 hours. Twelve-lead Holter ECGs were performed from 1.5 hours before until 24 hours after single-dose re-initiation. Atrioventricular blocks (AVBs) and sinus pauses (RR >2 seconds) were categorized according to dose level, discontinuation period, and resting and nonresting hours., Findings: Of the enrolled 138 subjects, 117 were evaluated. Demographic and baseline characteristics were comparable between the treatment groups. Subjects rechallenged at the combination of 4 mg/192 hours (highest investigated dose and longest discontinuation period [7 missed doses]) exhibited the highest decrease in pooled, placebo-adjusted heart rate (HR) of 14.53 beats/min. The magnitude of the negative chronotropic effect of siponimod re-initiation was dependent on both dose and duration of treatment discontinuation. Regardless of the dose, the placebo-adjusted HR reduction at re-initiation of drug treatment after up to 96 hours of drug discontinuation remained <10 beats/min. Except for 1 outlier for HR decrease under the 96-hour/placebo combination, no outliers were observed for any combination up to and including the 96-hour discontinuation periods. Most of the AVBs and sinus pauses were observed during nocturnal hours concurrent with increased vagal tone. All detected AVBs and sinus pauses were asymptomatic and not considered clinically relevant., Implications: Siponimod could be safely re-initiated without retitration after drug discontinuation periods up to 96 hours. Retitration is required if patients miss ≥ 4 consecutive doses., (Copyright © 2016. Published by Elsevier Inc.)

Background: After a first episode in schizophrenia guidelines recommend antipsychotic maintenance treatment (MT) for at least 1year. Recent RCTs on subsequent targeted intermittent treatment (IT) after stepwise drug discontinuation yielded noticeably higher relapse rates than during MT also in first-episode patients. Nevertheless, about 50% of patients remain stable under IT. Given the potential adverse effects of antipsychotics and the preference of many patients to discontinue drugs, valid predictors for the feasibility of IT are urgently needed to support decision making., Methods: Based on a one-year RCT phase comparing MT with IT in first-episode patients after 1year of MT, conducted within the German Research Network on Schizophrenia (GRNS), predictors for deterioration under IT in 19 feasible patients were identified by logistic regression analysis., Results: Deterioration occurred in 10 patients (52.6%). Univariate analyses indicated a lower PANSS positive score after acute treatment as well as after one year of MT as significant predictors; in multivariate logistic regression, in addition to the lower PANSS positive score after acute treatment, reaching enduring remission and having had a deterioration both during MT evolved as significant predictors and indicate a higher risk for deterioration., Conclusions: Although limited by the small sample size, our findings suggest that patients who show a favorable response and full and enduring symptom remission during antipsychotic treatment, as well as those with marked deterioration despite MT should rather be recommended to remain on treatment because they are at higher risk for symptom re-exacerbation after (stepwise) drug discontinuation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The objective in percutaneous coronary intervention (PCI) is to treat flow-limiting atherothrombotic coronary plaques mechanically. Many types of antithrombotic drugs are used to prevent ischemic complications during manipulation of catheters, guidewires, balloons, and stents in coronary arteries while minimizing the risk of bleeding. However, many other types of pharmacologic agents are also used to facilitate PCI. This review focuses on the most commonly used adjunct drugs during PCI. In addition, a recommendation of which drugs should be stopped or interrupted in patients undergoing PCI is provided., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The clinical success of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) as therapeutic agents has prompted great interest in their further development and clinical testing for a wide variety of malignancies. However, most studies have focused on the efficacy of TKI, and few studies have been done on the criteria for their discontinuation. The current standard for drug discontinuation is "until progression", based on change in tumor size. However, tumor size is not related to the gene expression which determines the efficacy of TKI in the final analysis, and it is also difficult to make a thorough and correct prediction based on tumor size when the TKI is discontinued. Nevertheless, clinical evaluation of the criteria for TKI discontinuation is still in its early days. Some promising findings have started to emerge. With the improving knowledge of EGFR and its inhibitors, it is expected that the criteria for discontinuation of EGFR inhibitor therapy will become clearer.