Pathophysiology of Patients Over the Age of 65 with Acute Myeloid Leukemia (AML).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 992-992
Author(s):  
Henna Malik ◽  
Lucas Wong ◽  
Sarju Waghela ◽  
Lisa Go ◽  
William Koss ◽  
...  

Abstract Abstract 992 Poster Board I-14 Background: Acute myeloid leukemia (AML) is a common disease in individuals ≥ 65 years old. Overall survival (OS) is significantly shorter in older patients compared with younger patients. Many patients do not receive chemotherapy due to age or co-morbidities. The aim of our study is to investigate the biologic characteristics of AML in the elderly using variables on survival. Methods: For this single-center, retrospective study, authors analyzed the following variables for the outcome patients ≥ 65 years old: age at diagnosis, gender, WBC, HGB, LDH, % blasts, risk factors, chemotherapy, co-morbidities, cytogenetics, and documented MDS/cancer. Statistical Analysis: All variables were summarized using descriptive statistics: mean (SD) for continuous variables and frequency (percent) for categorical variables. Kaplan-Meier survival curves were obtained, and univariate Cox proportional hazards models and multivariate Cox proportional hazards models were applied. A p-value of less than 0.05 indicated a statistical significance. SAS 9.1.3 (SAS Institute INC, Cary, NC) was used for data management and statistical analysis. Results: Seventy-four patients 65 or older were included for the analysis by Kaplan – Meier survival. The median survival time was 3.8 months. Seventy patients have died and 4 have survived until 1/2009. Patients over 80 years old had the worst survival, 0.7 month, compare to age 65 – 70 group which was 4 months and 71 – 80 group which was 4.6 months. Results with univariate Cox proportional hazards model shows WBC group (p=0.0390), LDH group (p=0.0153), and chemotherapy (p<0.0001) were significant variables on survival. LDH group and cytogenetics were not included in the multivariate model due to many missing measurements (43%; 32 out of 74) and (27%; 17 out of 74), respectively. Final multivariate model including all significant variables revealed significant effect of WBC group (p=0.0074) and chemotherapy (p<0.0001) on survival. Discussion and Conclusions: Prior results from clinical trials and single-center studies evaluating the prognostic factors in older patients are conflicting. In our study, patients who received chemotherapy (standard or intensive chemotherapy) had better survival (median 5.2 months) compare to untreated patients with median survival 0.4 months (p<0.0001). The tendency is to exclude elderly patients for the treatment because of poor performance status (PS), organ dysfunction, and co-morbid conditions. The approach to withhold chemotherapy in elderly patients is not supported by our results. To the contrary, it appears that chemotherapy should be pursued and may offer longer survival except for elderly patients over the age of 80. High WBC ' 10 × 103 /μL at presentation had an adverse impact on survival rates (p=0.034). Other studies have shown mixed results in regards to survival. LDH > 300 U/L was an adverse prognostic factor for survival. A higher leukocyte count probably is representative of high tumor burden and more aggressive disease biology. Cytogenetics (with MDS and without MDS) at diagnosis was not predictive of survival but our cytogenetic evaluation was incomplete due to missing data. Co-morbidities such as cardiovascular disease, diabetes, hepatic disease, pulmonary disease, and cancer did not impact on the survival. We observed adverse impact of increasing age on survival only in patients over 80. Some investigators reported no effects, and others showed increasing age as a poor prognostic factor for both CR and survival or survival alone. The cause of this discrepancy is not clear. Patients > 80 years comprise 28% of our study group and exhibited the worst survival time; they may represent a different patient population with distinct biological features. We conclude that age, biological features, chemotherapy and leukocyte count are the most important determinants of survival. Disclosures: No relevant conflicts of interest to declare.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 253-253
Author(s):  
Christine Cho-Shing Hsu ◽  
Abhishek Goyal ◽  
Rosa Hidalgo ◽  
Elizabeth Verna ◽  
Jean Emond ◽  
...  

253 Background: High alpha-fetoprotein (AFP) is associated with worse survival in hepatocellular carcinoma (HCC) patients. CA19-9 is a glycoprotein biomarker of biliary and pancreatic cancer. To our knowledge, no prospective study has examined CA19-9 as a prognostic biomarker in HCC. We hypothesized that it may add to our ability to risk stratify patients. Methods: We prospectively enrolled 122 patients with newly diagnosed HCC between 10/2008 and 7/2012 and followed until July 23, 2012. HCC was defined by AASLD criteria. CA 19-9 and AFP were measured on enrollment: 50% patients had CA19-9 >37 U/mL and 22% had CA 19-9>100. Pathology specimens were available for 50% of patients and none were consistent with mixed HCC-cholangiocarcinoma (HCC-CC) or pure CC. We evaluated the relationship between CA19-9 and overall survival using Kaplan Meier curves, univariate, and multivariate Cox Proportional Hazards Models. Results: The mean age of the cohort was 62.1 and 79% were male. 59% had underlying HCV and 16% had HBV. In univariate analysis, CA19-9>100 predicted worse survival (HR=3.44, 95% CI: 1.79-6.61, p=0.0002). Other cut-points for CA19-9 yielded similar results, although not all were significant. In a multivariate model including CP Score (B vs. A), Milan (outside vs. within), and AFP (>100 vs. ≤100), CA19-9 >100 remained an independent risk factor for increased mortality (HR 3.95, 95% CI: 1.95-7.97, p=0.0001). CP score and Milan status had HRs of 2.57 (95% CI: 1.31-5.02, p=0.006) and 5.27 (95% CI: 2.05-13.57 p=0.0006). AFP was not an independent risk factor for worse survival with a HR of 1.69 (95% CI: 0.85-3.37, p=0.14). We also looked at models using different cut-points for AFP; CA19-9 added additional risk stratification in all models. Among patients with AFP>100, median survival was 15.5 months vs. 3.8 months when comparing those with CA19-9 ≤100 with CA19-9>100 (p=0.01, log-rank). Conclusions: CA 19-9 is a readily available biomarker that may be a novel predictor of survival in HCC patients. In our multivariate model, CA 19-9>100 almost quadrupled mortality risk. It might be particularly useful to risk stratify patients with normal AFP and those with very high AFP being considered for transplant.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Kochav ◽  
R.C Chen ◽  
J.M.D Dizon ◽  
J.A.R Reiffel

Abstract Background Theoretical concern exists regarding AV block (AVB) with class I antiarrhythmics (AADs) when bundle branch block (BBB) is present. Whether this is substantiated in real-world populations is unknown. Purpose To determine the relationship between type of AAD and incidence of AVB in patients with preexisting BBB. Methods We retrospectively studied all patients with BBB who received class I and III AADs between 1997–2019 to compare incidence of AVB. We defined index time as first exposure to either drug class and excluded patients with prior AVB or exposed to both classes. Time-at-risk window ended at first outcome occurrence or when patients were no longer observed in the database. We estimated hazard ratios for incident AVB using Cox proportional hazards models with propensity score stratification, adjusting for over 32,000 covariates from the electronic health record. Kaplan-Meier methods were used to determine treatment effects over time. Results Of 40,120 individuals with BBB, 148 were exposed to a class I AAD and 2401 to a class III AAD. Over nearly 4,200 person-years of follow up, there were 22 and 620 outcome events in the class I and class III cohorts, respectively (Figure). In adjusted analyses, AVB risk was markedly lower in patients exposed to class I AADs compared with class III (HR 0.48 [95% CI 0.30–0.75]). Conclusion Among patients with BBB, exposure to class III AADs was strongly associated with greater risk of incident AVB. This likely reflects differences in natural history of patients receiving class I vs class III AADs rather than adverse class III effects, however, the lack of worse outcomes acutely with class I AADs suggests that they may be safer in BBB than suspected. Funding Acknowledgement Type of funding source: None


2011 ◽  
Vol 29 (30) ◽  
pp. 4029-4035 ◽  
Author(s):  
David J. Biau ◽  
Peter C. Ferguson ◽  
Robert E. Turcotte ◽  
Peter Chung ◽  
Marc H. Isler ◽  
...  

Purpose To examine the effect of age on the recurrence of soft tissue sarcoma in the extremities and trunk. Patients and Methods This was a multicenter study that included 2,385 patients with median age at surgery of 57 years. The end points considered were local recurrence and metastasis. Cox proportional hazards models were used to estimate hazard ratios across the age ranges with and without adjustment for known confounding factors. Results Older patients presented with tumors that were larger (P < .001) and of higher grade (P < .001). The proportion of positive margins increased significantly as patients age (P < .001), but radiation therapy was relatively underused in patients older than age 60 years. The 5-year cumulative incidences of local recurrence were 7.2% (95% CI, 4% to 11.7%) for patients age 30 years or younger and 12.9% (95% CI, 9.1% to 17.5%) for patients age 75 years or older. The corresponding 5-year cumulative incidences of metastasis were 17.5% (95% CI, 12.1% to 23.7%) and 33.9% (95% CI, 28.1% to 39.8%) for the same groups. Regression models showed that age was significantly associated with local recurrence (P < .001) and metastasis (P < .001) in nonadjusted models. After adjusting for imbalance in presentation and treatment variables, age remained significantly associated with local recurrence (P = .031) and metastasis (P = .019). Conclusion Older patients have worse outcomes because they tend to present with worse tumors and are treated less aggressively. However, there remained a significant increase in the risk of both local and systemic recurrence associated with increasing age that could not be explained by tumor or treatment characteristics.


2017 ◽  
Vol 117 (06) ◽  
pp. 1072-1082 ◽  
Author(s):  
Xiaoyan Li ◽  
Steve Deitelzweig ◽  
Allison Keshishian ◽  
Melissa Hamilton ◽  
Ruslan Horblyuk ◽  
...  

SummaryThe ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA2DS2-VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59–0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54–0.65) than warfarin initiators. Different types of stroke/SE and major bleeding – including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding – were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA2DS2-VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest “real-world” study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard-and low-dose apixaban dose regimens.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2728-2728
Author(s):  
Tingting Shao ◽  
Yuan Feng ◽  
Ninghan Zhang ◽  
Rong Wang ◽  
Ting Pan ◽  
...  

Background: Acute myeloid leukemia (AML) is an aggressive hematological disease. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and chemotherapy are major treatment regimens for AML. However, prognostic markers cannot guide the decision for a specific treatment, as they are related with a various prognosis regardless of the given treatment. HOXA (homeobox A) genes cluster could promote tumor survival, proliferation, invasion, and increase the resistance of AML. The aim of this study was to screen potential miRNAs (microRNAs) that would target HOXA genes, and evaluate the utility of miRNAs in AML, help patients choose a better treatment between chemotherapy and allo-HCST. Methods: Clinical data and RNA-Seq expression data of selected cases were provided by The Cancer Genome Atlas (TCGA). Genome-wide screening was performed to identify miRNA in a heterogeneous AML population. Univariable Cox proportional hazards models and Multivariable Cox proportional hazards models were employed to identify whether OS and EFS would be affected by other variables. Results: In this study, totally 162 AML patients were recruited. All patients were firstly divided into the chemotherapy and allo-HSCT groups. Subsequently, according to median values of miR-340, patients were divided into miR-340high and miR-340low expressers, respectively. In chemotherapy group, no difference was found in clinical characteristics, such as the median age, FAB subtypes, karyotypes and genes mutation between miR-340high and miR-340low expressers. However, miR-340low expressers often accompanied with high first relapse rate or death rate in one year than high expressers (P=0.012; 82.2% vs 55.6%). To identify the independent prognostic role of miR-340 in chemotherapy group patients, Univariable and Multivariable Cox proportional hazards models were performed. We found that miR-340lowpatients showed shorter OS (P=0.0005; 5-year OS, 35.6% vs. 5.4%) and EFS (P=0.0005) compared with high expressers. In multivariable analysis, miR-340low patients showed reduced OS (P=0.004; HR: 2.07) and EFS (P=0.01; HR: 1.909) after adjusting other co-variates, such as age, WBC count and several genes mutation in chemotherapy group. Therefore, low miR-340 amounts could be an independent adverse bio-marker in AML patients undergoing chemotherapy. However, in the allo-HSCT group, miR-340 expression level was not associated with outcome in AML patients. To further explore the potential of allo-HSCT in overcoming the adverse characteristics of low miR-340 amounts, the whole 162 patients were regrouped into miR-340low and miR-340high groups. Then patients were divided into chemotherapy and allo-HSCT subgroups. Subgroup analysis revealed that miR-340low patients had significantly longer OS (P<0.0001; HR: 0.316; 95%CI: 0.167-0.459) and EFS (P=0.002; HR: 0.391; 95%CI: 0.231-0.622) in allo-HSCT subgroup than in chemotherapy subgroup (Figure 1). However, in cases highly expressing miR-340, no difference in survival events was detected between the two treatment subgroups. These findings indicated, allo-HSCT may overcome the adverse prognostic effects of low mir-340 expression. Therefore, for low miR-340 cases, early allo-HSCT may be a better option. To explore underlying biological functions of miR-340, we examined gene expression signatures related to the miR-340 expression in AML patients. We observed 135 genes expression levels that associated with miR-340 expression, with 61 and 74 showing positive and negative correlations, respectively. Gene Ontology showed that these genes involved in cellular and developmental processes, transcription regulation, immune system process, cell apoptosis and proliferation, myeloid cell differentiation and hematopoietic organ development. Furthermore, miR-340 expression was negatively correlated with HOXA and HOXB cluster levels. Strikingly, HOXA10, HOXB2, MEIS1 and PRDM16 were predicted miR-340 targets according to in silico analysis. The results hint a prospective regulatory mechanism that links miR-340 to HOXA genes associated with AML. Conclusions: Our data indicate that decreased miR-340 expression predicts an adverse prognosis and allo-HSCT may overcome the potential adverse characteristics of low miR-340 expression. Therefore, lower miR-340 cases should be strongly considered for early allo-HSCT. Disclosures No relevant conflicts of interest to declare.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
D. A. Patt ◽  
Z. Duan ◽  
G. Hortobagyi ◽  
S. H. Giordano

560 Background: Adjuvant chemotherapy for breast cancer is associated with the development of secondary AML, but this risk in an older population has not been previously quantified. Methods: We queried data from the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database for women who were diagnosed with nonmetastatic breast cancer from 1992–1999. We compared the risk of AML in patients with and without adjuvant chemotherapy (C), and by differing C regimens. The primary endpoint was a claim with an inpatient or outpatient diagnosis of AML (ICD-09 codes 205–208). Risk of AML was estimated using the method of Kaplan-Meier. Cox proportional hazards models were used to determine factors independently associated with AML. Results: 36,904 patients were included in this observational study, 4,572 who had received adjuvant C and 32,332 who had not. The median patient age was 75.3 (66.0–103.3). The median follow up was 63 months (13–132). Patients who received C were significantly younger, had more advanced stage disease, and had lower comorbidity scores (p<0.001). The unadjusted risk of developing AML at 10 years after any adjuvant C for breast cancer was 1.6% versus 1.1% for women who had not received C. The adjusted HR for AML with adjuvant C was 1.72 (1.16–2.54) compared to women who did not receive C. HR for radiation was 1.21 (0.86–1.70). HR was higher with increasing age but p>0.05. An analysis was performed among women who received C. When compared to other C regimens, anthracycline-based therapy (A) conveyed a significantly higher hazard for AML HR 2.17 (1.08–4.38), while patients who received A plus taxanes (T) did not have a significant increase in risk HR1.29 (0.44–3.82) nor did patients who received T with some other C HR 1.50 (0.34–6.67). Another significant independent predictor of AML included GCSF use HR 2.21 (1.14–4.25). In addition, increasing A dose was associated with higher risk of AML (p<0.05). Conclusions: There is a small but real increase in AML after adjuvant chemotherapy for breast cancer in older women. The risk appears to be highest from A-based regimens, most of which also contained cyclophosphamide, and may be dose-dependent. T do not appear to increase risk. The role of GCSF should be further explored. No significant financial relationships to disclose.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 453-453
Author(s):  
Kelly Elizabeth Orwat ◽  
Samuel Lewis Cooper ◽  
Michael Ashenafi ◽  
M. Bret Anderson ◽  
Marcelo Guimaraes ◽  
...  

453 Background: Systemic therapies for unresectable liver malignancies may provide a survival benefit, but eventually prove intolerable or ineffective. TARE provides an additional liver-directed treatment option to improve local control for these patients, but there is limited data on patient factors associated with survival. Methods: All patients that received TARE at the Medical University of South Carolina from March 2006 through May of 2014 were included in this analysis of overall survival (OS) and toxicity. Kaplan-Meier estimates of OS from date of first procedure are reported. Potential prognostic factors for OS were evaluated using log rank tests and Cox proportional hazards models. Results: In 114 patients that received TARE at our institution, median follow-up was 6.4 months [range 0-86], with the following tumor histology: colorectal (CR) n=55, hepatocellular (HC) n=20, cholangiocarcinoma (CC) n=16, neuroendocrine (NE) n=12, breast (BR) n=6, other n=5. At least 1 line of systemic therapy prior to TARE was noted in 79% of patients. Median OS was 6.6 months and 1-year OS was 30.7%. The percentage of patients who died within 3 months of TARE were 46.2% for patients with albumin < 3 but only 20.3% for patients with albumin ≥ 3. Grade ≥ 2 toxicity was observed in 22 patients (19.3%) including 9 (7.9%) with Grade 3 and 1 (0.9%) with Grade 4 toxicity. A single patient with a pre-existing pulmonary arteriovenous malformation experienced Grade 3 pneumonitis that resolved with steroids. No deaths were attributed to radiation-induced liver disease. Conclusions: TARE is a relatively safe and effective treatment for unresectable intrahepatic malignancies. Patients with NE or BR histology as well as those with better hepatic synthetic function were associated with significantly better survival. Our data suggest that patients with albumin below 3 may not benefit from TARE. [Table: see text]


2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Zhou ◽  
Xuerong Sun ◽  
Na Yu ◽  
Shuang Zhao ◽  
Keping Chen ◽  
...  

Background: The results of studies on the obesity paradox in all-cause mortality are inconsistent in patients equipped with an implantable cardioverter-defibrillator (ICD). There is a lack of relevant studies on Chinese populations with large sample size. This study aimed to investigate whether the obesity paradox in all-cause mortality is present among the Chinese population with an ICD.Methods: We conducted a retrospective analysis of multicenter data from the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device–implanted Patients (SUMMIT) registry in China. The outcome was all-cause mortality. The Kaplan–Meier curves, Cox proportional hazards models, and smooth curve fitting were used to investigate the association between body mass index (BMI) and all-cause mortality.Results: After inclusion and exclusion criteria, 970 patients with an ICD were enrolled. After a median follow-up of 5 years (interquartile, 4.1–6.0 years), in 213 (22.0%) patients occurred all-cause mortality. According to the Kaplan–Meier curves and multivariate Cox proportional hazards models, BMI had no significant impact on all-cause mortality, whether as a continuous variable or a categorical variable classified by various BMI categorization criteria. The fully adjusted smoothed curve fit showed a linear relationship between BMI and all-cause mortality (p-value of 0.14 for the non-linearity test), with the curve showing no statistically significant association between BMI and all-cause mortality [per 1 kg/m2 increase in BMI, hazard ratio (HR) 0.97, 95% CI 0.93–1.02, p = 0.2644].Conclusions: The obesity paradox in all-cause mortality was absent in the Chinese patients with an ICD. Prospective studies are needed to further explore this phenomenon.


2021 ◽  
pp. 1-14 ◽  
Author(s):  
Olga Mitelman ◽  
Hoda Z. Abdel-Hamid ◽  
Barry J. Byrne ◽  
Anne M. Connolly ◽  
Peter Heydemann ◽  
...  

Background: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. Objective: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. Methods: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. Results: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: –3.3 vs. –6.0 percentage points annually, p < 0.0001). Conclusions: Study 405 highlights the functional benefits of eteplirsen on ambulatory and pulmonary function outcomes up to 7 years of follow-up in comparison to external controls.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0242467
Author(s):  
Yu-Chen Yeh ◽  
Joseph C. Cappelleri ◽  
Xiaocong L. Marston ◽  
Ahmed Shelbaya

Objective To examine pregabalin dose titration and its impact on treatment adherence and duration in patients with neuropathic pain (NeP). Methods MarketScan database (2009–2014) was used to extract a cohort of incident adult pregabalin users with NeP who had at least 12 months of follow-up data. Any dose augmentation within 45 days following the first pregabalin claim was defined as dose titration. Adherence (measured by medication possession ratio/MPR) and persistence (measured as the duration of continuous treatment) were compared between the cohorts with and without dose titration. Logistic regressions and Cox proportional hazards models were used to identify the factors associated with adherence (MPR ≥ 0.8) and predictors of time to discontinuation. Results Among the 5,186 patients in the analysis, only 18% of patients had dose titration. Patients who had dose titration were approximately 2.6 times as likely to be adherent (MPR ≥ 0.8) (odds ratio = 2.59, P < 0.001) than those who did not have dose titration. Kaplan-Meier analysis shows that the time to discontinuation or switch was significantly longer among patients who had dose titration (4.99 vs. 4.04 months, P = 0.009). Conclusions Dose titration was associated with improved treatment adherence and persistence among NeP patients receiving pregabalin. The findings will provide valuable evidence to increase physician awareness of dose recommendations in the prescribing information and to educate patients on the importance of titration and adherence.


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